leptin and Weight-Loss

Obesity-related asthma is associated with a high disease burden and a poor response to existent asthma therapies, suggesting that it is a distinct asthma phenotype. The proposed mechanisms that contribute to obesity-related asthma include the effects of the mechanical load of obesity, adipokine perturbations, and immune dysregulation. Each of these influences airway smooth muscle function. Mechanical fat load alters airway smooth muscle stretch affecting airway wall geometry, airway smooth muscle contractility, and agonist delivery; weight loss strategies, including medically induced weight loss, counter these effects. Among the metabolic disturbances, insulin resistance and free fatty acid receptor activation influence distinct signaling pathways in the airway smooth muscle downstream of both the M2 muscarinic receptor and the β

Topics: Asthma; Humans; Insulin Resistance; Leptin; Pediatric Obesity; Weight Loss

Bariatric procedures are considered to be the most effective treatment options for obesity. One of them is laparoscopic sleeve gastrectomy (LSG), which is nowadays very popular and widely used. LSG leads to weight loss and metabolic improvement and also changes adipokine levels, although it is just a restrictive operation. We describe changes in pro-inflammatory (leptin, resistin, visfatin and chemerin) and anti-inflammatory adipokines (adiponectin, omentin), with adiponectin and leptin being most studied. Their levels are markedly changed after LSG and this may partially explain the weight loss seen after LSG. Adipokines are closely connected to insulin resistance and chronic inflammation both being positively influenced after LSG. Leptin regulates amount of body fat, appetite, thermogenesis and metabolic rate and its levels are positively correlated with both weight and BMI changes after operation. Resistin influences insulin sensitivity, modulates body cholesterol trafficking and its changes after operation correlate with BMI, waist circumference, fat mass, LDL cholesterol and C-reactive protein. Chemerin, an important component of immune system, decreases after bariatric surgery and its levels correlate with BMI, triglyceride levels, and blood glucose. On the other hand, pro-inflammatory adipokine adiponectin, which influences fatty acid oxidation, browning of fat tissue and energy metabolism, is declining after LSG. This decline explains improvement of glucose status after bariatric surgery in patients with diabetes and is correlated with BMI loss, waist circumference and LDL cholesterol level. Effect of LSG goes beyond calory restriction and the changes of adipokines have a great impact on health status of the bariatric patients.

Topics: Adipokines; Adiponectin; Cholesterol, LDL; Gastrectomy; Humans; Insulin Resistance; Laparoscopy; Leptin; Obesity, Morbid; Resistin; Weight Loss

Adiponectin, leptin, and pro- and anti-inflammatory cytokines are implicated in breast cancer risk and recurrence. Weight loss, via the dynamic interplay of energy balance through exercise and/or caloric restriction, decreases risk of breast cancer recurrence.. We investigated the effects of lifestyle modifications (exercise only, or combined caloric restriction and exercise) on adipokines, IL2, IL6, IL8, IL10, C-reactive protein (CRP), and TNFα biomarkers in breast cancer survivors. Searches were completed in June and July of 2019 to identify randomized controlled trials that met inclusion criteria. Weighted mean difference was calculated using random- or fixed-effects models based on the heterogeneity of the studies.. 2501 records were identified, with 30 ultimately meeting inclusion criteria of the systematic review; 21 studies provided data suitable for meta-analysis. We observed leptin levels were significantly reduced in the exercise-only group compared with sedentary control [WMD -5.66; 95% confidence interval (CI), -11.0 to -0.33;. Leptin may be a primary mediator of exercise-induced improvements in breast cancer recurrence.. This is the first review and meta-analysis to examine combined exercise and caloric restriction programs in breast cancer survivors. Future studies should further examine combined programs and their efficacy for altering leptin.

Topics: Biomarkers; Biomarkers, Tumor; Body Mass Index; Breast Neoplasms; Cancer Survivors; Diet, Healthy; Exercise; Female; Humans; Inflammation; Leptin; Neoplasm Recurrence, Local; Weight Loss

Weight loss is traditionally viewed as straightforward counting of calories in and calories out, with little regard to the role of the adipocytes tasked with storing said calories. However, the body executes a complex compensatory response to any intervention that depletes its energy stores. Here, the authors discuss the methods used to attain weight loss, the body's response to this weight loss, and the difficulties in maintaining weight loss. Furthermore, the authors provide an overview of the literature on the physiological effects of liposuction.. To describe the role of adipose tissue in energy homeostasis, methods of weight loss, weight regain, and the effect of liposuction on endocrine signaling.. The authors conducted a narrative review of representative studies.. A variety of strategies for weight loss exist, and optimizing one's weight status may in turn optimize the aesthetic outcomes of liposuction. This is most apparent in the preferential reaccumulation of fat in certain areas after liposuction and the ability to avoid this with a negative energy balance.

Topics: Combined Modality Therapy; Diet, Healthy; Exercise Therapy; Humans; Leptin; Lipectomy; Lipid Metabolism; Obesity; Recurrence; Subcutaneous Fat; Treatment Outcome; Weight Gain; Weight Loss

Obstructive sleep apnea (OSA), obesity, and disturbed glucose homeostasis are usually considered distinct clinical condition, although they are tightly related to each other. The aim of our manuscript is to provide an overview of the current evidence on OSA, obesity, and disturbed glucose homeostasis providing epidemiologic evidence, biological insights, and therapeutic strategies.. The mechanisms hypothesized to be involved in this complex interplay are the following: (1) "direct weight-dependent" mechanisms, according to which fat excess compromises respiratory mechanics, and (2) "indirect weight-dependent" mechanisms such as hyperglycemia, insulin resistance and secondary hyperinsulinemia, leptin resistance and other hormonal dysregulations frequently found in subjects with obesity, type 2 diabetes, and/or sleep disorders. Moreover, the treatment of each of these clinical conditions, through weight loss induced by diet or bariatric surgery, the use of anti-obesity or antidiabetic drugs, and continuous positive airway pressure (CPAP), seems to positively influence the others. These recent data suggest not only that there are multiple connections among these diseases but also that treating one of them may result in an improvement of the others.

Topics: Bariatric Surgery; Body Weight; Continuous Positive Airway Pressure; Diabetes Mellitus, Type 2; Diet; Glucose; Homeostasis; Humans; Hyperinsulinism; Insulin Resistance; Leptin; Obesity; Risk Factors; Sleep Apnea, Obstructive; Weight Loss

Different adipokines secreted from adipose tissue, exert a range of physiological effects. The aim of present systematic review and meta-analysis was to critically investigate the consequence of bariatric surgery on circulating adipokines, that is, adiponectin, leptin, visfatin, resistin, plasminogen activator inhibitor, and chemerin. After systematically checking the following electronic databases: ISI web of Science, Scopus and PubMed without limitation in time and language up to February 2019, a pool based on a random effect model was established. Eighty-five eligible studies were entered for quantitative analysis. Our meta-analysis revealed that circulating adiponectin increased significantly after bariatric surgery [Standardized mean difference (SMD)=1.401, 95% CI: 1.101, 1.701, p<0.001]; whilst leptin (SMD=-2.178, 95% CI: -2.433, -1.923, p<0.001), PAI-1 (-14.928 ng/ml 95% CI: -21.794, -8.063, p<0.001), and chemerin (-50.238 ng/ml 95% CI: -85.708, -14.768, p<0.001) decreased. However, serum visfatin (2.05 ng/ml, 95% CI: -5.07, 9.17, p=0.573) and resistin (-2.080 ng/ml, 95% CI: -5.352, 1.192, p=0.21) were unchanged. In conclusion, bariatric surgery is associated with a reduction in specific adipokines including leptin, chemerin, and PAI-1, whereas adiponectin is raised, adaptations that could be indicative of improved fat mass and function.

Topics: Adiponectin; Adipose Tissue; Bariatric Surgery; Chemokines; Cytokines; Diabetes Mellitus, Type 2; Humans; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Organ Size; Plasminogen Activator Inhibitor 1; Postoperative Period; Resistin; Weight Loss

This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of resveratrol intake on weight loss. We searched the following databases until July 2018: MEDLINE, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Out of 831 reports, 36 RCTs were eligible for including to our meta-analysis. The pooled results, using random-effects model showed that resveratrol supplementation significantly decreased body weight (SMD = -0.17; 95% CI, -0.33, -0.01;

Topics: Adiponectin; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Leptin; Obesity; Randomized Controlled Trials as Topic; Resveratrol; Weight Loss

Leptin resistance refers to states in which leptin fails to promote its anticipated effects, frequently coexisting with hyperleptinaemia. Leptin resistance is closely associated with obesity and also observed in physiological situations such as pregnancy and in seasonal animals. Leptin resensitisation refers to the reversion of leptin-resistant states and is associated with improvement in endocrine and metabolic disturbances commonly observed in obesity and a sustained decrease of plasma leptin levels, possibly below a critical threshold level. In obesity, leptin resensitisation can be achieved with treatments that reduce body adiposity and leptinaemia, or with some pharmacological compounds, while physiological leptin resistance reverts spontaneously. The restoration of leptin sensitivity could be a useful strategy to treat obesity, maintain weight loss and/or reduce the recidivism rate for weight regain after dieting. This review provides an update and discussion about reversion of leptin-resistant states and modulation of the molecular mechanisms involved in each situation.

Topics: Adiposity; Animals; Blood Pressure; Body Weight; Diet; Eating; Energy Intake; Female; Fertility; Humans; Hyperglycemia; Leptin; Male; Mice; Obesity; Phosphorylation; Photoperiod; Pregnancy; Pregnancy, Animal; Signal Transduction; Thermogenesis; Weight Loss

Obesity is a severe medical problem endangering the health of individuals worldwide. Sleeve gastrectomy (SG), one of the most commonly performed bariatric procedures, has been widely applied to the treatment of such patients. Currently, the potential mechanisms underlying the significant weight loss and metabolic improvement after SG have been well studied. First, and most importantly, by removing a large volume of stomach, the SG directly or indirectly restricts food intake. Then, there are alterations in the absorption and metabolism of both macro- and micronutrients, which may benefit or worsen the patients' well-being. Another profound change is enhanced secretion of the satiety gut hormone and reduced secretion of the hunger hormone as a consequence of the operation. Additionally, adjustment of gastrointestinal motility, alteration in the gut microbial community, and an inflammatory response were found after surgery. Therefore, the purpose of the present review was focused on such hypotheses and to compile the accumulated facts on the physiologic mechanism of bariatric surgery so that these results can help improve the understanding of how SG produces substantial weight loss and a significant improvement in the metabolism of patients with metabolic syndrome.

Topics: Animals; Bariatric Surgery; Eating; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Motility; Ghrelin; Humans; Leptin; Mice; Obesity; Rats; Signal Transduction; Weight Loss

The pathogenesis of osteoarthritis (OA) is not clear; leptin may be related to its pathogenesis.. We reviewed articles on leptin in OA, chondrocytes, and in vitro experiments. It is concluded that leptin may lead to OA via some signaling pathways. At the same time, the concentration of leptin in vitro experiments and OA/rheumatoid arthritis (RA) patients was summarized.. Leptin levels in serum and synovial fluid of OA/RA patients were higher than normal person. In the condition of infection and immunity, serum leptin levels in the peripheral blood significantly increase. Because of the close relationship between obesity, leptin, and OA, it is crucial to study the effects of weight loss and exercise intervention on serum leptin levels to improve the symptoms of OA patients.. Treatment for leptin-increased obesity may be a treatment for OA. The role of leptin in OA cannot be ignored and needs to be further studied.

Topics: Arthritis, Rheumatoid; Chondrocytes; Humans; Leptin; Obesity; Osteoarthritis; Risk Factors; Signal Transduction; Synovial Fluid; Weight Loss

Metabolic adaptations occur with weight loss that result in increased hunger with discordant simultaneous reductions in energy requirements-producing the so-called

Topics: Appetite; Basal Metabolism; Diet, Reducing; Energy Intake; Energy Metabolism; Ghrelin; Humans; Hunger; Leptin; Life Style; Obesity; Thermodynamics; Weight Gain; Weight Loss

Leptin is secreted from adipocytes and acts mainly on the hypothalamus causing weight loss due to suppression of appetite and increased energy expenditure. On the other hand, the leptin receptor is also expressed in hematopoietic cells and its action on the immune system has become known, and the significance of leptin in autoimmune diseases has gradually become clear. It has been shown that leptin acts as an exacerbating factor in many autoimmune diseases and it is suggested that inhibition of leptin signal may be a novel therapeutic method for autoimmune diseases. In this article, we will outline the significance of leptin in the immune system based on the current reports.

Topics: Adipocytes; Appetite; Arthritis, Rheumatoid; Autoimmune Diseases; Disease Progression; Energy Metabolism; Hematopoietic Stem Cells; Humans; Hypothalamus; Leptin; Lupus Erythematosus, Systemic; Molecular Targeted Therapy; Receptors, Leptin; Signal Transduction; Weight Loss

Suction-assisted lipectomy is one of the most frequent procedures in plastic surgery. The aim of this study was to investigate whether suction-assisted lipectomy causes changes in the carbohydrates and lipid metabolism and the potential effects on cardiovascular risk factors.. We interrogated five databases: Medline, American College of Physicians Journal Club Database, Cochrane central register of controlled trials, Cochrane database of systematic reviews, Database of abstracts of reviews of effects. A systematic review of the literature was performed in order to compare results of randomized controlled trials and observational studies concerning changes in weight, metabolism, endocrinology, inflammatory markers and cardiovascular risk factors after suction-assisted lipectomy. All articles were assessed by criteria from Oxford Center For Evidence Based Medicine (OCEBM).. The search resulted in 40 articles: 12 experimental animal studies and 28 human studies.. Different metabolic parameters are affected by suction-assited lipectomy. First, all articles point out a decrease of body weight after suction-assisted lipectomy. Weight lost only affects fat mass without any change of lean mass. The potential compensatory growth of visceral fat seems to be counteracted by physical activity. Then, resting energy expenditure seems to be stable or decrease after the surgery. This reduction is significantly related to the decrease of leptin levels and also seems to be counteracted by physical activity. About adipocytokines, leptin level decreases after suction-assisted lipectomy while results are contradictory about adiponectin and resistin levels. However adiponectin seems to tend to increase after surgery. Inflammatory markers seem to increase within first hours after surgery. Then they seem to decrease or remain at the preoperative levels. Fasting insulin level decreases and is linked to the aspirated volume. So insulin sensitivity seems to be improved. Concerning lipid profil, it tends to remain the same or to be improved by suction-assisted lipectomy. In conclusion, regarding all the literature, there is still debate about metabolic effect of suction-assisted lipectomy. Prospective clinical studies are needed to confirm or invalidate some hypotheses. These studies must consider some potential biases as physical activity, diet and medical treatment modifications (statins).

Topics: Adipokines; Animals; Cholesterol; Energy Metabolism; Humans; Insulin; Leptin; Lipectomy; Lipids; Suction; Weight Loss

Obesity is a growing health risk with few successful treatment options and fewer still that target both obesity and obesity-associated comorbidities. Despite ongoing scientific efforts, the most effective treatment option to date was not developed from basic research but by surgeons observing outcomes in the clinic. Bariatric surgery is the most successful treatment for significant weight loss, resolution of type 2 diabetes and the prevention of future weight gain. Recent work with animal models has shed considerable light on the molecular underpinnings of the potent effects of these 'metabolic' surgical procedures. Here we review data from animal models and how these studies have evolved our understanding of the critical signalling systems that mediate the effects of bariatric surgery. These insights could lead to alternative therapies able to accomplish effects similar to bariatric surgery in a less invasive manner.

Topics: Animals; Disease Models, Animal; Energy Intake; Energy Metabolism; Feeding Behavior; Gastrectomy; Gastric Bypass; Homeostasis; Leptin; Lipids; Mice; Obesity; Paracrine Communication; Peptide Hormones; Rats; Weight Loss

Leptin, the first described adipokine, interplays with hepatic metabolism. The aim of this review was to summarize available data on the association between leptin and nonalcoholic fatty liver disease (NAFLD). Leptin has a potential dual action on NAFLD experimental models, exerting a possible anti-steatotic, but also a proinflammatory and profibrogenic action. Observational clinical studies have shown higher or similar leptin levels between simple steatosis and nonalcoholic steatohepatitis (NASH) compared with controls. Interventional studies showed that circulating leptin diminishes together with body mass index after successful weight loss following lifestyle modifications or bariatric surgery. Studies providing evidence for the effect of other medications on leptin levels in NAFLD populations are limited and of low power. Data from small studies claim that recombinant leptin administration had a possibly beneficial effect on steatosis, but not fibrosis, in NAFLD patients with hypoleptinemia. Although the aforementioned dual leptin action has not yet been validated in humans, leptin administration in NAFLD patients with normoleptinemia or hyperleptinemia is discouraged. Further well-controlled studies in cautiously selected populations are needed to elucidate whether leptin has any prognostic and therapeutic role in NAFLD patients.

Topics: Animals; Body Mass Index; Humans; Leptin; Non-alcoholic Fatty Liver Disease; Observational Studies as Topic; Weight Loss

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea hypopnea syndrome (OSAHS), but previous studies assessing the effect of CPAP on leptin in patients with OSAHS yielded conflicting results. In this study, we conducted a meta-analysis to determine whether CPAP therapy could reduce serum leptin levels.. Databases of PubMed, Elsevier, and SCI were thoroughly searched by 2 independent reviewers.. RevMan (version 5.2) was used for data synthesis. Weighted mean difference (WMD) before and after CPAP therapy was calculated to estimate the effects of CPAP therapy.. A total of 11 studies involving 413 participants were included. Meta-analysis showed that the total WMD for leptin levels was 1.44 units (95% confidence interval: 1.11-1.77, P < .01) before and after CPAP therapy. Subgroup analysis exhibited that leptin was decreased within 3 days after the therapy, and it was further reduced within 1 to 3 months and beyond.. The results of our meta-analysis showed that CPAP could significantly reduce leptin levels in OSAHS patients without concomitant weight loss.

Topics: Continuous Positive Airway Pressure; DNA-Binding Proteins; Humans; Leptin; Sleep Apnea, Obstructive; Transcription Factors; Weight Loss

Achieving maintenance of weight loss is crucial to combat obesity. However, most individuals tend to regain weight. Data from successful maintainers show that they remain vigilant and constantly apply techniques to oppose the course of regaining. On the other hand, current advances in obesity research show that the reduced obese state is a state of altered physiology in terms of energy balance. This review describes the physiological adaptations occurring after weight loss that predispose to regaining. Specifically, changes regarding body composition, hormonal background, energy expenditure and control of food intake are discussed. Moreover, metabolites that can act as regain predictors and dietary techniques to oppose regaining are presented.

Topics: Body Composition; Energy Metabolism; Humans; Leptin; Obesity; Weight Gain; Weight Loss

Fat loss is associated with shorter survival and reduced quality of life in cancer patients. Effective intervention for fat loss in cachexia requires identification of the condition using prognostic biomarkers for early detection and prevention of further depletion. No biomarkers of fat mass alterations have been defined for application to the neoplastic state. Several inflammatory cytokines have been implicated in mediating fat loss associated with cachexia; however, plasma levels may not relate to adipose atrophy. Zinc-α2-glycoprotein may be a local catabolic mediator within adipose tissue rather than serving as a plasma biomarker of fat loss. Plasma glycerol and leptin associate with adipose tissue atrophy and mass, respectively; however, no study has evaluated their potential as a prognostic biomarker of cachexia-associated fat loss. This review confirms the need for further studies to identify valid prognostic biomarkers to identify loss of fat based on changes in plasma levels of biomarkers.

Topics: Adipokines; Adipose Tissue; Biomarkers; Cachexia; Carrier Proteins; Cytokines; Glycerol; Glycoproteins; Humans; Inflammation; Leptin; Lipid Metabolism; Lipolysis; Neoplasms; Prognosis; Weight Loss

Numerous laboratory studies involving both animal and human models indicate that weight loss induces changes in leptin, ghrelin and insulin sensitivity, which work to promote weight regain. It is unclear, however, whether these biological changes serve as a biomarker for predicting weight regain in free-living humans in which biological, behavioral and environmental factors are likely at play. We identified 12 studies published between January 1995 and December 2011 that reported changes in leptin, ghrelin or insulin during intentional weight loss with a follow-up period to assess regain. Two of the nine studies examining leptin suggested that larger decreases were associated with greater regain, three studies found the opposite (smaller decreases were associated with greater regain), whereas four studies found no significant relationship; none of the studies supported the hypothesis that increases in ghrelin during weight loss were associated with regain. One study suggested that improvements in insulin resistance were associated with weight gain, but five subsequent studies reported no association. Changes in leptin, ghrelin or insulin sensitivity, taken alone, are not sufficient to predict weight regain following weight loss in free-living humans. In future studies, it is important to include a combination of physiological, behavioral and environmental variables in order to identify subgroups at greatest risk of weight regain.

Topics: Biomarkers; Body Mass Index; Body Weight; Diet, Reducing; Exercise; Female; Ghrelin; Humans; Insulin; Insulin Resistance; Leptin; Male; Obesity; Predictive Value of Tests; Weight Gain; Weight Loss

Obesity and migraine are both highly prevalent disorders in the general population, influenced by genetic and environmental risk factors. In recent studies, obesity was found to be a strong risk factor for transformed migraine and, among migraineurs, obesity was associated with frequent headaches and higher disability scores. Suggested mechanisms included: (i) obesity as a pro-inflammatory state may be associated with neurovascular inflammation in patients with migraine; (ii) elevated levels of plasma calcitonin gene-related peptide (CGRP) in obese individuals may play a role as an important post-synaptic mediator of trigeminovascular inflammation in migraine; (iii) dismodulation in the hypothalamic neuropeptide, orexin, in obese persons may be associated with increased susceptibility to neurogenic inflammation causing migraine attacks; and (iv) leptin and adiponectin can activate proinflammatory cytokine release that is involved in the pathogenesis of migraine. In addition, both conditions are associated with psychiatric co-morbidities, such as depression and anxiety, that can further increase headache frequency and disability. Therefore, the effect of obesity on migraine outcome is important. Weight and BMI should be measured and calculated in all children presenting with migraine, and weight control should be a part of the treatment.

Topics: Adiponectin; Calcitonin Gene-Related Peptide; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Migraine Disorders; Neurogenic Inflammation; Neuropeptides; Orexins; Pediatric Obesity; Risk Factors; Weight Loss

Despite the known glucose-lowering effects of metformin, more recent clinical interest lies in its potential as a weight loss drug. Herein, we discuss the potential mechanisms by which metformin decreases appetite and opposes unfavorable fat storage in peripheral tissues.. Many individuals struggle to maintain clinically relevant weight loss from lifestyle and bariatric surgery interventions. Long-term follow-up from the Diabetes Prevention Program demonstrates that metformin produces durable weight loss, and decreased food intake by metformin is the primary weight loss mechanism. Although the effect of metformin on appetite is likely to be multifactorial, changes in hypothalamic physiology, including leptin and insulin sensitivity, have been documented. In addition, novel work in obesity highlights the gastrointestinal physiology and circadian rhythm changes by metformin as not only affecting food intake, but also the regulation of fat oxidation and storage in liver, skeletal muscle, and adipose tissue.. Metformin induces modest weight loss in overweight and obese individuals at risk for diabetes. A more detailed understanding of how metformin induces weight loss will likely lead to optimal co-prescription of lifestyle modification with pharmacology for the treatment of obesity independent of diabetes.

Topics: Appetite Depressants; Diabetes Mellitus, Type 2; Eating; Humans; Hypoglycemic Agents; Hypothalamus; Insulin Resistance; Leptin; Metformin; Obesity; Risk Reduction Behavior; Signal Transduction; Treatment Outcome; Weight Loss

Adaptive thermogenesis (AT) with weight loss refers to underfeeding-associated fall in resting and non-resting energy expenditure (REE, non-REE); this is independent of body weight and body composition. In humans, the existence of AT was inconsistently shown and its clinical significance has been questioned.. Discrepant findings are mainly due to different definitions of AT, the use of various and nonstandardized study protocols, and the limits of accuracy of methods to assess energy expenditure. With controlled underfeeding, AT takes more than 2 wk to develop. AT accounts to an average of 0.5 MJ (or 120 kcal) with a considerable between subject variance.. Low-sympathetic nervous system activity, 3,5,3'-tri-iodothyronine (T3) and leptin are likely to add to AT; however, the kinetic changes of their plasma levels with underfeeding differ from the time course of AT and controlled intervention studies substituting and titrating these hormones are rare in humans. AT in response to underfeeding is independent of thermogenesis in response to either diet or cold. Although fat-free mass (FFM) and, thus, liver, and skeletal muscle are considered as major sites of AT, cold-induced nonshivering thermogenesis relates to the metabolism of brown adipose tissue (BAT). In humans, diet-induced thermogenesis is related to postprandial substrate metabolism of FFM with a questionable role of BAT. Obviously, the REE component of AT differs from and its non-REE component with respect to organ contribution as well as mechanisms. Thus, AT cannot be considered as unique.. AT should be characterized based on individual components of daily energy expenditure, detailed body composition analyses, and mathematical modeling. The biological basis of AT as well as the influences of age, sex, obesity, stress, and inflammation remain to be established in humans.

Topics: Adipose Tissue, Brown; Body Composition; Body Weight; Diet; Energy Intake; Energy Metabolism; Humans; Leptin; Rest; Sympathetic Nervous System; Thermogenesis; Weight Loss

Mutations in genes involved in energy balance regulation within the central nervous system lead to monogenic forms of obesities. Individuals with these mutations are characterized by early-onset obesity and in some cases by endocrine abnormalities. Carriers of leptin gene mutations are able to normalize their body weight after daily subcutaneous leptin administration. Pharmacotherapy targeting the specific-gene deficiencies has not clinically been tested in other monogenic obesities. Mutations in the melanocortin 4 receptor gene (MC4R) represent the most common monogenic cause of human obesity. Several treatment options have been investigated in subjects with MC4R mutations. Few studies showed that an intensive life-style intervention induces similar weight reduction in MC4R mutation carriers in comparison to MC4R mutation noncarriers. However, long-term body weight maintenance is hardly ever achieved in MC4R mutation carriers. Sibutramine, serotonin and noradrenalin reuptake inhibitor, in MC4R mutation carriers induced weight reduction and improved cardiometabolic health risks. This result was also found in our homozygous MC4R mutation carrier. In vitro studies of melanocortin agonists efficiently activate mutated MC4R with impaired endogenous agonist functional response and thus, further research in the development of drugs for MC4R mutations is needed. An administration of intranasal adrenocorticotropic hormone was not shown to be effective in subjects with pro-opiomelanocortin gene mutations. Bariatric surgery has also been performed in few of MC4R mutation carriers. After gastric banding, lower body weight reduction and worse improvement of metabolic complications was found in MC4R mutation carriers versus noncarriers. However, preliminary results suggest that diversionary operations as gastric bypass represent a suitable method also for MC4R mutation carriers. In conclusion, the management of monogenic obesities still remains a challenge.

Topics: Bariatric Surgery; Body Mass Index; Body Weight; Child; Cyclobutanes; Energy Metabolism; Heterozygote; Homozygote; Humans; Leptin; Mutation; Obesity; Pro-Opiomelanocortin; Receptor, Melanocortin, Type 4; Weight Loss

The prevalence of obesity is increasing which becomes worrisome due to its association with several diseases and certain types of cancers. While weight control through dietary caloric restriction and/or physical activity protects against cancer in animal models, the underlying mechanisms are not fully defined. Weight loss due to negative energy balance is associated with alterations of multiple growth factors and endocrine hormones. The altered hormones and hormone-related functions appear to be responsible for anti-cancer mechanisms. In this review, we summarize the recent studies related to weight loss and the altered endocrine hormones, focusing on the reduced levels of the mitogenic insulin-like growth factor 1 (IGF-1) and adipokine leptin as well as the raised levels of adiponectin and glucocorticoids. The potential molecular targets of these hormone-dependent signalling pathways are also discussed. Considering the increasing trends of obesity throughout the world, a better understanding of the underlying mechanisms between body weight, endocrine hormones and cancer risk may lead to novel approaches to cancer prevention and treatment.

Topics: Adiponectin; Animals; Caloric Restriction; Glucocorticoids; Humans; Insulin-Like Growth Factor I; Leptin; Neoplasms; Obesity; Prevalence; Weight Loss

Diets involving a reduction in caloric intake are frequently prescribed for the treatment of obesity, but their long-term efficacy is questionable. We considered a calorie restricted diet successful if the weight loss was ≥ 5% after at least 3 years follow up. From published data, calculating a definitive percentage of successful cases is difficult because of the way data are presented and because loss to follow-up is not corrected for in many studies. Judging by the best data available, the success rate is very low. Most individuals will regain weight and sometimes even more than they lost in the first place. The mechanisms driving this weight increase are a decrease in energy expenditure and an increased appetite which is mediated by factors such as leptin. If the first attempt to lose weight fails, the advice to go on a diet should not be endlessly repeated; stabilizing the individual's weight would probably be a more realistic goal.

Topics: Caloric Restriction; Energy Intake; Energy Metabolism; Humans; Leptin; Obesity; Treatment Failure; Treatment Outcome; Weight Gain; Weight Loss

Obesity markedly increases the risk of hypertension and cardiovascular disease, which may be related to activation of the sympathetic nervous system (SNS). Sympathetic overactivity directly and indirectly contributes to blood pressure (BP) elevation in obesity, including stimulation of the renin-angiotensin-aldosterone system (RAAS). The adipocyte-derived peptide leptin suppresses appetite, increases thermogenesis, but also raises SNS activity and BP. Obese individuals exhibit hyperleptinemia but are resistant to its appetite-suppressing actions. Interestingly, animal models of obesity exhibit preserved sympathoexcitatory and pressor actions of leptin, despite resistance to its anorexic and metabolic actions, suggesting selective leptin resistance. Disturbance of intracellular signaling at specific hypothalamic neural networks appears to underlie selective leptin resistance. Delineation of these pathways should lead to novel approaches to treatment. In the meantime, treatment of obesity-hypertension has relied on antihypertensive drugs. Although sympathetic blockade is mechanistically attractive in obesity-hypertension, in practice its effects are disappointing because of adverse metabolic effects and inferior outcomes. On the basis of subgroup analyses of obese patients in large randomized clinical trials, drugs such as diuretics and RAAS blockers appear superior in preventing cardiovascular events in obesity--hypertension. An underused alternative approach to obesity-hypertension is induction of weight loss, which reduces circulating leptin and insulin, partially reverses resistance to these hormones, decreases sympathetic activation and improves BP and other risk factors. Though weight loss induced by lifestyle is often modest and transient, carefully selected pharmacological weight loss therapies can produce substantial and sustained antihypertensive effects additive to lifestyle interventions.

Topics: Humans; Hypertension; Leptin; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Weight Loss

Obesity is now considered the new world epidemic. In an attempt to face this menace to public health, several treatments, apart from the traditional nutritional modification and oral medication, have been introduced, among them bariatric surgery and gut hormone-based treatments. The gastrointestinal (GI) tract is a powerful endocrine organ, releasing active peptides and influencing appetite and glycaemic control. Alteration of the GI tract, in ways that exaggerate the secretion and levels of the gut hormones, creates a new functional equilibrium that further contributes to weight loss. The purpose of this review is to explore the mechanisms that drive this gut hormone-derived body regulation, as well as the changes that occur to them after bariatric surgery. Close to that, leptin, a hormone secreted by adipose tissue will be analysed, as its pathways are closely related to those of the gut hormones. Gut hormones are strongly implicated in energy control, and various effects of bariatric surgery in weight loss are directly related to the alteration of the levels of these hormones.

Topics: Appetite Regulation; Bariatric Surgery; Energy Metabolism; Female; Gastrointestinal Hormones; Homeostasis; Humans; Leptin; Male; Obesity, Morbid; United Kingdom; Weight Loss

Obesity is now recognised as one of the most important risk factors for heart disease. Obese individuals have high circulating levels of leptin, a hormone secreted by adipose tissue and involved in energy homeostasis. Growing evidence suggests that leptin may contribute to the development of cardiac dysfunction. In a large prospective study leptin has been shown to be an independent risk factor for coronary heart disease. An independent positive association has also been found between plasma leptin levels and heart rate in hypertensive patients and heart transplant recipients. In animal studies chronic leptin infusion increased heart rate and blood pressure. It has also been demonstrated that circulating leptin levels are elevated in patients with heart failure. The level of plasma leptin was associated with increased myocardial wall thickness and correlated with left ventricular mass, suggesting a role for this hormone in mediating left ventricular hypertrophy in humans. Moreover, leptin directly induced hypertrophy and hyperplasia in human and rodent cardiomyocytes, accompanied by cardiac extracellular matrix remodelling. Leptin may also influence energy substrate utilisation in cardiac tissue. These findings suggest that leptin acting directly or through the sympathetic nervous system may have adverse effects on cardiac structure and function, and that chronic hyperleptinaemia may greatly increase the risk of cardiac disorders. Additional studies are needed to define the role of leptin in cardiac physiology and pathophysiology, nevertheless the reduction in plasma leptin levels with caloric restriction and weight loss may prevent cardiac dysfunction in obese patients.

Topics: Adipose Tissue; Cardiovascular Diseases; Coronary Artery Disease; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Myocardium; Myocytes, Cardiac; Obesity; Ventricular Remodeling; Weight Loss

Calorie restriction (CR)-induced weight loss has been shown to lower the risk of chronic disease in obese individuals. Although the mechanisms that link weight loss to disease risk reduction remain unclear, evidence suggests adipokines may play a role. What has yet to be determined, however, is the dose-response effect of body weight loss and visceral fat mass loss on adipokines. Accordingly, this review examines how varying degrees of CR-induced weight loss (i.e., >10%, 5-10%, and <5% from baseline) impact plasma levels and expression of adiponectin, leptin, resistin, interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and retinol-binding protein 4 (RBP-4). The dose-response relationship between visceral fat mass loss and adipokine profile improvement will also be explored. Results from this review demonstrate that even mild weight loss induced by CR may have beneficial effects on leptin levels, but it has no clear impact on adiponectin, resistin, IL-6, IL-8, MCP-1, or RBP-4 concentrations.

Topics: Adiponectin; Biomarkers; Caloric Restriction; Humans; Leptin; Obesity; Weight Loss

Leptin is a pleiotropic cytokine-like hormone that is involved in the regulation of energy intake and expenditure, neuroendocrine function, immunity and lipid and glucose metabolism. The few humans with genetically based leptin deficiency provide a unique model to assess those effects. We have identified five Turkish patients (one male and two female adults; one boy and one girl) with congenital leptin deficiency due to a missense mutation in the leptin gene. Four of these patients were treated with physiological doses of recombinant methionyl human leptin. Body composition, brain structure and function, behaviour, immunity and endocrine and metabolic parameters were evaluated before and during treatment. Our results showed that leptin has peripheral, hypothalamic and extra-hypothalamic effects. Within the endocrine system, leptin regulates the circadian rhythms of cortisol, thyroid-stimulating hormone, luteinizing hormone and follicle-stimulating hormone. In the brain, leptin controls energy balance and body weight, and plays a role on neurogenesis and brain function. Leptin is a key element of the adiposinsular axis, enhances immune response, and regulates inflammation, coagulation, fibrinolysis and platelet aggregation. Our 10-year experience in treating these unique patients provided valuable data on the peripheral and central effects of leptin. Those results can be taken into account for the development of leptin-based therapies for other diseases.

Topics: Adult; Body Composition; Child; Energy Intake; Energy Metabolism; Female; Humans; Leptin; Male; Mutation, Missense; Obesity; Pedigree; Weight Loss

Asthma and obesity have been increasing in prevalence internationally among children. Evidence points to an association between these chronic morbidities, suggesting the development of an 'obese asthma' phenotype in childhood. This review summarises the evidence that the proinflammatory environment created by excess adiposity may provide a mechanism leading to obese asthma in children and adolescents. Weight loss studies conducted in children without asthma have demonstrated a reduction in systemic inflammation. However, the impact of weight loss in the obese paediatric population with asthma has not been investigated. The paucity of information highlights the need for high quality randomised controlled trials of weight loss in this population that include assessment of systemic and airway inflammation, and clinical asthma outcomes. This will lead to refinements in management approaches for these patients.

Topics: Adiponectin; Adolescent; Asthma; C-Reactive Protein; Child; Comorbidity; Humans; Inflammation; Leptin; Obesity; Phenotype; Tumor Necrosis Factor-alpha; Weight Loss

Obesity is a chronic disease and a major global health challenge. Apart from bariatric surgery, which is costly and not without risk, there are currently no successful long-term treatment options for obesity. The history of pharmacological agents for obesity has been turbulent with many examples of drugs being removed from the market due to significant side effects. Orlistat and sibutramine (the latest drugs on the market) provide only modest weight loss and are both associated with high attrition rates due to intolerable side effects. Furthermore, sibutramine was recently withdrawn from the market. There is a need for the development of safe and efficacious drug treatments for obesity.. This review covers the history of leptin therapy as an orphan drug, leptin-replacement therapy as a treatment for obesity, preclinical studies showing the efficacy of leptin/amylin combination and finally, the very promising early clinical findings using pramlintide/meteleptin combination therapy in overweight to obese individuals.. Combination pharmacological therapy, such as pramlintide/metreleptin, for the treatment of obesity is very promising and is supported by encouraging weight loss results and improvement in metabolic makers in early-phase clinical studies. However, the latest randomized clinical trial on pramlintide/metreleptin was recently stopped due to safety concerns.

Topics: Animals; Anti-Obesity Agents; Drug Therapy, Combination; Humans; Islet Amyloid Polypeptide; Leptin; Obesity; Treatment Outcome; Weight Loss

Obesity plays a major role in the development of type 2 diabetes mellitus, and it has long been accepted that weight loss plays a significant role in diabetes therapy. This weight loss has traditionally been accomplished through lifestyle changes including diet and exercise. What has only more recently gained acceptance is that bariatric surgery may have a role to play in diabetes therapy as well. This article discusses the pathophysiology of type 2 diabetes mellitus and obesity and provides a basic understanding of these diseases, which forms the basis for understanding the importance of weight loss in their treatment.

Topics: Animals; Bariatric Surgery; Body Mass Index; Comorbidity; Diabetes Mellitus, Type 2; Disease Progression; Energy Intake; Energy Metabolism; Humans; Insulin Resistance; Leptin; Obesity; Risk Factors; Weight Loss

The clinical outcomes achieved by bariatric surgery have been impressive. However, the physiologic mechanisms and complex metabolic effects of bariatric surgery are only now beginning to be understood. Ongoing research has contributed a large amount of data and shed new light on the science behind obesity and its treatment, and this article reviews the current understanding of metabolic and bariatric surgery physiology.

Topics: Bariatric Surgery; Diabetes Mellitus, Type 2; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Neuropeptide Y; Obesity, Morbid; Peptide YY; Weight Loss

Obesity in men, particularly when central, is associated with lower total testosterone [TT], free testosterone [FT] and sex hormone-binding globulin [SHBG], and a greater decline in TT and FT with increasing age compared with lean men. Obesity-related conditions such as obstructive sleep apnea, insulin resistance and type 2 diabetes mellitus are independently associated with decreased plasma testosterone. Possible mechanisms include decreased LH pulse amplitude, inhibitory effects of oestrogen at the hypothalamus and pituitary and the effects of leptin and other peptides centrally and on Leydig cells. Obese men have reduced sperm concentration and total sperm count compared to lean men but sperm motility and morphology appear unaffected. The cause and effect relationships between low plasma androgen levels, obesity and the metabolic syndrome, and associated cardiometabolic risk remain unclear. While weight loss normalizes TT and FT in obese men, androgen replacement in the short term does not significantly improve cardiometabolic risk profile despite reducing fat mass.

Topics: Aging; Animals; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Leptin; Luteinizing Hormone; Male; Metabolic Syndrome; Obesity; Risk Factors; Signal Transduction; Sleep Apnea, Obstructive; Spermatogenesis; Testis; Testosterone; Weight Loss

Acute or long-term energy deficit in lean or obese rodents or humans stimulates food intake or appetite and reduces metabolic rate or energy expenditure. These changes contribute to weight regain in post-obese animals and humans. Some studies show that the reduction in metabolic rate with energy deficit in overweight people is transient. Energy restriction has been shown in some but not all studies to reduce physical activity, and this may represent an additional energy-conserving adaptation. Energy restriction up-regulates expression of the orexigenic neuropeptide Y, agouti related peptide and opioids and down-regulates that of the anorexigenic alpha-melanocyte stimulating hormone or its precursor pro-opioomelanocortin and the co-expressed cocaine and amphetamine-regulated transcript in the arcuate nucleus of the hypothalamus. Recapitulating these hypothalamic changes in sated animals mimics the effects of energy deficit, namely increased food intake, reduced physical activity and reduced metabolic rate, suggesting that these energy-conserving adaptations are at least partially mediated by the hypothalamus.

Topics: Agouti-Related Protein; Animals; Appetite; Arcuate Nucleus of Hypothalamus; Body Weight; Eating; Energy Metabolism; Fasting; Humans; Leptin; Motor Activity; Nerve Tissue Proteins; Neuropeptide Y; Obesity; Oxygen Consumption; Pro-Opiomelanocortin; Signal Transduction; Weight Loss

Leptin is a hormone secreted by adipose tissue in direct proportion to amount of body fat. The circulating leptin levels serve as a gauge of energy stores, thereby directing the regulation of energy homeostasis, neuroendocrine function, and metabolism. Persons with congenital deficiency are obese, and treatment with leptin results in dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese persons are resistant to the weight-reducing effects of leptin. Recent studies suggest that leptin is physiologically more important as an indicator of energy deficiency, rather than energy excess, and may mediate adaptation by driving increased food intake and directing neuroendocrine function to converse energy, such as inducing hypothalamic hypogonadism to prevent fertilization. Current studies investigate the role of leptin in weight-loss management because persons who have recently lost weight have relative leptin deficiency that may drive them to regain weight. Leptin deficiency is also evident in patients with diet- or exercise-induced hypothalamic amenorrhea and lipoatrophy. Replacement of leptin in physiologic doses restores ovulatory menstruation in women with hypothalamic amenorrhea and improves metabolic dysfunction in patients with lipoatrophy, including lipoatrophy associated with HIV or highly active antiretroviral therapy. The applications of leptin continue to grow and will hopefully soon be used therapeutically.

Topics: Adipose Tissue; Amenorrhea; Animals; Atrophy; Energy Metabolism; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Neurosecretory Systems; Obesity; Recombinant Proteins; Weight Loss

Active weight loss and the maintenance of a weight-reduced state elicit potent counter-regulatory responses in multiple neurochemical pathways rendering monotherapy-based anti-obesity agents relatively ineffective. Herein, we highlight potential strategies for overcoming counter-regulatory responses to states of negative energy balance using combinatorial approaches. We discuss methodological and practical considerations for preclinical modeling of additive/synergistic weight loss combinations that have emerged in our translational research program aimed at identifying naturally occurring neurohormonal synergies. As an example of synergy, pharmacological and mechanistic findings with the combined administration of the beta-cell hormone amylin and the adipokine leptin are reviewed. Finally, we briefly discuss what the future landscape of neurohormonal anti-obesity combinations may hold.

Topics: Anti-Obesity Agents; Combined Modality Therapy; Humans; Islet Amyloid Polypeptide; Leptin; Obesity; Weight Loss

Roux-en-Y gastric bypass is a well-accepted tool for the treatment of obesity and, compared to conventional weight loss methods (eg, diet and exercise) and other weight loss surgeries (eg, gastric banding), it results in considerable weight loss that is maintained long term. Although successful, the mechanisms for weight loss are not completely understood and it is thought that gastrointestinal hormones play a role. Several gastrointestinal hormones have been identified for their effects on appetite, including glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), leptin, and ghrelin. This review encompasses a literature search that included 45 primary articles and shows that there are alterations in GLP-1, PYY, leptin, and ghrelin postoperatively. GLP-1 and PYY concentrations were usually found to be higher, whereas ghrelin levels were typically lower post- Roux-en-Y gastric bypass than in individuals with obesity, those who were overweight or of normal weight, and in those who underwent procedures other than Roux-en-Y gastric bypass or who achieved weight loss by lifestyle modification. An understanding of how gastrointestinal hormones change after Roux-en-Y gastric bypass may help dietetics practitioners optimize nutrition care for this patient population. A review of the literature also highlighted some research gaps that should be taken into consideration when designing future studies.

Topics: Appetite Regulation; Follow-Up Studies; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Obesity, Morbid; Peptide YY; Treatment Outcome; Weight Loss

In several investigations on mountaineers under moderate hypoxia, at altitudes between 2,500 m and 4,500 m, weight loss occurs, fat levels in the serum and insulin resistance (in diabetic mountaineers) are reduced. Animal studies with different time dosage regimens of hypoxia in animal cages revealed different and partly confusing results regarding fat metabolism under hypoxia.. Hypothesis for the change in glucose and fat metabolism include a HIF promoted higher leptin rate under hypoxia and an increased glucose transport in peripheral organs.. This short review discusses some of the different investigations in this topic. In a second part it is shown how studies of metabolism in yeast cells with an upregulated glycolysis in the cell itself under hypoxic conditions could help to better understand metabolic changes under hypoxia.

Topics: Adaptation, Physiological; Blood Glucose; Energy Metabolism; Glycolysis; Humans; Hypoxia; Insulin Resistance; Leptin; Lipids; Models, Biological; Up-Regulation; Weight Loss; Yeasts

Although energy balance is tightly regulated in order to maintain a specific level of adiposity, the incidence of obesity continues to increase. Consequently, it is essential that effective therapeutics for the treatment and prevention of obesity be developed. This review provides a brief update on some recent advances in the characterization of neuroendocrine targets for obesity therapy.. During the review period, considerable progress occurred in the understanding of previously described neuroendocrine regulators of energy balance, and several novel targets have been identified. Moreover, the understanding of the neural circuitry and molecular mechanisms of the neuroendocrine regulation of energy homeostasis has been expanded.. Energy balance is maintained by neuroendocrine signals arising from many tissues including the gastrointestinal tract and adipose tissue. These signals are integral to the cessation of meals and to the ability of the brain to monitor energy status and respond accordingly. Many current targets for obesity therapy are based on manipulating the activity of these signals and their receptors; however, to date, clinical-weight loss based on this strategy has been minimal and alternative approaches such as combinatorial therapies are emerging.

Topics: Adipose Tissue; Animals; Appetite Regulation; Cholecystokinin; Energy Intake; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Leptin; Mice; Neurosecretory Systems; Obesity; Weight Loss

Gastric bypass surgery (GBP), in addition to weight loss, results in dramatic remission of type 2 diabetes (T2DM). The mechanisms by which this remission occurs are unclear. Besides weight loss and caloric restriction, the changes in gut hormones that occur after GBP are increasingly gaining recognition as key players in glucose control. Incretins are gut peptides that stimulate insulin secretion postprandially; the levels of these hormones, particularly glucagon-like peptide-1, increase after GBP in response to nutrient stimulation. Whether these changes are causal to changes in glucose homeostasis remain to be determined. The purpose of this review is to assess the evidence on incretin changes and T2DM remission after GBP, and the possible mechanisms by which these changes occur. Our goals are to provide a thorough update on this field of research so that recommendations for future research and criteria for bariatric surgery can be evaluated.

Topics: Animals; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Gastric Bypass; Gastric Emptying; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Gluconeogenesis; Glucose; Homeostasis; Humans; Incretins; Intestine, Small; Leptin; Liver; Obesity, Morbid; Peptide YY; Randomized Controlled Trials as Topic; Remission Induction; Weight Loss

Hypoleptinemia is a key endocrinological feature of anorexia nervosa (AN). Several symptoms in acute AN are related to the low circulating leptin levels including amenorrhea and semi-starvation-induced hyperactivity. The drop in leptin levels results from the loss of fat mass; once leptin levels fall below specific thresholds the hypothalamic-pituitary-gonadal and -thyroid axes are down-regulated; in contrast, the hypothalamic-pituitary-adrenal axis is up-regulated. Hypoleptinemia is the major signal underlying both somatic and behavioral adaptations to starvation. Because the mechanisms involved in this adaptation are similar in rodents and humans, rodent models can be used to investigate the relevant central pathways which underly the respective starvation-induced symptoms. During therapeutically induced weight gain, leptin levels can intermittently increase above normal concentrations. This hyperleptinemia could predispose to renewed weight loss.

Topics: Adolescent; Amenorrhea; Anorexia Nervosa; Body Weight; Female; Humans; Leptin; Motor Activity; Neurosecretory Systems; Osteoporosis; Starvation; Weight Loss

Obesity is a major risk factor for hypertension. Adipose tissue releases numerous substances that act on the pathophysiologic mechanisms of blood pressure. Management of obese patients with high blood pressure includes weight loss efforts, but antihypertensive treatment is most often necessary. Beta-blockers, alone or with thiazide diuretics, increase the risk of diabetes in hypertensive patients. Treatment against hypertension must include a renin-angiotensin system blocker, with a calcium channel blocker or a thiazide diuretic, if necessary.

Topics: Adiponectin; Adipose Tissue; Antihypertensive Agents; Blood Pressure; Combined Modality Therapy; Humans; Hypertension; Insulin Resistance; Leptin; Obesity; Sympathetic Nervous System; Weight Loss

According to the definition (body mass index>97 degrees percentile), overweight and obesity concern 15% of French children. The parallel trends in the increase in asthma and obesity may indicate a potential link between these two conditions. The purpose of this study was to review the epidemiological data indicating a relationship between asthma and obesity, to evaluate the consequences of obesity on asthma and to assess the mechanisms of this association. We conclude with the implications for treatment strategies.

Topics: Adipokines; Adolescent; Adrenal Cortex Hormones; Airway Resistance; Anti-Asthmatic Agents; Asthma; Body Mass Index; Child; Child, Preschool; Comorbidity; Cross-Sectional Studies; Exercise; Humans; Leptin; Longitudinal Studies; Lung Volume Measurements; Obesity; Overweight; Respiratory Hypersensitivity; Risk Factors; Treatment Outcome; Weight Loss

The discovery of leptin in 1994 was a seminal event in obesity research. It helped to establish that body weight is tightly regulated by a complex neurohormonal feedback system and that obesity should be viewed as a disorder with a strong biological basis rather than simply the result of poor lifestyle choices and lack of willpower.Leptin, secreted from adipocytes, acts as a prototypic long-term (tonic) adiposity signal. Although nonclinical and clinical studies have provided unequivocal evidence that leptin plays a unique, pivotal role in body weight regulation, efforts to develop recombinant leptin (metreleptin) as a monotherapy for obesity have proven unsuccessful. Amylin, secreted from pancreatic beta-cells, fulfills the criteria for a short-term (episodic) satiety signal. The amylin analog pramlintide elicits sustained reductions in food intake and body weight in obese rodents and humans.A translational research program aimed at elucidating the interaction between different islet-, gut-, and adipocyte-derived hormones led to the discovery that combined amylin/leptin agonism induces marked, synergistic, fat-specific weight loss in leptin-resistant diet-induced obese rodents. In obese humans, combination treatment with pramlintide/metreleptin led to an approximately 13% weight loss after 24 weeks, significantly more than after treatment with pramlintide or metreleptin alone.Collectively, these findings suggest that combined amylin/leptin agonism may have therapeutic utility as part of an integrated, neurohormonal approach to obesity pharmacotherapy.

Topics: Amyloid; Animals; Anti-Obesity Agents; Drug Design; Drug Therapy, Combination; Feedback, Physiological; Humans; Islet Amyloid Polypeptide; Leptin; Neurotransmitter Agents; Obesity; Satiety Response; Signal Transduction; Weight Loss

The epidemic of obesity in the United States and around the world is intensifying in severity and scope and has been implicated as an underlying mechanism in systemic hypertension. Obese hypertensive individuals characteristically exhibit volume congestion, relative elevation in heart rate, and high cardiac output with concomitant activation of the renin-angiotensin-aldosterone system. When the metabolic syndrome is present, insulin resistance and hyperinsulinemia may contribute to hypertension through diverse mechanisms. Blood pressure can be lowered when weight control measures are successful, using, for example, caloric restriction, aerobic exercise, weight loss drugs, or bariatric surgery. A major clinical challenge resides in converting short-term weight reduction into a sustained benefit. Pharmacotherapy for the obese hypertensive patient may require multiple agents, with an optimal regimen consisting of inhibitors of the renin-angiotensin-aldosterone system, thiazide diuretics, beta-blockers, and calcium channel blockers if needed to attain contemporary blood pressure treatment goals.

Topics: Antihypertensive Agents; Bariatric Surgery; Blood Pressure; Drug Therapy, Combination; Hemodynamics; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Renin-Angiotensin System; Risk Reduction Behavior; Sympathetic Nervous System; Weight Loss

In this review, we discuss the role of inactivity and exercise on appetite regulation, both in the short and long term, and the potential mechanisms involved. A better short-term appetite control has been described in active compared to sedentary men, and an exercise intervention was shown to improve appetite control in previously sedentary individuals. The mechanisms whereby exercise improves short-term appetite control remain obscure and although the changes in the postprandial release of satiety peptides are attractive hypotheses, it remains unproven. The impact of exercise on habitual food intake is also controversial and likely to be dependent on restraint level and body weight. We hypothesize that the beneficial impact of exercise on appetite regulation can contribute to its well-established efficacy in the prevention of weight regain in obese individuals. However, more studies are needed in the obese population to clearly establish the role of exercise on appetite control in this group.

Topics: Appetite Regulation; Eating; Energy Intake; Energy Metabolism; Exercise; Humans; Leptin; Motivation; Obesity; Weight Loss

The metabolic syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is a primary risk factor for diabetes and cardiovascular disease. We showed for the first time that the metabolic syndrome is associated with a higher fraction of oxidized LDL and thus with higher levels of circulating oxidized LDL. Hyperinsulinemia and impaired glycaemic control, independent of lipid levels, were associated with increased in vivo LDL oxidation, as reflected by the higher prevalence of high oxidized LDL. High levels of oxidized LDL were associated with increased risk of future myocardial infarction, even after adjustment for LDL-cholesterol and other established cardiovascular risk factors. This association is in agreement with the finding that accumulation of oxidized LDL, which activates/induces subsets of smooth muscle cells and macrophages to gelatinase production, was associated with upstream localization of a vulnerable plaque phenotype. Dyslipidemia and insulin resistance in obese LDL receptor-deficient mice were associated with increased oxidative stress and impaired HDL-associated antioxidant defence associated with accelerated atherosclerosis due to increased macrophage infiltration and accumulation of oxidized LDL in the aorta. The accumulation of oxidized LDL was partly due to an impaired HDL-associated antioxidant defence due to a decrease in PON. Our data in this experimental model are thus the more relevant because a decrease in PON activity was found to be associated with a defective metabolism of oxidized phospholipids by HDL from patients with type 2 diabetes. Weight loss in leptin-deficient, obese, and insulin-resistant mice was associated with expressional changes of key genes regulating adipocyte differentiation, glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. We established an important relationship between PPAR-gamma and SOD1 for the prevention of the oxidation of LDL in the arterial wall. For example we showed that rosuvastatin decreased the oxidized LDL accumulation by increasing the expression of PPAR-gamma and SOD1. In addition, we established a relation between increased PPAR-alpha expression in the adipose tissue and a change in the gene expression pattern, which explains the decrease of free fatty acids, triglycerides and the increase in insulin sensitivity. We demonstrated

Topics: Animals; Cardiovascular Diseases; Comorbidity; Humans; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Lipoproteins, LDL; Metabolic Syndrome; Mice; Obesity; Oxidation-Reduction; Oxidative Stress; Risk Factors; Weight Loss

The sympathetic nervous system is activated in human obesity and in the analogous experimental obesity produced by overfeeding. The causes remain uncertain and may be multiple. The consequences include hypertension, probably attributable to activation of the sympathetic outflow to the kidneys, and, more disputed, insulin resistance. The pattern of sympathetic activation in normal-weight and obesity-related hypertension differs in terms of the firing characteristics of individual sympathetic fibers (increased rate of nerve firing in normal-weight hypertensives, increased number of active fibers firing at a normal rate in obesity-hypertension) and the sympathetic outflows involved. The underlying mechanisms and the adverse consequences of the two modes of sympathetic activation may differ. Should antihypertensive drug therapy in obesity-hypertension specifically target the existing neural pathophysiology? Such an approach can be advocated on theoretical grounds. Perhaps more important is the requirement that chosen antihypertensives do not cause weight gain or insulin resistance.

Topics: Adrenergic beta-3 Receptor Agonists; Humans; Hyperinsulinism; Hypertension; Leptin; Obesity; Risk Factors; Sleep Apnea, Obstructive; Sympathetic Nervous System; Weight Loss

It has been long known that the frequency of overweight and obese people is higher among depressed and bipolar patients than in the general population. The marked alteration of body weight (and appetite) is one of the most frequent of the 9 symptoms of major depressive episode, and these symptoms occur during recurrent episodes of depression with a remarkably high consequence. According to studies with representative adult population samples, in case of obesity (BMI over 30) unipolar or bipolar depression is significantly more frequently (20-45%) observable. Since in case of depressed patients appetite and body weight reduction is observable during the acute phase, the more frequent obesity in case of depressed patients is related (primarily) not only to depressive episodes, but rather to lifestyle factors, to diabetes mellitus also more frequently occurring in depressed patients, to comorbid bulimia, and probably to genetic-biological factors (as well as to pharmacotherapy in case of medicated patients). At the same time, according to certain studies, circadian symptoms of depression give rise to such metabolic processes in the body which eventually lead to obesity and insulin resistance. According to studies in unipolar and bipolar patients, 57-68% of patients is overweight or obese, and the rate of metabolic syndrome was found to be between 25-49% in bipolar patients. The rate of metabolic syndrome is further increased by pharmacotherapy. Low total and HDL cholesterol level increases the risk for depression and suicide and recent studies suggest that omega-3-fatty acids possess antidepressive efficacy. Certain lifestyle factors relevant to healthy metabolism (calorie reduction in food intake, regular exercise) may be protective factors related to depression as well. The depression- and possibly suicide-provoking effect of sibutramine and rimonabant used in the pharmacotherapy of obesity is one of the greatest recent challenges for professionals and patients alike.

Topics: Anti-Obesity Agents; Antidepressive Agents; Appetite Depressants; Appetite Regulation; Bipolar Disorder; Circadian Rhythm; Cyclobutanes; Depression; Depressive Disorder, Major; Dietary Carbohydrates; Energy Intake; Ghrelin; Humans; Hypothalamo-Hypophyseal System; Insulin Resistance; Leptin; Obesity; Piperidines; Pituitary-Adrenal System; Pyrazoles; Rimonabant; Seasonal Affective Disorder; Sleep Wake Disorders; Surveys and Questionnaires; Weight Gain; Weight Loss

Appetite suppressants have been available as weight-reducing aids for over 50 years. The first discovered was amphetamine, which was potent, but possessed undesirable side effects (it is a stimulant and elevates blood pressure). Subsequently, a variety of appetite drugs was developed, all structurally related to amphetamine, but mostly lacking unwanted side effects. Until recently, fenfluramine (FEN) was the most widely used; presently, sibutramine is the most commonly used appetite suppressant. While these appetite suppressants are effective at reducing hunger and food intake when given as a single dose or for short periods of time, their effectiveness diminishes when administered chronically. The biological mechanisms underlying this tolerance have not been carefully studied, but many possibilities have been identified, including the down-regulation in brain of neurotransmitter receptors that might mediate the action of these drugs and adaptive responses of the appetite control circuitry in brain. To date, however, few studies have examined these possibilities in any detail. This article focuses on the question of why appetite suppressants lose efficacy, when given chronically, because this issue is important to the development of the next generation of appetite suppressants. Chronic efficacy should be an issue studied relatively early in the drug development process. This issue is of particular relevance, since obesity treatment is now recognized as a long-term, not a short-term, process. If appetite suppressants are to become a more important tool in obesity treatment, agents that do not lose efficacy when administered for extended periods of time must be identified.

Topics: Animals; Appetite Depressants; Body Weight; Cyclobutanes; Drug Tolerance; Eating; Fenfluramine; Humans; Leptin; Obesity; Rats; Time Factors; Weight Loss

Obesity and type 2 diabetes are the most prevalent metabolic diseases in the western world. Alarmingly, the cluster of pathologies characteristic of obesity-induced disease have started to emerge in children, a phenomenon that up until a decade ago was inconceivable. Hence, the development of new strategies to treat 'metabolic disease' is most warranted. Growing evidence suggests that during type 2 diabetes, a state of chronic low-grade inflammation exists in metabolically active tissues such as the liver, adipose tissue and skeletal muscle. This inflammation is often secondary to lipid accumulation in insulin-responsive tissues. Recent studies have focused on the therapeutic potential of ciliary neurotrophic factor (CNTF). CNTF is a pluripotent neurocytokine and, has shown promise as a potential anti-obesogenic therapy. CNTF acts both centrally and peripherally, mimics the biological actions of leptin while overcoming "leptin resistance", remains effective even after termination of therapy if administered centrally, and appears to reduce inflammatory signaling cascades associated with lipid accumulation in liver and skeletal muscle. The advantages and disadvantages of CNTF as a therapeutic strategy to alleviate obesity-associated diseases will be highlighted in this review.

Topics: Brain; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Leptin; Obesity; Receptor, Ciliary Neurotrophic Factor; Signal Transduction; Weight Loss

An activation of the endocannabinoid system (ECS) in obesity with increased concentrations of endocannabinoids in several tissues and in the circulation is described in this review. This increased availability of endocannabinoids might stimulate cannabinoid receptors in a pathophysiological manner. The successful use of the cannabinoid receptor CB(1) inverse agonists rimonabant and taranabant for weight loss and the treatment of obesity-associated metabolic disorders might well be through blocking this overstimulation of cannabinoid receptors. At present, no single mechanism has been identified that explains the increased bioavailability of endocannabinoids in obesity. Both increased synthesis and decreased degradation appear to operate in a species- and tissue-dependent manner, but many pieces of the puzzle still need to be collected. For example, most data show decreased fatty acid amide hydrolase (FAAH) expression and/or activity as a result of obesity or high-fat intake, but the endocannabinoid predominantly increased in tissues is 2-arachidonoylglycerol (2-AG), which is not degraded by FAAH in vivo. Furthermore, the influence of dietary fatty acids on the synthesis of endocannabinoids needs to be studied in much more detail. Although weight loss does not seem to influence activation of the endocannabinoid system (ECS) in human obesity, suggesting an underlying mechanisms independent of body weight, no such mechanism at the genetic level has yet been identified either. Thus, activation of the ECS is a hallmark of abdominal obesity, and explains the success of pharmacological CB(1) blockade, but serious attempts have to be made to clarify the underlying mechanisms of this activation.

Topics: Adipose Tissue; Animals; Brain; Cannabinoid Receptor Modulators; Diet; Dietary Fats, Unsaturated; Disease Models, Animal; Endocannabinoids; Humans; Leptin; Liver; Obesity; Pancreas; Receptors, Cannabinoid; Weight Loss

The prevalences of both obesity and asthma have clearly increased in recent decades, giving rise to speculation that they may be related. Studies have found that obesity precedes and predicts the onset of asthma (time effect), that increased obesity leads to more severe asthma (dose-response effect), that weight reduction (by diet or gastric bypass) improves asthmatic symptoms, and that obesity co-occurs with intermediate asthma phenotypes (obese young girls undergoing early menarche). In the light of that evidence, we can finally suggest a causal relationship between obesity and asthma. Various biological mechanisms (immunologic and inflammatory, hormonal, genetic, nutritional, mechanical, and others related to physical activity) have been put forth to explain the relationship. However, this relation is complex, involving not only the interaction of genetic and environmental factors in triggering both diseases but also the likely participation of several mechanisms at once.

Topics: Adolescent; Adult; Airway Resistance; Asthma; Child; Chromosome Mapping; Cytokines; Diet; Disease Susceptibility; Female; Hormones; Humans; Inflammation; Leptin; Male; Menarche; Motor Activity; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Respiratory Mechanics; Sex Factors; Weight Loss

Morbid obesity is associated with low-grade systemic inflammation and immune activation. Thereby various pro-inflammatory cytokines like TNF-alpha, IL-1, IL-6, IFN-gamma and hormones, such as leptin are synthesized and released in human adipose tissue. The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is widely distributed in mammals and is inducible preferentially by IFN-gamma. IDO degrades the essential amino acid tryptophan to form N-formyl kynurenine which, depending on cell type and enzymatic repertoires, is subsequently converted to finally form niacin. More recently, it has been proposed that activation of IDO is also critically involved in the regulation of immune responses. In obesity plasma tryptophan concentrations have been shown to be decreased and to be independent of weight reduction or dietary intake. In addition, we previously demonstrated that IDO mediated tryptophan catabolism due to chronic immune activation is the cause for such reduced tryptophan plasma levels in morbidly obese patients compared to lean individuals. Furthermore, these tryptophan metabolic changes may subsequently reduce serotonin production and cause mood disturbances, depression, and impaired satiety ultimately leading to increased caloric uptake and obesity. IDO-mediated tryptophan degradation due to chronic immune activation can therefore be considered as the driving force for food intake. We here review the potential pathogenic links between chronic immune activation and decreased IDO mediated tryptophan and serotonin levels in morbid obesity.

Topics: Adipose Tissue; Animals; Bariatric Surgery; Ghrelin; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Leptin; Macrophages; Obesity, Morbid; Peptide Hormones; Serotonin; Substance-Related Disorders; Tryptophan; Weight Loss

The literature presented in this paper argues that our limited ability to maintain energy balance in a weight-reduced state is the product of our difficulty in compensating for the weight loss-induced reduction in total energy expenditure. The end result, translated into the overwhelming complexity of preserving long-term weight loss, is presented as being a consequence of compromised appetite control. Given the present-day food landscape and the resultant susceptibility to passive overconsumption, the focus of this review will be on the peripheral ("bottom-up") signals (leptin, PYY, ghrelin, and GLP-1) and the evidence highlighting their influence on feeding behaviour. As we continue studying paradigms of body mass reduction, specifically the data emerging from patients of bariatric surgery, it is becoming clearer that counter-regulatory adaptations, possibly through down-(leptin, PYY, and GLP-1) or upregulation (ghrelin) of peptides, have an impact on energy balance. In itself, food deprivation influences some of the peptides that ultimately provide the physiological input for the overt expression of feeding behaviour; these peripheral adaptations are expected to serve as feeding cues--cues that, in the end, can serve to compromise the maintenance of energy balance. In a potentially novel intervention to increase compliance to long-term reductions in energy intake, it is proposed that manipulating the pattern of food intake to favourably alter the profile of gastrointestinal peptides would lead to better dietary control.

Topics: Appetite; Appetite Regulation; Energy Metabolism; Food; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Peptide Hormones; Peptide YY; Time Factors; Weight Loss

A cluster of risk factors associated with obesity defines the metabolic syndrome and identifies cardiometabolic risk. Accumulation of fat in the visceral depot is a more reliable predictor of cardiovascular disease than is total body mass or body mass index. The recent discovery of the endocannabinoid-CB1 receptor system and its impact on the regulation of energy metabolism represents a significant advance that will help target visceral fat and its metabolic implications. As a highly active endocrine organ, visceral fat secretes many bioactive molecules, known as adipokines. Dysregulation of these adipokines contributes to the pathogenesis of the obesity-associated metabolic syndrome, resulting in insulin resistance, type 2 diabetes, hypertension, hyperlipidemia, and vascular disease. Even modest weight reduction leads to reduced cardiometabolic risk by affecting the individual components comprising the metabolic syndrome.

Topics: Adiponectin; Anti-Obesity Agents; Blood Coagulation; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet; Dyslipidemias; Exercise; Fatty Acids; Humans; Hypertension; Inflammation Mediators; Insulin Resistance; Intra-Abdominal Fat; Leptin; Life Style; Metabolic Syndrome; Obesity; Practice Guidelines as Topic; Risk Factors; Weight Loss

Climbers at high altitude (>5000 m) lose weight. This impairs performance and safety, but the mechanisms are not entirely due to an imbalance between energy intake and expenditure. There is some evidence of carbohydrate malabsorption, but there are also changes in fat metabolism and total body water. This paper considers the physiological control of weight and then discusses the changes in each parameter before addressing the practical implications.

Topics: Altitude; Appetite; Basal Metabolism; Body Composition; Energy Intake; Exercise; Humans; Intestinal Absorption; Leptin; Weight Loss

In this review, we would like to consider several aspects of the discovery of leptin and its evolution as a therapeutic agent. It has been shown that the administration of leptin in congenital leptin deficiency that there was improvement in satiety and weight loss. In hypoleptinemic patients with lipodystrophy, there is a dramatic improvement in glucose metabolism, dyslipidemia and hepatic steatosis. Leptin is the first and only adipokine administered to humans long term to produce such an effect.

Topics: Diabetes Mellitus; Dyslipidemias; Fatty Liver; Glucose; Humans; Insulin Resistance; Leptin; Lipodystrophy; Obesity; Satiation; Weight Loss

Obesity is a very common disease worldwide, resulting from a disturbance in the energy balance. The metabolic syndrome is also a cluster of abnormalities with basic characteristics being insulin resistance and visceral obesity. The major concerns of obesity and metabolic syndrome are the comorbidities, such as type 2 diabetes, cardiovascular disease, stroke, and certain types of cancers. Sympathetic nervous system (SNS) activity is associated with both energy balance and metabolic syndrome. Sympathomimetic medications decrease food intake, increase resting metabolic rate (RMR), and thermogenic responses, whereas blockage of the SNS exerts opposite effects. The contribution of the SNS to the daily energy expenditure, however, is small ( approximately 5%) in normal subjects consuming a weight maintenance diet. Fasting suppresses, whereas meal ingestion induces SNS activity. Most of the data agree that obesity is characterized by SNS predominance in the basal state and reduced SNS responsiveness after various sympathetic stimuli. Weight loss reduces SNS overactivity in obesity. Metabolic syndrome is characterized by enhanced SNS activity. Most of the indices used for the assessment of its activity are better associated with visceral fat than with total fat mass. Visceral fat is prone to lipolysis: this effect is mediated by catecholamine action on the sensitive beta(3)-adrenoceptors found in the intraabdominal fat. In addition, central fat distribution is associated with disturbances in the hypothalamo-pituitary-adrenal axis, suggesting that a disturbed axis may be implicated in the development of the metabolic syndrome. Furthermore, SNS activity induces a proinflammatory state by IL-6 production, which in turn results in an acute phase response. The increased levels of inflammatory markers seen in the metabolic syndrome may be elicited, at least in part, by SNS overactivity. Intervention studies showed that the disturbances of the autonomic nervous system seen in the metabolic syndrome are reversible.

Topics: Eating; Energy Metabolism; Humans; Leptin; Metabolic Syndrome; Obesity; Sympathetic Nervous System; Weight Gain; Weight Loss

Fatty tissue synthesizes and secretes a wide range of products that may be directly involved in the pathogenesis of the complications associated with obesity. These so-called adipokines may trigger or sustain a chronic inflammatory process. By manipulating the secretory function of fat cells, it might in future be possible to prevent the development of the metabolic and cardiovascular complications of obesity. Current data already suggest that weight reduction and certain substances with an anti-inflammatory action reduce the risk for the metabolic and cardiovascular complications of obesity. To date, however, the evidence available is only indirect, and is insufficient to definitively establish causal relationships between certain secretory products of adipocytes and the comorbidities of adiposity. Further clinical studies are needed.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Coronary Disease; Diabetes Mellitus, Type 2; Humans; Hypertension; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Metabolic Syndrome; Obesity; Plasminogen Inactivators; Risk Factors; Thromboembolism; Weight Loss

Leptin is synthesized and secreted primarily by adipocytes, and is present in serum in direct proportion to the amount of adipose tissue. The primary role of leptin is to provide to the central nervous system a signal of energy intake and energy stores in the body so that the hypothalamus can efficiently maintain a stable body weight. The receptor for leptin in the hypothalamus signals by activation of an associated janus kinase which phosphorylates signal transducer and activator of transcription (STAT) proteins that regulate neuronal gene expression. Genetic mutations in leptin and its receptor can result in obesity in both rodents and humans, supporting a central role for leptin in the regulation of body weight. Leptin has also been implicated in a variety of physiological processes other than body weight homeostasis. Many of these functions are mediated through the central nervous system; however, the presence of leptin receptors in tissues throughout the body suggests that leptin can also have direct effects on cells and tissues. Serum leptin levels have been associated with cardiovascular risk factors after correction for adiposity. Leptin can promote platelet aggregation, which requires expression of functional leptin receptors on the platelet. Leptin-induced increases in sympathetic nerve activity have been suggested to contribute to hypertension, and leptin has been observed to increase oxidative stress in cultured endothelial cells. Many of these pathophysiologic effects of leptin on the vasculature are most likely of importance when leptin levels are elevated in obese subjects due to resistance to the weight-reducing effects of the hormone. An improved understanding of the effects of leptin on the vasculature will provide valuable insight into the relationship between obesity and cardiovascular disease.

Topics: Adipose Tissue; Animals; Body Mass Index; Female; Gene Expression Regulation; Humans; Leptin; Male; Mutation; Obesity; Oxidative Stress; Receptors, Cell Surface; Receptors, Leptin; Sensitivity and Specificity; Severity of Illness Index; Weight Loss

The obesity hypoventilation syndrome, which is defined as a combination of obesity and chronic hypoventilation, utimately results in pulmonary hypertension, cor pulmonale, and probable early mortality. Since the classical description of this syndrome nearly fifty years ago, research has led to a better understanding of the pathophysiologic mechanisms involved in this disease process, and to the development of effective treatment options. However, recent data indicate the obesity hypoventilation syndrome is under-recognized, and under-treated. Because obesity has become a national epidemic, it is critical that physicians are able to recognize and treat obesity-associated diseases. This article reviews current definitions of the obesity hypoventilation syndrome, clinical presentation and diagnosis, present understanding of the pathophysiology, and treatment options.

Topics: Humans; Hypoventilation; Leptin; Obesity; Respiration, Artificial; Respiratory System; Sleep Apnea, Obstructive; Syndrome; Weight Loss

Topics: Animals; Bacterial Infections; Blood Glucose; Chemokines; Diabetes Mellitus, Type 2; Eating; Energy Metabolism; Humans; Immunity; Leptin; Listeriosis; Liver; Obesity; Risk; Weight Loss

Chronic obstructive pulmonary disease (COPD) is one of the major diseases worldwide. Nutritional depletion is a common problem in COPD patients and also an independant predictor of survival in these patients. Many data are helpful for determining nutritional depletion, including anthropometric measurement, laboratory markers, body composition analysis (fat-free mass and lean mass), and body weight. The mechanism of nutritional depletion in patients with COPD is still uncertain. It may be associated with energy/metabolism imbalance, tissue hypoxia, systemic inflammation, and leptin/orexin disorders. In patients with nutritional depletion, growth hormone and testosterone can be used for nutritional therapy in addition to nutrition supplementation.

Topics: Body Composition; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Lung Diseases, Obstructive; Neuropeptides; Nutrition Assessment; Nutrition Disorders; Orexins; Weight Loss

The last decade witnessed a dramatic increase in knowledge concerning regulation of body weight and obesity. According to recent concepts constancy of body weight is a side product of regulatory events which ensure constant glucose fluxes to the brain. Within these control systems glucocorticoids and melanocortins play a fundamental role at several sites. The melanocortin neurons in the arcuate nucleus of the hypothalamus are important mediators of the feedback effects of leptin and insulin. Glucocorticoid and mineralocorticoid receptors in hippocampal neurons are crucial, as they define the balance between glucose allocation processes and food intake. Thereby, the hippocampal structures determine the setpoint for body weight regulation. A modulation of these brain structures by intranasal administration of melanocortin and inhisulin has been shown to reduce body weight and body fat mass in humans. So the manipulation of weight-regulating centers in the brain opens a novel approach to a pathogenetically based treatment of obesity.

Topics: Administration, Intranasal; alpha-MSH; Animals; Arcuate Nucleus of Hypothalamus; Body Weight; Cannabinoids; Disease Models, Animal; Energy Intake; Feedback; Glucocorticoids; Glucose; Hippocampus; Humans; Hypothalamus; Insulin; Leptin; Obesity; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; Weight Loss

Topics: Animals; Anorexia; Humans; Leptin; Weight Loss

Many studies have reported the difficulty most subjects have in maintaining weight loss. Leptin is a cytokine-like protein made in adipose tissue and is transported into the brain by the blood-brain barrier where it inhibits food intake by altering the expression of hypothalamic neurotransmitters. The discovery of leptin raised the hope that a natural compound had been found that could cause weight loss without adverse effects. However, the majority of obese people have high levels of circulating leptin and it is not surprising that clinical trials published so far have shown that leptin only works effectively to suppress food intake in subjects who are hyperphagic as a result of low leptin levels. Obesity secondary to leptin deficiency is rare, most being associated with leptin insensitivity. To overcome leptin insensitivity, higher leptin levels in the CNS may be required. However, there is evidence that the leptin transport mechanism is saturated at low plasma leptin concentrations, limiting the effectiveness of peripherally-administered hormone. It is concluded that for leptin to have therapeutic potential, it either needs to be modified or the transport system by which leptin enters the brain needs to be upregulated to allow leptin to enter the brain more easily. To achieve effective weight loss, it may also be necessary to overcome central leptin insensitivity by developing agents that act downstream of leptin action.

Topics: Animals; Appetite Depressants; Clinical Trials as Topic; Humans; Leptin; Lipodystrophy; Treatment Failure; Weight Loss

Patients with anorexia nervosa (AN) often show normal to elevated physical activity levels despite severe weight loss and emaciation. This is seemingly in contrast to the loss of energy and fatigue characteristic of other starvation states associated with weight loss. Despite the fact that historical accounts and clinical case studies of AN have regularly commented on the elevated activity levels, the behavior has become only recently the subject of systematic study. Because rodents and other species increase their activity upon food restriction leading to weight loss when given access to an activity wheel--a phenomenon referred to as activity-based anorexia or semi-starvation-induced hyperactivity (SIH)-it has been proposed that the hyperactivity in AN patients may reflect the mobilization of phylogenetically old pathways in individuals predisposed to AN. Exogeneous application of leptin in this animal model of AN has recently been shown to suppress completely the development of SIH. Hypoleptinemia, as a result of the food restriction, may represent the initial trigger for the increased activity levels in AN patients and in food-restricted rats. In the first and second parts of our review, we will summarize the relevant findings pertaining to hyperactivity in AN patients and in the rat model, respectively. We conclude with a synopsis and implications for future research.

Topics: Animals; Anorexia Nervosa; Disease Models, Animal; Exercise; Female; Humans; Hyperkinesis; Leptin; Motor Activity; Rats; Starvation; Weight Loss

Leptin is the first of a group of adipocyte-secreted hormones to be used clinically to treat hypoleptinemic states. In children with congenital leptin deficiency and extreme obesity, leptin induces satiety and a dramatic loss of weight. In hypoleptinemic patients with extreme insulin resistance and lipodystrophy, leptin ameliorates insulin resistance, hyperglycemia, hyperinsulinemia, dyslipidemia and hepatic steatosis. In both these leptin-deficient states, leptin therapy restores gonadotrophin secretion, as well as luteinizing hormone and thyroid-stimulating hormone pulsitility.

Topics: Animals; Humans; Hypothalamo-Hypophyseal System; Insulin Resistance; Leptin; Lipodystrophy; Obesity; Pituitary-Adrenal System; Satiation; Weight Loss

Leptin, an adipocyte secreted hormone, acts in the hypothalamus to inhibit appetite and promote thermogenic metabolism, thereby reducing adiposity and body weight. Leptin has multiple autonomic and cardiovascular actions, including sympathetic activation, increases in endothelium derived nitric oxide (NO), and angiogenesis. The predominant cardiovascular effect of chronic hyperleptinemia is a pressor effect mediated by increased sympathetic activity. The sympathetic and cardiovascular actions of leptin are discussed and evidence derived from studies of obese mice for the novel concept of selective leptin resistance is reviewed. This concept holds that in some obese states, there is preservation of the sympathoexcitatory actions of leptin despite resistance to the satiety and weight-reducing actions of the hormone. Selective leptin resistance might explain how hyperleptinemia could contribute to increases in sympathetic activity and arterial pressure in obese states where there is resistance to the metabolic (satiety and weight-reducing) actions of leptin. It is speculated here, that this concept may have potential implications for human obesity, which is often associated with elevated plasma leptin and partial resistance to the satiety effects of leptin. If selective leptin resistance occurs in obese humans, then leptin could contribute to the sympathetic overactivity and hypertension despite resistance to its metabolic actions.

Topics: Animals; Appetite Regulation; Cardiovascular System; Drug Resistance; Humans; Leptin; Obesity; Sympathetic Nervous System; Weight Loss

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by a remarkable regression of liver steatosis in most patients, although increased inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients.

Topics: Cytokines; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Fatty Liver; Humans; Insulin Resistance; Leptin; Obesity; Oxidative Stress; Prognosis; Weight Loss

Over the lifespan there is a decline in food intake. This has been termed the physiological anorexia of aging. It has many causes, including alterations in the gastrointestinal satiating system, the effect of elevated leptin levels, especially in men, and a variety of changes in central nervous system neurotransmitters. Beyond the age of 70 years body mass declines. This includes both loss of adipose tissue and muscle mass. The loss of muscle mass in older individuals is termed sarcopenia. There is increasing evidence that this is caused, in men, partly by the decline in testosterone. Illness results in an increase of cytokines that produce both anorexia and cause protein wasting. Many of the causes of cachexia in older individuals are treatable. Depression is the most common cause of weight loss in older individuals. Dieting in older individuals is associated with a loss of skeletal tissue as well as fat mass. This can place older individuals at risk of becoming the 'fat frail'.

Topics: Aged; Aging; Anorexia; Body Composition; Cytokines; Diet, Reducing; Female; Food Services; Humans; Leptin; Male; Muscular Atrophy; Testosterone; Weight Loss

Acrocyanosis is undoubtedly the most commonplace acrosyndrome, both in terms of pathogenesis and prognosis. Patients experience functional impairment and an esthetic prejudice that must not be neglected. Adopting the nosological classifications described for Raynaud's syndrome, primary acrocyanosis must be distinguished from exceptional secondary phenomena that have a radically different clinical course. Primary acrocyanosis is generally observed in a young woman who appears thin or has recently lost weight. No paroxysmal episode (syncope, cyanosis, suspicious event involving the fingers) is found. The physical examination is negative and no complementary explorations are needed. Current pathophysiological hypotheses remain insufficient but suggest that vasospasticity rather than hemorheology is involved. The hypothesis that a thermoregulation disorder could be associated with weight loss deserves further study. Symptomatic care relies on dietary and hygiene counseling, emphasizing the importance of warm clothing. The psychological element must also be considered even in the most common forms.

Topics: Adult; Arteritis; Body Temperature Regulation; Cold Temperature; Cyanosis; Diagnosis, Differential; Female; Fingers; Hemorheology; Humans; Hypothalamus; Ischemia; Leptin; Muscle Spasticity; Muscle, Smooth, Vascular; Nail Diseases; Nails; Prevalence; Raynaud Disease; Retrospective Studies; Vasoconstriction; Weight Loss

Topics: Biomarkers; Cachexia; Circadian Rhythm; Electrocardiography; Energy Metabolism; Heart Rate; Homeostasis; Humans; Leptin; Lung Diseases, Obstructive; Signal Processing, Computer-Assisted; Weight Loss

Evidence has existed for more than 50 years in support of the hypothesis that body energy stored in the form of fat is homeostatically regulated. Implicit in this concept is the existence of a biological system that operates dynamically over time to match cumulative energy intake to energy expenditure. For example, to compensate for weight loss induced by energy restriction, animals must enter a period of positive energy balance (i.e., energy intake greater than energy expenditure) that is sustained for as long as it takes to correct the deficit in body fat stores. Having reached this point, the animal must return to a state of neutral energy balance if stable fat mass is to be maintained. The identification of neuronal circuits in the hypothalamus that, when activated, exert potent, unidirectional effects on energy balance provides a cornerstone of support for this model. The additional finding that these central effector pathways are regulated by humoral signals generated in proportion to body fat stores, including the hormones insulin and leptin, helps to round out the picture of how energy homeostasis is achieved. The goal of this overview is to highlight the evidence that specific subsets of hypothalamic neurons containing specific signaling molecules participate in this dynamic regulatory process, and to put these observations in the larger context of a biological system that controls body adiposity.

Topics: Body Weight; Brain; Eating; Energy Intake; Energy Metabolism; Feeding Behavior; Humans; Insulin; Leptin; Neurons; Obesity; Weight Loss

From all nutritional variables optimal energy supply is considered as most vital for human performance. It is postulated that lack of energy homeostasis is the basic problem in the development of overtraining. Most if not all clinical symptoms are directly or indirectly related to the physiological mechanisms of energy homeostasis. The rapidly increasing knowledge in the field of body weight control with several new regulatory neuro-peptides such as leptin, will give new opportunities to tackle this unbalance between training load and energy availability. The central role of leptin and insulin as adiposity signals has focussed attention on the anti-obesity aspects of leptin. However as member of the cytokine family, leptin is also closely linked to the immune and reproductive system. New data indicates clearly the dual function of leptin at both ends at the energy balance; starvation vs. overfeeding. It links also nutrition to the reproductive system. Lack of available energy has a much greater impact on leptin levels than exercise stress. It is suggested that application of the rapidly increasing knowledge in the obesity field will benefit the research on the mechanisms involved in the derailment of the delicate balance between training load and energy homeostasis in athletes.

Topics: Energy Metabolism; Exercise; Homeostasis; Humans; Leptin; Obesity; Sports; Weight Loss

Many experts consider obesity a chronic disease that may require long-term therapy. A loss of 5-15% of body weight is associated with improvements in cardiovascular risk factors and morbidity. However, most studies show that the majority of patients who lose weight relapse. Patients may be unable to maintain a low energy intake when confronted with an almost limitless supply of food. Moreover, a number of physiological mechanisms favour a set point for body weight, that may be altered with anti-obesity drugs.. In the current paper we describe actions and effects of current anti-obesity drugs. The centrally acting drug, sibutramine, is an adrenaline and serotonine re-uptake inhibitor which was recently approved in the USA for obesity. The USA, the European Union and Norway have approved orlistat, a pancreatic lipase inhibitor for weight reduction for up to two years. Patients must maintain a low fat intake in order to avoid gastrointestinal discomfort. In recent studies, orlistat and diet reduced body weight by 9% versus 6% on placebo and diet. No studies have documented long-term safety of anti-obesity drugs.. Treatment of a lifestyle-related disease like obesity with medications is controversial, however, such treatment may not differ substantially from treatment of type II diabetes, hyperlipidaemia or hypertension.

Topics: Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Fenfluramine; Humans; Lactones; Leptin; Obesity; Obesity, Morbid; Orlistat; Phentermine; Selective Serotonin Reuptake Inhibitors; Weight Loss

Topics: Animals; Appetite Depressants; Cyclobutanes; Humans; Leptin; Mice; Mice, Obese; Obesity; Weight Loss

Although there remains controversy regarding the role of macronutrient balance in the etiology of obesity, the consumption of high-fat diets appears to be strongly implicated in its development. Evidence that fat oxidation does not adjust rapidly to acute increases in dietary fat, as well as a decreased capacity to oxidize fat in the postprandial state in the obese, suggest that diets high in fat may lead to the accumulation of fat stores. Novel data is also presented suggesting that in rodents, high-fat diets may lead to the development of leptin resistance in skeletal muscle and subsequent accumulations of muscle triacylglycerol. Nevertheless, several current fad diets recommend drastically reduced carbohydrate intake, with a concurrent increase in fat content. Such recommendations are based on the underlying assumption that by reducing circulating insulin levels, lipolysis and lipid oxidation will be enhanced and fat storage reduced. Numerous supplements are purported to increase fat oxidation (carnitine, conjugated linoleic acid), increase metabolic rate (ephedrine, pyruvate), or inhibit hepatic lipogenesis (hydroxycitrate). All of these compounds are currently marketed in supplemental form to increase weight loss, but few have actually been shown to be effective in scientific studies. To date, there is little or no evidence supporting that carnitine or hydroxycitrate supplementation are of any value for weight loss in humans. Supplements such as pyruvate have been shown to be effective at high dosages, but there is little mechanistic information to explain its purported effect or data to indicate its effectiveness at lower dosages. Conjugated linoleic acid has been shown to stimulate fat utilization and decrease body fat content in mice but has not been tested in humans. The effects of ephedrine, in conjunction with methylxanthines and aspirin, in humans appears unequivocal but includes various cardiovascular side effects. None of these compounds have been tested for their effectiveness or safety over prolonged periods of time.

Topics: Animals; Anti-Obesity Agents; Aspirin; Carnitine; Citrates; Dietary Fats; Dietary Supplements; Ephedrine; Humans; Insulin; Leptin; Linoleic Acid; Lipid Metabolism; Lipolysis; Mice; Muscle, Skeletal; Obesity; Oxidation-Reduction; Pyruvates; Rats; Triglycerides; Weight Loss; Xanthines

Topics: Adipose Tissue; Anti-Obesity Agents; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Metabolism; Glucose; Humans; Insulin; Insulin Resistance; Insulin Secretion; Leptin; Muscle, Skeletal; Obesity; Risk Factors; Weight Loss

Growth hormone (GH) secretion, either spontaneous or evoked by provocative stimuli, is markedly blunted in obesity. In fact obese patients display, compared to normal weight subjects, a reduced half-life, frequency of secretory episodes and daily production rate of the hormone. Furthermore, in these patients GH secretion is impaired in response to all traditional pharmacological stimuli acting at the hypothalamus (insulin-induced hypoglycaemia, arginine, galanin, L-dopa, clonidine, acute glucocorticoid administration) and to direct somatotrope stimulation by exogenous growth hormone releasing hormone (GHRH). Compounds thought to inhibit hypothalamic somatostatin (SRIH) release (pyridostigmine, arginine, galanin, atenolol) consistently improve, though do not normalize, the somatotropin response to GHRH in obesity. The synthetic growth hormone releasing peptides (GHRPs) GHRP-6 and hexarelin elicit in obese patients GH responses greater than those evoked by GHRH, but still lower than those observed in lean subjects. The combined administration of GHRH and GHRP-6 represents the most powerful GH releasing stimulus known in obesity, but once again it is less effective in these patients than in lean subjects. As for the peripheral limb of the GH-insulin-like growth factor I (IGF-I) axis, high free IGF-I, low IGF-binding proteins 1 (IGFBP-1) and 2 (IGFBP-2), normal or high IGFBP-3 and increased GH binding protein (GHBP) circulating levels have been described in obesity. Recent evidence suggests that leptin, the product of adipocyte specific ob gene, exerts a stimulating effect on GH release in rodents; should the same hold true in man, the coexistence of high leptin and low GH serum levels in human obesity would fit in well with the concept of a leptin resistance in this condition. Concerning the influence of metabolic and nutritional factors, an impaired somatotropin response to hypoglycaemia and a failure of glucose load to inhibit spontaneous and stimulated GH release are well documented in obese patients; furthermore, drugs able to block lipolysis and thus to lower serum free fatty acids (NEFA) significantly improve somatotropin secretion in obesity. Caloric restriction and weight loss are followed by the restoration of a normal spontaneous and stimulated GH release. On the whole, hypothalamic, pituitary and peripheral factors appear to be involved in the GH hyposecretion of obesity. A SRIH hypertone, a GHRH deficiency or a functional failure of the somatotro

Topics: Body Composition; Diet, Reducing; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Leptin; Nutritional Physiological Phenomena; Obesity; Proteins; Weight Loss

Obesity is associated with an increased incidence of insulin resistance, dyslipoproteinemia, and hypercoagulability. In a more recently established hypothesis of body weight control and regulation of metabolism, the adipocyte secretes leptin and locally expresses TNF-alpha, the latter being responsible for the expression of metabolic cardiovascular risk factors. TNF-a mRNA expression and TNF-alpha protein are greatly increased in adipose tissue from obese animals and humans. Elevated TNF-alpha expression induces insulin resistance by downregulating the tyrosine kinase activity of the insulin receptor and decreasing the expression of GLUT-4 glucose transporters. TNF-alpha also reduces lipoprotein lipase activity in white adipocytes, stimulates hepatic lipolysis, and increases plasminogen activator inhibitor-1 content in adipocytes. Moreover, adipocytes secrete leptin, a molecule with a secondary cytokine structure whose concentrations correlate with the amount of fat tissue. Increased leptin levels downregulate appetite and increase sympathetic activity and thermogenesis in the hypothalamus. Diet-induced weight loss reduces adipose TNF-alpha expression and serum leptin levels and is associated with improved insulin sensitivity and lipid metabolism. Although exercise has also been shown to reduce leptin levels, an influence on TNF-a expression in adipocytes or muscle cells has not yet been demonstrated.

Topics: Animals; Arteriosclerosis; Coronary Disease; Diet; Exercise; Humans; Insulin Resistance; Leptin; Obesity; Proteins; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss

Topics: Adipose Tissue; Animals; Body Weight; Endocrine System Diseases; Homeostasis; Humans; Hypothalamo-Hypophyseal System; Leptin; Neuropeptide Y; Pituitary-Adrenal System; Proteins; Starvation; Wasting Syndrome; Weight Loss

A mitochondrial protein that uncouples the respiratory chain from oxidative phosphorylation and generates heat is found in brown adipose tissue (BAT) of rodents. Although humans have little BAT, a second uncoupling protein has been discovered that is widely distributed in human tissues. It is induced in mice by a high-fat diet and in mice with obese mutations, and may play a role in human body weight regulation.

Topics: Adipose Tissue, Brown; Animals; Humans; Leptin; Mice; Mice, Inbred C57BL; Proteins; Uncoupling Agents; Weight Loss

The existence of mice (ob/ob mice) with a genetic defect causing obesity and type II diabetes has been known since 1950. The mutated ob gene was recently identified and characterized. The gene encodes a 167 amino acid protein that has been given the name leptin, from the greek word leptos, meaning thin. The functionally active hormone, which is synthesised and secreted by adipocytes, is lacking in homozygote ob/ob mice, causing an increase in body fat. Injection of recombinant leptin in ob/ob mice induces loss of fat due to decreased appetite and increased energy expenditure. The ob gene product leptin acts via binding sites in the hypothalamus, where the centre for appetite and satiety is located. Research is now focused on the identification, characterization and cloning of leptin-receptors. Other mice, also with a genetic defect causing obesity and type II diabetes, do not respond to leptin treatment and are therefore suspected to have defective leptin receptors.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Leptin; Mice; Mice, Obese; Mutation; Proteins; Weight Loss

Topics: Adult; Appetite Regulation; Energy Metabolism; Female; Humans; Leptin; Male; Middle Aged; Obesity; Proteins; Starvation; Treatment Failure; Weight Loss

Leptin, the protein encoded by the recently cloned obese gene, has the properties of a hormone released by adipose tissue, regulating appetite and energy expenditure. Injected leptin reduces body weight and food intake in mice, and in obese, diabetic mice (with a mutated obese gene), it also reduces plasma insulin and glucose. Leptin release is stimulated by insulin; leptin appears to act on the hypothalamus by inhibiting the release of the neuropeptide Y.

Topics: Adipose Tissue; Animals; Appetite; Blood Glucose; Energy Metabolism; Humans; Hypothalamus; Insulin; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Neuropeptide Y; Obesity; Proteins; Weight Loss

Physiological investigation has demonstrated that the central nervous system monitors body composition and adjusts energy intake and expenditure to stabilize total adipose tissue mass. Genetic variations in the signalling molecules involved in this regulatory system account for the heritable component of body fat content. The application of molecular techniques to rodent models of Mendelian obesity has resulted in the characterization of five loci at which mutations produce an abnormal accumulation of body fat. The genes at these loci include agouti, which encodes a molecule that antagonizes the binding of alpha melanocyte-stimulating hormone to its receptor; fat, which encodes carboxypeptidase E; tubby, which encodes a putative phosphodiesterase; obese, which encodes a circulating satiety protein; and diabetes, which encodes the receptor for the obese gene product. A more detailed understanding of the functional interrelationships of these genes should lead to important new insights into the causes and potential therapies for human obesity.

Topics: Adaptor Proteins, Signal Transducing; Adipose Tissue; Agouti Signaling Protein; alpha-MSH; Animals; Brain; Carrier Proteins; Chromosome Mapping; Disease Models, Animal; Eating; Energy Metabolism; Gene Expression Regulation; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Proteins; Receptors, Cell Surface; Receptors, Leptin; Receptors, Pituitary Hormone; Satiation; Signal Transduction; Weight Loss

Excess adiposity is characterized by alterations in adipokine secretion such that circulating leptin concentrations are increased with reductions in adiponectin. An emerging biomarker for the assessment of this adipose tissue (AT) dysfunction is the adiponectin:leptin (AL) ratio. A low AL ratio may be suggestive of dysfunctional AT and, consequently, a heightened cardiometabolic disease risk. This ancillary study investigated the relationship between the AL ratio and cardiometabolic health among community-dwelling older adults with obesity, as well as the effects of a 12-month exercise and diet intervention on changes in the AL ratio.. Participants (n = 163, 70.2 ± 4.7 years, 38.0% male) were randomized to the exercise only group, exercise + nutrient-dense weight maintenance group (exercise + weight maintenance), or exercise + nutrient-dense caloric restriction of 500 kcal/d group (exercise + intentional weight loss) (clinicaltrials.gov #NCT00955903). Total and regional adiposity as determined by magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA), anthropometrics, and cardiometabolic biomarkers were assessed at baseline and 12 months.. The AL ratio was significantly (p < 0.05) inversely correlated with body mass index, waist circumference, measures of adiposity, and insulin among all participants at baseline. Among females only, significant positive and inverse correlations were also observed between this ratio and high-density lipoprotein cholesterol and the inflammatory biomarkers high sensitivity C-reactive protein and interleukin-6, respectively. While controlling for biological sex, a significant time by intervention group interaction effect (p < 0.05) was observed such that the AL ratio significantly increased from baseline to study completion among participants in the exercise + weight maintenance group and exercise + intentional weight loss group. Post hoc analysis revealed that the exercise + intentional weight loss group exhibited a significantly greater AL ratio at study completion compared to other groups (p < 0.05 all).. Results are in support of the AL ratio as a measure of AT dysfunction among older adults. Furthermore, results suggest that a 12-month exercise and diet intervention with intentional weight loss assists in improving the AL ratio in this population.

Topics: Adiponectin; Aged; Biomarkers; Cardiovascular Diseases; Diet, Reducing; Female; Humans; Leptin; Male; Obesity; Weight Loss

Lifestyle interventions including meal replacement are suitable for prevention and treatment of obesity and type-2-diabetes. Since leptin is involved in weight regulation, we hypothesised that a meal replacement-based lifestyle intervention would reduce leptin levels more effectively than lifestyle intervention alone. In the international, multicentre, randomised-controlled ACOORH-trial (Almased-Concept-against-Overweight-and-Obesity-and-Related- Health-Risk), overweight or obese participants with metabolic syndrome criteria (n = 463) were randomised into two groups and received telemonitoring devices and nutritional advice. The intervention group additionally used a protein-rich, low-glycaemic meal replacement. Data were collected at baseline, after 1, 3, 6, and 12 months. All datasets providing leptin data (n = 427) were included in this predefined subanalysis. Serum leptin levels significantly correlated with sex, body mass index, weight, and fat mass at baseline (p < 0.0001). Stronger leptin reduction has been observed in the intervention compared to the control group with the lowest levels after 1 month of intervention (estimated treatment difference −3.4 µg/L [1.4; 5.4] for females; −2.2 µg/L [1.2; 3.3] for males; p < 0.001 each) and was predictive for stronger reduction of body weight and fat mass (p < 0.001 each) over 12 months. Strongest weight loss was observed after 6 months (−5.9 ± 5.1 kg in females of the intervention group vs. −2.9 ± 4.9 kg in the control group (p < 0.0001); −6.8 ± 5.3 kg vs. −4.1 ± 4.4 kg (p = 0.003) in males) and in those participants with combined leptin and insulin decrease. A meal replacement-based lifestyle intervention effectively reduces leptin which is predictive for long-term weight loss.

Topics: Body Mass Index; Diet, Reducing; Female; Humans; Hypoglycemia; Leptin; Male; Obesity; Overweight; Weight Loss

Topics: Adult; Blood Glucose; Diet, Mediterranean; Fasting; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Overweight; Pilot Projects; Weight Loss

Inclusion of dairy in diet patterns has been shown to have mixed effects on weight loss. A prevailing hypothesis is that dairy improves weight loss by influencing endocrine systems associated with satiety and food intake regulation.. The objective of the current study was to evaluate the effect of weight loss with or without adequate dietary dairy on subjective and objective appetitive measures.. Men and women who were habitual low dairy consumers (n = 65, 20-50 y) participated in a 12-wk randomized controlled feeding weight loss trial. During the 12-wk intervention, a low-dairy (<1 serving dairy/d) was compared with an adequate-dairy (3-4 servings dairy/d) diet, both with a 500-kcal deficit/d. Test days, before and at the end of the intervention, began with 2 fasting blood draws and visual analog scale (VAS) measures, followed by a standard breakfast (25% of prescribed restricted calories), 5 postbreakfast blood draws and VASs, a standard lunch (40% of restricted energy amount), and 12 postlunch blood draws and VASs. Blood samples were used for satiety hormone measurements. On a separate day when matching standard meals were consumed, an ad libitum buffet meal was provided as dinner, at a self-selected time. Meal duration and intermeal interval were recorded.. Weight loss (-6.1 kg), irrespective of dairy, resulted in reduced fasting insulin (-20%) and leptin (-25%), and increased fasting acylated ghrelin (+25%) and VAS desire to eat (+18%) (P < 0.05). There were no effects of dairy on objective or subjective satiety measures. Weight loss marginally reduced the intermeal interval (289 min compared with 276 min, P = 0.059) between lunch and the ad libitum buffet.. These results do not support the hypothesis that inclusion of dairy in long-term dietary patterns influences appetite during weight loss. Weight loss per se has a modest impact on select systems that regulate hunger and satiety.This trial was registered at clinicaltrials.gov as NCT00858312.

Topics: Adult; Dairy Products; Diet; Female; Gastrointestinal Tract; Ghrelin; Humans; Insulin; Leptin; Male; Middle Aged; Postprandial Period; Satiety Response; Weight Loss; Young Adult

We investigated the effects of the macronutrient composition of diets with differing satiety values on fasting appetite-related hormone concentrations after weight loss and examined whether the hormone secretion adapted to changes in body fat mass (FM) and fat-free mass (FFM) during the weight maintenance period (WM).. Eighty-two men and women with obesity underwent a 7-week very-low-energy diet (VLED) and were then randomised to a higher-satiety food (HSF) group or a lower-satiety food (LSF) group during 24-weeks of the WM. The groups consumed isoenergetic foods with different satiety ratings and macronutrient compositions.. During the WM, the HSF group consumed more protein and dietary fibre and less fat than the LSF group, but the groups showed similar changes in body weight and fasting appetite-related hormones. In the whole study sample, VLED induced 12 kg (p < 0.001) weight loss. At the end of the WM, weight regain was 1.3 kg (p = 0.004), ghrelin concentration increased, whereas leptin, insulin, and glucose concentrations decreased compared to pre-VLED levels (p < 0.001 for all). Peptide YY did not differ from pre-VLED levels. Changes in ghrelin levels were inversely associated with changes in FFM during weeks 0-12 of the WM (p = 0.002), while changes in leptin and insulin levels were positively associated with changes in FM during weeks 0-12 (p = 0.015 and p = 0.038, respectively) and weeks 12-24 (p < 0.001 and p = 0.022) of the WM.. The macronutrient composition of an isoenergetic WM diet did not affect fasting appetite-related hormone concentrations. Leptin and insulin adjusted to the reduced FM, whereas ghrelin reflected FFM during the first months of the WM.. isrctn.com, ID 67529475.

Topics: Appetite; Body Weight Maintenance; Diet; Fasting; Female; Ghrelin; Humans; Insulin; Leptin; Male; Nutrients; Weight Loss

This study aimed to compare cytokine and adipokine levels in patients with obesity with and without type 2 diabetes (T2D) at baseline and 6 months after Roux-en-Y gastric bypass (RYGB) with healthy controls.. A total of 34 patients (21 with T2D) with BMI of 30 to 45 kg/m. Significant decreases in weight and glycated hemoglobin A. The altered cytokine profile of patients with obesity persisted after RYGB despite large weight loss and improved metabolic status, thus reflecting an inherent inflammatory state.

Topics: Adipokines; Adult; Case-Control Studies; Cytokines; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Postoperative Period; Preoperative Period; Weight Loss

The expansion of adipose tissue increases leptin secretion associated with a reduction of adiponectin concentration, which negatively affects health of adolescents with obesity. This study aims to investigate the effects of non-intensive interdisciplinary therapy on cardiometabolic parameters including leptin, adiponectin and adiponectin/leptin ratio as a dependent manner on its magnitude of weight loss reduction.. Thirty-eight adolescents (14-19 y.o) were enrolled in an interdisciplinary therapy for 20 weeks. Body composition, biochemical parameters, leptin and adiponectin were measured at baseline and after therapy. The adolescents were divided into two groups according to the magnitude of total weight loss, less than 5% (<5%-n = 18) or greater than or equal to 5% (≥5%-n = 20). Leptin decreased in whole group after therapy, while adiponectin, and adiponectin/leptin ratio increased. Additionally, body composition was improved. Only the group who lost ≥5% of body weight could reduce the inflammatory state.. The interdisciplinary therapy contributes to improve cardiometabolic parameters that could be involved on inflammation in adolescents with obesity, this improvement occurred mainly when the weight loss is ≥5% of body weight. It could be a target for control the inflammatory process related to obesity in adolescents.

Topics: Adiponectin; Adolescent; Humans; Leptin; Obesity; Weight Loss; Young Adult

Taurine (Tau), an endogenous non-protein and sulfuric-amino acid, is involved in various biological pathways including anti-inflammatory, anti-oxidation, insulin resistance inhibition, and lipid profile improvement. According to some experimental and clinical studies, insulin resistance and excess body weight are associated with reduced serum level of Tau. Therefore, this study was aimed to evaluate Tau supplementation and a diet-induced weight-loss intervention on body composition and some biochemical indices of obese women. Participants were divided randomly into the intervention (standard weight-loss group + cap Tau 3 g/day for 8 weeks, n = 20) and control (standard weight-loss group + cap placebo for 8 weeks, n = 18) groups. To achieve weight loss, all participants received an individualized diet that included a 30% reduction in their total energy intake. Chi-square test was applied to compare categorical variables between two groups at baseline. Paired t test and independent-sample t test were also used to analyze the parametric continuous data within and between the two groups, respectively. Analysis of covariance was run for controlling the confounding variables. At the post-intervention, the mean changes of total cholesterol (p = 0.03), low-density lipoprotein cholesterol (p = 0.03), leptin (p = 0. 006), total adiponectin (p = 0.04), and high sensitivity C-reactive protein (p = 0.03) decreased significantly in Tau group compared with the control group. No significant results were found in the mean changes of high-density lipoprotein cholesterol, anthropometric measurements, glycemic indices, and liver enzymes between the two groups (p > 0.05). The findings showed that Tau supplementation along with a weight-loss diet may be more effective in improving the lipid profile and metabolic risk factors compared with a weight-loss diet alone.

Topics: Adiponectin; Adult; Biomarkers; Body Composition; C-Reactive Protein; Cholesterol, LDL; Diet, Reducing; Dietary Supplements; Energy Intake; Female; Glycemic Index; Humans; Leptin; Middle Aged; Obesity; Taurine; Weight Loss

Obesity is a common disease of developing countries, including Pakistan. Obesity is a risk factor for many diseases which can be life threatening or making the person unable to perform daily routine work. In the current study, clinical trials were designed to evaluate the effects of medical intervention by comparing the effects of placebo control drug "Plasicure" with the herbal medicinal formulation "Obesecure". The test drug formulation was designed on the basis of the screening study for Leptogenic drugs. To evaluate the safety of the test drug, the toxicity index and the safety profile of test formulation was assessed on animal models. The drug was found safe for further clinical study. Randomized Controlled Clinical Trials were conducted. The statistical analysis was carried out by the application of Two-Way Repeated Analysis of Variance test. The clinical findings of randomized controlled trial revealed that the test drug was Leptogenic and effective in weight reduction as compared to control drug Plasicure therapy as the p-value deduced was 0.001 in leptin level and 0.000 in case of BMI after the conduction of Two-Way Repeated Analysis of Variance test. Hence it is concluded that obscure therapy is more significant than control drug Plasicure therapy in the management and treatment of obesity.

Topics: Adult; Anti-Obesity Agents; Biomarkers; Body Mass Index; Double-Blind Method; Drugs, Chinese Herbal; Female; Humans; Leptin; Male; Middle Aged; Obesity; Pakistan; Prospective Studies; Time Factors; Treatment Outcome; Weight Loss; Young Adult

A common G-to-A transition located 75 base pairs upstream (rs670) from transcription start site of the APOA1 gene has been related with some metabolic parameters. Our aim was to analyze the effects of rs670 APOA1 gene polymorphism on lipid profile and metabolic changes after two different hypocaloric diets.. 282 obese subjects were randomly allocated during 12 weeks (Diet HF - high fat diet vs. Diet LF - low fat diet). Anthropometric and biochemical status were evaluated.. Body mass index, weight, fat mass, waist circumference, systolic blood pressure, leptin levels and waist circumference decreased in all patients in average after both diets. In A allele carriers after 12 weeks with both diets, insulin levels (Delta diet HF: -5.3 + 1.2 UI/L; P = 0.02 and Delta diet LF: -5.8 + 1.3 UI/L; P = 0.02) and HOMA-IR (Delta diet HF: -2.9 + 0.8 units; P = 0.01 and Delta diet LF: -2.2 + 0.9 units; P = 0.03) improved in a significant way. With the low fat diet, A allele carriers showed a statistical improvement in HDL-cholesterol levels (Delta: 4 + 1 mg/dl; P = 0.03).. Our study showed the association of rs670 ApoA1 polymorphism with a decrease of insulin resistance induced by both diets and provided additional evidence on HDL-cholesterol increase after a LF hypocaloric diet in A allele carriers.

Topics: Adult; Aged; Apolipoprotein A-I; Blood Pressure; Body Composition; Body Mass Index; Caloric Restriction; Cholesterol, HDL; Diet, Fat-Restricted; Diet, High-Fat; Female; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Waist Circumference; Weight Loss

The objective of this study was to evaluate the effects of high-intensity resistance and endurance exercise on body composition and plasma leptin and ghrelin concentrations in overweight individuals. One hundred participants were randomly assigned to 3 exercise interventions: high-resistance-low-aerobic exercise (Re), low-resistance-high-aerobic exercise (rE), low-resistance-low-aerobic exercise (re). Interventions began with 3 weeks of residential supervision (phase 1) after which participants had to manage the physical activity programs individually (phase 2). Body composition and plasma variables were measured at baseline and after phase 1 as well as after 3, 6, and 12 months. Significant decreases in body weight and fat were observed after phase 1 (

Topics: Adipose Tissue; Aged; Body Composition; Exercise; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Overweight; Physical Endurance; Weight Loss

The aim of the study was to compare the impact of 6 weeks of reducing daily caloric intake by 20% of total daily energy expenditure (TDEE)-CRI vs. reducing daily caloric intake by 30% of TDEE-CRII on body mass reduction and insulin metabolism in former athletes.. 94 males aged 35.7 ± 5.3 years, height 180.5 ± 4.1 cm, and body mass 96.82 ± 6.2 kg were randomly assigned to the CRI (. After adhering to the CR I diet, significant differences were observed in FFM, MM and TG. After adhering to the CR II diet, significant differences were registered in tCh, TL and LDL. Both diets had a significant influence on leptin and adiponectin concentrations. Significant differences in FFM, MM, and tCh were observed between the CR I and CR II groups. At the end of the dietary intervention, significant differences in BF, FFM, MM and TBW were observed between the CR I and CR II groups.. The 6 weeks of CR II diet appeared to be more effective in reducing BF and lipid profile and proved to be especially suitable for subjects with high body fat content and an elevated level of lipoproteins and cholesterol. Both reductive diets were effective in improving the levels of leptin and adiponectin in obese former athletes.

Topics: Adiponectin; Adiposity; Adult; Athletes; Biomarkers; Body Composition; Caloric Restriction; Humans; Leptin; Lipids; Male; Obesity; Time Factors; Treatment Outcome; Weight Loss

Studies have reported contradictory findings regarding the effect of a mixture of 2 conjugated linoleic acid (CLA) isomers on body weight and some serum indices. This study aims to investigate the effect of daily supplementation of these 2 isomers on body composition and serum leptin and insulin levels in obese adults.. This randomized, double-blind clinical trial was performed on 54 adults with class I obesity. The subjects were randomly assigned into 2 groups of 27 and were followed for 3 months so that a total of 3000 mg of CLA supplement and placebo were administered in 3 daily doses in the intervention and control groups, respectively. Body composition indices as well as fasting serum levels of insulin and leptin were also measured. The paired t-test was used for evaluating within-group effects from baseline. The independent t-test was used to compare between-group differences for variables with normal distribution.. Although body weight and body mass index (BMI) were not significantly decreased during intervention in groups, but the body fat mass (BFM) (P=0.034), body fat percentage (P=0.022) and trunk fat (P=0.027) decreased significantly during intervention with CLA. The fasting plasma sugar (P=0.042) and Homeostatic model assessment for insulin resistance (HOMA/IR) (P=0.044) in the intervention group declined during 12 weeks of intervention. Serum leptin was associated with a significant decrease during the intervention period (P=0.039).. CLA supplementation could reduce body fat and serum leptin. Hence, it could be taken into account as a factor for weight loss but not to control or prevent diabetes.

Topics: Adipose Tissue; Adult; Body Composition; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Leptin; Linoleic Acids, Conjugated; Male; Obesity; Weight Loss

Bariatric surgery (BS) promotes carotid intima-media thickness (C-IMT) regression as early as 6 months post-surgery. To verify whether C-IMT regression occurs even earlier, we aimed at the effect of Roux-en-Y gastric bypass (RYGBP) and biliopancreatic diversion (BPD) on C-IMT 1-2 months and 12 months post-surgery.. Prospective trial. BS was performed on 109 patients either with (RYGBP = 42; BDP = 40) or without type 2 diabetes (RYGBP = 27). Healthy volunteers served as control group.. baseline, 1-2 months, 12 months post-surgery.. changes (∆) in C-IMT, weight, body mass index, fat mass, waist and neck circumferences, blood pressure, HbA1c, glucose, insulin, insulin sensitivity [HOMA-IR; OGIS, from meal tolerance test], lipids, C-reactive protein, leptin, adiponectin, MCP-1.. All surgery subgroups had similar levels of ∆-C-IMT. C-IMT in the pooled surgery group reduced from [mean (95% confidence interval)] 0.81 (0.77-0.84) mm to 0.66 (0.63-0.69) mm, p < 0.001 [-17.1 (-20.4 to -13.8)%] at 1-2 months, and to 0.63 (0.59-0.66) mm, p < 0.001 [-21.8 (-25.3 to -18.4)%] at 12 months post-surgery. ∆-C-IMT 1-2 months and 12 months post-surgery correlated to baseline C-IMT, and with ∆-leptin at 1-2 months, but not at 12 months post-surgery. In linear regression analysis, ∆-leptin and baseline C-IMT were predictors of ∆-C-IMT 1-2 months post-surgery.. A remarkable C-IMT regression occurred as early as 1-2 months after BS in obese patients either with or without type 2 diabetes, which was associated to the early reduction in leptin, (at least partially) independent of weight loss. Whether this is a causative or correlative association needs further investigation.

Topics: Adult; Bariatric Surgery; Body Mass Index; Carotid Arteries; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Obesity, Morbid; Time Factors; Tunica Intima; Weight Loss; Young Adult

Very few weight and fat loss supplements undergo finished-product research to examine efficacy. The purpose of this study was to determine the effects of an 8-week diet and exercise program on body composition, hip and waist girth, and adipokines and evaluate whether a dietary supplement containing raspberry ketone, capsaicin, caffeine, garlic, and Citrus aurantium enhanced outcomes.. Overweight men and women completed this randomized, placebo-controlled, double-blind study. Participants consumed 4 capsules/d of supplement (EXP; n = 18) or placebo (PLA; n = 18). Participants underwent 8 weeks of daily supplementation, calorie restriction (500 kcal < RMR [resting metabolic rate] × 1.2), and supervised progressive exercise training 3 times a week. Body composition, girth, and adipokines were assessed at baseline and postintervention (T1 and T2).. Significant decreases in weight (-2.6 ± 0.57 kg, p < 0.001), fat mass (-1.8 ± 0.20 kg; p < 0.001), and percentage body fat (-3.7% ± 0.29%, p < 0.001) and a significant increase in lean body mass (LBM; 1.5 ± 0.26 kg; p < 0.001) were seen from T1 to T2 in both groups. For men, only those in the EXP group increased LBM from T1 to T2 (1.3 ± 0.38 kg; p < 0.05). Hip girth was also reduced, with the women in the EXP group (-10.7 ± 2.15 cm, p < 0.001) having a greater reduction. There was a time by group interaction, with significant decreases in leptin (p < 0.001) and significant increases in adiponectin (p < 0.05) in the EXP group.. Significant improvements in adipokines and leptin support the utility of exercise, diet, and fat loss for impacting inflammatory biomarkers. The improvement in adiponectin with EXP may suggest a unique health mechanism.

Topics: Adipokines; Adult; Body Composition; Caffeine; Caloric Restriction; Capsaicin; Citrus; Diet; Dietary Supplements; Double-Blind Method; Exercise; Female; Garlic; Hip; Humans; Ketones; Leptin; Male; Middle Aged; Overweight; Placebos; Rubus; Sex Factors; Waist Circumference; Weight Loss

Indirect comparisons suggest that alternate-day fasting (ADF) may produce greater improvements in body composition, fat distribution, and/or the adipokine profile compared to daily calorie restriction (CR), but this has not been tested directly. In a pre-planned secondary analysis of a randomized controlled trial, we compared changes in the VAT:SAT ratio, FFM:total mass ratio, and the adipokine profile between ADF and CR.. Overweight and obese participants (n = 100) were randomized to 1) ADF (alternating every 24-h between consuming 25% or 125% of energy needs); 2) CR (consuming 75% of needs every day); or 3) control (consuming 100% of needs every day) for 24 wk.. The VAT:SAT ratio did not change in any group. The FFM:total mass ratio increased in both ADF (0.03 ± 0.00) and CR (0.03 ± 0.01) compared to the control group (P < 0.01), with no differences between the intervention groups. Circulating leptin decreased in both the ADF group (-18 ± 6%) and CR group (-31 ± 10%) relative to the control group (P < 0.05), with no differences between the intervention groups. Circulating levels of adiponectin, resistin, IL-6, and TNF-α did not change in either intervention group relative to the control group.. ADF and CR similarly improve the FFM:total mass ratio and reduce leptin after a 24-wk intervention.. Clinicaltrials.gov, number NCT00960505.

Topics: Adipokines; Adult; Body Composition; Body Weight; Caloric Restriction; Diet, Reducing; Exercise; Fasting; Female; Humans; Leptin; Male; Middle Aged; Obesity; Overweight; Treatment Outcome; Weight Loss

High-protein (HP) diets have shown benefits in cardiometabolic markers such as insulin or triglycerides but the responsible mechanisms are not known. We aimed to assess the effect of three energy-restricted diets with different protein contents (20%, 27%, and 35%; ∼80% coming from animal source) on plasma adipokine concentration and its association with changes in cardiometabolic markers.. Seventy-six women (BMI 32.8 ± 2.93) were randomized to one of three calorie-reduced diets, with protein, 20%, 27%, or 35%; carbohydrates, 50%, 43%, or 35%; and fat, 30%, for 3 months. Plasma adipokine (leptin, resistin, adiponectin, and retinol-binding protein 4; RBP4) levels were assessed.. After 3 months, leptin concentration decreased in all groups without differences among them, while resistin levels remained unchanged. Adiponectin concentration heterogeneously changed in all groups (P for trend = 0.165) and resistin concentration did not significantly change. RPB4 significantly decreased by -17.5% (-31.7, -3.22) in 35%-protein diet (P for trend = 0.024 among diets). Triglycerides improved in women following the 35%-protein diet regardless of weight loss; RBP4 variation significantly influenced triglyceride concentration change by 24.9% and 25.9% when comparing 27%- and 35%- with 20%-protein diet, respectively.. A 35%-protein diet induced a decrease in RBP4 regardless of weight loss, which was directly associated with triglyceride concentration improvement. These findings suggest that HP diets improve the cardiometabolic profile, at least in part, through changes in adipokine secretion. Whether this beneficial effect of HP diet is due to improvements in hepatic or adipose tissue functionality should be elucidated.. The clinical trial has been registered in ClinicalTrials.gov (Identifier: NCT02160496).

Topics: Adipokines; Adiponectin; Adult; Biomarkers; Caloric Restriction; Dietary Proteins; Female; Humans; Leptin; Middle Aged; Obesity; Resistin; Retinol-Binding Proteins, Plasma; Spain; Time Factors; Treatment Outcome; Triglycerides; Weight Loss

Chemerin has been suggested as a potential link between obesity and associated comorbidities in humans. Therefore, we studied the relationships between chemerin, parameters of fat mass, and Metabolic Syndrome (MetS) in obese children before and after weight reduction.. We determined chemerin, bioactive leptin (bioLep), BMI-SDS, waist circumference (WC), body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index HOMA, and blood pressure in 88 obese children participating in a lifestyle intervention at baseline and 1 year later. Furthermore, we determined chemerin concentrations in 23 normal-weight children.. Obese children demonstrated significantly (p < 0.001) higher chemerin concentrations compared to normal-weight children (96.2 ± 23.0 versus 63.1 ± 12.4 ng/ml). The chemerin concentrations were not related to age or gender. Prepubertal children had higher (p = 0.024) chemerin concentrations than pubertal children (71.0 ± 13.4 versus 58.0 ± 8.9 ng/ml). Weight loss was associated with a decrease of chemerin (-14.0 ± 22.0 ng/ml; p < 0.001) and an improvement of all parameters of the MetS. Chemerin was significantly related to BMI-SDS, WC, and bioLep in cross-sectional and longitudinal analyses. Chemerin and its changes were significantly related to insulin, HDL-cholesterol, triglycerides and their changes in multiple linear regression analyses adjusted to age, gender, pubertal stage, leptin and BMI.. Since chemerin was related to parameters of central fat mass and MetS both in cross-sectional and longitudinal analyses these findings suggest an impact of chemerin on factors of the MetS in obese children.

Topics: Biomarkers; Blood Glucose; Body Mass Index; Chemokines; Child; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Longitudinal Studies; Male; Metabolic Syndrome; Pediatric Obesity; Treatment Outcome; Triglycerides; Waist Circumference; Weight Loss; Weight Reduction Programs

Huntington's disease (HD) is a rare progressive neurodegenerative disorder of genetic origin, with no definitive treatment. Unintentional weight loss (UWL) is a clinical feature of symptomatic HD subjects. To prevent UWL, a customized HD diet is designed and its impact on plasma miRNA HD footprint and neurological parameters is examined.. Eleven participants are included, BMI ≤ 18 kg m. A customized HD-diet prevents UWL and modified miRNAs HD-footprint. The normalization of miRNA values suggests its potentially use as HD-biomarkers.

Topics: Adult; Aged; Body Composition; Body Mass Index; Circulating MicroRNA; Energy Intake; Female; Humans; Huntington Disease; Leptin; Male; MicroRNAs; Middle Aged; Nutrition Assessment; Precision Medicine; Weight Loss

We assessed the associations between changes in total and abdominal fat and changes in biomarkers for breast cancer risk using data of the SHAPE-2 trial. In the SHAPE-2 trial, 243 postmenopausal overweight women were included. The intervention in this trial consisted of 5-6 kg weight loss either by diet only or exercise plus diet. After 16 weeks, we measured serum sex hormones, inflammatory markers, total body fat (measured by DEXA scan) and intra and subcutaneous abdominal fat (measured by MRI). Associations between changes in different body fat depots and biomarkers were analysed by linear regression using the study cohort irrespective of randomisation to make maximal use of the distribution of changes in fat measures. We found that a loss in total body fat was associated with favourable changes in free oestradiol, free testosterone, leptin and sex hormone binding globulin (SHBG). The loss of intra-abdominal fat was associated with a decrease in free testosterone, hsCRP and leptin, and an increase in SHBG. In the multivariable analysis, the best fitted models for the biomarkers free oestradiol, SHBG leptin and adiponectin included only total body fat. For free testosterone, this was subcutaneous abdominal fat, and for hsCRP and IL-6, only intra-abdominal fat change was important. For IL-6 and adiponectin, however, associations were weak and not significant. We conclude that, in our population of healthy overweight postmenopausal women, loss of fat at different body locations was associated with changes in different types of biomarkers, known to be related to risk of breast cancer.

Topics: Adiponectin; Adipose Tissue; Aged; Biomarkers; Body Fat Distribution; Breast Neoplasms; C-Reactive Protein; Diet; Estradiol; Exercise; Female; Humans; Interleukin-6; Leptin; Middle Aged; Overweight; Postmenopause; Risk Factors; Sex Hormone-Binding Globulin; Testosterone; Weight Loss

The molecular mechanisms implicated in pronounced weight loss and metabolic benefits after bariatric surgery are still unknown. Adipocyte phenotype and metabolism have not been entirely explored. However, some features of adipocyte function have been studied, such as adipocyte size and inflammation, which are both reduced after bariatric surgery. Adipocyte fat metabolism, which is partly regulated by leptin, is likely modified, since adipocyte area is decreased. Here, we show that leptin receptor expression is increased, while adipocyte size is decreased 8 months after Roux-en-Y gastric bypass. Thus, adipocyte function is possibly modified by improved leptin signaling after bariatric surgery.

Topics: Adipocytes; Adult; Cell Size; Female; Gastric Bypass; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Receptors, Leptin; Subcutaneous Fat; Weight Loss

Thousands of genetic variants have been associated with complex traits through genome-wide association studies. However, the functional variants or mechanistic consequences remain elusive. Intermediate traits such as gene expression or protein levels are good proxies of the metabolic state of an organism. Proteome analysis especially can provide new insights into the molecular mechanisms of complex traits like obesity. The role of genetic variation in determining protein level variation has not been assessed in obesity. To address this, we design a large-scale protein quantitative trait locus (pQTL) analysis based on a set of 1129 proteins from 494 obese subjects before and after a weight loss intervention. This reveals 55 BMI-associated cis-pQTLs and trans-pQTLs at baseline and 3 trans-pQTLs after the intervention. We provide evidence for distinct genetic mechanisms regulating BMI-associated proteins before and after weight loss. Finally, by functional analysis, we identify and validate FAM46A as a trans regulator for leptin.

Topics: Adolescent; Adult; Body Mass Index; Female; Gene Regulatory Networks; Humans; Leptin; Male; Middle Aged; Obesity; Polynucleotide Adenylyltransferase; Proteins; Proteomics; Quantitative Trait Loci; Regulatory Elements, Transcriptional; Weight Loss; Young Adult

Dietary calorie restriction and exercise promote weight loss and may have additive effects for improving insulin sensitivity, independent of weight loss. It is not known if these effects are attributable to changes in circulating cytokines. We evaluated the hypothesis that modest, matched weight loss induced by calorie restriction and exercise have additive effects on circulating cytokines and these changes correlate with improvements in insulin sensitivity. Overweight and sedentary women and men (n = 52, 45-65 years) were randomized to undergo 7 % weight loss by using 3-6 months of calorie restriction, exercise, or a combination of both calorie restriction and exercise. Concentrations of cytokines and hormones were measured in fasting and oral glucose tolerance test blood samples. Insulin sensitivity was estimated based on oral glucose tolerance test for glucose and insulin. With all groups combined, fasting leptin (p < 0.0001) and high molecular weight adiponectin (p = 0.04) decreased and pentraxin-3 increased (p < 0.0001), in a manner that correlated with improvements in insulin sensitivity (all p ≤ 0.0002). These changes, combined with decreases in glucose-dependent insulinotropic polypeptide from the oral glucose tolerance test, explained 63 % of the variance (p < 0.0001) in insulin sensitivity improvements. Exercise and calorie restriction had additive effects on leptin, with a similar trend for high molecular weight adiponectin. Monocyte chemoattractant protein-1 and C-reactive protein concentrations did not change. Calorie restriction and exercise had opposite effects on soluble tumor necrosis factor receptor-1. Modest weight loss in overweight adults decreases serum leptin and high molecular weight adiponectin, and increases pentraxin-3 concentrations in a manner that correlates with increased insulin sensitivity. Exercise has additive effects to those induced by calorie restriction for reductions in leptin and possibly adiponectin. These changes may contribute to the additive effects of calorie restriction and exercise for improving insulin sensitivity.

Topics: Adiponectin; Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Caloric Restriction; Combined Modality Therapy; Cytokines; Diabetes Mellitus, Type 2; Exercise; Female; Follow-Up Studies; Gastric Inhibitory Polypeptide; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Missouri; Overweight; Peptide Fragments; Risk; Serum Amyloid P-Component; Weight Loss

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) cause weight loss and metabolic improvement, but results of published studies are contradictory.. The aim of this study was to compare the effects of SG and RYGB on ghrelin, leptin, and glucose homeostasis in a randomized controlled trial.. University hospital, Poland.. Seventy-two morbidly obese patients were randomly selected to undergo either SG (n = 36) or RYGB (n = 36). Fasting ghrelin, leptin, glucose, insulin, C-peptide, glucagon, glycated hemoglobin, and homeostasis model assessment of insulin resistance were assessed preoperatively and at 1, 6, and 12 months postoperatively. No differences were found in anthropometric and biochemical parameters between the study groups at baseline.. Sixty-nine (95.8%) patients completed the study. Percentage of excess weight loss at 12 months was 67.6±19.3% after SG and 64.2±18.5% after RYGB (P>.05). Fasting ghrelin levels decreased 1 month after SG (from 76.8 pmol/L to 35.3 pmol/L; P<.05) and remained reduced until 12 months (41.6 pmol/L; P<.05) but increased 12 months after RYGB from 74.6 pmol/L to 130.2 pmol/L (P<.05). Leptin, glucose, insulin, and C-peptide concentrations and glycated hemoglobin and homeostasis model assessment of insulin resistance values decreased significantly in both groups during 12 months.. RYGB and SG induce comparable weight loss and improvement in metabolism of glucose. Ghrelin levels decrease after SG and increase after RYGB, but this difference does not affect similar outcomes of these procedures during 1-year follow-up. The contribution of ghrelin to weight loss or metabolic benefits after bariatric surgery is not straightforward, but rather influenced by multiple factors.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Female; Gastrectomy; Gastric Bypass; Ghrelin; Glucagon; Glycated Hemoglobin; Homeostasis; Humans; Insulin Resistance; Laparoscopy; Leptin; Male; Middle Aged; Obesity, Morbid; Operative Time; Prospective Studies; Weight Loss; Young Adult

The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown.. To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting.. Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months.. Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9 kg for free T3 (P. In this diet-induced weight loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight loss diets.

Topics: Adult; Aged; Body Mass Index; Body Weight Maintenance; Caloric Restriction; Diet, Reducing; Energy Metabolism; Female; Humans; Leptin; Male; Middle Aged; Overweight; Thyroid Hormones; Waist Circumference; Weight Loss

The continued growth in biofuel production has led to a search for alternative value-added applications of its main by-product, crude glycerin. The surplus glycerin production and a higher cost of feedstuffs have increased the emphasis on evaluating its nutritive value for animal feeding. The aim of this research was to evaluate the effect of the dietary addition of crude glycerin on sow and litter performance, and to determine the serum concentrations of hormones related to energy metabolism and feed intake in sows during gestation and lactation. A total of 63 sows were assigned randomly to one of three dietary treatments, containing 0, 3 or 6% crude glycerin (G0, G3 and G6, respectively) added to a barley-soybean meal-based diet. During gestation, none of the dietary treatments had an effect on performance, while during lactation, glycerin-fed sows consumed less feed than those fed the control diet (3.8 v. 4.2kg DM/day; P=0.007). Although lactating sows fed the G3 diet had a higher BW loss than those fed the control diet (���20.6 v. ���8.7 kg; P=0.002), this difference was not reflected in litter performance. In gestation, the inclusion of glycerin did not affect blood concentrations of insulin or cortisol. However, pregnant sows fed diets supplemented with glycerin showed lower concentrations of acyl-ghrelin and higher concentrations of leptin (���55 and +68%, respectively; P<0.001). In lactating sows, there were no differences between dietary treatments for any of the hormones measured. Pre-prandial acyl-ghrelin concentrations were positively correlated with cortisol concentrations during gestation (r=0.81; P=0.001) and lactation (r=0.61; P=0.015). In conclusion, the inclusion of up to 6% crude glycerin did not affect the performance of sows during the gestation period; however it had a negative effect on the feed intake and weight loss of lactating sows. Moreover, further research is needed to elucidate the potential relationship between glycerin inclusion levels in the diet and the serum concentrations of hormones related to feed intake and energy balance control.

Topics: Acylation; Animal Feed; Animals; Diet; Eating; Energy Metabolism; Female; Ghrelin; Glycerol; Hydrocortisone; Lactation; Leptin; Litter Size; Pregnancy; Pregnancy, Animal; Sus scrofa; Swine; Weight Loss

Sex differences in weight loss are often seen despite using the same weight loss program. There has been relatively little investigation of physiological influences on weight loss success in males and females, such as energy homeostasis and appetite regulating hormones. The aims were to 1) characterise baseline plasma leptin, ghrelin and adiponectin concentrations in overweight and obese males and females, and 2) determine whether baseline concentrations of these hormones predict weight loss in males and females. Subjects were overweight or obese (BMI 25-40 kg/m(2)) adults aged 18-60 years. Weight was measured at baseline, and after three and six months participation in a weight loss program. Baseline concentrations of leptin, adiponectin and ghrelin were determined by enzyme-linked immunosorbent assay (ELISA). An independent t-test or non-parametric equivalent was used to determine any differences between sex. Linear regression determined whether baseline hormone concentrations were predictors of six-month weight change. Females had significantly higher baseline concentrations of leptin, adiponectin and unacylated ghrelin as well as ratios of leptin:adiponectin and leptin:ghrelin. The ratio of acylated:unacylated ghrelin was significantly higher in males. In males and females, a higher baseline concentration of unacylated ghrelin predicted greater weight loss at six months. Additionally in females, higher baseline total ghrelin predicted greater weight loss and a higher ratio of leptin:ghrelin predicted weight gain at six months. A higher pre-weight-loss plasma concentration of unacylated ghrelin is a modest predictor of weight loss success in males and females, while a higher leptin:ghrelin ratio is a predictor of weight loss failure in females. Further investigation is required into what combinations and concentrations of these hormones are optimal for weight loss success.

Topics: Acylation; Adiponectin; Adult; Appetite; Body Mass Index; Energy Metabolism; Female; Ghrelin; Homeostasis; Humans; Leptin; Male; Middle Aged; Obesity; Overweight; Sex Factors; Treatment Outcome; Weight Loss

Obesity induces insulin resistance (IR), the key etiologic defect of type 2 diabetes mellitus (T2DM). Therefore, an incidence of obesity-induced diabetes is expected to decrease if obesity is controlled. Although Metformin is currently one of the main treatment options for T2DM in obese patients, resulting in an average of 5% weight loss, adequate weight control in all patients cannot be achieved with Metformin alone. Thus, additional therapies with a weight loss effect, such as acupuncture, may improve the effectiveness of Metformin.Subjective:We designed this randomized clinical trial (RCT) to compare the effects of Metformin monotherapy with that of Metformin and acupuncture combined therapy on weight loss and insulin sensitivity among overweight/obese T2DM patients, to understand whether acupuncture plus Metformin is a better approach than Metformin only on treating diabetes. To understand whether acupuncture can be an insulin sensitizer and, if so, its therapeutic mechanism.. Our results show that Metformin and acupuncture combined therapy significantly improves body weight, body mass index (BMI), fasting blood sugar (FBS), fasting insulin (FINS), homeostasis model assessment (HOMA) index, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin, glucagon-like peptide-1 (GLP-1), resistin, serotonin, free fatty acids (FFAs), triglyceride (TG), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and ceramides.. Consequently, Metformin and acupuncture combined therapy is more effective than Metformin only, proving that acupuncture is an insulin sensitizer and is able to improve insulin sensitivity possibly by reducing body weight and inflammation, while improving lipid metabolism and adipokines. As a result, electro-acupuncture (EA) might be useful in controlling the ongoing epidemics in obesity and T2DM.

Topics: Acupuncture Therapy; Adiponectin; Adult; Biomarkers; Body Mass Index; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Metformin; Obesity; Resistin; Serotonin; Triglycerides; Tumor Necrosis Factor-alpha; Weight Loss

To evaluate the efficacy of an orlistat-resveratrol (O-R) combination in subjects with obesity over a 6-month period.. This study was a double-blind, parallel, randomized controlled clinical trial. Patients fulfilling the selection criteria (age from 20 to 60 years and body mass index (BMI) ≥30 and ≤39.9 kg/m(2) ) consumed an energy-reduced diet with 500 fewer calories than their usual diet for 2 weeks. Then the participants were randomly assigned to four groups, placebo, resveratrol, orlistat, or O-R, and they consumed the energy-reduced diet for 6 months. The study consisted of seven visits. During each visit, a 24-h recall was performed, along with measurements of anthropometric and serum biochemical parameters.. A total of 161 participants were selected. Of these, 84 participants completed the study. A significant weight loss of -6.82 kg (95% CI -8.37 to -5.26) was observed in the O-R group compared with -3.50 kg (-5.05 to -1.95, P = 0.021) in the placebo group. In contrast, the -6.02 kg (-7.68 to -4.36) orlistat and -4.68 kg (-6.64 to -2.71) resveratrol monotherapy losses did not significantly differ from the placebo. Significant decreases in BMI, waist circumference, fat mass, triglycerides, leptin, and leptin/adiponectin ratio were observed with the O-R combination.. The O-R combination was the most effective weight loss treatment.

Topics: Adult; Aged; Anthropometry; Anti-Obesity Agents; Body Mass Index; Caloric Restriction; Diet; Double-Blind Method; Drug Therapy, Combination; Energy Intake; Female; Humans; Lactones; Leptin; Male; Mexico; Middle Aged; Obesity; Orlistat; Placebos; Resveratrol; Stilbenes; Treatment Outcome; Triglycerides; Weight Loss

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that is capable of progressing to end-stage liver disease, but generally has a benign course. Non-alcoholic steatohepatitis (NASH) is a growing public health problem with no approved therapy. NASH projected to be the leading cause of liver transplantation in the United States by 2020. Obesity, non-insulin-dependent diabetes mellitus and hyperlipidaemia are the most common associations of the disease. Global prevalence of NASH is 10-24% amongst general population but increases to 25-75% in obese diabetic individuals.. There is an urgent need for efficient therapeutic options as there is still no approved medication. The aim of this study was to detect changes in biochemical parameters including insulin resistance, cytokines, blood lipid profile and liver enzymes following weight loss in patients with non-alcoholic steatohepatitis.. One hundred obese patients with NASH, their age between 35-50 years, body mass index (BMI) from 30 to 35 Kg/m(2) were included in the study in two subgroups; the first group (A) received moderate aerobic exercise training in addition to diet regimen , where the second group (B) received no treatment intervention.. The mean values of leptin, TNF-α, IL6, IL8, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Homeostasis Model Assessment-Insulin Resistance- index (HOMA-IR), Total Cholesterol (TC), Low Density Lipoprotein Cholesterol (LDL-c) , Triglycerides (TG) and BMI were significantly decreased in group (A), where the mean value of Adiponectin and High Density Lipoprotein Cholesterol (HDL-c) were significantly increased, while there were no significant changes in group (B). Also, there was a significant difference between both groups at the end of the study.. Weight loss modulates insulin resistance, adiponectin, leptin, inflammatory cytokine levels and markers of hepatic function in patients with nonalcoholic steatohepatitis.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Biomarkers; Body Mass Index; Diabetes Complications; Diet; Exercise; Female; Humans; Inflammation Mediators; Insulin Resistance; Interleukins; Leptin; Lipids; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Single-Blind Method; Tumor Necrosis Factor-alpha; Weight Loss; Weight Reduction Programs

An aim of weight loss is to reduce the risk of type 2 diabetes (T2D) in obese subjects. However, the relation with long-term glycemic improvement remains unknown.. We evaluated the changes in lipid composition during weight loss and their association with long-term glycemic improvement.. We investigated the plasma lipidome of 383 obese, nondiabetic patients within a randomized, controlled dietary intervention in 8 European countries at baseline, after an 8-wk low-caloric diet (LCD) (800-1000 kcal/d), and after 6 mo of weight maintenance.. After weight loss, a lipid signature identified 2 groups of patients who were comparable at baseline but who differed in their capacities to lose weight and improve glycemic control. Six months after the LCD, one group had significant glycemic improvement [homeostasis model assessment of insulin resistance (HOMA-IR) mean change: -0.92; 95% CI: -1.17, -0.67)]. The other group showed no improvement in glycemic control (HOMA-IR mean change: -0.26; 95% CI: -0.64, 0.13). These differences were sustained for ≥1 y after the LCD. The same conclusions were obtained with other endpoints (Matsuda index and fasting insulin and glucose concentrations). Significant differences between the 2 groups were shown in leptin gene expression in adipose tissue biopsies. Significant differences were also observed in weight-related endpoints (body mass index, weight, and fat mass). The lipid signature allowed prediction of which subjects would be considered to be insulin resistant after 6 mo of weight maintenance [validation's receiver operating characteristic (ROC) area under the curve (AUC): 71%; 95% CI: 62%, 81%]. This model outperformed a clinical data-only model (validation's ROC AUC: 61%; 95% CI: 50%, 71%; P = 0.01).. In this study, we report a lipid signature of LCD success (for weight and glycemic outcome) in obese, nondiabetic patients. Lipid changes during an 8-wk LCD allowed us to predict insulin-resistant patients after 6 mo of weight maintenance. The determination of the lipid composition during an LCD enables the identification of nonresponders and may help clinicians manage metabolic outcomes with further intervention, thereby improving the long-term outcome and preventing T2D. This trial was registered at clinicaltrials.gov as NCT00390637.

Topics: Adiposity; Adult; Biomarkers; Biopsy, Needle; Body Mass Index; Body Weight Maintenance; Cohort Studies; Diet, Reducing; Europe; Gene Expression Regulation; Glycemic Index; Humans; Hyperlipidemias; Insulin Resistance; Leptin; Models, Biological; Obesity; Patient Dropouts; Risk Factors; ROC Curve; Subcutaneous Fat, Abdominal; Weight Loss

Weight loss interventions such as Roux-en-Y gastric bypass (RYGB) and very low calorie diets (VLCD) lead to improvement of glucose metabolism in obese individuals with type-2 diabetes. Weight loss can also positively influence the unfavorable inflammatory profile associated with obesity. However, a direct comparison of the effect of VLCD and RYGB on systemic inflammation is lacking.. Systemic inflammation was investigated in age- and BMI-matched morbidly obese T2DM women by determining the number and activation- or memory status of peripheral blood leukocytes by flow cytometry, in addition to measuring circulating levels of cytokines and CRP. Systemic inflammation was assessed one month before and three months after RYGB (n=15) or VLCD (n=12). An age matched group of lean women (n=12) was studied as control group.. Three months after the intervention, CRP and leptin levels were reduced whereas adiponectin levels were increased both by RYGB and VLCD. TNF-α levels were increased by RYGB, but reduced by VLCD. IL-2 and IL-6 levels were reduced and IL-4 levels were increased by VLCD but not affected by RYGB. The number of activated peripheral cytotoxic T (CD8+CD25+) and B (CD19+CD38+) cells was significantly higher after RYGB than after VLCD.. In conclusion, RYGB and VLCD have differential effects on the activation status of peripheral leukocytes and levels of cytokines in obese women with T2DM, despite comparable weight loss three months after the intervention. VLCD seems to have more favorable effects on the inflammatory profile as compared to RYGB.

Topics: Adiponectin; Adult; Blood Glucose; C-Reactive Protein; Caloric Restriction; Cytokines; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Humans; Inflammation; Insulin; Leptin; Lymphocyte Count; Middle Aged; Obesity, Morbid; Treatment Outcome; Weight Loss

We compared the effects of three weight loss interventions on serum concentrations of adiponectin and leptin in obese premenopausal women.. 114 obese Caucasian women were randomized into three groups receiving a low-calorie diet (LC; n = 39), an isocaloric diet with 500 mg of metformin twice a day (IM; n = 38), and an isocaloric diet with 120 mg of orlistat three times a day (IO; n = 37), for three months. Serum concentrations of adiponectin and leptin were evaluated, along with anthropometric and body composition parameters, at baseline and after the study.. Both IO and LC, but not IM, caused an increase in serum adiponectin concentration (p < 0.01, p < 0.05 respectively). A decrease in serum leptin level was documented in the LC (p < 0.001), IM (p < 0.01), and IO group (p < 0.01). Beneficial changes in anthropometric and body composition values were observed following all interventions with the greatest advantage seen in the IO group. The strongest correlations, of Δadiponectin with Δbody weight (r = -0.54), ΔBMI (r = -0.49), ΔFAT [%] (r = -0.48), ΔFAT [kg] (r = -0.48), and Δlean [%] (r = 0.48); and of Δleptin with Δbody weight, ΔBMI, Δwaist, Δfat, and Δlean, were documented in the IO group.. Beneficial effects were observed on serum leptin concentration, weight loss, and body composition for all interventions and in all examined groups, with the greatest advantage being associated with the orlistat treatment. Improvements in serum adiponectin concentrations resulted from the low-calorie and isocaloric diets with orlistat, but not from the isocaloric diet with metformin. We find these strategies more promising for the treatment of obesity and its related complications in obese premenopausal women.

Topics: Adiponectin; Aged; Caloric Restriction; Diet, Reducing; Female; Humans; Hypoglycemic Agents; Lactones; Leptin; Metformin; Middle Aged; Obesity; Orlistat; Postmenopause; Prospective Studies; Weight Loss

Recent data suggest that chronic low-grade inflammation, a characteristic of obesity, is associated with altered tryptophan (Trp) and tyrosine (Tyr) metabolism and plays a role in neuropsychiatric symptoms. The present study assessed the effect of an extreme short-term diet on Trp breakdown and inflammatory biomarkers in overweight adults.. Thirty-eight overweight participants (16 women, 22 men; average body mass index: 29 kg/m², mean age 52.8 years) were randomized into two diet groups: a very low kcal diet group (VLCD; Ø 600 kcal/day, n = 21) and a low kcal diet group (LCD; Ø 1,200 kcal/day, n = 17). Assays included the measurement of Trp, kynurenine (Kyn), and their ratio, neopterin, phenylalanine (Phe), Tyr, as biologic markers; leptin, plasma insulin, glucose, and homeostatic model assessment-insulin resistance; and interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as biochemical and inflammatory markers at baseline and after 2 weeks of treatment.. Weight loss diet lowered leptin levels in both groups by 46%, although not reaching significance. Trp and Kyn decreased significantly by 21 and 16% for VLCD and by 15 and 17% for the LCD group, respectively. A significant reduction in Phe was only seen after VLCD. Inflammatory biomarkers, neopterin, and Tyr were not significantly altered during the study period. Leptin was significantly correlated with Trp breakdown before and after the intervention (P < 0.02).. Since disturbed metabolism of Trp affects biosynthesis of serotonin and might be associated with increased susceptibility for mood disturbances and carbohydrate craving, strategies to supplement Trp while dieting could be highly useful in treating uncontrolled weight gain or in preventing neuropsychiatric symptoms.

Topics: Austria; Biomarkers; Body Mass Index; Caloric Restriction; Diet, Reducing; Female; Humans; Inflammation Mediators; Kynurenine; Leptin; Male; Middle Aged; Mood Disorders; Neopterin; Overweight; Phenylalanine; Risk; Tryptophan; Tyrosine; Weight Loss

Compensatory metabolic changes that accompany weight loss, for example, increased ghrelin, contribute to weight regain and difficulty in long-term weight loss maintenance; however, the separate effects of long-term caloric restriction and exercise on total circulating ghrelin in humans are unknown.. A 12-month randomized controlled trial comparing: i) dietary weight loss with a 10% weight loss goal ('diet'; n = 118); ii) moderate-to-vigorous intensity aerobic exercise for 45 min/day, 5 days/week ('exercise'; n = 117); iii) dietary weight loss and exercise ('diet + exercise'; n = 117); or iv) no-lifestyle-change control (n = 87).. 439 overweight or obese postmenopausal women (50-75 y).. Fasting total serum ghrelin was measured by radioimmunoassay at baseline and 12 months. Fasting serum leptin, adiponectin and insulin were also measured.. Fasting total ghrelin significantly increased in the diet + exercise arm (+7·4%, P = 0·008) but not in either the diet (+6·5%, P = 0·07) or exercise (+1·0%, P = 0·53) arms compared with control. Greater weight loss was associated with increased ghrelin concentrations, regardless of intervention. Neither baseline ghrelin nor body composition modified the intervention effects on changes in total ghrelin. The 12-month change in total ghrelin was inversely associated with changes in leptin, insulin and insulin resistance, and positively associated with change in adiponectin.. Greater weight loss, achieved through a reduced calorie diet or exercise, is associated with increased total ghrelin concentrations in overweight or obese postmenopausal women.

Topics: Adiponectin; Aged; Diet; Exercise; Fasting; Female; Ghrelin; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Overweight; Radioimmunoassay; Treatment Outcome; Weight Loss

Weight loss intervention is the principal non-pharmacological method for prevention and treatment of type 2 diabetes. However, little is known whether it influences insulin sensitivity directly or via its anti-inflammatory effect. The aim of this study was to assess the independent role of changes in inflammation status and weight loss on insulin sensitivity in this population.Overweight and obese nondiabetic participants without co-morbidities underwent a one-year weight loss intervention focused on caloric restriction and behavioral support. Markers of inflammation, body composition, anthropometric para-meters, and insulin sensitivity were recorded at baseline, 6, and 12 months. Insulin sensitivity was assessed with frequently sampled intravenous glucose tolerance test and Minimal Model. Twenty-eight participants (F: 15, M: 13, age 39±5 years, BMI 33.2±4.6 kg/m(2)) completed the study, achieving 9.4±6.9% weight loss, which was predominantly fat mass (7.7±5.6 kg, p<0.0001). Dietary intervention resulted in significant decrease in leptin, leptin-to-adiponectin ratio, hs-CRP, and IL-6 (all p<0.02), and improvement in HOMA-IR and Insulin Sensitivity Index (SI) (both p<0.001). In response to weight loss IL-1β, IL-2, leptin, and resistin were significantly associated with insulin, sensitivity, whereas sICAM-1 had only marginal additive effect. Moderate weight loss in otherwise healthy overweight and obese individuals resulted in an improvement in insulin sensitivity and in the overall inflammation state; the latter played only a minimal independent role in modulating insulin sensitivity.

Topics: Adult; Blood Glucose; Body Composition; Body Mass Index; C-Reactive Protein; Caloric Restriction; Diet; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Lipids; Male; Middle Aged; National Institutes of Health (U.S.); Obesity; Overweight; Prospective Studies; United States; Weight Loss

Recent studies indicate that glucagon-like peptide (GLP)-1 inhibits appetite in part through regulation of soluble leptin receptors. Thus, during weight loss maintenance, GLP-1 receptor agonist (GLP-1RA) administration may inhibit weight loss-induced increases in soluble leptin receptors thereby preserving free leptin levels and preventing weight regain.. In a randomized controlled trial, 52 healthy obese individuals were, after a diet-induced 12% body weight loss, randomized to treatment with or without administration of the GLP-1RA liraglutide (1.2 mg per day). In case of weight gain, low-calorie diet products were allowed to replace up to two meals per day to achieve equal weight maintenance. Glucose tolerance and hormone responses were investigated before and after weight loss and after 52 weeks weight maintenance. Primary end points: increase in soluble leptin receptor plasma levels and decrease in free leptin index after 52 weeks weight loss maintenance.. Soluble leptin receptor increase was 59% lower; 2.1±0.7 vs 5.1±0.8 ng ml(-1) (-3.0 (95% confidence interval (CI)=-0.5 to -5.5)), P<0.001 and free leptin index decrease was 43% smaller; -62±15 vs -109±20 (-47 (95% CI=-11 to -83)), P<0.05 with administration of GLP-1RA compared with control group. The 12% weight loss was successfully maintained in both the groups with no significant change in weight after 52 weeks follow-up. The GLP-1RA group had greater weight loss during the weight maintenance period (-2.3 kg (95% CI=-0.6 to -4.0)), and had fewer meal replacements per day compared with the control group (minus one meal per day (95% CI=-0.6 to -1)), P<0.001. Fasting glucose was decreased by an additional -0.2±0.1 mmol l(-1) in the GLP-1RA group in contrast to the control group, where glucose increased 0.3±0.1 mmol l(-1) to the level before weight loss (-0.5mmol l(-1) (95% CI=-0.1 to -0.9)), P<0.005. Meal response of peptide PYY3-36 was higher at week 52 in the GLP-1RA group compared with the control group, P<0.05.. The weight maintaining effect of GLP-1RAs may be mediated by smaller decrease in free leptin and higher PYY3-36 response. Low dose GLP-1RA therapy maintained 12% weight loss for 1 year and may prevent pre-diabetes in obesity.

Topics: Adult; Appetite; Body Mass Index; Caloric Restriction; Denmark; Female; Glucagon-Like Peptide-1 Receptor; Humans; Incretins; Leptin; Liraglutide; Male; Obesity; Prediabetic State; Treatment Outcome; Weight Loss

It is unknown whether leptin and peptide YY (PYY) influence changes in resting energy expenditure (REE), independently of fat mass (FM) and fat-free mass (FFM) in addition to changes in other energy expenditure (EE) components during weight loss.. The objective of the study was to examine the relationships between leptin, PYY, and body composition with different EE components before and after weight loss and whether changes in leptin and PYY were associated with differences in predicted vs measured REE after the intervention.. This was a randomized controlled design.. The study was conducted in a laboratory.. Participants were ninety-three overweight/obese postmenopausal women (aged 58.1 ± 4.8 y; body mass index 32.1 ± 4.3 kg/m(2)).. Interventions included a 6-month caloric restriction diet alone or caloric restriction diet+resistance training.. Body composition (dual energy x-ray absorptiometry), REE (indirect calorimetry), total EE (TEE; doubly labeled water), and fasting leptin and total PYY before and after weight loss were measured.. Both interventions yielded significant decreases in weight, FFM, REE, and leptin, whereas a significant time × group interaction was noted for FM (greater decrease in FM in the diet+resistance training group) (P < .05 for all outcomes). No significant differences in TEE, physical activity EE, and PYY were noted between baseline and after the intervention. Age, FFM, leptin, and PYY were the best predictors of baseline REE (R(2) = 0.77; P = .0001), whereas age, FFM, and FM were associated with REE after the intervention (R(2) = 0.88; P = .0001). The same predictors, except for leptin, were significantly related to TEE at baseline (R(2) = 0.70; P = .0001) and after the intervention (R(2) = 0.29; P = .0001), whereas only PYY was a significant predictor of physical activity EE at baseline and after the intervention. Changes in FM and leptin accounted for 27% of the variance in ΔREE (P = .0001). Greater predicted vs measured REE was noted after the intervention (P = .02). However, Δ leptin and ΔPYY were not significant predictors of the differences between postintervention measurement and predicted REE.. Δ Leptin and ΔFM were strong contributors to changes in REE. However, Δ leptin and ΔPYY were not significant predictors of the differences between predicted and measured REE after the intervention.

Topics: Basal Metabolism; Caloric Restriction; Diet, Reducing; Down-Regulation; Energy Metabolism; Female; Humans; Leptin; Middle Aged; Obesity; Overweight; Peptide YY; Rest; Weight Loss

Gut hormones change with weight loss in adults but are not well studied in obese youth.. The primary aim was to evaluate how gut hormones and subjective appetite measure change with dietary weight loss in obese adolescents.. Participants were a subset of those taking part in the 'Eat Smart Study'. They were aged 10-17 years with body mass index (BMI) > 90th centile and were randomized to one of three groups: wait-listed control, structured reduced carbohydrate or structured low-fat dietary intervention for 12 weeks. Outcomes were fasting glucose, insulin, leptin, adiponectin, total amylin, acylated ghrelin, active glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide (GIP), pancreatic polypeptide (PP) and total peptide tyrosine-tyrosine. Pre- and postprandial subjective sensations of appetite were assessed using visual analogue scales.. Of 87 'Eat Smart' participants, 74 participated in this sub-study. The mean (standard deviation) BMI z-score was 2.1 (0.4) in the intervention groups at week 12 compared with 2.2 (0.4) in the control group. Fasting insulin (P = 0.05) and leptin (P = 0.03) levels decreased, while adiponectin levels increased (P = 0.05) in the intervention groups compared with control. The intervention groups were not significantly different from each other. A decrease in BMI z-score at week 12 was associated with decreased fasting insulin (P < 0.001), homeostatic model of assessment-insulin resistance (P < 0.001), leptin (P < 0.001), total amylin (P = 0.03), GIP (P = 0.01), PP (P = 0.02) and increased adiponectin (P < 0.001). There was no significant difference in appetite sensations.. Modest weight loss in obese adolescents leads to changes in some adipokines and gut hormones that may favour weight regain.

Topics: Adiponectin; Adolescent; Adult; Appetite; Body Mass Index; Body Weight; Fasting; Female; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Leptin; Male; Pediatric Obesity; Peptide YY; Postprandial Period; Weight Loss

To evaluate the potential body weight-lowering effects of dietary supplementation with eicosapentaenoic acid (EPA) and α-lipoic acid separately or combined in healthy overweight/obese women following a hypocaloric diet.. This is a short-term double-blind placebo-controlled study with parallel design that lasted 10 weeks. Of the randomized participants, 97 women received the allocated treatment [Control, EPA (1.3 g/d), α-lipoic acid (0.3 g/d), and EPA+α-lipoic acid (1.3 g/d+0.3 g/d)], and 77 volunteers completed the study. All groups followed an energy-restricted diet of 30% less than total energy expenditure. Body weight, anthropometric measurements, body composition, resting energy expenditure, blood pressure, serum glucose, and insulin and lipid profile, as well as leptin and ghrelin levels, were assessed at baseline and after nutritional intervention.. Body weight loss was significantly higher (P<0.05) in those groups supplemented with α-lipoic acid. EPA supplementation significantly attenuated (P<0.001) the decrease in leptin levels that occurs during weight loss. Body weight loss improved lipid and glucose metabolism parameters but without significant differences between groups.. The intervention suggests that α-lipoic acid supplementation alone or in combination with EPA may help to promote body weight loss in healthy overweight/obese women following energy-restricted diets.

Topics: Administration, Oral; Adult; Antioxidants; Body Composition; Cholesterol; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Eicosapentaenoic Acid; Energy Metabolism; Female; Ghrelin; Glucose; Humans; Insulin; Leptin; Lipid Metabolism; Middle Aged; Obesity; Thioctic Acid; Treatment Outcome; Weight Loss; Young Adult

Olanzapine is used for treatment of psychiatric conditions but causes substantial weight gain. This study assessed safety, efficacy, and changes in metabolic cytokines associated with olanzapine administration in patients with cachexia due to advanced cancer.. Patients with cancer-related cachexia were treated with olanzapine (doses ranging from 2.5 to 20 mg daily by mouth). Patients also received anti-neoplastic treatments. Serum samples were collected at baseline and after weeks 1, 2, 4, and 8 for analysis of levels of leptin, growth hormone, ghrelin, and interleukin-6 (IL-6).. Of the 39 participants, 31 were evaluable for weight change (N = 6 excluded for new ascites; N = 2, incomplete body weight of data). Toxicities related to olanzapine were somnolence (n = 1), pancreatitis (n = 1), extrapyramidal symptoms (n = 1), and nausea/vomiting (n = 1) (all grade 2). The recommended dose of Olanzapine is 20 mg PO daily for cancer patients (same as FDA approved dose for psychiatric conditions). Samples from 29 patients were eligible for analysis of serum cytokine levels. Mean values of leptin, ghrelin, and growth hormone did not change on treatment, though IL-6 levels increased, perhaps due to tumor progression. There was no association between changes in cytokines and weight. The mean change in slope of weight loss before versus after therapy was 0.24 (95 % CI, -0.08, 0.56; p = 0.13) indicating a trend, albeit not reaching statistical significance, toward attenuation of weight loss.. Changes in metabolic cytokines and body weight did not correlate. Treatment with olanzapine had only a modest effect in altering the trajectory of weight loss.

Topics: Adult; Aged; Benzodiazepines; Body Weight; Cachexia; Cytokines; Dose-Response Relationship, Drug; Female; Ghrelin; Humans; Interleukin-6; Leptin; Male; Middle Aged; Neoplasms; Olanzapine; Weight Gain; Weight Loss

Energetic adaptations induced by bariatric surgery have not been studied in adolescents or for extended periods postsurgery. Energetic, metabolic, and neuroendocrine responses to Roux-en-Y gastric bypass (RYGB) surgery were investigated in extremely obese adolescents.. At baseline and at 1.5, 6, and 12 months post-baseline, 24-h room calorimetry, body composition, and fasting blood biochemistries were measured in 11 obese adolescents relative to five matched controls.. In the RYGB group, mean weight loss was 44 ± 19 kg at 12 months. Total energy expenditure (TEE), activity EE, basal metabolic rate (BMR), sleep EE, and walking EE significantly declined by 1.5 months (P = 0.001) and remained suppressed at 6 and 12 months. Adjusted for age, sex, fat-free mass, and fat mass, EE was still lower than baseline (P = 0.001). Decreases in serum insulin, leptin, and triiodothyronine (T3), gut hormones, and urinary norepinephrine (NE) paralleled the decline in EE. Adjusted changes in TEE, BMR, and/or sleep EE were associated with decreases in insulin, homeostatic model assessment, leptin, thyroid stimulating hormone, total T3, peptide YY3-36, glucagon-like peptide-2, and urinary NE and epinephrine (P = 0.001-0.05).. Energetic adaptations in response to RYGB-induced weight loss are associated with changes in insulin, adipokines, thyroid hormones, gut hormones, and sympathetic nervous system activity and persists 12 months postsurgery.

Topics: Adaptation, Physiological; Adipokines; Adolescent; Bariatric Surgery; Basal Metabolism; Body Composition; Energy Metabolism; Female; Gastrointestinal Hormones; Humans; Insulin; Leptin; Male; Obesity, Morbid; Pediatric Obesity; Peptide Fragments; Peptide YY; Weight Loss

It has been found that the expression of fatty acid-binding protein 2 gene mRNA is under dietary control. The polymorphism Ala54Thr of this protein was associated with high insulin resistance.. The aim of our study was to investigate the influence of Thr54 polymorphism on metabolic response, weight loss and serum adipokine levels secondary to high-protein/low-carbohydrate vs. standard hypocaloric diets during 9 months.. A population of 193 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 9-month period in which subjects received 1 of 2 diets (diet HP: high-protein/low-carbohydrate vs. diet S: standard diet).. With both diets and in both genotype groups, body mass index, weight, fat mass, waist circumference, systolic blood pressure and leptin levels decreased. With both diets and only in wild genotype (diet HP vs. diet S), glucose (-6.2 ± 2.1 vs. -4.9 ± 2.0 mg/dl; p < 0.05), insulin levels (-5.0 ± 3.9 vs. -2.0 ± 2.1 UI/l; p < 0.05), homeostasis model assessment for insulin resistance (HOMA-R) (-1.1 ± 0.9 vs. -0.7 ± 1.0 units; p < 0.05) decreased. The improvement in these parameters was higher with diet HP than HS. With both diets and only in the wild genotype, total cholesterol and LDL-total cholesterol levels decreased.. Carriers of Thr54 allele have a different metabolic response after weight loss than wild type non-A carriers obese, with a lack of decrease of LDL-cholesterol, glucose, insulin levels and HOMA-R.

Topics: Adipokines; Adult; Blood Pressure; Body Mass Index; Body Weight; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diet, Carbohydrate-Restricted; Diet, Reducing; Dietary Carbohydrates; Dietary Proteins; Fatty Acid-Binding Proteins; Female; Genotype; Genotyping Techniques; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Risk Factors; Waist Circumference; Weight Loss

Fatty tissue derived adipocytokines regulate appetite, but in abnormal concentration impair systemic metabolic homeostasis and make the patients prone to inflammatory related disorders. The aim of study was to examine whether weight loss in patients after implementation of a gastric balloon is reflected in changes in chosen anthropometrical parameters and in the concentration of leptin and adiponectin in serum.. The study group consisted of 18 extreme obese patients (BMI>39.9, mean age 39.5±12.1 years, 12 men, 6 women), undergoing implementation of a gastric balloon for 6 months. The control group consisted of 18 healthy volunteers. The adiponectin and leptin concentrations in the sera and the calculated % body fat and indicators: BMI, WHR, VAI, BAI, WHtR were determined prior to implementation and after the balloon removal and then further parameters were calculated: % excessive weight loss, % weight loss.. All the parameters and leptin concentration in the tested group were markedly upregulated and adiponectin concentration was significantly lower compared to controls. Reduction in the body mass in patients subjected to BIB, reflected in leptin and anthropometrical parameters down-regulation, (except WHR and VAI), was accompanied with normalization of adiponectin concentration that affect metabolism and is important regulator of hunger and satiety.

Topics: Adiponectin; Adult; Anthropometry; Female; Gastric Balloon; Humans; Leptin; Male; Obesity, Morbid; Up-Regulation; Weight Loss

Natural killer (NK) cells are the first defense against malignant cells, and their functions are severely impaired in individuals with obesity. However, it is not known whether functions can be re-activated after weight loss. The alterations of NK cell functions after fat mass reduction were investigated.. Thirty-two healthy adults with obesity were divided into control and experimental groups. Participants of the experimental group performed a 3-month program of exercise training and nutrition. Anthropometric, physiological, and metabolic parameters and plasma adipocytokines were determined. Peripheral blood mononuclear cells were analyzed by means of flow cytometry and Western blot assay for various NK cell-specific functional parameters and leptin signaling components. NK cell-mediated cytotoxicity assay with leptin stimulation was performed.. Male participants significantly decreased their body fat mass (P < 0.05) and increased physical fitness (P < 0.05). Plasma leptin levels were significantly reduced (P < 0.05) and intracellular interferon gamma (IFN-γ) expression in CD56(dim) NK cells was significantly increased (P < 0.001) 3 months after study end. Stimulation of NK-92 cells with different leptin dosages revealed a significant dose-dependent decrease of specific tumor cell lysis.. The present study demonstrates a reactivation of NK cell functionality after body fat mass reduction in persons with obesity.

Topics: Adipokines; Adult; Anthropometry; Exercise; Female; Flow Cytometry; Humans; Interferon-gamma; Killer Cells, Natural; Leptin; Lymphocyte Activation; Male; Middle Aged; Obesity; Signal Transduction; Weight Loss; Weight Reduction Programs

Obesity is related to hormonal disorders that affect the reproductive system. Low-glycemic index (LGI) diets seem to exert a positive effect on weight loss and on metabolic changes that result from obesity.. We investigated the effects of a hypocaloric diet with an LGI and low glycemic load on anthropometric and metabolic variables, ghrelin and leptin concentrations, and the pregnancy rate in overweight and obese infertile women who were undergoing in vitro fertilization (IVF).. The study was a randomized block-design controlled trial in which we analyzed 26 overweight or obese infertile women. Patients were assigned to a hypocaloric LGI-diet group or a control group and followed the protocol for 12 wk. Body weight, body mass index (BMI), percentage of body fat, glucose, insulin, homeostasis model assessment of insulin resistance, serum lipids, reproductive hormones, leptin, acylated ghrelin, number of oocytes retrieved in the IVF cycle, and pregnancy rate were determined.. There were greater reductions in body mass, BMI, percentage of body fat, waist:hip ratio, and leptin in the LGI-diet group than in the control group (P < 0.05). Despite a change of 18% in mean values, there was no significant increase in acylated ghrelin concentrations in the LGI group compared with the control group (P = 0.215). The LGI-diet group had 85.4% more oocytes retrieved than did the control group (7.75 ± 1.44 and 4.18 ± 0.87, respectively; P = 0.039) in the IVF cycle. Three patients (21.4%) in the LGI group experienced a spontaneous pregnancy during the follow-up, which generated 3 live births.. The hypocaloric LGI diet promoted a decrease in BMI, percentage of body fat, and leptin concentrations, which improved oocyte development and pregnancy rate. These results support the clinical recommendation to advise overweight and obese women to lose weight through a balanced diet before being submitted for treatment with assisted reproduction technologies. A hypocaloric diet combined with LGI foods seems to be beneficial for these patients, but additional studies are required before this treatment is recommended. This trial was registered at clinicaltrials.gov as NCT02416960.

Topics: Adiposity; Adult; Body Mass Index; Brazil; Diet, Reducing; Female; Fertilization in Vitro; Follow-Up Studies; Ghrelin; Glycemic Index; Glycemic Load; Humans; Infertility, Female; Insulin Resistance; Leptin; Obesity; Overweight; Pregnancy; Pregnancy Rate; Risk; Waist-Hip Ratio; Weight Loss

Topics: Adult; Body Mass Index; Female; Gastric Balloon; Ghrelin; Growth Hormone; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Obesity, Morbid; Prospective Studies; Treatment Outcome; Weight Loss

The present study investigated the impact of a Lactobacillus rhamnosus CGMCC1.3724 (LPR) supplementation on weight loss and maintenance in obese men and women over 24 weeks. In a double-blind, placebo-controlled, randomised trial, each subject consumed two capsules per d of either a placebo or a LPR formulation (1.6 × 10(8) colony-forming units of LPR/capsule with oligofructose and inulin). Each group was submitted to moderate energy restriction for the first 12 weeks followed by 12 weeks of weight maintenance. Body weight and composition were measured at baseline, at week 12 and at week 24. The intention-to-treat analysis showed that after the first 12 weeks and after 24 weeks, mean weight loss was not significantly different between the LPR and placebo groups when all the subjects were considered. However, a significant treatment × sex interaction was observed. The mean weight loss in women in the LPR group was significantly higher than that in women in the placebo group (P = 0.02) after the first 12 weeks, whereas it was similar in men in the two groups (P= 0.53). Women in the LPR group continued to lose body weight and fat mass during the weight-maintenance period, whereas opposite changes were observed in the placebo group. Changes in body weight and fat mass during the weight-maintenance period were similar in men in both the groups. LPR-induced weight loss in women was associated not only with significant reductions in fat mass and circulating leptin concentrations but also with the relative abundance of bacteria of the Lachnospiraceae family in faeces. The present study shows that the Lactobacillus rhamnosus CGMCC1.3724 formulation helps obese women to achieve sustainable weight loss.

Topics: Adipose Tissue; Adult; Colon; Dietary Supplements; Double-Blind Method; Energy Intake; Feces; Female; Humans; Intention to Treat Analysis; Lacticaseibacillus rhamnosus; Leptin; Male; Middle Aged; Obesity; Probiotics; Sex Factors; Weight Loss; Young Adult

Although benefits have been attributed to the Mediterranean diet, its effect on glycaemic control has not been totally elucidated. The aim of this work was to compare the effect of two Mediterranean diets versus a low-fat diet on several parameters and indices related to glycaemic control in type 2 diabetic subjects.. A multicentric parallel trial was conducted on 191 participants (77 men and 114 women) of the PREDIMED study in order to compare three dietary interventions: two Mediterranean diets supplemented with virgin olive oil (n=67; body mass index (BMI)=29.4±2.9) or mixed nuts (n=74; BMI=30.1±3.1) and a low-fat diet (n=50; BMI=29.8±2.8). There were no drop-outs. Changes in body weight and waist circumference were determined. Insulin resistance was measured by HOMA-IR index, adiponectin/leptin and adiponectin/HOMA-R ratios after 1 year of follow-up.. Increased values of adiponectin/leptin ratio (P=0.043, P=0.001 and P<0.001 for low-fat, olive oil and nut diets, respectively) and adiponectin/HOMA-IR ratio (P=0.061, P=0.027 and P=0.069 for low-fat, olive oil and nut diets, respectively) and decreased values of waist circumference (P=0.003, P=0.001 and P=0.001 for low-fat, olive oil and nut diets, respectively) were observed in the three groups. In both Mediterranean diet groups, but not in the low-fat diet group, this was associated with a significant reduction in body weight (P=0.347, P=0.003 and P=0.021 for low-fat, olive oil and nut diets, respectively).. Mediterranean diets supplemented with virgin olive oil or nuts reduced total body weight and improved glucose metabolism to the same extent as the usually recommended low-fat diet.

Topics: Adipokines; Adiponectin; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Diet, Fat-Restricted; Diet, Mediterranean; Dietary Fats; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Nuts; Obesity; Olive Oil; Plant Oils; Waist Circumference; Weight Loss

Several studies have identified relationships between weight loss and adipokine levels; however, none have looked at the combined effect of aerobic exercise training with the consumption of a low- or a high-glycemic diet. We examined the effects of 12 wk of aerobic exercise combined with either a low-glycemic index diet (∼40 U) plus exercise (LoGIX) or a high-glycemic index diet (∼80 U) diet plus exercise (HiGIX) on plasma leptin and adiponectin (total and high molecular weight [HMW]) in 27 older obese adults (age = 65 ± 0.5 yr, body mass index = 34.5 ± 0.7 kg·m).. Insulin sensitivity was calculated from an oral glucose tolerance test. Fasting HMW adiponectin and leptin were quantified from plasma samples obtained before the insulin sensitivity index obtained from the oral glucose tolerance test. Glucose and insulin measures were obtained before and every 30 min during the test. Dual-energy x-ray absorptiometry and computerized tomography were used to determine body composition and to quantify subcutaneous and visceral abdominal adiposity, respectively.. Fasting leptin was significantly decreased in both groups (LoGIX: preintervention = 33.8 ± 4.7, postintervention = 19.2 ± 4.5; HiGIX: preintervention = 27.9 ± 4.2, postintervention = 11.9 ± 2.2 ng·mL; P = 0.004), and HMW adiponectin was significantly increased (LoGIX: preintervention = 1606.9 ± 34.6, postintervention = 3502.3 ± 57; HiGIX: preintervention = 3704.8 ± 38.1, postintervention = 4284.3 ± 52.8 pg·mL; P = 0.003) after the 12-wk intervention. Total body fat was reduced after both interventions. Visceral fat mass was inversely correlated with HMW adiponectin, whereas subcutaneous fat correlated with leptin.. The data suggest that exercise training, independent of dietary glycemic index, favorably alters HMW adiponectin and leptin secretion and that a reduction in visceral fat mass is a key factor regulating HMW adiponectin in older obese persons.

Topics: Adiponectin; Adiposity; Aged; Diet, Carbohydrate-Restricted; Exercise Therapy; Female; Glycemic Index; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Molecular Weight; Obesity; Weight Loss

Fibre intake among North Americans is currently less than half the recommended amount. Consumers are interested in food products that could promote weight loss and improve health. Consequently, evaluation of unique fibre sources with potential gut-mediated benefits for metabolic health warrants investigation. Our objective is to assess the effects of yellow pea fibre supplementation on weight loss and gut microbiota in an overweight and obese adult population.. In a double blind, placebo controlled, parallel group study, overweight and obese (BMI = 25-38) adults will be randomized to either a 15 g/d yellow pea fibre supplemented group or isocaloric placebo group for 12 weeks (n = 30/group). The primary outcome measure is a change in body fat from baseline to 12 weeks. Secondary outcomes include glucose tolerance, appetite regulation, serum lipids and inflammatory markers. Anthropometric data (height, weight, BMI, and waist circumference) and food intake (by 3-day weighed food records) will be measured at baseline and every 4 weeks thereafter. Subjective ratings of appetite will be recorded by participants at home on a weekly basis using validated visual analogue scales. At week 0 and at the end of the study (week 12), an ad libitum lunch buffet protocol for objective food intake measures and dual-energy X-ray absorptiometry (DXA) scan for body composition will be completed. Participants will be instructed not to change their exercise habits during the 12 week study. Glucose and insulin will be measured during an oral glucose tolerance test at weeks 0 and 12. Levels of lipids and CRP will be measured and inflammatory markers (adiponectin, leptin, TNF-α, IL-6 and IL-8) in the serum will be quantified using Milliplex kits. Mechanisms related to changes in gut microbiota, serum and fecal water metabolomics will be assessed.. Globally the development of functional foods and functional food ingredients are critically needed to curb the rise in metabolic disease. This project will assess the potential of yellow pea fibre to improve weight control via gut-mediated changes in metabolic health in overweight and obese adults.. ClinicalTrials.gov (NCT01719900) Registered October 23, 2012.

Topics: Absorptiometry, Photon; Adiponectin; Adolescent; Adult; Aged; Appetite; Body Composition; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Double-Blind Method; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Interleukin-6; Interleukin-8; Intestines; Leptin; Male; Microbiota; Middle Aged; Obesity; Overweight; Pisum sativum; Treatment Outcome; Triglycerides; Tumor Necrosis Factor-alpha; Weight Loss; Young Adult

This study was conducted to examine the effects of weight reduction on proteinuria, adipokines, and renal function in overweight immunoglobulin A nephropathy (IgAN) patients (body mass index > 23 kg/m2) with chronic proteinuria more than 6 months.. This was a single-center, prospective, randomized controlled trial. The study was performed at the outpatient clinic at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from July 2012 to February 2013.. Twenty-six overweight patients with chronic proteinuric biopsy-proven IgAN were randomized into a control group (n = 13) or a low-calorie normal protein diet group (n = 13). All patients received the maximum dosage of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and other antihypertensive agents to achieve a blood pressure less than 125/75 mmHg.. The study intervention was a low-calorie diet (target energy per day as 500-kcal subtraction from total energy requirement) for a 6-month period.. At baseline and after 6 months of a low-calorie diet, body weight, body content, and clinical and laboratory parameters were determined and compared.. After initiating a low-calorie diet for 6 months, the normalized protein nitrogen appearance values were not different, indicating comparable protein intake. The low-calorie group had lower total daily calorie intake (1,307.1 ± 171.8 vs. 1,772.2 ± 315.4 kcal/d, P < .01) and significant reductions in body weight (-5.1 ± 3.3%, P < .001), fat content (-12.7 ± 14.1%, P < .05), and 24-hour urine protein (-45.2 ± 15.4%, P < .001). Blood pressure and renal function parameters were unaltered. The low-calorie group had approximately 20% lower plasma levels of leptin but unchanged adiponectin. There were positive correlations between the amount of protein reduction and the changes of body weight, fat mass, and leptin.. A 6-month low-calorie diet leads to weight reduction and results in diminished fat content and decreased proteinuria in overweight IgAN patients with chronic proteinuria. This beneficial effect might be mediated by changes in adipokines.

Topics: Adiponectin; Adult; Blood Pressure; Body Composition; Caloric Restriction; Dietary Proteins; Female; Glomerulonephritis, IGA; Humans; Leptin; Male; Middle Aged; Overweight; Prospective Studies; Proteinuria; Thailand; Weight Loss

To evaluate the effect of sibutramine on weight loss in obese adolescents.. A double-blind controlled study lasting 13 months. The study included 73 obese adolescents of both sexes aged between 10 and 18 years. Laboratory tests and imaging studies were performed before, during wash-out, and at the end of 13 months.. The percentage of patients who lost 10% of their initial weight in the placebo group was 46%, and in the sibutramine group was 75%. When placebo was used, average weight rose by 1.61 kg, and BMI decreased by 0.24 kg/m(2) whereas with the use of sibutramine, weight decreased by 4.47 kg, and average BMI decreased, 2.38 kg/m(2), with p < 0.001.. Sibutramine induced significantly more weight loss in obese adolescents compared with placebo, without significant side effects. The weight loss curve was different depending on the moment sibutramine was introduced. This finding indicates that the best time to start sibutramine is when adhesion begins to fail.

Topics: Adolescent; Appetite Depressants; Blood Glucose; Body Mass Index; Child; Cholesterol; Cross-Over Studies; Cyclobutanes; Double-Blind Method; Female; Humans; Insulin; Leptin; Male; Patient Safety; Pediatric Obesity; Treatment Outcome; Triglycerides; Weight Loss

Few studies have investigated the likelihood of weight maintenance in obese persons with schizophrenia after their initial successful weight loss. This pilot open-label study examined the efficacy of topiramate in weight loss and the trajectory of weight changes after topiramate discontinuation.. This study enrolled 10 obese persons with schizophrenia. A 4-month treatment phase was started, followed by a 12-month discontinuation phase. Body weight was measured as the primary outcome every month. Secondary outcomes included leptin levels, fasting glucose, lipid profiles, and insulin resistance index.. After the 4-month addition of topiramate, participants lost 1.79 kg of their body weight (95% CI=-3.03 to -0.56, p=0.005). The maximum weight reduction was 4.32 kg, occurring when topiramate had been discontinued for 12 months (95% CI=-6.41 to -2.24, p<0.001).. The continuing weight-loss effect after topiramate discontinuation might have resulted from topiramate's potential to improve leptin functioning. These findings demonstrate that topiramate's weight-loss effect could not only persist during its administration, but also continue to improve after its discontinuation.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Female; Follow-Up Studies; Fructose; Humans; Leptin; Male; Middle Aged; Obesity; Schizophrenia; Time Factors; Topiramate; Weight Loss

This study investigated the dietary effect of including pigmented rice bran with or without plant sterols on lipid profiles during energy restriction-induced weight loss in overweight and obese adults not taking cholesterol-lowering medication. In addition, the study examined the effect of intervention on biomarkers of oxidative stress and inflammation.. A group of 24 overweight and obese adults (age: 43 ± 6 years, body mass index 32 ± 1 kg/m(2), 18 females) were randomized to a 25% calorie-restricted diet containing either pigmented rice bran (RB) or the RB with addition of plant sterols (RB+PS) snack bars for 8 weeks. The individualized nutrient-balanced diet contained ∼70% of daily energy needs assessed from indirect calorimetry measured resting energy expenditure (EE) and physical activity-related EE assessed using accelerometry. Anthropometrics, blood pressure, blood lipids, glucose, urinary F2-isoprostanes, C-reactive protein, insulin, and leptin were measured at baseline and after 8 weeks of intervention.. Participants lost approximately 4.7 ± 2.2 kg (p < 0.001). Weight loss was not significant between the RB+PS and RB group (p = 0.056). Changes in body fat corresponded to changes in body weight. Average decrease in total cholesterol was significantly higher in the RB+PS group than in the RB group (difference 36 ± 25 g/dL vs 7 ± 16 g/dL; p = 0.044). A similar pattern was observed for the decrease in low-density lipoprotein (LDL) cholesterol (difference 22.3 ± 25.2 g/dL vs 4.4 ± 18.9 g/dL; p = 0.062). Changes in systolic blood pressure, serum levels of leptin, and F2-isoprostanes were significant between baseline values and after 8 weeks on the diet in both groups (p < 0.05) but did not differ between the 2 groups.. A nutrient-balanced and energy-restricted diet supplemented with rice bran and plant sterols resulted in a significant decrease in total and LDL cholesterol in overweight and obese adults.

Topics: Adult; Basal Metabolism; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Caloric Restriction; Cholesterol, HDL; Cholesterol, LDL; Diet, Reducing; Dietary Fiber; Double-Blind Method; F2-Isoprostanes; Female; Humans; Insulin; Leptin; Male; Middle Aged; Motor Activity; Obesity; Overweight; Patient Compliance; Phytosterols; Triglycerides; Weight Loss; Young Adult

The frequency of obesity has risen dramatically in recent years but only few effective and safe drugs are available. We investigated if green-plant membranes, previously shown to reduce subjective hunger and promote satiety signals, could affect body weight when given long-term. 38 women (40-65 years of age, body mass index 25-33 kg/m(2)) were randomized to dietary supplementation with either green-plant membranes (5 g) or placebo, consumed once daily before breakfast for 12 weeks. All individuals were instructed to follow a three-meal paradigm without any snacking between the meals and to increase their physical activity. Body weight change was analysed every third week as was blood glucose and various lipid parameters. On days 1 and 90, following intake of a standardized breakfast, glucose, insulin and glucagon-like peptide 1 (GLP-1) in plasma were measured, as well as subjective ratings of hunger, satiety and urge for different palatable foods, using visual analogue scales. Subjects receiving green-plant membranes lost significantly more body weight than did those on placebo (p < 0.01). Mean weight loss with green-plant extract was 5.0 ± 2.3 kg compared to 3.5 ± 2.3 kg in the control group. Consumption of green-plant membranes also reduced total and LDL-cholesterol (p < 0.01 and p < 0.05 respectively) compared to control. Single-meal tests performed on day 1 and day 90 demonstrated an increased postprandial release of GLP-1 and decreased urge for sweet and chocolate on both occasions in individuals supplemented with green-plant membranes compared to control. Waist circumference, body fat and leptin decreased in both groups over the course of the study, however there were no differences between the groups. In conclusion, addition of green-plant membranes as a dietary supplement once daily induces weight loss, improves obesity-related risk-factors, and reduces the urge for palatable food. The mechanism may reside in the observed increased release of GLP-1.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Body Weight; Cholesterol, LDL; Diet; Dietary Supplements; Female; Glucagon-Like Peptide 1; Humans; Insulin; Leptin; Meals; Middle Aged; Overweight; Postprandial Period; Satiation; Single-Blind Method; Surveys and Questionnaires; Triglycerides; Vegetables; Waist Circumference; Weight Loss

The visceral fat is linked to insulin resistance, the metabolic syndrome, type 2 diabetes and an increased cardiovascular risk, but it is not clear whether it has a causative role.. Surgical resection of this fat depot is a research model to address this issue. Twenty premenopausal women with metabolic syndrome and grade III obesity were randomized to undergo Roux-en-Y gastric bypass (RYGBP) either alone or combined with omentectomy. Insulin sensitivity (IS; euglycemic-hyperinsulinemic clamp), acute insulin response to glucose (AIR; intravenous glucose tolerance test), disposition index (DI = AIR × IS measured by clamp), lipid profile, adipokine profile (leptin, adiponectin, resistin, visfatin, interleukin-6, TNF-α, MCP-1), ultra-sensitive C-reactive protein (CRP), body composition, and abdominal fat echography were assessed prior to surgery and 1, 6, and 12 months post-surgery.. Omentectomy was associated with greater weight loss at all time points. IS improved similarly in both groups. Omentectomy was associated to lower CRP after 12 months, but it did not influence adipokines and other metabolic parameters. Among non-diabetic subjects, omentectomy was associated with a preservation of baseline AIR after 12 months (as opposed to deterioration in the control group) and a greater DI after 6 and 12 months.. Although omentectomy did not enhance the effect of RYGBP on insulin sensitivity and adipokines, it was associated with a preservation of insulin secretion, a greater weight loss, and lower CRP.

Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Chemokine CCL2; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glucose Tolerance Test; Humans; Inflammation; Insulin Resistance; Insulin-Secreting Cells; Interleukin-6; Intra-Abdominal Fat; Leptin; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Obesity; Premenopause; Prospective Studies; Resistin; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss; Young Adult

The effect of weight loss on obesity-associated endothelial dysfunction is not clear because of conflicting data, demonstrating both improvement and no change in endothelial function after weight loss in obese subjects. A 2-year prospective study (n = 121) was conducted to examine: (1) the effect of obesity and weight loss (either a low-carbohydrate or and low-fat diet) on flow mediated vasodilatation (FMD), a measure of endothelial function.. Participants reduced body weight by 7.1% ± 4.4%, 8.7% ± 6.8%, 7.1% ± 7.8%, and 4.1% ± 7.7% at 3, 6, 12, and 24 months, respectively with no significant differences between the low-fat and low-carbohydrate groups.. Endothelial function was inversely correlated with waist circumference, triglyceride level, and directly correlated with leptin in obese persons prior to weight loss. These weight losses did not confer any improvements in FMD. There were no differences between the low-fat and low-carbohydrate diets in FMD at any time point. At 6 months (r = 0.26, P = 0.04) and 1 year (r =0.28, P = 0.03), there were positive correlations between change in FMD and change in leptin but not at 2 years.. There was no significant improvement in endothelial function after 7.1% ± 7.8% weight loss at 1 year and 4.1% ± 7.7% at 2 years, achieved by either a low carbohydrate or a low fat diet.

Topics: Adult; Blood Pressure; Body Mass Index; Body Weight; Brachial Artery; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Endothelium; Female; Humans; Image Processing, Computer-Assisted; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Risk Factors; Triglycerides; Vasodilation; Waist Circumference; Weight Loss

Weight loss helps reduce the symptoms of the metabolic syndrome (MetS) in the obese, but weight regain after active weight loss is common. The changes and predictive role of circulating adipokines and sex hormones for weight regain in men during dietary intervention, and also the effect of basal MetS status on weight regain, were investigated.. Twenty-four men who continued to lose weight (WL) and 24 men who regained weight (WR) during the 6-month follow-up period after weight loss were selected from the Diogenes Study. Their circulating concentrations of leptin, adiponectin, retinol-binding protein 4 (RBP4), luteinizing hormone, prolactin, progesterone, total and free testosterone, and sex hormone-binding globulin (SHBG) were measured at baseline, after 8-week low-calorie diet-induced active weight loss, and after a subsequent 26-week ad libitum weight maintenance diet, and analyzed together with anthropometrical and physiological parameters.. Overweight and obese men with MetS at baseline had higher risk to regain weight (odds ratio = 2.8, P = 0.015). High baseline RBP4, low total testosterone, and low SHBG are predictors of weight loss regain (different between WR and WL with P = 0.001, 0.038, and 0.044, respectively).. These variables may play roles in the link between MetS and weight loss regain.

Topics: Adiponectin; Adult; Caloric Restriction; Follow-Up Studies; Humans; Leptin; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Retinol-Binding Proteins, Plasma; Sex Hormone-Binding Globulin; Testosterone; Weight Gain; Weight Loss

Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations.. Overweight/obese postmenopausal women (n = 439) were randomized as follows: (i) a reduced calorie, weight-loss diet (diet; N = 118), (ii) moderate-to-vigorous intensity aerobic exercise (exercise; N = 117), (iii) a combination of a reduced calorie, weight-loss diet and moderate-to-vigorous intensity aerobic exercise (diet + exercise; N = 117), and (iv) control (N = 87). The reduced calorie diet had a 10% weight-loss goal. The exercise intervention consisted of 45 min of moderate-to-vigorous aerobic activity 5 days per week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay.. Adiponectin increased by 9.5% in the diet group and 6.6% in the diet + exercise group (both P ≤ 0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet + exercise, -40.1%, P < 0.0001; diet, -27.1%, P < 0.0001; exercise, -12.7%, P = 0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, P-trend = 0.0002; diet + exercise, P-trend = 0.0005) and directly associated with leptin (diet, P-trend < 0.0001; diet + exercise, P-trend < 0.0001).. Weight loss through diet or diet + exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet + exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin.

Topics: Adiponectin; Aged; Body Mass Index; Diet, Reducing; Exercise; Female; Follow-Up Studies; Humans; Leptin; Middle Aged; Obesity; Overweight; Postmenopause; Reference Values; Risk Assessment; Time Factors; Treatment Outcome; Weight Loss

Evaluate the safety and tolerability of beloranib, a fumagillin-class methionine aminopetidase-2 (MetAP2) inhibitor, in obese women over 4 weeks.. Thirty-one obese (mean BMI 38 kg/m2) women were randomized to intravenous 0.1, 0.3, or 0.9 mg/m2 beloranib or placebo twice weekly for 4 weeks (N = 7, 6, 9, and 9).. The most frequent AEs were headache, infusion site injury, nausea, and diarrhea. Nausea and infusion site injury occurred more with beloranib than placebo. The most common reason for discontinuation was loss of venous access. There were no clinically significant abnormal laboratory findings. In subjects completing 4 weeks, median weight loss with 0.9 mg/m2 beloranib was -3.8 kg (95% CI -5.1, -0.9; N = 8) versus -0.6 kg with placebo (-4.5, -0.1; N = 6). Weight change for 0.1 and 0.3 mg/m2 beloranib was similar to placebo. Beloranib (0.9 mg/m2) was associated with a significant 42 and 18% reduction in triglycerides and LDL-cholesterol, as well as improvement in C-reactive protein and reduced sense of hunger. Changes in β-hydroxybutyrate, adiponectin, leptin, and fibroblast growth factor-21 were consistent with the putative mechanism of MetAP2 inhibition. Glucose and blood pressure were unchanged.. Beloranib treatment was well tolerated and associated with rapid weight loss and improvements in lipids, C-reactive protein, and adiponectin.

Topics: 3-Hydroxybutyric Acid; Adiponectin; Aminopeptidases; Anti-Obesity Agents; Aspergillus; Biological Products; Blood Glucose; Blood Pressure; C-Reactive Protein; Cholesterol, LDL; Cyclohexanes; Double-Blind Method; Fatty Acids, Unsaturated; Female; Fibroblast Growth Factors; Glycoproteins; Humans; Hunger; Infusions, Intravenous; Leptin; Lipids; Methionyl Aminopeptidases; Middle Aged; Obesity; Sesquiterpenes; Triglycerides; Weight Loss

Obese individuals have high levels of circulating leptin and are resistant to the weight-reducing effect of leptin administration at physiological doses. Although Roux-en-Y gastric bypass (RYGB) is an effective weight loss procedure, there is a plateau in weight loss and most individuals remain obese. This plateau may be partly due to the decline in leptin resulting in a state of relative leptin insufficiency. The main objective of this study was to determine whether leptin administration to post-RYGB patients would promote further weight reduction.. This was a randomized, double-blind, placebo-controlled cross-over study of 27 women who were at least 18 months post-RYGB and lost on average 30.8% of their presurgical body weight. Subjects received either leptin or placebo via subcutaneous injection twice daily for 16 weeks, then crossed over to receive the alternate treatment for 16 weeks.. Weight change after 16 weeks of placebo was not significantly different from that after 16 weeks of leptin. No changes were observed in percent fat mass, resting energy expenditure, thyroid hormones, or cortisol levels.. Contrary to our hypothesis, we did not observe a significant effect of leptin treatment on body weight in women with relative hypoleptinemia after RYGB.

Topics: Adult; Cross-Over Studies; Double-Blind Method; Female; Gastric Bypass; Humans; Injections, Subcutaneous; Leptin; Middle Aged; Obesity, Morbid; Weight Loss

Undercarboxylated osteocalcin (ucOC) is a bone marker with potent metabolic effects. Leptin regulates Esp gene expression and osteocalcin carboxylation in animal models. We aim to elucidate day/night patterns of ucOC levels, whether short-term and/or chronic energy deprivation alters ucOC levels, and whether leptin may mediate these changes in humans.. Twelve healthy males and females were studied for 72 h in the fed state to study day/night pattern of ucOC. The six female subjects were also studied in a crossover interventional study in the fasting state for 72 h with administration of either placebo or metreleptin in physiological doses. Blood samples were obtained hourly from 0800 a.m. on day 3 until 0800 a.m. on day 4. In a separate study, eleven obese subjects who underwent bariatric surgery were followed for 24 weeks to examine the effects of postsurgery weight loss on ucOC levels.. Males have higher ucOC levels compared to females. There is no day/night variation pattern of circulating ucOC in humans. Short-term and chronic energy deprivation or leptin administrations do not alter ucOC levels.. The hypothesis that ucOC plays a role in energy homeostasis or of leptin in regulating ucOC in humans is not supported.

Topics: Adult; Bariatric Surgery; Body Mass Index; Carrier Proteins; Circadian Rhythm; Cross-Over Studies; Dose-Response Relationship, Drug; Energy Metabolism; Fasting; Female; Humans; Insulin; Leptin; Male; Middle Aged; Osteocalcin; Seminal Plasma Proteins; Sex Factors; Weight Loss; Young Adult

The objectives of the study were to determine the effects of nutritional restriction on ovarian function in llamas. Mature female llamas were assigned randomly to a Control group, fed 100% of maintenance energy requirements (MER) (n=8), or a Restricted group (n=8) fed from 70% to 40% of MER until a body condition score of 2.5 was attained. Blood samples were taken every-other-day to determine plasma concentrations of LH, estradiol, leptin and metabolic markers, and follicular dynamics were monitored daily by ultrasonography for 30 days (Experiment 1). Llamas were then treated with GnRH to compare the ovulatory response and corpus luteus (CL) development between groups (Experiment 2). Blood samples were taken to measure LH, leptin, progesterone and metabolic markers and ovarian structures were assessed as in Experiment 1. Llamas in the Restricted group had lower body mass and body condition scores than those in the Control group (P<0.001). Plasma concentrations of cholesterol, non-esterified fatty acids, triglycerides, and urea were higher in the Restricted group (P<0.05) than in the Control group. The day-to-day diameter profiles of the dominant follicles were smaller (P<0.05) in the Restricted group than in the Control group but plasma estradiol concentration did not differ. The ovulation rate and LH secretion in response to GnRH did not differ. Day-to-day profiles of CL diameter, plasma progesterone and leptin concentrations were smaller (P<0.01) in the Restricted group. In conclusion, nutritional restriction in llamas was associated with suppressed follicle and CL development, and lower plasma concentrations of progesterone and leptin.

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Constitution; Caloric Restriction; Camelids, New World; Female; Gonadotropin-Releasing Hormone; Hormones; Leptin; Luteinizing Hormone; Ovary; Ovulation; Ovulation Induction; Progesterone; Weight Loss

To evaluate the effects of combination caffeine/ephedrine and leptin A-200 on visceral fat mass and weight loss over 24 weeks.. In this randomized, double-blind, parallel-arm trial, 90 obese subjects received one of the three treatments for 24 weeks: 200 mg caffeine/20 mg ephedrine t.i.d. (CE), leptin A-200 (recombinant methionyl human Fc-leptin, 20 mg q.d.) (L), or combination leptin A-200 and caffeine/ephedrine (LCE). Outcomes included change in weight, visceral fat mass by computed tomography, lean mass and fat mass by dual energy X-ray absorptiometry.. Groups treated with CE and LCE lost significant amounts of weight (-5.9 ± 1.2% and -6.5 ± 1.1%, P < 0.05) and whole body fat mass (-9.6 ± 2.4% and -12.4 ± 2.3%, P < 0.05) compared to leptin only group. Only treatment with LCE significantly reduced visceral fat mass (-11.0 ± 3.3%, P < 0.05). There were no differences in lean mass between treatment groups.. Our study provides evidence that CE is a modestly effective weight loss agent and produces significant reductions in fat mass. Leptin A-200 was not effective in producing weight loss and did not have any significant additive or synergistic actions when combined with CE.

Topics: Absorptiometry, Photon; Adolescent; Adult; Body Composition; Body Weight; Caffeine; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Ephedrine; Female; Humans; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Obesity; Weight Loss; Young Adult

To determine the independent effect of long-term physical activity (PA) and the combined effects of long-term PA and weight loss (WL) on inflammation in overweight and obese older adults.. Eighteen-month randomized, controlled trial.. The community infrastructure of cooperative extension centers.. Overweight and obese (body mass index >28.0 kg/m(2) ) community-dwelling men and women aged 60 to 79 at risk for cardiovascular disease (CVD).. Physical activity + weight loss (PA + WL) (n = 98), PA only (n = 97), or successful aging (SA) health education (n = 93) intervention.. Biomarkers of inflammation (adiponectin, leptin, high-sensitivity interleukin (hsIL)-6, IL-6sR, IL-8, and soluble tumor necrosis factor receptor 1) were measured at baseline and 6 and 18 months.. After adjustment for baseline biomarker, wave, sex, and visit, leptin and hsIL-6 showed a significant intervention effect. Specifically, leptin was significantly lower in the PA + WL group (21.3 ng/mL, 95% confidence interval (CI) = 19.7-22.9 ng/mL) than in the PA (29.3 ng/mL, 95% CI = 26.9-31.8 ng/mL) or SA (30.3 ng/mL, 95% CI = 27.9-32.8 ng/mL) group (both P < .001), and hsIL-6 was significantly lower in the PA + WL group (2.1 pg/mL, 95% CI = 1.9-2.3 pg/mL) than in the PA (2.5 pg/mL, 95% CI = 2.3-2.7 pg/mL) or SA (2.4 pg/mL, 95% CI = 2.2-2.6 pg/mL) group (P = .02).. Addition of dietary-induced WL to PA reduced leptin and hsIL-6 more than PA alone and more than a SA intervention in older adults at risk for CVD. Results suggest that WL, rather than increased PA, is the lifestyle factor primarily responsible for improvement in the inflammatory profile.

Topics: Adiponectin; Aged; Analysis of Variance; Biomarkers; Community Health Centers; Diet, Reducing; Exercise; Female; Humans; Inflammation; Interleukin-6; Interleukin-8; Leptin; Male; Middle Aged; North Carolina; Obesity; Overweight; Receptors, Tumor Necrosis Factor, Type I; Treatment Outcome; Weight Loss

Obesity and weight loss influence thyroid hormone physiology. The effects of weight loss by calorie restriction vs Roux-en-Y gastric bypass (RYGB) in obese subjects have not been studied in parallel. We hypothesized that differences in transient systemic inflammation and catabolic state between the intervention types could lead to differential effects on thyroid hormone physiology.. We recruited 12 lean and 27 obese females with normal fasting glucose (normal glucose tolerant (NGT)) and 27 obese females with type 2 diabetes mellitus (T2DM) for this study. Weight loss was achieved by restrictive treatment (gastric banding or high-protein-low-calorie diet) or by RYGB. Fasting serum leptin, TSH, triiodothyronine (T₃), reverse T₃ (rT₃), and free thyroxine (fT₄) concentrations were measured at baseline and 3 weeks and 3 months after the start of the interventions.. Obesity was associated with higher TSH, T₃, and rT₃ levels and normal fT₄ levels in all the subjects when compared with the controls. After 3 weeks, calorie restriction and RYGB induced a decline in TSH levels and a rise in rT₃ and fT₄ levels. The increase in rT₃ levels correlated with serum interleukin 8 (IL8) and IL6 levels. After 3 months, fT₄ and rT₃ levels returned to baseline levels, whereas TSH and T₃ levels were persistently decreased when compared with baseline levels. No differences in the effects on thyroid hormone parameters between the interventions or between NGT and T2DM subjects were observed at any time point.. In summary, weight loss directly influences thyroid hormone regulation, independently of the weight loss strategy used. The effects may be explained by a combination of decreased leptin levels and transient changes in peripheral thyroid hormone metabolism.

Topics: Adult; Body Mass Index; Caloric Restriction; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Gastric Bypass; Humans; Leptin; Middle Aged; Obesity; Obesity, Morbid; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Weight Loss

Alternate day fasting (ADF; ad libitum "feed day", alternated with 25% energy intake "fast day"), is effective for weight loss and cardio-protection in obese individuals. Whether these effects occur in normal weight and overweight individuals remains unknown. This study examined the effect of ADF on body weight and coronary heart disease risk in non-obese subjects.. Thirty-two subjects (BMI 20-29.9 kg/m2) were randomized to either an ADF group or a control group for 12 weeks.. Body weight decreased (P < 0.001) by 5.2 ± 0.9 kg (6.5 ± 1.0%) in the ADF group, relative to the control group, by week 12. Fat mass was reduced (P < 0.001) by 3.6 ± 0.7 kg, and fat free mass did not change, versus controls. Triacylglycerol concentrations decreased (20 ± 8%, P < 0.05) and LDL particle size increased (4 ± 1 Å, P < 0.01) in the ADF group relative to controls. CRP decreased (13 ± 17%, P < 0.05) in the ADF group relative to controls at week 12. Plasma adiponectin increased (6 ± 10%, P < 0.01) while leptin decreased (40 ± 7%, P < 0.05) in the ADF group versus controls by the end of the study. LDL cholesterol, HDL cholesterol, homocysteine and resistin concentrations remained unchanged after 12 weeks of treatment.. These findings suggest that ADF is effective for weight loss and cardio-protection in normal weight and overweight adults, though further research implementing larger sample sizes is required before solid conclusion can be reached.

Topics: Adiponectin; Adult; Aged; Body Composition; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Diet, Reducing; Energy Intake; Fasting; Female; Humans; Leptin; Male; Middle Aged; Overweight; Risk Factors; Surveys and Questionnaires; Triglycerides; Weight Loss

The purpose of the present secondary analysis study was to investigate the ability of the body adiposity index (BAI) to detect changes in % body fat levels before and after a weight loss intervention when compared to % body fat levels measured using dual-energy X-ray absorptiometry (DXA) and to examine the relationship between the BAI with cardiometabolic risk factors.. The study population for this secondary analysis included 132 non-diabetic obese sedentary postmenopausal women (age: 57.2 ± 4.7 years, BMI: 35.0 ± 3.7 kg/m(2)) participating in a weight loss intervention that consisted of a calorie-restricted diet with or without resistance training. We measured: (1) visceral fat using CT-scan, (2) body composition using DXA, (3) hip circumference and height from which the BAI was calculated, and (4) cardiometabolic risk factors such as insulin sensitivity (using the hyperinsulinemic-euglycemic clamp), blood pressure as well as fasting plasma lipids, hsC-reactive protein (CRP), leptin, and glucose.. Percent body fat levels for both methods significantly decreased after the weight loss intervention. In addition, the percent change in % body fat levels after the weight loss intervention was significantly different between % body fat measured using the DXA and the BAI (-4.5 ± 6.6 vs. -5.8 ± 5.9%; p = 0.03, respectively). However, we observed a good overall agreement between the two methods, as shown by the Bland-Altman analysis, for percent change in % body fat. Furthermore, similar correlations were observed between both measures of % body fat with cardiometabolic risk factors. However, results from the multiple linear regression analysis showed that % body fat using the BAI appeared to predict cardiometabolic risk factors differently than % body fat using the DXA in our cohort.. Estimating % body fat using the BAI seems to accurately trace variations of % body fat after weight loss. However, this index showed differences in predicting cardiometabolic risk factors when compared to % body fat measured using DXA.

Topics: Absorptiometry, Photon; Adiposity; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Caloric Restriction; Cardiovascular Diseases; Cohort Studies; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Linear Models; Middle Aged; Obesity; Postmenopause; Risk Factors; Triglycerides; Weight Loss

Obesity is a chronic disease defined by an excess amount of adipose tissue and presents a low-grade inflammatory state, increasing cardiovascular risk.. To assess the effect of weight loss magnitude on the inflammatory profile and carotid intima-media thickness (cIMT) in obese adolescents engaged in interdisciplinary therapy.. Seventy-seven postpubertal obese adolescents with a BMI greater than the 95th percentile (37·18 ± 5·14), of both genders and between the ages of 14 and 19 years (16·74 ± 1·59) were subjected to a 1-year period of interdisciplinary intervention (nutrition, psychology, physical exercise and clinical support).. Blood samples were collected to analyse glucose, lipid and adipokine concentrations. Body composition, anthropometric profiles and cIMT were measured. The results are presented according to quartiles of weight loss: 1st (≤5·80 kg) = low; 2nd (5·80-10·90 kg) = low to moderate; 3rd (10·90-15·90 kg) = moderate; and 4th (>15·90 kg) = massive.. Leptin, the leptin/adiponectin ratio and plasminogen activator inhibitor 1 (PAI-1) were decreased significantly in the low-to-moderate weight loss. The cIMT was reduced in the moderate weight loss. Moreover, adiponectin was increased only in the massive weight loss. Additionally, weight loss was an independent predictor of changes in leptin level, the adiponectin/leptin ratio (A/L ratio) and PAI-1 when the data were adjusted for age and gender. BMI changes were predictors of changes in leptin and PAI-1 levels. A/L ratio was associated with lean body mass (%), independent of gender and age. In addition, changes in A/L ratio were independent predictors of cIMT alterations.. Interdisciplinary therapy may reduce cardiovascular risk factors among adolescents depending on their degree of weight loss (moderate to massive) and when correlated with their inflammatory profile, metabolic state and cIMT.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adolescent; Blood Glucose; Body Composition; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cholesterol, VLDL; Exercise; Female; Humans; Leptin; Male; Obesity; Plasminogen Activator Inhibitor 1; Regression Analysis; Risk Factors; Time Factors; Treatment Outcome; Triglycerides; Weight Loss

Given that the repetitive loss and regain of body weight, termed weight cycling, is a prevalent phenomenon that has been associated with negative physiological and psychological outcomes, the purpose of this study was to investigate weight change and physiological outcomes in women with a lifetime history of weight cycling enrolled in a 12-month diet and/or exercise intervention.. 439 overweight, inactive, postmenopausal women were randomized to: i) dietary weight loss with a 10% weight loss goal (N=118); ii) moderate-to-vigorous intensity aerobic exercise for 45 min/day, 5 days/week (n=117); ii) both dietary weight loss and exercise (n=117); or iv) control (n=87). Women were categorized as non-, moderate- (≥3 losses of ≥4.5 kg), or severe-cyclers (≥3 losses of ≥9.1 kg). Trend tests and linear regression were used to compare adherence and changes in weight, body composition, blood pressure, insulin, C-peptide, glucose, insulin resistance (HOMA-IR), C-reactive protein, leptin, adiponectin, and interleukin-6 between cyclers and non-cyclers.. Moderate (n=103) and severe (n=77) cyclers were heavier and had less favorable metabolic profiles than non-cyclers at baseline. There were, however, no significant differences in adherence to the lifestyle interventions. Weight-cyclers (combined) had a greater improvement in HOMA-IR compared to non-cyclers participating in the exercise only intervention (P=.03), but no differences were apparent in the other groups.. A history of weight cycling does not impede successful participation in lifestyle interventions or alter the benefits of diet and/or exercise on body composition and metabolic outcomes.

Topics: Adiponectin; Blood Glucose; Blood Pressure; Body Composition; C-Peptide; C-Reactive Protein; Diet, Reducing; Exercise; Female; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Linear Models; Middle Aged; Overweight; Postmenopause; Weight Gain; Weight Loss

Our recently published randomised clinical trial evaluated the effect of a low-calorie diet with carbohydrates eaten at dinner. This dietary pattern led to lower hunger scores, and better anthropometric, biochemical and inflammatory outcomes compared to a standard low-calorie diet. In the same study, changes in diurnal secretion patterns of leptin, ghrelin and adiponectin were investigated.. Seventy-eight police officers (body mass index (BMI) > 30) were randomly allocated to experimental (carbohydrates at dinner) or control weight loss diets for 6 months. Sixty-three subjects finished the programme. On days 0, 7, 90 and 180 blood samples and hunger scores were collected every 4 h from 8:00 to 20:00. Hormonal profiles were available for 39. The dietary manipulation led to changes in daylight hormonal profiles in the experimental group. Leptin's secretion curve became convex, with a nadir later in the day (significant difference compared to baseline at morning and evening, p = 0.023, p = 0.021, respectively). Ghrelin's secretion curve became concave, peaking only in the evening hours. Adiponectin's curve was elevated only after the experimental diet (significant difference compared to baseline at afternoon, p = 0.044).. We propose that a low-calorie diet with carbohydrates eaten at dinner can modulate daytime hormonal profiles. Taken together with our earlier results, we believe this diet regime may prevent mid-day hunger, better support weight loss and improve metabolic outcomes compared to conventional weight loss diets. The trial is registered at controlled-trials.com, ISRCTN37829376, December 2009.

Topics: Adiponectin; Adult; Body Mass Index; Caloric Restriction; Diet, Reducing; Dietary Carbohydrates; Female; Ghrelin; Humans; Leptin; Male; Meals; Middle Aged; Obesity; Weight Loss

Satiety decline is one of the factors that are involved in weight regain in the postoperative period of bariatric surgery. Nutrients such as long-chain n-3 polyunsaturated fatty acid and fibers could assist in food intake control by increasing satiety. Flaxseed is a source of these nutrients, and its consumption could help with possible glycemic control and increased satiety. The aim of this study was to evaluate the influence of whole flaxseed and defatted flaxseed on satiety, postprandial blood glucose, and leptin in post-bariatric women.. A single-blind crossover and randomized study was performed with 18 women in the late postoperative of Roux-en-Y gastric bypass (RYGBP). All women received three test meals containing whole flaxseed, defatted flaxseed, and placebo with 1 week of washout. Satiety was evaluated by a Visual Analog Scale during the fasting period; immediately after ingestion; and 60, 120, and 180 min after meals.. There was no difference between test meals for the variables of hunger, satisfaction, fullness, and desire to eat. The basal and postprandial glucose and leptin levels did not differ between the test meals. The intake of defatted flaxseed and placebo muffins resulted in reduced postprandial blood glucose. Postprandial leptin was higher than the baseline (p = 0.02); however, only defatted flaxseed showed increased postprandial leptin levels (p = 0.044).. Whole flaxseed and defatted flaxseed did not promote satiety in women in the late postoperative of RYGBP. However, the test meals with a lower fat content increased the serum leptin levels.

Topics: Adult; Aged; Blood Glucose; Body Weight; Brazil; Cross-Over Studies; Diet Records; Eating; Female; Flax; Gastric Bypass; Humans; Leptin; Meals; Middle Aged; Obesity, Morbid; Postoperative Period; Satiation; Single-Blind Method; Time Factors; Treatment Outcome; Weight Loss

The aim of this article is to longitudinally investigate racial differences in serum adiponectin and leptin in European-American (EA) and African-American (AA) women in the overweight and weight-reduced states. Sixty-two EA and 58 AA premenopausal women were weight reduced from body mass index (BMI) 27-30 kg/m(2) to BMI ≤ 24. Fasting serum adiponectin and leptin were determined; body composition and intra-abdominal adipose tissue (IAAT) were measured with dual-energy X-ray absorptiometry and computed tomography, respectively. In repeated-measure MANOVA, there was a significant race effect for IAAT and total fat mass; compared to AA women, EA women had higher IAAT and total fat mass (p < 0.0001 and p = 0.027, respectively). In the mixed-model for adiponectin that adjusted for IAAT, limb fat, and total fat, race was significantly associated with adiponectin (p = 0.046). AA women had significantly lower adjusted adiponectin compared to EA women at baseline [7.67 (6.85, 8.60) vs. 9.32 (8.34, 10.4) μg/ml, p < 0.05] and following weight loss [9.75 (8.70, 10.9) vs. 11.8 (10.6, 13.2) μg/ml, p < 0.05]. In a mixed-model for leptin that adjusted for insulin, estradiol, and fat mass, race was significantly associated with leptin (p < 0.0001). AA women had significantly higher adjusted leptin compared to EA women at baseline [24.7 (22.3, 27.4) vs. 19.9 (18.1, 21.8) ng/dl, p < 0.05] and following weight loss [11.7 (10.2, 13.3) vs. 8.48 (7.50, 9.57) ng/dl, p < 0.05]. Despite having a more favorable body fat distribution, AA women had lower adjusted adiponectin and higher leptin. Differences in body composition and fat distribution do not appear to be significant factors in explaining lower adiponectin and higher leptin in AA women.

Topics: Adiponectin; Adult; Black or African American; Body Composition; Female; Humans; Insulin; Leptin; Longitudinal Studies; Overweight; Premenopause; Weight Loss; White People

Obesity and aging are associated with increased arterial stiffness as indicated by an increased pulse-wave velocity (PWV). We evaluated the independent and combined effects on PWV and body composition of a hypocaloric diet and low-intensity resistance exercise training (LIRET) with slow movement.. Forty-one postmenopausal women (mean age, 54±6 years; body mass index (BMI), 33.8±0.5kg/m(2)) were randomly assigned to LIRET (n = 14), diet (n = 13), or diet + LIRET (n = 14) for 12 weeks. The women's PWV, mean arterial pressure (MAP), body composition by dual-en ergy x-ray absorptiometry (DXA), and plasma adipokine and insulin levels were measured before and after the interventions.. Body weight (P = 0.0001), trunk-fat mass (FM, P = 0.0001), and the serum concentration of leptin (P = 0.02 and P = 0.004) decreased similarly with diet and diet + LIRET, but not with LIRET alone. Leg lean mass (LM) decreased (P = 0.02) with diet, but did not change with diet + LIRET or with LIRET alone. Leg muscle strength increased similarly with LIRET (P = 0.001) and diet + LIRET (P = 0.0001), but did not change with diet alone. Brachial-ankle PWV (baPWV) decreased with diet (P = 0.04) and diet + LIRET (P = 0.01), whereas femoral-ankle PWV (legPWV) decreased only with diet (P = 0.01). Mean arterial pressure (MAP) decreased after LIRET (P = 0.03), diet (P = 0.04), and diet + LIRET (P = 0.004). Carotid-femoral PWV, serum adiponectin concentration, and insulin were not significantly affected by the interventions examined in the study. The reductions in baPWV and legPWV were correlated with one another (r = 0.73, P = 0.0001), and the reductions in legPWV and trunk FM were also correlated with one another (r = 0.36, P = 0.03).. A hypocaloric diet decreases baPWV mainly by reducing legPWV, and this reduction is related to the loss of truncal fat. Although LIRET alone does not affect PWV or body composition, LIRET combined with diet improves baPWV and muscle strength while preventing loss of lean body mass in obese postmenopausal women.

Topics: Absorptiometry, Photon; Adiposity; Body Composition; Body Mass Index; Diet, Reducing; Exercise; Female; Humans; Insulin; Leptin; Middle Aged; Muscle Strength; Obesity; Postmenopause; Pulse Wave Analysis; Resistance Training; Vascular Stiffness; Weight Loss

A silent intragenic polymorphism (1359 G/A) of the cannabinoid receptor 1 gene resulting in the substitution of the G to A at nucleotide position 1359 in codon 435 (Thr) was reported as a common polymorphism in Caucasian populations. Intervention studies with this polymorphism have not been realized.. We decide to investigate the role of missense polymorphism (G1359A) of cannabinoid receptor 1 gene on adipocytokines response and weight loss secondary to a low-fat versus a low-carbohydrate diet in obese patients.. A population of 249 patients was analyzed. A nutritional evaluation was performed at the beginning and at the end of a 3-month period in which subjects received one of two diets (diet I: low fat vs. diet II: low carbohydrate).. One hundred forty three patients (57.4%) had the genotype G1359G (wild-type group), and 106 (42.6%) patients had G1359A (92 patients, or 36.9%) or A1359A (14 patients, or 5.6%; mutant-type group). With both diets in wild-type and mutant-type groups, body mass index (BMI), weight, fat mass, waist circumference and systolic blood pressure levels decreased. With both diets and in wild-type group, glucose, total cholesterol and insulin levels and homeostasis model assessment test score decreased. No metabolic effects were observed in mutant-type group. Leptin levels decreased significantly in the wild-type group with both diets (diet I: 10.8% vs. diet II: 28.9%; P<.05).. The novel finding of this study is the lack of metabolic improvement of the mutant-type groups G1359A and A1359A after weight loss with both diets. Decrease in leptin level was higher with low-carbohydrate diet than low-fat diet.

Topics: Adipokines; Adult; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Female; Genotype; Humans; Insulin; Leptin; Male; Middle Aged; Mutation, Missense; Obesity; Polymorphism, Single Nucleotide; Prospective Studies; Receptor, Cannabinoid, CB1; Weight Loss

The objective of this study was to determine the effects of high and moderate non-structural carbohydrates (NSC) hay on insulin, glucose, triglyceride, and leptin concentrations in overweight Arabian geldings. Eight adult overweight (average BCS 7 [9-point scale]) Arabian geldings were fed each of two orchardgrass hays, high NSC (18% DM) and moderate NSC (12% DM), in a cross over design during two 28-day periods. Body weight and body condition score assessment along with blood sampling to measure insulin, glucose, leptin, and triglyceride concentrations were performed on days 0, 7, 14, 21 and 28 of each period. Effects of hay, period, day, and day*hay on plasma glucose and serum leptin were not detected. Serum insulin was influenced by hay (p = 0.001), day (p = 0.03), and day*hay (p = 0.04). Insulin concentrations were higher on day 7 in the high NSC group (15.6 μIU/ml) than the moderate NSC group (9.5 μIU/ml), but not by day 14 (p = 0.0007). Plasma triglyceride was influenced by period (p = 0.0003), day*period (p < 0.0001), and day*hay (p = 0.02). Hyperinsulinaemia was not observed in the overweight Arabian geldings fed either a moderate or high NSC hay.

Topics: Animal Feed; Animals; Blood Glucose; Cross-Over Studies; Diet; Dietary Carbohydrates; Horse Diseases; Horses; Insulin; Leptin; Male; Overweight; Weight Loss

Obese breast cancer survivors have increased risk of recurrence and death compared to their normal weight counterparts. Rural women have significantly higher obesity rates, thus weight control intervention may be a key strategy for prevention of breast cancer recurrence in this population. This one-arm treatment study examined the impact of a group-based weight control intervention delivered through conference call technology to obese breast cancer survivors living in remote rural locations. The intervention included a reduced calorie diet incorporating prepackaged entrees and shakes, physical activity gradually increased to 225 min/week of moderate intensity exercise, and weekly group phone sessions. Outcomes included anthropomorphic, diet, physical activity, serum biomarker, and quality of life changes. Ninety-one percent of participants (31 of 34) attended >75% of intervention sessions and completed post-treatment data collection visits. At 6 months, significant changes were observed for weight (-12.5 ± 5.8 kg, 13.9% of baseline weight), waist circumference (-9.4 ± 6.3 cm), daily energy intake (-349 ± 550 kcal/day), fruits, and vegetables (+3.7 ± 4.3 servings/day), percent kcal from fat (-12.6 ± 8.6%), physical activity (+1235 ± 832 kcal/week; all P values <0.001), as well as significant reductions in fasting insulin (16.7% reduction, P = 0.006), and leptin (37.1% reduction, P < 0.001). Significant improvements were also seen for quality of life domains including mood, body image, and sexuality. In conclusion, the intervention produced >10% weight loss as well as significant improvements across multiple endpoints. The group phone-based treatment delivery approach may help disseminate effective weight control intervention to hard-to-reach breast cancer survivors.

Topics: Aged; Analysis of Variance; Biomarkers; Breast Neoplasms; Caloric Restriction; Exercise Therapy; Female; Group Processes; Humans; Insulin; Kansas; Leptin; Middle Aged; Obesity; Quality of Life; Remote Consultation; Rural Health Services; Surveys and Questionnaires; Survivors; Telephone; Time Factors; Treatment Outcome; Weight Loss

Individuals who are weight-reduced or leptin deficient have a lower energy expenditure coupled with higher hunger and disinhibition and/or delayed satiation compared with never-weight-reduced control subjects. Because exogenous leptin inhibits feeding in congenitally leptin-deficient humans, reduced leptin signaling may reduce the expression of feeding inhibition in humans.. The objective was to test the hypothesis that reduced leptin signaling may reduce the expression of feeding inhibition (ie, blunt satiation) in humans by examining the effects of leptin repletion on feeding behavior after weight loss.. Ten obese humans (4 men, 6 women) were studied as inpatients while they received a weight-maintaining liquid-formula diet. Satiation was studied by measuring intake and ratings of appetite-related dispositions 3 h after ingestion of 300 kcal of the liquid-formula diet. The subjects were studied at each of 3 time periods: 1) while they maintained their usual weight (Wt(initial)) and then after weight reduction and stabilization at 10% below initial weight and while they received 5 wk of either 2) twice-daily injections of placebo (Wt(-10%placebo)) or 3) "replacement doses" of leptin (Wt(-10%leptin)) in a single-blind crossover design with a 2-wk washout period between treatments. Energy expenditure was also measured at each study period.. Both energy expenditure and visual analog scale ratings that reflect satiation were significantly lower at Wt(-10%placebo) than at Wt(initial) and Wt(-10%leptin).. The results are consistent with the hypothesis that the absence of leptin signaling after weight loss may blunt the expression of feeding inhibition in humans.

Topics: Adult; Appetite; Cross-Over Studies; Diet, Reducing; Energy Metabolism; Female; Humans; Leptin; Male; Obesity; Satiation; Single-Blind Method; Weight Loss

The objective was to determine the effect of metformin on the concentrations of resistin and other markers of insulin resistance or inflammation (C-reactive protein, cytokines, body weight, HbA1c, among others) in minors with glucose intolerance. Patients aged 4 to 17 years with glucose intolerance were studied. They were randomized to receive 850 mg of either metformin or placebo twice daily for 12 weeks, during which all followed an iso-caloric diet and an exercise program. High sensitivity C-reactive protein, TNF-alpha, IL-6, IL1-beta, resistin, leptin, adiponectin, glucose, insulin, HbA1c, lipid profile and transaminases were measured at the beginning and at the end of the period. Fifty-two patients were included, 11.9±2.6 years old; 28 (12 males/16 females) received metformin and 24 placebo (11 males/13 females). Baseline characteristics were similar between groups (except for body mass index, which in the metformin group was slightly higher). Percentage weight loss was greater in the metformin group (-5.86% vs 2.75%, P<.05). At study end, there were statistically significant differences in resistin concentrations, even after adjusting for confounding variables (F=7.714; P<.006). Also, metformin was associated with a significant decrease in HOMA-IR index (P=.032) and HbA1c levels (P=.001), but no change was observed in the concentration of other markers of inflammation. Metformin resulted in significant reductions of plasma resistin levels in minors with glucose intolerance. This change is independent of its effects on body weight. In contrast, metformin did not alter the concentration of inflammatory markers.

Topics: Adiponectin; Adolescent; Biomarkers; C-Reactive Protein; Child; Child, Preschool; Drug Administration Schedule; Energy Intake; Exercise; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation; Interleukin-1beta; Interleukin-6; Leptin; Male; Metformin; Resistin; Tumor Necrosis Factor-alpha; Weight Loss

This study aimed to determine in obese women if endocannabinoid receptor antagonism has effects on fatty acid and triglyceride metabolism and insulin sensitivity which are independent from the metabolic effects of weight loss. Fourteen obese (BMI=33.0±0.5 kg/m(2)) (mean±SEM) Caucasian post-menopausal women, aged 57.8±4.7 years were studied. The women were randomised to 2 groups, one group received the endocannabinoid receptor antagonist rimonabant (20 mg/d) for 12 weeks. A control group achieved the same weight loss by a hypocaloric dietary intervention over 12 weeks. Palmitate production rate (Ra), a measure of lipolysis, and palmitate oxidation rate, and VLDL(1) and VLDL(2) triglyceride (TG) kinetics, were measured using isotopic tracers before and after the intervention. Weight loss was not different in the 2 groups; 2.6±0.5 kg with rimonabant and 3.1±1.0 kg in the control group. Palmitate Ra increased with rimonabant with no change in the control group (p=0.03 between groups). Palmitate oxidation rate increased with rimonabant but decreased in the control group (p=0.005 between groups). VLDL(1) TG secretion rate decreased in the control group and increased in the rimonabant group (p=0.008 between groups). There was no significant effect on insulin sensitivity. This study suggests that endocannabinoid receptor antagonism for 12 weeks in obese women increased lipolysis and fatty acid oxidation. The increase in VLDL(1) TG secretion rate may be due to the increase in lipolysis which exceeded the increase in fatty acid oxidation.

Topics: Adiponectin; Aged; Breath Tests; Cannabinoid Receptor Antagonists; Cholesterol; Diet, Reducing; Energy Intake; Energy Metabolism; Fatty Acids; Female; Humans; Insulin Resistance; Leptin; Lipolysis; Lipoproteins, VLDL; Middle Aged; Obesity; Oxidation-Reduction; Palmitic Acids; Piperidines; Pyrazoles; Rimonabant; Triglycerides; United Kingdom; Weight Loss

A sedentary lifestyle predisposes to cardiometabolic diseases. Lifestyle changes such as increased physical activity improve a range of cardiometabolic risk factors. The objective of this study was to examine whether functional changes in adipose tissue were related to these improvements.. Seventy-three sedentary, overweight (mean BMI 29.9 ± 3.2 kg/m2) and abdominally obese, but otherwise healthy men and women (67.6 ± 0.5 years) from a randomised controlled trial of physical activity on prescription over a 6-month period were included (control n = 43, intervention n = 30). Detailed examinations were carried out at baseline and at follow-up, including fasting blood samples, a comprehensive questionnaire and subcutaneous adipose tissue biopsies for fatty acid composition analysis (n = 73) and quantification of mRNA expression levels of 13 candidate genes (n = 51), including adiponectin, leptin and inflammatory cytokines.. At follow-up, the intervention group had a greater increase in exercise time (+137 min/week) and a greater decrease in body fat mass (-1.5 kg) compared to the control subjects (changes of 0 min/week and -0.5 kg respectively). Circulating concentrations of adiponectin were unchanged, but those of leptin decreased significantly more in the intervention group (-1.8 vs -1.1 ng/mL for intervention vs control, P < 0.05). The w6-polyunsaturated fatty acid content, in particular linoleic acid (18:2w6), of adipose tissue increased significantly more in the intervention group, but the magnitude of the change was small (+0.17 vs +0.02 percentage points for intervention vs control, P < 0.05). Surprisingly leptin mRNA levels in adipose tissue increased in the intervention group (+107% intervention vs -20% control, P < 0.05), but changes in expression of the remaining genes did not differ between the groups.. After a 6-month period of increased physical activity in overweight elderly individuals, circulating leptin concentrations decreased despite increased levels of leptin mRNA in adipose tissue. Otherwise, only minor changes occurred in adipose tissue, although several improvements in metabolic parameters accompanied the modest increase in physical activity.

Topics: Adiponectin; Aged; Exercise; Fatty Acids; Female; Gene Expression; Humans; Leptin; Linear Models; Male; Obesity, Abdominal; Statistics, Nonparametric; Subcutaneous Fat; Transcriptome; Treatment Outcome; Weight Loss

Obesity is an energy balance problem caused by overeating. Obesity treatment includes diet, exercise, behaviour treatment, pharmacotherapy and surgery; in addition, acupuncture is also an option.. To investigate the effect of acupuncture on weight loss and whether a brief acupuncture treatment of 5 weeks can change circulating levels of leptin, ghrelin, insulin and cholecystokinin (CCK) in obese women.. 40 women with a body mass index (BMI)>30 kg/m(2) were equally randomised to either an acupuncture group or a sham (non-penetrating) acupuncture group and received treatment at LI4, HT7, ST36, ST44 and SP6 bilaterally. Both groups had two sessions of 20 min/week for a total of 10 sessions. Serum insulin, leptin, plasma ghrelin and CCK levels were measured by ELISA.. Acupuncture treatment decreased insulin and leptin levels and induced weight loss, together with a decrease in BMI compared with sham acupuncture. Furthermore, between-group analyses demonstrated increases in plasma ghrelin and CCK levels in subjects who received acupuncture treatment.. These findings suggest that acupuncture may help to regulate weight owing to its beneficial effects on hormones such as insulin, leptin, ghrelin and CCK in obese subjects even after a few weeks of treatment.

Topics: Acupuncture Points; Acupuncture Therapy; Adult; Body Mass Index; Cholecystokinin; Female; Ghrelin; Humans; Insulin; Leptin; Middle Aged; Obesity; Weight Loss

Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied.. To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss.. A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings.. After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low-glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks.. Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components.. Compared with the pre-weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d), intermediate with the low-glycemic index diet (-166 [-227 to -106] kcal/d), and least with the very low-carbohydrate diet (-138 [-198 to -77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115] kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol, P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged.. Among overweight and obese young adults compared with pre-weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low-glycemic index diet, and least with the very low-carbohydrate diet.. clinicaltrials.gov Identifier: NCT00315354.

Topics: Adult; Cholesterol, HDL; Cross-Over Studies; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Energy Metabolism; Female; Glycemic Index; Humans; Hydrocortisone; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Nutritive Value; Obesity; Overweight; Plasminogen Activator Inhibitor 1; Triglycerides; Weight Loss; Young Adult

The present study determined the effect of black soy peptide supplementation on body weight and body fat in overweight/obese subjects. In a double-blind controlled trial, participants (n = 80) were randomized to either soy peptide supplementation (the test group) or to a placebo (the placebo group). Sixty-four people completed the study, and anthropometric parameters, serum inflammatory markers, and leptin and lipid profiles were measured. After 6 weeks, the test group (n = 35) had significant reductions in body weight (p = 0.003) and body mass index (BMI) (p = 0.004), body fat mass (p = 0.038). After 12 weeks, they also had significant reductions in body weight (p < 0.001), BMI (p < 0.001), body fat percentage (p = 0.002), and body fat mass (p = 0.001). However, these significances were not observed in the placebo group (n = 29). In addition, net changes in body weight and body fat mass in the test group were significantly bigger than those in the placebo group after 12 weeks. Leptin levels were significantly reduced in the test groups (p = 0.047), but were not observed in the placebo group (p = 0.323). Interestingly, the subjects with weight reductions ≥1kg in the test group had greater reductions in circulating leptin levels (p = 0.002). Additionally, fasting insulin levels were significantly reduced in the test groups. The conclusion is that black soy peptide supplementation may be beneficial for body weight control in overweight/obese subjects.

Topics: Adipose Tissue; Adult; Aged; Apolipoprotein A-I; Apolipoproteins B; Biomarkers; Blood Glucose; Body Composition; Body Mass Index; C-Reactive Protein; Dietary Supplements; Double-Blind Method; Fasting; Female; Glycine max; Humans; Insulin; Interleukin-1beta; Leptin; Lipids; Male; Middle Aged; Obesity; Overweight; Soybean Proteins; Tumor Necrosis Factor-alpha; Weight Loss

To compare the effects of aerobic training (AT) with aerobic plus resistance training (AT+RT) in nonalcoholic fatty liver disease (NAFLD) obese adolescents.. Long-term interdisciplinary weight-loss therapy (1 year of clinical, nutritional, psychological, and exercise-related intervention).. Fifty-eight postpubertal obese adolescents were randomized to AT or AT+RT according to NAFLD diagnosis. Adipokine and neuropeptide concentrations were measured by enzyme-linked immunosorbent assay, visceral fat by ultrasound, and body composition by plethysmography.. The NAFLD group that followed the AT+RT protocol presented lower insulin, homeostasis model assessment-insulin resistance (HOMA-IR), and alanine transaminase (ALT) values after intervention compared with AT. It was verified that there was a higher magnitude of change in the subcutaneous fat, glycemia, total cholesterol (TC), low-density lipoprotein-cholesterol, ALT, and adiponectin in response to AT+RT than in the control group (AT). All patients who underwent the AT+RT exhibited significantly higher adiponectin, leptin, and Δadiponectin and lower melanin-concentrating hormone (MCH) concentrations after therapy compared with the AT group. In the simple linear regression analysis, changes in glycemia, insulin, and HOMA-IR were independent predictors of significant improvement in adiponectin concentration. Indeed, ΔAST (aspartate transaminase) and ΔGGT (γ-glutamyl transpeptidase) were independent predictors of ΔALT, while Δfat mass and ΔAgRP (agouti-related protein) were independent predictors of ΔMCH. Although the number of patients was limited, we showed for the first time the positive effects of AT+RT protocol in a long-term interdisciplinary therapy to improve inflammatory biomarkers and to reduce orexigenic neuropeptide concentrations in NAFLD obese adolescents.. The long-term interdisciplinary therapy with AT+RT protocol was more effective in significantly improving noninvasive biomarkers of NAFLD that are associated with the highest risk of disease progression in the pediatric population.

Topics: Adipokines; Adiponectin; Adiposity; Adolescent; Biomarkers; Blood Glucose; Body Mass Index; Brazil; Enzyme-Linked Immunosorbent Assay; Exercise; Fatty Liver; Female; Humans; Hypothalamic Hormones; Inflammation Mediators; Insulin; Intra-Abdominal Fat; Leptin; Linear Models; Lipids; Male; Melanins; Neuropeptides; Non-alcoholic Fatty Liver Disease; Obesity; Pituitary Hormones; Plethysmography; Resistance Training; Time Factors; Treatment Outcome; Ultrasonography; Weight Loss; Young Adult

The aim of the study was to compare the baseline and the 18-month follow-up for weight and metabolic characteristics of superobese (SO) (body mass index [BMI] ≥50 kg/m(2)) and morbidly obese (MO) (BMI <50 kg/m(2)) adolescents who participated in a prospective longitudinal study of gastric banding delivered in an adolescent multidisciplinary treatment program.. Clinical information was extracted from an institutional review board-approved database of bariatric adolescents. Fasting cytokine and acute phase protein serum levels were analyzed by enzyme-linked immunosorbent assay. Liver histopathologies were assessed using the Kleiner's classification score.. Other than BMI, MO (n = 11) and SO (n = 7) patients have similar degree of insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease. Serum C-reactive protein (10.2 ± 5.6 SO vs 4 ± 3.9 μg/mL MO [P < .02]) and leptin (71 ± 31 SO vs 45 ± 28 MO ng/mL [P = .04]) were more elevated in SO patients. Although weight loss is similar (30 ± 19 kg MO vs 28 ± 12 kg SO, P = .8 at 18 months; mean percent change in BMI, 22.8% ± 11.6% vs 20.5% ± 10.3% SO, P = .2), SO patients has less resolution of insulin resistance and dyslipidemia but experienced significantly improved health-related quality of life.. The SO adolescents demonstrate equivalent short-term weight loss and improved quality of life but delayed metabolic response to a gastric banding-based weight loss treatment program compared with MO patients, illustrating the importance of early referral for timely intervention of MO patients.

Topics: Acute-Phase Proteins; Adolescent; Biomarkers; Body Mass Index; Cross-Sectional Studies; Cytokines; Dyslipidemias; Enzyme-Linked Immunosorbent Assay; Fatty Liver; Follow-Up Studies; Gastroplasty; Humans; Insulin Resistance; Laparoscopy; Leptin; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity, Morbid; Prospective Studies; Treatment Outcome; Weight Loss; Weight Reduction Programs

To assess the effects of weight loss on adipokines, asthma-related symptoms, exercise-induced bronchospasm (EIB) and lung function, and to evaluate the role of leptin and adiponectin levels on lung function after treatment in obese adolescents.. 84 postpubertal obese adolescents were enrolled and distributed in quartiles according to weight loss (low (<2.5 kg), low to moderate (>2.5 and <8 kg), moderate (<8 and <14 kg) and massive (<14 kg)). Body composition was measured by plethysmography, and visceral and subcutaneous fat were detected by ultrasound. Serum levels of adiponectin and leptin were analyzed. Lung function, asthma and EIB were evaluated according to the American Thoracic Society criteria. Patients were submitted to 1 year of interdisciplinary intervention consisting of physiotherapy, medical, nutritional, exercise, and psychological therapy.. After treatment the moderate and massive weight loss promoted an increase in adiponectin and adiponectin/leptin (A/L) ratio as well as a decrease in leptin levels and a reduction in EIB frequency and asthma-related symptoms. Furthermore, the reduction in leptin levels was a predictor factor to improvement in lung function.. Interdisciplinary therapy was able to decrease EIB and asthma-related symptoms and to improve pro/anti-inflammatory adipokines. Additionally, the leptin concentration was a predictor factor to explain changes in lung function.

Topics: Adiponectin; Adolescent; Asthma; Asthma, Exercise-Induced; Diet; Exercise; Female; Humans; Leptin; Lung; Male; Obesity; Physical Therapy Modalities; Psychotherapy; Weight Loss; Weight Reduction Programs

Low-fat (LF) and high-fat (HF) weight loss diets improve brachial artery flow-mediated dilation (FMD) in obese individuals, although results are conflicting. Moreover, the role that adipose tissue plays in mediating these diet-related effects are unknown.. This study examined how modulations in FMD by HF and LF diets relate to changes in adipocyte parameters.. Obese subjects (n = 17) were randomized to a HF diet (60% kcal as fat) or a LF diet (25% kcal as fat) for 6 weeks. Both groups were restricted by 25% of energy needs.. Body weight decreased (P <0.05) in both groups (HF: -6.6 ± 0.5 kg, LF: -4.7 ± 0.6 kg). Fat mass and waist circumference were reduced (P <0.05) in the LF group only (-4.4 ± 0.3 kg; -3.6 ± 0.8 cm, respectively). FMD improved (P <0.05) in the LF group (7.4 ± 0.8% to 9.8 ± 0.8; 32% increase) and was impaired in the HF group (8.5 ± 0.6% to 6.9 ± 0.7; 19% reduction). Increases in plasma adiponectin (P <0.05, 16 ± 5%), and decreases in resistin (P <0.05, -26 ± 11%), were shown by the LF diet only. Greater decreases in leptin were observed with LF (-48 ± 9%) versus HF (-28 ± 12%) (P <0.05, diet × time). Increased FMD by the LF diet was associated with increased adiponectin, and decreased fat mass, waist circumference, leptin, and resistin.. Beneficial modulations in vascular health by LF diets may be mediated by improvements in adipocyte parameters.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Adult; Analysis of Variance; Body Composition; Body Weight; Cardiovascular Diseases; Diet, Fat-Restricted; Dietary Fats; Female; Humans; Leptin; Male; Obesity; Random Allocation; Risk Factors; Weight Loss

Obesity has been associated with increased cardiac sympathetic activation during wakefulness, but the effect on sleep-related sympathetic modulation is not known. The aim of this study was to investigate the effect of fat gain on cardiac autonomic control during wakefulness and sleep in humans. We performed a randomized, controlled study to assess the effects of fat gain on heart rate variability. We recruited 36 healthy volunteers, who were randomized to either a standardized diet to gain ≈4 kg over 8 weeks followed by an 8-week weight loss period (n=20) or to serve as a weight-maintainer control (n=16). An overnight polysomnogram with power spectral analysis of heart rate variability was performed at baseline, after weight gain, and after weight loss to determine the ratio of low-frequency to high-frequency power and to examine the relationship between changes in heart rate variability and changes in insulin, leptin, and adiponectin levels. Mean weight gain was 3.9 kg in the fat gain group versus 0.1 kg in the maintainer group. Low frequency/high frequency increased both during wakefulness and sleep after fat gain and returned to baseline after fat loss in the fat gain group and did not change in the control group. Insulin, leptin, and adiponectin also increased after fat gain and fell after fat loss, but no clear pattern of changes was seen that correlated consistently with changes in heart rate variability. Short-term fat gain in healthy subjects is associated with increased cardiac sympathetic activation during wakefulness and sleep, but the mechanisms remain unclear.

Topics: Adolescent; Adult; Autonomic Nervous System; Blood Glucose; Body Composition; Female; Heart Rate; Humans; Insulin; Leptin; Male; Middle Aged; Polysomnography; Sleep; Wakefulness; Weight Gain; Weight Loss

In obesity, metabolic stress and inflammation in injured tissues could favour enhanced shedding of procoagulant microparticles (MPs). At sites of endothelium injury, the swift recruitment of procoagulant leukocyte-derived MPs enables the initiation of blood coagulation and thrombus growth.. In obese females, we sought to evaluate the impact of a very low-calorie diet (VLCD) on procoagulant MP levels, fibrinolytic status, inflammation and endothelium damage.. Circulating biomarkers of vascular damage, fibrinolytic status, platelet activation and inflammation were measured before, 30 and 90 days after starting a short-term VLCD. MPs were measured by flow cytometry and capture assays. Their procoagulant potential was quantified using functional prothrombinase assays and their cellular origin were determined using flow cytometry (endothelium, platelet, leukocyte, lymphocyte and erythrocyte-derived MP) or capture assays.. A total of 24 obese females (39 ± 10 years) with a mean body mass index of 35 ± 4  kg m(-2) were prospectively enroled. Procoagulant leukocyte-derived MPs were associated with the waist circumference at baseline (r=0.534; P=0.010) and at 90 days follow-up (r=0.487; P=0.021). At 90 days, weight reduction (-9.8%) was associated with a lowering of blood pressure, improvement of metabolic parameters and a significant reduction of plasminogen activator inhibitor-1 (PAI-1) (-38%), procoagulant platelet-derived MPs (-43%), leukocyte-derived MPs (-28%) and leptin (-32%) levels.. In obese females, a short-term VLCD results in an overall improvement of the haemostatic balance characterized by the reduction of PAI-levels, diminished release of platelet and leukocyte-derived MPs and a reduction in leptin levels, an adipocyte-derived cytokine.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Coagulation Factors; Blood Platelets; Caloric Restriction; Endothelium, Vascular; Erythrocytes; Female; Hemostasis; Humans; Leptin; Leukocytes; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Prospective Studies; Thromboplastin; Thrombosis; Weight Loss; Young Adult

This study was designed to investigate the effect of a low-calorie diet with carbohydrates eaten mostly at dinner on anthropometric, hunger/satiety, biochemical, and inflammatory parameters. Hormonal secretions were also evaluated. Seventy-eight police officers (BMI >30) were randomly assigned to experimental (carbohydrates eaten mostly at dinner) or control weight loss diets for 6 months. On day 0, 7, 90, and 180 blood samples and hunger scores were collected every 4 h from 0800 to 2000 hours. Anthropometric measurements were collected throughout the study. Greater weight loss, abdominal circumference, and body fat mass reductions were observed in the experimental diet in comparison to controls. Hunger scores were lower and greater improvements in fasting glucose, average daily insulin concentrations, and homeostasis model assessment for insulin resistance (HOMA(IR)), T-cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were observed in comparison to controls. The experimental diet modified daily leptin and adiponectin concentrations compared to those observed at baseline and to a control diet. A simple dietary manipulation of carbohydrate distribution appears to have additional benefits when compared to a conventional weight loss diet in individuals suffering from obesity. It might also be beneficial for individuals suffering from insulin resistance and the metabolic syndrome. Further research is required to confirm and clarify the mechanisms by which this relatively simple diet approach enhances satiety, leads to better anthropometric outcomes, and achieves improved metabolic response, compared to a more conventional dietary approach.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adult; Blood Glucose; C-Reactive Protein; Cholesterol; Diet, Carbohydrate-Restricted; Diet, Reducing; Dietary Carbohydrates; Fasting; Feeding Behavior; Female; Humans; Hunger; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Obesity, Abdominal; Tumor Necrosis Factor-alpha; Weight Loss

The objective was to examine the effects of weight loss and leptin administration following weight loss on calciotropic hormones and bone turnover. This was a prospective, single-blinded study of 12 subjects (8 women, 4 men; 2 nonobese, 10 obese; age range, 19-46 years) who were studied on an inpatient basis while maintaining their usual weight [Wt(initial)] and during maintenance of 10% weight loss while receiving twice-daily injections of either a placebo [Wt(-10%P)] or replacement doses of leptin [Wt(-10%L)]. The main outcome measures were markers of bone formation (bone alkaline phosphatase and procollagen type 1 amino terminal propeptide) and resorption (N-telopeptide) as well as parathyroid hormone, calcium, and 25-hydroxy vitamin D measured from fasting morning serum. As expected, serum leptin declined with weight loss. Bone alkaline phosphatase decreased by 12.3% ± 3.9% between Wt(initial) and Wt(-10%P) and remained suppressed after leptin administration (both P < .01 compared with baseline). N-telopeptides increased by 37.2% ± 11.3% from Wt(initial) to Wt(-10%L) (P < .01). Procollagen type 1 amino terminal propeptide, parathyroid hormone, calcium, and 25-hydroxy vitamin D did not change. These results suggest that both decreased bone formation and increased bone resorption underlie bone loss associated with weight loss. Leptin administration did not prevent the uncoupling of bone remodeling that accompanies weight loss.

Topics: Adult; Bone Remodeling; Collagen Type I; Cross-Over Studies; Female; Humans; Leptin; Male; Middle Aged; Peptides; Prospective Studies; Single-Blind Method; Vitamin D; Weight Loss

Short-term energy deprivation reduces leptin concentrations and alters the levels of circulating hormones of the hypothalamic-pituitary-peripheral axis in lean subjects. Whether the reduction in leptin concentration during long-term weight loss in obese individuals is linked to the same neuroendocrine changes seen in lean, leptin-sensitive subjects remains to be fully clarified.. In this study, 24 overweight and obese adults (16 women and eight men; body mass index (BMI): 27.5-38.0 kg/m(2)) were prescribed a hypocaloric diet (-500 kcal/day) and were randomized to receive recombinant methionyl leptin (n=18, metreleptin, 10 mg/day self-injected s.c.) or placebo (n=6, same volume and time as metreleptin) for 6 months.. Metreleptin administration did not affect weight loss beyond that induced by hypocaloric diet alone (P for interaction=0.341) but increased the serum concentrations of total leptin by six- to eight-fold (P<0.001) and led to the generation of anti-leptin antibodies. Despite free leptin concentration (P for interaction=0.041) increasing from 9±1 ng/ml at baseline to 43±15 and 36±12 ng/ml at 3 and 6 months, respectively, changes in circulating hormones of the thyroid and IGF axes at 3 and 6 months were not significantly different in the placebo- and metreleptin-treated groups.. Leptin does not likely mediate changes in neuroendocrine function in response to weight loss induced by a mild hypocaloric diet in overweight and obese subjects.

Topics: Adult; Aged; Caloric Restriction; Diet, Reducing; Drug Administration Schedule; Female; Humans; Leptin; Male; Middle Aged; Obesity; Osmolar Concentration; Overweight; Signal Transduction; Somatomedins; Thyroid Gland; Thyroid Hormones; Time Factors; Weight Loss; Young Adult

The aim of this study was to verify the effects of a multidisciplinary therapy (24 weeks) on neurohormonal control of food intake, specifically in orexigenic (total ghrelin, agouti-related protein [AgRP], neuropeptide Y [NPY], and melanin-concentrating hormone) and anorexigenic factors (leptin, insulin, and alpha-melanocyte stimulating hormone [α-MSH]), in obese adolescents.. A total of 88 adolescents (38 boys and 50 girls), including 62 obese and 26 normal-weight, aged 15-19 years were recruited. Obese adolescents were submitted to a 24-week multidisciplinary therapy. AgRP, NPY, melanin-concentrating hormone, leptin, insulin, glucose, α-MSH, total ghrelin, and food intake were measured at three stages (at baseline, after 12 weeks, and after 24 weeks).. At baseline, obese adolescents showed hyperleptinemia (circulating leptin levels, which were, in boys and girls, 40 and 35 times higher than in normal-weight subjects, respectively). After 24 weeks, these values decreased in all obese patients. Our results showed no differences in ghrelin levels between obese and normal-weight adolescents, in both genders. However, obese boys reduced their plasma ghrelin concentration after 24 weeks of therapy (p < .05). The multidisciplinary therapy decreased NPY and AgRP values and increased α-MSH; simultaneously with these changes there was a decrease in total food intake after 24 weeks of therapy.. We can conclude that the multidisciplinary therapy was efficient to modulate neurohormonal control of food intake in obese adolescents.

Topics: Adolescent; Adolescent Health Services; Agouti-Related Protein; alpha-MSH; Body Weight; Combined Modality Therapy; Diet, Reducing; Exercise; Feeding Behavior; Female; Ghrelin; Humans; Hypothalamic Hormones; Leptin; Male; Melanins; Neuropeptide Y; Obesity; Peptide Hormones; Pituitary Hormones; Weight Loss

Maintenance of a 10% or greater reduced body weight results in decreases in the energy cost of low levels of physical activity beyond those attributable to the altered body weight. These changes in nonresting energy expenditure are due mainly to increased skeletal muscle work efficiency following weight loss and are reversed by the administration of the adipocyte-derived hormone leptin. We have also shown previously that the maintenance of a reduced weight is accompanied by a decrease in ratio of glycolytic (phosphofructokinase) to oxidative (cytochrome c oxidase) activity in vastus lateralis muscle that would suggest an increase in the relative expression of the myosin heavy chain I (MHC I) isoform. We performed analyses of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle metabolic properties as well as mRNA expression of different isoforms of the MHC and sarcoplasmic endoplasmic reticular Ca(2+)-dependent ATPase (SERCA) in subjects studied before weight loss and then again after losing 10% of their initial weight and receiving twice daily injections of either placebo or replacement leptin in a single blind crossover design. We found that the maintenance of a reduced body weight was associated with significant increases in the relative gene expression of MHC I mRNA that was reversed by the administration of leptin as well as an increase in the expression of SERCA2 that was not significantly affected by leptin. Leptin administration also resulted in a significant increase in the expression of the less MHC IIx isoform compared with subjects receiving placebo. These findings are consistent with the leptin-reversible increase in skeletal muscle chemomechanical work efficiency and decrease in the ratio of glycolytic/oxidative enzyme activities observed in subjects following dietary weight loss.

Topics: Adaptation, Physiological; Adiposity; Analysis of Variance; Biopsy; Cross-Over Studies; Energy Metabolism; Female; Gene Expression Regulation; Humans; Injections, Subcutaneous; Leptin; Male; Muscle Contraction; Muscle Strength; Myosin Heavy Chains; Obesity; Quadriceps Muscle; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Single-Blind Method; Time Factors; Treatment Outcome; Weight Loss

After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss.. We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite.. Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001).. One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Long-term strategies to counteract this change may be needed to prevent obesity relapse. (Funded by the National Health and Medical Research Council and others; ClinicalTrials.gov number, NCT00870259.).

Topics: Body Mass Index; Body Weight; Cholecystokinin; Diet, Reducing; Female; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Intention to Treat Analysis; Leptin; Male; Middle Aged; Obesity; Peptide YY; Peptides; Postmenopause; Weight Loss

Sibutramine and metformin are drugs commonly used to obtain weight loss. We aimed to compare the effects of sibutramine alone with that of sibutramine plus metformin combination on weight loss, insulin sensitivity, leptin and C reactive protein in obese women. Seventy obese women were included. After a diet period of month (baseline), each individual was randomly assigned to receive 15 mg sibutramine (sibutramine group; n = 36) or 15 mg sibutramine plus 1,700 mg metformin per day (sibutramine plus metformin group; n = 34) during the next 12 months. Body weight, insulin resistance by the homeostasis model assessment model (HOMA-IR), leptin and C reactive protein were measured at baseline, after 3 months and after 12 months. Mean weight losses in sibutramine and sibutramine plus metformin groups were 5.3 +/- 4.0% (P < 0.001) and 6.8 +/- 3.9% (P < 0.001) after 3 months, and 10.5 +/- 4.4% (P < 0.001) and 15.7 +/- 4.6% (P = 0.007) after 12 months, respectively. HOMA-IR value also decreased in both sibutramine (P = 0.045 and P = 0.002) and sibutramine plus metformin groups (P = 0.04 and P = 0.015) after 3 and 12 months, respectively. Similarly, serum leptin levels decreased in both sibutramine (P = 0.04, P = 0.01) and sibutramine plus metformin groups (P = 0.023, P = 0.025) after 3 and 12 months, respectively. There was also significant reductions in serum C reactive protein levels in both sibutramine (P = 0.045, P = 0.02) and sibutramine plus metformin groups (P = 0.007, P = 0.001) after 3 and 12 months, respectively. These decrements of body weight, HOMA-IR, serum leptin and C reactive protein levels were not statistical significance between these two groups both after 3 and 12 months (P > 0.05). Combination of sibutramine with metformin did not result in any further effects on weight loss, insulin resistance, leptin and C reactive protein levels when compared to sibutramine alone.

Topics: Adult; Appetite Depressants; C-Reactive Protein; Cyclobutanes; Drug Therapy, Combination; Female; Humans; Insulin Resistance; Leptin; Metformin; Middle Aged; Obesity; Treatment Outcome; Weight Loss

The goal of this study was to understand the mechanisms of greater weight loss by gastric bypass (GBP) compared to gastric banding (GB) surgery. Obese weight- and age-matched subjects were studied before (T0), after a 12 kg weight loss (T1) by GBP (n = 11) or GB (n = 9), and at 1 year after surgery (T2). peptide YY(3-36) (PYY(3-36)), ghrelin, glucagon-like peptide-1 (GLP-1), leptin, and amylin were measured after an oral glucose challenge. At T1, glucose-stimulated GLP-1 and PYY levels increased significantly after GBP but not GB. Ghrelin levels did not change significantly after either surgery. In spite of equivalent weight loss, leptin and amylin decreased after GBP, but not after GB. At T2, weight loss was greater after GBP than GB (P = 0.003). GLP-1, PYY, and amylin levels did not significantly change from T1 to T2; leptin levels continued to decrease after GBP, but not after GB at T2. Surprisingly, ghrelin area under the curve (AUC) increased 1 year after GBP (P = 0.03). These data show that, at equivalent weight loss, favorable GLP-1 and PYY changes occur after GBP, but not GB, and could explain the difference in weight loss at 1 year. Mechanisms other than weight loss may explain changes of leptin and amylin after GBP.

Topics: Adult; Amyloid; Appetite Regulation; Follow-Up Studies; Gastric Bypass; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Hormones; Humans; Islet Amyloid Polypeptide; Leptin; Metabolome; Middle Aged; Peptide YY; Time Factors; Weight Loss

We evaluated the effects of body weight (BW) loss on blood pressure (BP) in overweight non-obese patients with stage 1 hypertension. We enrolled 376 overweight (body mass index (BMI) >or=25 and <30 kg m(-2)) stage 1 hypertensive patients in this prospective 12-month trial. Each patient received tailored, low caloric dietary advice. After 6 months, patients with a BW reduction <5% were excluded. Body weight, BMI, BP, fasting plasma glucose (FPG), fasting plasma insulin (FPI), leptin (pL), renin and aldosterone levels were evaluated at baseline and after 6 and 12 months. In 222 patients who completed the study, a mean weight reduction of 8.1 kg reduced systolic blood pressure (SBP) by 4.2 mm Hg and diastolic blood pressure (DBP) by 3.3 mm Hg (P<0.05), which was accompanied by a significant decrease in FPI, pL and aldosterone levels (P<0.05). Larger SBP/DBP reductions were observed in 106 patients with normalized BMI (-5/-4.5 mm Hg, P<0.01) compared with the 116 patients who did not become normalized (-3.3/-1.6 mm Hg). The former also presented with greater decreases in FPG, FPI, pL, renin and aldosterone levels. Of the 106 patients who had normalized BMI, 52 also had normalized BP. Clinical and metabolic characteristics of these patients were similar to those of the 56 patients who did not have normalized BP. In overweight, mild hypertensive patients, weight loss was effective in reducing BP and in reversing some endocrinologic alterations associated with being overweight. Half of the patients who had normalized BMI also had normalized BP, which could indicate that these patients essentially did not have a form of hypertension but that these effects were instead secondary to being overweight.

Topics: Aged; Aldosterone; Blood Glucose; Blood Pressure; Body Mass Index; Diet, Reducing; Female; Humans; Hypertension; Insulin; Leptin; Male; Middle Aged; Overweight; Prospective Studies; Renin; Weight Loss

The reason for weight loss at high altitudes is largely unknown. To date, studies have been unable to differentiate between weight loss due to hypobaric hypoxia and that related to increased physical exercise. The aim of our study was to examine the effect of hypobaric hypoxia on body weight at high altitude in obese subjects. We investigated 20 male obese subjects (age 55.7 +/- 4.1 years, BMI 33.7 +/- 1.0 kg/m(2)). Body weight, waist circumference, basal metabolic rate (BMR), nutrition protocols, and objective activity parameters as well as metabolic and cardiovascular parameters, blood gas analysis, leptin, and ghrelin were determined at low altitude (LA) (Munich 530 m, D1), at the beginning and at the end of a 1-week stay at high altitude (2,650 m, D7 and D14) and 4 weeks after returning to LA (D42). Although daily pace counting remained stable at high altitude, at D14 and D42, participants weighed significantly less and had higher BMRs than at D1. Food intake was decreased at D7. Basal leptin levels increased significantly at high altitude despite the reduction in body weight. Diastolic blood pressure was significantly lower at D7, D14, and D42 compared to D1. This study shows that obese subjects lose weight at high altitudes. This may be due to a higher metabolic rate and reduced food intake. Interestingly, leptin levels rise in high altitude despite reduced body weight. Hypobaric hypoxia seems to play a major role, although the physiological mechanisms remain unclear. Weight loss at high altitudes was associated with clinically relevant improvements in diastolic blood pressure.

Topics: Altitude; Atmospheric Pressure; Basal Metabolism; Blood Pressure; Body Mass Index; Body Weight; Energy Intake; Exercise; Humans; Hypoxia; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Weight Loss

Metabolic syndrome, a constellation of metabolic risk factors for type 2 diabetes and cardiovascular disease, is one of the fastest growing disease entities in the world. Weight loss is thought to be a key to improving all aspects of metabolic syndrome. Research studies have suggested benefits from diets rich in vegetables and fruits in helping individuals reach and achieve healthy weights.. To evaluate the effects of a ready to serve vegetable juice as part of a calorie-appropriate Dietary Approaches to Stop Hypertension (DASH) diet in an ethnically diverse population of people with Metabolic Syndrome on weight loss and their ability to meet vegetable intake recommendations, and on their clinical characteristics of metabolic syndrome (waist circumference, triglycerides, HDL, fasting blood glucose and blood pressure).A secondary goal was to examine the impact of the vegetable juice on associated parameters, including leptin, vascular adhesion markers, and markers of the oxidative defense system and of oxidative stress.. A prospective 12 week, 3 group (0, 8, or 16 fluid ounces of low sodium vegetable juice) parallel arm randomized controlled trial. Participants were requested to limit their calorie intake to 1600 kcals for women and 1800 kcals for men and were educated on the DASH diet. A total of 81 (22 men & 59 women) participants with Metabolic Syndrome were enrolled into the study. Dietary nutrient and vegetable intake, weight, height, leptin, metabolic syndrome clinical characteristics and related markers of endothelial and cardiovascular health were measured at baseline, 6-, and 12-weeks.. There were significant group by time interactions when aggregating both groups consuming vegetable juice (8 or 16 fluid ounces daily). Those consuming juice lost more weight, consumed more Vitamin C, potassium, and dietary vegetables than individuals who were in the group that only received diet counseling (p < 0.05).. The incorporation of vegetable juice into the daily diet can be a simple and effective way to increase the number of daily vegetable servings. Data from this study also suggest the potential of using a low sodium vegetable juice in conjunction with a calorie restricted diet to aid in weight loss in overweight individuals with metabolic syndrome.

Topics: Adult; Aged; Beverages; Biomarkers; Blood Pressure; Counseling; Diet Records; Diet, Sodium-Restricted; Female; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Sodium, Dietary; Texas; Vegetables; Weight Loss

Leptin plays an important role in energy metabolism. The primary objective of the study was to investigate whether baseline leptin levels predict weight loss during a dietary intervention in overweight and obese individuals.. A total of 324 individuals (138 men and 186 women, aged 20-40 years, BMI 27.5-32.5) were recruited in Iceland, Ireland and Spain. The intervention lasted for 8 consecutive weeks, and subjects were instructed to follow a diet, energy restricted by 30%. Anthropometric variables were assessed before and after the intervention. Leptin concentration was measured at baseline and corrected for fat mass. Linear models were used to find out which variables predicted weight loss.. At end point, significant weight loss was observed (5.16 +/- 3.06 kg, p < 0.001). High baseline leptin concentrations were a significant negative predictor of weight loss in men (p = 0.028), with a predicted difference of 1.8 kg between the lowest and highest leptin quartile.. Our study underlines the importance of leptin in energy metabolism. Plasma leptin concentrations at baseline are a predictor of weight loss in overweight men after an 8-week dietary intervention. The same effect was not observed in overweight women, which suggests that the role of leptin in the regulation of weight is gender specific.

Topics: Adult; Anthropometry; Diet; Female; Humans; Iceland; Ireland; Leptin; Linear Models; Male; Models, Statistical; Motor Activity; Overweight; Patient Compliance; Predictive Value of Tests; Sex Characteristics; Spain; Weight Loss

The ability of alternate-day fasting (ADF) to modulate adipocyte parameters in a way that is protective against coronary heart disease (CHD) has yet to be tested. Accordingly, we examined the effects of ADF on adipokine profile, body composition, and CHD risk indicators in obese adults. Sixteen obese subjects (12 women/4 men) participated in a 10-week trial with three consecutive dietary intervention phases: (i) 2-week baseline control phase, (ii) 4-week ADF controlled feeding phase, and (iii) 4-week ADF self-selected feeding phase. After 8 weeks of treatment, body weight and waist circumference were reduced (P < 0.05) by 5.7 ± 0.9 kg, and 4.0 ± 0.9 cm, respectively. Fat mass decreased (P < 0.05) by 5.4 ± 0.8 kg, whereas fat-free mass did not change. Plasma adiponectin was augmented (P < 0.05) by 30% from baseline. Leptin and resistin concentrations were reduced (P < 0.05) by 21 and 23%, respectively, post treatment. Low-density lipoprotein cholesterol (LDL-C) and triacylglycerol concentrations were 25% and 32% lower (P < 0.05), respectively, after 8 weeks of ADF. High-density lipoprotein cholesterol (HDL-C), C-reactive protein, and homocysteine concentrations did not change. Decreases in LDL-C were related to increased adiponectin (r = -0.61, P = 0.01) and reduced waist circumference (r = 0.39, P = 0.04). Lower triacylglycerol concentrations were associated with augmented adiponectin (r = -0.39, P = 0.04) and reduced leptin concentrations (r = 0.45, P = 0.03) post-treatment. These findings suggest that adipose tissue parameters may play an important role in mediating the cardioprotective effects of ADF in obese humans.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adult; Biomarkers; Body Composition; Coronary Disease; Diet, Reducing; Fasting; Female; Humans; Leptin; Lipids; Male; Middle Aged; Obesity; Resistin; Risk Factors; Waist Circumference; Weight Loss

To investigate in severely obese adolescents the effects of a 3-week multidisciplinary weight-reduction intervention involving moderate energy restriction, individualised physical activity and behavior therapy on the response of some hormonal and metabolic parameters to meals and exercise.. Clinical longitudinal study on inpatients in a specialised institution.. A total of 20 obese adolescents (10 boys and 10 girls) aged 12-17 yr [body mass index (BMI): 37.7±6.1 kg/m2; fat mass (FM): 44.8±13.2 kg].. The changes in plasma concentration of leptin, ghrelin, GH, IGF-I, insulin, glucose, and non-esterified fatty acids (NEFA) in response to standardised meals and exercise bouts were measured before and after the weight-reduction intervention. At the same times, body composition was assessed by bioelectrical impedance as well as appetite sensations using a visual analog scale.. At the end of the intervention, the adolescents had lost body weight and FM (expressed both in kg and %) (p<0.05), without any significant fat-free mass loss (in % terms). In response to both meals and exercise, after the 3-week intervention, plasma leptin concentration decreased significantly (p<0.05), whereas the other hormones (insulin, ghrelin, GH, and IGF-I) and metabolic parameters (glucose and NEFA) did not change. Interestingly, appetite was not affected by the intervention.. This 3-week multidisciplinary intervention in obese adolescents induced a significant body weight loss with beneficial changes in body composition. However, despite there being no change in metabolic parameters and ghrelin in response to meals and exercise after the intervention, plasma concentrations of leptin were decreased. The failure of ghrelin levels to increase by this approach might explain the good control of appetite observed at the end of the study.

Topics: Adolescent; Child; Combined Modality Therapy; Eating; Exercise; Female; Ghrelin; Humans; Interdisciplinary Communication; Leptin; Male; Obesity; Peptide Hormones; Reference Standards; Weight Loss

Our aim was to determine the influence of weight reduction on total (T-) and high-molecular weight (HMW-) adiponectin in obese (OB) prepubertal children. Seventy OB prepubertal white patients were followed for 18 months and studied after reducing their BMI by 1 (n = 51) and 2 standard deviation scores (SDS) (n = 21) under conservative treatment, and 6 months after achieving weight loss (n = 44). Body composition dual-energy X-ray absorptiometry (DXA) and serum levels of T- and HMW-adiponectin, resistin, leptin, leptin soluble receptor (sOB-R), tumoral necrosis factor-α and interleukin-6 were determined. The control group consisted of 61 healthy prepubertal children. At diagnosis T-adiponectin was higher (P < 0.01; confidence interval (+0.04) - (+0.15)) and HMW-adiponectin lower (P < 0.001; confidence interval (-0.45) - (-0.21)) in OB children than in controls. A reduction in body fat increased T- and HMW-adiponectin and sOB-R (all P < 0.001) and decreased leptin (P < 0.001) and interleukin-6 levels (P < 0.05). After 6 months of sustained weight reduction a decrease in tumoral necrosis factor-α (P < 0.01) occurred, whereas weight recovery increased leptin (P < 0.001) and decreased T-adiponectin (P < 0.05). HMW-adiponectin levels negatively correlated with homeostasis model assessment (HOMA) index and BMI in the whole cohort (both P < 0.001), as did T-adiponectin levels and HOMA index in OB patients (P < 0.01), but neither T- nor HMW-adiponectin correlated with body fat content (BFC) in OB children. We conclude that the impairment of T- and HMW-adiponectin levels in childhood obesity is different to that in elder OB patients, showing closer relationship with carbohydrate metabolism parameters than with BFC, but increasing their levels after weight loss and in association with metabolic improvement.

Topics: Absorptiometry, Photon; Adiponectin; Adipose Tissue; Body Mass Index; Case-Control Studies; Child; Female; Humans; Insulin Resistance; Interleukin-6; Leptin; Male; Obesity; Reference Values; Tumor Necrosis Factor-alpha; Weight Gain; Weight Loss

Obesity is an escalating global health problem associated with both an increased risk of death and an increased risk of cardiovascular events. Our goal was to use magnetic resonance imaging (MRI) to determine the effect of obesity and weight loss, in the absence of the traditional cardiovascular risk factors, on aortic pulse wave velocity (PWV) a reliable, reproducible, and accurate clinical measure of aortic stiffness linked to increased mortality. Fifty obese (BMI 38.3 ± 6.8 kg/m(2)) and eighteen normal-weight controls (BMI 22.0 ± 1.7 kg/m(2)) with no identifiable cardiovascular risk factors underwent vascular MRI to assess PWV between the ascending aorta at the level of the pulmonary artery and the abdominal aorta (AA). Twenty-eight subjects underwent repeat imaging after a 1-year period of weight loss. Both groups were well matched for age, systolic blood pressure, fasting glucose, and total cholesterol. Obesity was associated with a 14% increase in PWV (P = 0.021), and with elevated C-reactive protein (CRP) (P < 0.01) and leptin levels (P < 0.001) factors known to cause increase arterial stiffness. Weight loss (average 50% excess weight) was associated with a 14% improvement in PWV (P = 0.03), and with reductions in serum leptin levels (P < 0.01). Obesity, in the absence of the traditional cardiovascular risk factors, is associated with increased aortic PWV, a noninvasive clinical measure of aortic stiffness independently predictive of cardiovascular mortality. Significant weight loss results in improvements in aortic PWV. This may provide a potential link between both obesity and increased mortality, and the reduction in mortality that occurs with weight loss.

Topics: Adult; Aorta; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Leptin; Magnetic Resonance Angiography; Male; Middle Aged; Obesity; Pulsatile Flow; Pulse; Risk Factors; Vascular Resistance; Weight Loss

To assess the additional effect of sudden visceral fat reduction by omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in patients with grade III obesity (G-III O) undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB).. Twenty-two patients were randomized into two groups, LRYGB alone or with omentectomy. Levels of interleukin-6, C-reactive protein, tumor necrosis factor-alpha, leptin, adiponectin, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, as well as clinical characteristics, were evaluated before surgery and at 1, 3, 6, and 12 months after surgery. Results were compared between groups.. Baseline characteristics were comparable in both groups. Mean operative time was significantly higher in the group of patients who underwent omentectomy (P < 0.001). Median weight of the omentum was 795 +/- 341 g. In one patient, a duodenal perforation occurred at the time of omentectomy. BMI, blood pressure, glucose, total cholesterol, LDL, and triglycerides significantly improved in both groups at 1, 3, 6, and 12 months of follow-up when compared with basal values. However, there were no consistent statistically significant differences among the groups in terms of metabolic syndrome components, acute-phase reactants, and inflammatory mediators.. Omentectomy does not have an ancillary short-term significant impact on the components of metabolic syndrome and does not induce important changes in the inflammatory mediators in patients undergoing LRYGB. Operative time is more prolonged when omentectomy is performed.

Topics: Acute-Phase Proteins; Adiponectin; Adult; Blood Glucose; C-Reactive Protein; Female; Gastric Bypass; Humans; Inflammation Mediators; Interleukin-6; Intra-Abdominal Fat; Laparoscopy; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity, Morbid; Omentum; Pilot Projects; Prospective Studies; Tumor Necrosis Factor-alpha; Weight Loss

Exercise interventions elicit only modest weight loss, which might reflect a compensatory reduction in nonprescribed physical activity energy expenditure (PAEE).. The objective was to investigate whether there is a reduction in nonprescribed PAEE as a result of participation in a 6-mo structured exercise intervention in middle-aged men.. Sedentary male participants [age: 54 ± 5 y; body mass index (in kg/m²): 28 ± 3] were randomly assigned to a 6-mo progressive exercise (EX) or control (CON) group. Energy expenditure during structured exercise (prescribed PAEE) and nonprescribed PAEE were determined with the use of synchronized accelerometry and heart rate before the intervention, during the intervention (2, 9, and 18 wk), and within a 2-wk period of detraining after the intervention.. Structured prescribed exercise increased total PAEE and had no detrimental effect on nonprescribed PAEE. Indeed, there was a trend for greater nonprescribed PAEE in the EX group (P = 0.09). Weight loss in the EX group (-1.8 ± 2.2 kg compared with +0.2 ± 2.2 kg in the CON group, P < 0.02) reflected only ≈40% of the 300-373 kcal/kg body mass potential energy deficit from prescribed exercise. Serum leptin concentration decreased by 24% in the EX group (compared with 3% in the CON group, P < 0.03), and we estimate that this was accompanied by a compensatory increase in energy intake of ≈100 kcal/d.. The adoption of regular structured exercise in previously sedentary, middle-aged, and overweight men does not result in a negative compensatory reduction in nonprescribed physical activity. The less-than-predicted weight loss is likely to reflect a compensatory increase in energy intake in response to a perceived state of relative energy insufficiency.

Topics: Body Mass Index; Energy Intake; Energy Metabolism; Exercise; Exercise Therapy; Humans; Leptin; Male; Middle Aged; Motor Activity; Overweight; Sedentary Behavior; Weight Loss

We previously reported that baclofen, a GABA(B) agonist, reduces body weight in obese mice. In this clinical study, we examined the possibility that baclofen might serve as an effective therapeutic agent for obesity in humans.. Seven women and three men ranging from 25-51 years of age and 31.3-41.0 kg/m(2) body mass index were included in the study. Baclofen, which was started at a dose of 15 mg/day and increased to 30 mg/day in 10 days, was administered for 12 weeks.. Administration of baclofen for 12 weeks significantly decreased both body weight (baseline: 93.30 ± 9.80 kg, 12 weeks: 91.70 ± 10.30 kg) and waist circumference (baseline: 107.9 ± 9.0 cm, 12 weeks: 105.6 ± 10.0 cm). Serum leptin levels, which possibly reflect the amount of adipose stores, were also decreased significantly by the treatment. On the other hand, there were no significant changes in the blood pressure or metabolism of glucose and lipid. No adverse effects were observed.. Although the anti-obesity effects of baclofen in the present study were mild, this pilot study suggests the possibility that baclofen might serve as a new anti-obesity drug in humans.

Topics: Adiponectin; Adult; Animals; Anti-Obesity Agents; Appetite; Baclofen; Blood Glucose; Blood Pressure; Female; GABA-B Receptor Agonists; Humans; Leptin; Lipids; Male; Mice; Middle Aged; Obesity; Pilot Projects; Weight Loss

To compare the effects of protein vs. simple sugars on weight loss, body composition, and metabolic and endocrine parameters in polycystic ovary syndrome (PCOS).. A 2-month, free-living, randomized, single-blinded study.. University PCOS clinic.. Thirty-three patients with PCOS.. To achieve a final energy reduction of 450 kcal/day, first the daily energy intake was reduced by 700 kcal; then a 240-kcal supplement containing either whey protein or simple sugars was added.. Changes in weight, fat mass, fasting glucose and insulin, plasma lipoproteins, and sex steroids.. Twenty-four subjects (13 in the simple sugars group and 11 in the protein group) completed the study. The protein group lost more weight (-3.3 +/- 0.8 kg vs. -1.1 +/- 0.6 kg) and more fat mass (-3.1 +/- 0.9 kg vs. -0.5 +/- 0.6 kg) and had larger decreases in serum cholesterol (-33.0 +/- 8.4 mg/dL vs. -2.3 +/- 6.8 mg/dL), high-density lipoprotein cholesterol (-4.5 +/- 1.3 mg/dL vs. -0.4 +/- 1.3 mg/dL), and apoprotein B (-20 +/- 5 mg/dL vs. 3 +/- 5 mg/dL).. In patients with PCOS, a hypocaloric diet supplemented with protein reduced body weight, fat mass, serum cholesterol, and apoprotein B more than the diet supplemented with simple sugars.

Topics: Adolescent; Adult; Body Composition; Body Mass Index; Calorimetry; Diet, Reducing; Dietary Carbohydrates; Dietary Proteins; Dietary Sucrose; Energy Intake; Female; Humans; Leptin; Middle Aged; National Institutes of Health (U.S.); Polycystic Ovary Syndrome; Single-Blind Method; United States; Weight Loss; Young Adult

Energy restriction affects circulating leptin and ghrelin concentrations.. To investigate whether seafood consumption affects fasting leptin and ghrelin concentrations in addition to weight loss.. In this 8-week dietary intervention, subjects (324 Icelandic, Spanish and Irish subjects, 20-40 years, BMI 27.5-32.5 kg/m(2)) were randomized to energy-restricted diets (-30%) of identical macronutrient composition but different amount of seafood: control (no seafood); lean fish (150 g cod, three times per week); fatty fish (150 g salmon, three times per week); EPA&DHA [daily docosahexaenoic (DHA)/eicosapentaenoic acid (EPA) capsules]. Anthropometric data, ghrelin, leptin, and insulin were measured at baseline and endpoint. Linear models investigated the effects of seafood on fasting leptin, ghrelin and insulin.. Body weight (-5.2 +/- 3.0 kg), leptin (-34.8%) and insulin (-13.5%) decreased, while ghrelin increased (5.6%) (all P < 0.001). According to linear models endpoint insulin was significantly lower in the EPA&DHA group (-16.4%, P = 0.025) compared to control, endpoint leptin in men was lower in the salmon group (-22.9%, P = 0.026), and the EPA&DHA group tended to have higher endpoint ghrelin (5.6%, P = 0.060), an effect seen only in women indicated by a significant gender x EPA&DHA interaction. Weight loss explained the effects of fatty seafood on leptin and ghrelin, but not insulin.. Consumption of fatty seafood can modulate fasting insulin, ghrelin and leptin during an 8-week intervention. Effects are partly gender specific and are partly explained by weight loss. Consumption of lean fish does not affect circulating hormones in comparison to control. The most consistent effect on circulating hormones is mediated by weight loss.

Topics: Adult; Body Mass Index; Caloric Restriction; Diet; Dietary Fats; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fasting; Female; Ghrelin; Humans; Leptin; Male; Obesity; Seafood; Sex Characteristics; Weight Loss

Green tea (epigallocatechin gallate + caffeine) and protein each were shown to improve body weight maintenance after weight loss.. We investigated the effect of a green tea-caffeine mixture added to a high-protein (HP) diet on weight maintenance (WM) after body weight loss in moderately obese subjects.. A randomized, placebo-controlled, double-blind parallel trial was conducted in 80 overweight and moderately obese subjects [age (mean +/- SD): 44 +/- 2 y; body mass index (BMI; in kg/m(2)): 29.6 +/- 2.0] matched for sex, age, BMI, height, body mass, and with a habitually low caffeine intake. A very-low-energy diet intervention during 4 wk was followed by 3 mo of WM; during the WM period, the subjects received a green tea-caffeine mixture (270 mg epigallocatechin gallate + 150 mg caffeine/d) or placebo, both in addition to an adequate protein (AP) diet (50-60 g protein/d) or an HP diet (100-120 g protein/d).. Subjects lost 7.0 +/- 1.6 kg, or 8.2 +/- 2.0%, body weight (P < 0.001). During the WM phase, WM, resting energy expenditure, and fat-free mass (FFM) increased relatively in both the HP groups and in the AP + green tea-caffeine mixture group (P < 0.05), whereas respiratory quotient and body fat mass decreased, all compared with the AP + placebo group. Satiety increased only in both HP groups (P < 0.05). The green tea-caffeine mixture was only effective with the AP diet.. The green tea-caffeine mixture, as well as the HP diet, improved WM independently through thermogenesis, fat oxidation, sparing FFM, and, for the HP diet, satiety; a possible synergistic effect failed to appear.

Topics: Adolescent; Adult; Appetite; Blood Glucose; Body Composition; Body Weight; Caffeine; Catechin; Dietary Proteins; Fatty Acids, Nonesterified; Female; Glycerol; Humans; Insulin; Leptin; Male; Middle Aged; Tea; Thermogenesis; Triglycerides; Weight Loss; Young Adult

Adipose tissue is an active endocrine organ that secretes signaling molecules involved in the regulation of insulin sensitivity, food intake and inflammation. Apelin is a peptide secreted by adipose tissue that has been shown to modulate cardiovascular tone in animals. The aim of this study was to measure abdominal fat, blood pressure and circulating apelin, adiponectin, leptin, ghrelin, TNF-alpha and IL-6 levels in patients with the metabolic syndrome after a diet-induced weight loss.. 35 obese individuals with the metabolic syndrome underwent an 8-week very-low-calorie diet (VLCD) and a 6-month weight maintenance period (WM) with 120mg orlistat or placebo administered 3 times daily. VLCD and WM (-15.1+/-1.0kg) decreased mean arterial pressure (MAP), insulin, leptin, triglycerides and visceral and subcutaneous adipose tissue. Moreover, adiponectin increased in response to the weight loss. However, the overall changes in plasma apelin, TNF-alpha and IL-6 were non-significant. A correlation between plasma apelin and TNF-alpha was observed at baseline (0.41, p<0.05), and the minor changes in plasma apelin levels were associated with changes in BMI during VLCD and MAP and TNF-alpha during VLCD and WM periods.. Despite reductions in BMI, body adiposity, MAP and enhancement of glucose metabolism and adiponectin in response to weight loss, no significant changes in plasma apelin, TNF-alpha and IL-6 were observed. However, apelin significantly correlated with TNF-alpha and MAP. These results suggest that apelin may not be that strongly correlated with the fat mass as an adipokine like the more abundant adipokines adiponectin or leptin and it might be involved in the regulation of inflammation and cardiovascular tone.

Topics: Adiponectin; Adipose Tissue; Anti-Obesity Agents; Apelin; Biomarkers; Blood Glucose; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Female; Ghrelin; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Interleukin-6; Lactones; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Placebos; Tumor Necrosis Factor-alpha; Weight Loss

To investigate the influence of the Trp64Arg polymorphism in the beta 3-adrenoreceptor gene on adipocytokines, insulin resistance and weight loss secondary to a low fat versus a low carbohydrate diet.. A population of 193 obese patients was analyzed. A nutritional evaluation was performed at the beginning and at the end of a 2-month period in which subjects received 1 of 2 hypocaloric diets.. 172 (89.1%; 44 males, 128 females) subjects had the genotype Trp64/Trp64 (wild-type group) and 21 subjects (10.9%; 4 males, 17 females) had Trp64/Arg64 (mutant-type group). In the wild-type group BMI, weight, fat mass, waist circumference, systolic blood pressure, glucose, triglycerides, insulin, homeostasis model assessment (HOMA) and leptin decreased significantly regardless of the diet. In the mutant-type group, this was the case for BMI, weight, waist circumference, fat mass and leptin levels. Only leptin levels have a significant decrease in the wild-type group (diet I 13.7%, diet II 26.3%, p < 0.05 for both). In the mutant group, leptin decreased as well (diet I 22.5%, diet II 30.1%, p < 0.05 for both).. The metabolic effect of mild weight reduction by 2 hypocaloric diets is greatest in subjects homozygous for the normal beta 3-adrenoreceptor gene. Improvement in glucose, insulin and HOMA is better than in the mutant-type group.

Topics: Adipokines; Anthropometry; Calorimetry, Indirect; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Diet, Reducing; Female; Genotype; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Mutation; Obesity; Polymorphism, Genetic; Prospective Studies; Receptors, Adrenergic, beta-3; Resistin; Weight Loss

This study evaluated the efficacy and safety of lamotrigine in binge-eating disorder (BED) associated with obesity. Fifty-one outpatients with BED by Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria, and obesity were randomized to receive either lamotrigine (N=26) or placebo (N=25) in a 16-week, double-blind, flexible-dose study. Lamotrigine (236+/-150 mg/day) and placebo had similar rates of reduction of weekly frequency of binge-eating episodes and binge days, weight and BMI, measures of eating pathology, obsessive-compulsive symptoms, impulsivity, and global severity of illness. However, lamotrigine was associated with a numerically greater amount of weight loss (1.17 vs. 0.15 kg) and significant reductions in fasting levels of glucose, insulin, and triglycerides. It was also well tolerated and associated with no serious adverse events. As a result of an exceptionally high placebo response, it is likely that for efficacy measures except for body weight and metabolic indices, the study was incapable of detecting potentially clinically important drug-placebo difference.

Topics: Adolescent; Adult; Aged; Antimanic Agents; Body Mass Index; Bulimia Nervosa; Double-Blind Method; Female; Ghrelin; Humans; Impulsive Behavior; Lamotrigine; Leptin; Male; Middle Aged; Obesity; Obsessive-Compulsive Disorder; Psychiatric Status Rating Scales; Treatment Outcome; Triazines; Weight Loss; Young Adult

The objective of the study was to investigate the effect of long-term (3.2 years) weight loss on serum levels of the nontraditional cardiovascular risk factors interleukin (IL)-18 and matrix metalloproteinase (MMP)-9. Moreover, we wanted to assess the significance of the magnitude of the weight loss and evaluate the potential effects of 36 months of treatment with the lipase inhibitor orlistat on these parameters. Sixty-eight abdominally obese subjects completed 8 weeks of very low energy diet (600-800 kcal/d) followed by 36 months of randomized treatment with either orlistat or placebo together with lifestyle intervention. Serum levels of IL-18, MMP-9, and leptin were measured by flowmetric xMAP technology (Luminex, Austin, TX). Changes in the levels of IL-18, MMP-9, and leptin were similar in the orlistat and the placebo group during this study. Thus, the 2 groups were combined for further analysis. A weight loss of 8.4 +/- 8.8 kg from baseline to 3.2 years was associated with significant decreases in IL-18 (P < .001), MMP-9 (P < .01), and leptin (P < .001). Matrix metalloproteinase-9 was, however, significantly increased after 8 weeks of very low energy diet-induced weight loss (P < .05). The long-term changes in IL-18 were significantly associated with changes in body mass index independent of changes in blood pressure and lipids (P < .05). Levels and changes of IL-18 and MMP-9 were significantly positively associated at 3.2 years (P < .01). Long-term changes in leptin were significantly associated with changes in IL-18 (P < .01) at 3.2 years. Diet-induced long-term weight loss decreased IL-18 and MMP-9. The decrease in IL-18 was associated with changes in body mass index independent of changes in blood pressure and lipids, indicating that even a minor weight reduction (>5%) has beneficial effects on nontraditional cardiovascular risk markers. Orlistat treatment had no independent effects on IL-18, MMP-9, or leptin in the present study.

Topics: Adolescent; Adult; Anti-Obesity Agents; Blood Pressure; Cholesterol; Double-Blind Method; Female; Humans; Interleukin-18; Lactones; Leptin; Linear Models; Male; Matrix Metalloproteinase 9; Middle Aged; Obesity; Orlistat; Triglycerides; Waist Circumference; Weight Loss; Young Adult

The aims of this randomized study are to examine the effect of auricular acupuncture on obese women and to explore the relationship between the effect of auricular acupuncture and obesity-related hormone peptides.. Forty-five of 60 obese women aged between 16 and 65 years with body mass index (BMI) >27 kg/m2 and who had not received any other weight control maneuvers within the last 3 months completed this study. The subjects were blinded and randomly divided into groups A and B. Group A (n = 23) received auricular acupuncture, and group B (n = 22) received sham auricular acupuncture using placebo needles, twice each week for 6 weeks. The subjects' body weight (BW), BMI, waist circumference (WC), and obesity-related hormone peptides were measured at the beginning of the study and after 6 weeks of treatment. The data were compared and expressed as percent reductions.. This study found no statistical difference in percent reduction in BW, BMI, and WC between the group receiving 6 weeks of auricular acupuncture treatment and the control group. After treatment, group A revealed a significant increase in ghrelin level and decrease in leptin level. On the other hand, group B, who received sham auricular acupuncture, showed no significant difference in ghrelin and leptin levels.. This study found no statistical difference in percent reduction in BW, BMI, and WC between the two groups. No adverse effects of short-term auricular acupuncture treatment were seen in the study. Auricular acupuncture may have potential benefit on obesity-related hormone peptides.

Topics: Acupuncture Points; Acupuncture, Ear; Adolescent; Adult; Aged; Body Mass Index; Double-Blind Method; Female; Ghrelin; Humans; Leptin; Middle Aged; Obesity; Treatment Outcome; Waist-Hip Ratio; Weight Loss; Women's Health; Young Adult

To examine the effect of an equivalent weight loss, by gastric bypass surgery (GBP) or by diet, on peptide YY3-36 (PYY3-36), ghrelin, and leptin levels and to determine the effect of diabetes status on PYY3-36 levels.. The increased PYY3-36 levels after GBP may be involved in the magnitude and the sustainability of weight loss after surgery.. Of the 30 morbidly obese women who participated in the study, 21 had type 2 diabetes mellitus, and were studied before and after equivalent weight loss of 10 kg by either GBP (n = 11) or by diet (n = 10).. : PYY3-36 levels were higher in obese diabetic as compared with nondiabetic individuals (64.1 +/- 34.4 pg/mL vs. 39.9 +/- 21.1 pg/mL; P < 0.05). PYY3-36 levels increased markedly in response to oral glucose after GBP (peak: 72.3 +/- 20.5 pg/mL-132.7 +/- 49.7 pg/mL; P < 0.001; AUC0-180: 51.5 +/- 23.3 pg/mL x min-91.1 +/- 32.2 pg/mL x min P < 0.001), but not after diet (peak: 85.5 +/- 51.9 pg/mL-84.8 +/- 41.13 pg/mL; P = NS; AUC0-180: 68.3 +/- 38.5 pg/mL x min-61.1 +/- 42.2 pg/mL.min P = NS). Fasting ghrelin levels increased after diet (425 +/- 91 pg/mL-519 +/- 105 pg/mL; P < 0.05), but did not change after GBP (506 +/- 121 pg/mL-482 +/- 196 pg/mL; P = NS).. Diabetes status seems to be a determinant of PYY3-36 levels. GBP, but not diet-induced weight loss, resulted in markedly increased glucose-stimulated PYY3-36 levels. The increase in stimulated PYY3-36 levels after GBP is likely a result of the surgery rather than a secondary outcome of weight loss. Changes in PYY3-36 levels and ghrelin could contribute to the success of GBP in sustaining weight loss.

Topics: Adult; Body Mass Index; Caloric Restriction; Cohort Studies; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Ghrelin; Humans; Leptin; Middle Aged; Obesity, Morbid; Peptide Fragments; Peptide YY; Weight Loss

The neurohormonal control of body weight involves a complex interplay between long-term adiposity signals (e.g., leptin), and short-term satiation signals (e.g., amylin). In diet-induced obese (DIO) rodents, amylin/leptin combination treatment led to marked, synergistic, fat-specific weight loss. To evaluate the weight-lowering effect of combined amylin/leptin agonism (with pramlintide/metreleptin) in human obesity, a 24-week, randomized, double-blind, active-drug-controlled, proof-of-concept study was conducted in obese or overweight subjects (N = 177; 63% female; 39 +/- 8 years; BMI 32.0 +/- 2.1 kg/m(2); 93.3 +/- 13.2 kg; mean +/- s.d.). After a 4-week lead-in period with pramlintide (180 microg b.i.d. for 2 weeks, 360 microg b.i.d. thereafter) and diet (40% calorie deficit), subjects achieving 2-8% weight loss were randomized 1:2:2 to 20 weeks of treatment with metreleptin (5 mg b.i.d.), pramlintide (360 microg b.i.d.), or pramlintide/metreleptin (360 microg/5 mg b.i.d.). Combination treatment with pramlintide/metreleptin led to significantly greater weight loss from enrollment to week 20 (-12.7 +/- 0.9%; least squares mean +/- s.e.) than treatment with pramlintide (-8.4 +/- 0.9%; P < 0.001) or metreleptin (-8.2 +/- 1.3%; P < 0.01) alone (evaluable, N = 93). The greater reduction in body weight was significant as early as week 4, and weight loss continued throughout the study, without evidence of a plateau. The most common adverse events with pramlintide/metreleptin were injection site events and nausea, which were mostly mild to moderate and decreased over time. These results support further development of pramlintide/metreleptin as a novel, integrated neurohormonal approach to obesity pharmacotherapy.

Topics: Adiposity; Adult; Amyloid; Anti-Obesity Agents; Body Mass Index; Combined Modality Therapy; Double-Blind Method; Drug Combinations; Energy Intake; Feeding Behavior; Female; Humans; Islet Amyloid Polypeptide; Leptin; Male; Middle Aged; Obesity; Overweight; Receptors, Islet Amyloid Polypeptide; Receptors, Leptin; Receptors, Peptide; Satiation; Signal Transduction; Time Factors; Treatment Outcome; United States; Weight Loss

Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been reported to be associated with acute coronary syndrome, but its association with obesity has not been elucidated. In this study, we examined whether weight reduction would reduce the serum levels of sLOX-1 in a 12-week weight reduction intervention. Thirty-eight overweight middle-aged men were enrolled in the study, and 32 completed the intervention. The serum level of sLOX-1 was measured using a chemiluminescent enzyme-linked immunoassay. After the intervention program, body weight and the serum level of sLOX-1 decreased significantly (-7.5% +/- 4.8% and -72.1% +/- 35.9%, respectively). Changes in serum levels of sLOX-1 were positively correlated with changes in body weight (r = 0.54, P = .003), body mass index (r = 0.57, P = .001), body fat mass (r = 0.57, P = .002), total cholesterol (r = 0.41, P = .03), subcutaneous fat area (r = 0.50, P = .007), high-sensitivity C-reactive protein (r = 0.56, P = .002), leptin (r = 0.47, P = .01), and tumor necrosis factor-alpha (r = 0.32, P = .09); but no correlations were observed with fasting glycemic-related factors (blood glucose, hemoglobin A(1c), and insulin). Changes in body mass index and high-sensitivity C-reactive protein were selected as significant predictors of sLOX-1 changes by multiple regression analyses. These results suggest that LOX-1 induction may be related to adipocyte metabolism, inflammation, and immune response associated with obesity.

Topics: Adult; Aged; Body Fat Distribution; Body Mass Index; C-Reactive Protein; Diet Therapy; Exercise Therapy; Humans; Insulin; Leptin; Male; Middle Aged; Overweight; Scavenger Receptors, Class E; Tumor Necrosis Factor-alpha; Weight Loss

Leptin resistance is discussed to be involved in the genesis of obesity. Therefore, we hypothesized that leptin levels were negatively associated with degree of weight loss in obese children participating in a lifestyle intervention.. We studied 248 obese children aged 8-14 years attending the "Obeldicks" lifestyle intervention (mean age 10.6+/-0.2 years, 53% female, 48% pubertal, mean body mass index (BMI) 27.8+/-0.3 kg/m2, and mean standard deviation score [SDS]-BMI 2.43+/-0.03). Baseline leptin concentrations were correlated with change of weight status, waist circumference, and percentage body fat, as calculated from skinfold measurements in the one-year intervention by Pearson correlation and multiple linear regression analyses. Furthermore, the relationship between leptin and cardiovascular risk factors (insulin, insulin resistance index HOMA, blood pressure, lipids, and glucose) were analyzed.. A total of 212 children (85%) reduced their overweight, 9 children (4%) dropped out, and 27 children (11%) did not reduce their overweight in the lifestyle intervention "Obeldicks". The mean reduction of SDS-BMI was 0.34+/-0.02. The reduction of SDS-BMI (r=- 0.27), waist circumference (r=- 0.64), and percentage body fat (r=- 0.26) were significantly negatively associated with baseline leptin levels both in univariate analyses and in multiple regression analyses, adjusted to baseline age, BMI, gender and pubertal stage. Baseline leptin concentrations were significantly associated with BMI, pubertal stage, gender, waist circumference, and insulin, but not to any other cardiovascular risk factors in multiple regression analyses.. The finding that baseline leptin concentrations were significantly negatively correlated with the degree of weight loss in a lifestyle intervention supports the hypothesis of leptin resistance in obesity. This study is registered at clinicaltrials.gov (NCT00435734).

Topics: Adiposity; Adolescent; Behavior Therapy; Biomarkers; Body Mass Index; Child; Combined Modality Therapy; Exercise Therapy; Female; Humans; Leptin; Linear Models; Male; Nutrition Therapy; Obesity; Overweight; Risk Assessment; Risk Factors; Risk Reduction Behavior; Skinfold Thickness; Time Factors; Treatment Outcome; Waist Circumference; Weight Loss

Obesity, characterized by hyperleptinemia and hypoghrelinemia, has become a major health problem all over the world and is associated with an increased risk of complications including insulin resistance, hypertension, dyslipidemia, diabetes mellitus and atherosclerosis. The use of the pancreatic lipase inhibitor Orlistat can help seriously overweight people to achieve and maintain weight loss. The aim of our study was to compare the serum leptin and ghrelin levels in obese subjects who take orlistat with those receiving only dietary treatment. Twenty-one obese patients and 10 control subjects participated. The obese patients were divided into two groups; one group (n=11) took orlistat (120 mg, 3 times daily) and received dietary treatment and the other (n=10) only received the dietary treatment. The study lasted twelve weeks. The concentrations of serum ghrelin, leptin, insulin and C-peptide, and routine biochemical parameters, were measured in both groups. The serum ghrelin level was higher in control (183+/-62 fmol/ml) than obese (59+/-30 fmol/ml) subjects while the plasma leptin level was lower in control (8.7+/-12 microg/L) than obese (36.7+/-19 microg/L) subjects (all p<0.001). BMI and the total blood cholesterol, LDL and triglyceride levels fell significantly after both orlistat and dietary treatment in the obese subjects (all p<0.01), and the plasma ghrelin level rose (p<0.01). The leptin level demonstrated the opposite trend in both groups but only the patients taking orlistat showed a significant change (p<0.05).Taken together, these results show that orlistat has no effect on body weight in obese subjects additional to that conferred by a non-pharmacological life-style intervention. We therefore conclude that weight lost rather than type of treatment might be more valuable in obesity.

Topics: Adult; Anti-Obesity Agents; Diet, Reducing; Enzyme Inhibitors; Female; Ghrelin; Humans; Lactones; Leptin; Lipase; Lipids; Male; Middle Aged; Obesity; Orlistat; Weight Loss

Human obesity is characterized by high levels of leptin, and it has been suggested that obese patients may be leptin-resistant.. The aim of our study was to investigate the influence of Lys656Asn polymorphism in the LEPR gene on leptin response secondary to a low fat versus a low carbohydrate diet in obese patients.. A population of 78 obesity patients was enrolled. Before and after 2 months of two diets, a nutritional evaluation was performed.. 52 patients had genotype Lys656/Lys656 (wild group) and 26 patients Lys656/Asn656 or Asn656/Asn656 (mutant group). In the low fat and wild groups, BMI, weight, fat mass, glucose, total cholesterol, triglyceride, insulin, and blood pressure decreased. In mutant type (MT), BMI, weight and fat mass decreased. In wild type (WT) with low carbohydrate diet, BMI, weight, fat mass, waist circumference, waist-to-hip ratio, total cholesterol, and blood pressures decreased. In MT, BMI, weight and fat mass decreased. Only leptin concentrations have a significant decrease in WT with both diets (diet I: 30.3%; p < 0.05) and (diet II: 15.5%; p < 0.05).. In WT patients, the changes in serum leptin concentration due to 2 months' intervention with low fat are higher than with a low carbohydrate diet.

Topics: Asparagine; Body Mass Index; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Female; Genotype; Humans; Leptin; Lysine; Male; Middle Aged; Obesity; Polymorphism, Genetic; Prospective Studies; Receptors, Leptin; Weight Loss

Increased hunger and food intake during attempts to maintain weight loss are a critical problem in clinical management of obesity. To determine whether reduced body weight maintenance is accompanied by leptin-sensitive changes in neural activity in brain regions affecting regulatory and hedonic aspects of energy homeostasis, we examined brain region-specific neural activity elicited by food-related visual cues using functional MRI in 6 inpatient obese subjects. Subjects were assessed at their usual weight and, following stabilization at a 10% reduced body weight, while receiving either twice daily subcutaneous injections of leptin or placebo. Following weight loss, there were predictable changes in neural activity, many of which were reversed by leptin, in brain areas known to be involved in the regulatory, emotional, and cognitive control of food intake. Specifically, following weight loss there were leptin-reversible increases in neural activity in response to visual food cues in the brainstem, culmen, parahippocampal gyrus, inferior and middle frontal gyri, middle temporal gyrus, and lingual gyrus. There were also leptin-reversible decreases in activity in response to food cues in the hypothalamus, cingulate gyrus, and middle frontal gyrus. These data are consistent with a model of the weight-reduced state as one of relative leptin deficiency.

Topics: Adult; Appetite Regulation; Brain; Cerebral Cortex; Echo-Planar Imaging; Female; Food; Humans; Hypothalamus; Injections, Subcutaneous; Leptin; Limbic System; Male; Nervous System Physiological Phenomena; Oxygen; Photic Stimulation; Weight Loss

Nutritional strategies to treat obesity often influence neuroendocrine factors related to body weight control. The present study aimed to investigate whether the inclusion of three fatty fish servings per week within a hypocaloric diet may have specific healthy effects on insulin and leptin functions.. Thirty-two subjects (body mass index = 31.6 +/- 3.5 kg m(-2)) aged 36 +/- 7 years, were assigned to a control or fish-based energy-restricted diet over an 8-week period. Anthropometry, body composition, lipid profile, leptin and insulin values were measured at the start and at the end of the dietary intervention.. Both experimental diets resulted in a similar mean weight loss (control = 5.3 +/- 2.6% versus fish-based = 5.5 +/- 2.5%; P = 0.783). A significant reduction in insulin resistance, as determined by the homeostatic model assessment index (HOMA-IR = insulin x glucose/22.5), was observed after the fish-based intervention. The change in circulating leptin was higher in the fish-based diet compared to the control group. Sixteen percent of the variability in the change of adjusted-leptin could be explained (P = 0.034) by the HOMA index change and the type of diet.. Three servings a week of fatty fish included in an energy-restricted diet appears to be a valid strategy for specifically improving insulin sensitivity and leptin levels in obese subjects, which could involve a better body weight regulation after a nutritional intervention period.

Topics: Adult; Anthropometry; Body Composition; Body Mass Index; Diet, Reducing; Dietary Fats, Unsaturated; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Obesity; Patient Compliance; Seafood; Weight Loss

Obestatin and ghrelin, which are derived from the same gene, are observed to have opposite effects on weight status. The aims of this study were to compare obestatin concentrations in obese and normal-weight children and to analyse the effect of weight loss on obestatin and ghrelin levels.. We examined anthropometrical markers and fasting serum obestatin, ghrelin, leptin, glucose and insulin concentrations in 44 obese children (mean age 11.2 years) before and after participating in a 1-year outpatient obesity intervention programme based on a high-carbohydrate, fat-reduced diet and increased physical activity. Additionally, total ghrelin, obestatin and leptin levels were determined in 22 normal-weight healthy children of similar age, gender and pubertal stage.. Obestatin and leptin concentrations were significantly (P < 0.001) higher and ghrelin concentrations were significantly (P < 0.001) lower in obese children compared to nonobese children. In contrast to the 13 children without weight loss, substantial weight loss in 31 children led to a significant (P = 0.007) increase in obestatin and to a significant (P < 0.05) decrease in leptin and insulin concentrations, while ghrelin concentrations did not change significantly. Children with substantial weight loss demonstrated significantly (P = 0.009) lower obestatin and a tendency (P = 0.064) to higher ghrelin concentrations at baseline. Changes in insulin were not related to changes in ghrelin or obestatin.. The increase in obestatin and the decrease in ghrelin in obese children point towards an adaptation process of weight status. Weight reduction due to a long-term lifestyle intervention resulted in an increase in obestatin levels.

Topics: Adolescent; Child; Fasting; Female; Ghrelin; Humans; Insulin; Leptin; Male; Obesity; Overweight; Weight Loss

This study was undertaken to investigate the effects of green tea on weight reduction in obese Thais. A randomized, controlled trial involving 60 obese subjects (body mass index, BMI > 25 kg/m2) was conducted. All subjects consumed a Thai diet containing 3 meals (8373.6 kJ/day) for 12 weeks, prepared by the Nutritional Unit at Srinagarind Hospital. The diet contained 65% carbohydrates, 15% protein, and 20% fat. Body weight, BMI, body composition, resting energy expenditure, and substrate oxidation were measured at baseline, and during weeks 4, 8, and 12 of the study. Serum levels of leptin and urine VMA were measured at baseline and during the 12th week. Differences over time and between the treatments (green tea or placebo) over time were determined using two-factor ANOVA with repeated measures. In comparing the two groups, differences in weight loss were 2.70, 5.10, and 3.3 kg during the 4th, 8th, and 12th weeks of the study, respectively. At the 8th and 12th weeks of the study, body weight loss was significantly different (P < 0.05). At the 8th week, the difference in resting energy expenditure was 183.38 kJ/day (P < 0.001), the difference in the respiratory quotient was 0.02 (P < 0.05), and no significant differences existed in satiety score, food intake, or physical activity. Urine VMA was significantly different in the 12th week of the study (P < 0.05). We conclude that green tea can reduce body weight in obese Thai subjects by increasing energy expenditure and fat oxidation.

Topics: Adult; Analysis of Variance; Blood Pressure; Body Composition; Body Mass Index; Double-Blind Method; Energy Metabolism; Female; Heart Rate; Humans; Leptin; Male; Middle Aged; Obesity; Pain Measurement; Tea; Thailand; Time Factors; Vanilmandelic Acid; Weight Loss

Biliopancreatic diversion (BPD) restores normal glucose tolerance in a few weeks in morbid obese subjects with type 2 diabetes, improving insulin sensitivity. However, there is less known about the effects of BPD on insulin secretion. We tested the early effects of BPD on insulin secretion in obese subjects with and without type 2 diabetes.. Twenty-one consecutive morbid obese subjects, 9 with type 2 diabetes (T2DM) and 12 with normal fasting glucose (NFG) were evaluated, just before and 1 month after BPD, by measuring body weight (BW), glucose, adipocitokines, homeostasis model assessment of insulin resistance (HOMA-IR), acute insulin response (AIR) to e.v. glucose and the insulinogenic index adjusted for insulin resistance ([DeltaI5/DeltaG5]/HOMA-IR).. Preoperatively, those with T2DM differed from those with NFG in showing higher levels of fasting glucose, reduced AIR (57.9 +/- 29.5 vs. 644.9 +/- 143.1 pmol/l, P < 0.01) and reduced adjusted insulinogenic index (1.0 +/- 0.5 vs. 17.6 +/- 3.9 1/mmol(2), P < 0.001). One month following BPD, in both groups BW was reduced (by approximately 11%), but all subjects were still severely obese; HOMA-IR and leptin decreased significanlty, while high-molecular weight (HMW) adiponectin and adjusted insulinogenic index increased. In the T2DM group, fasting glucose returned to non-diabetic values. AIR did not change in the NFG group, while in the T2DM group it showed a significant increase (from 58.0 +/- 29.5 to 273.8 +/- 47.2 pmol/l, P < 0.01). In the T2DM group, the AIR percentage variation from baseline was significantly related to changes in fasting glucose (r = 0.70, P = 0.02), suggesting an important relationship exists between impaired AIR and hyperglycaemia.. BPD is able to restore AIR in T2DM even just 1 month after surgery. AIR restoration is associated with normalization of fasting glucose concentrations.

Topics: Adiponectin; Adult; Biliopancreatic Diversion; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Insulin Secretion; Leptin; Male; Obesity; Weight Loss

Ghrelin has been proposed to be a regulator of energy balance, and its dysregulation may be important in obesity. The aims of this study were (i) to compare short- and long-term changes in circulating ghrelin concentration after increasing energy expenditure vs. its changes after decreasing energy intake, (ii) to determine factors associated with changes in ghrelin level, and (iii) to assess relationships of ghrelin concentration with metabolic syndrome (MetS) in prepubescent obese children.. Randomized controlled trial.. About 100 obese children aged 7-9 years.. After baseline testing, children were randomly assigned to two interventional groups, either receiving dietary recommendations or engaging in physical training classes for 6 months. Ghrelin, insulin, leptin, fasting blood sugar, lipid profile and anthropometric indexes, as well as energy intake and expenditure were measured.. Of the participants, 92 completed the 6-month trial, and 87 returned for the 1-year follow-up. Except ghrelin level, other biochemical variables had no significant change at 12- vs. 6-month follow-up. In both groups, ghrelin showed a progressive increase in the periods of time with significant reduction of overweight and negative energy balance; while after the end of the trial, when children regained weight, it decreased toward baseline levels. Baseline ghrelin had strong negative correlation with measures of central obesity. The odds of having the MetS were 12% lower in the middle and 37% lower in the highest tertile of ghrelin level. As the number of MetS components increased, there was a progressive decrease in ghrelin and quantitative insulin sensitivity check index (QUICKI), with a progressive increase in serum insulin, HOMA-R and leptin levels.. Ghrelin increases in response to overweight reduction and negative energy balance resulting from either an exercise intervention or reduction in food intake in prepubescent obese children. It is unlikely to regulate long-term energy balance in young obese children.

Topics: Body Composition; Child; Diet Therapy; Exercise Therapy; Female; Follow-Up Studies; Ghrelin; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Obesity; Puberty; Time Factors; Weight Loss

Our objective was to assess alterations in metabolic risk factors, body weight, fat mass and hormonal parameters following 6 weeks of lifestyle intervention with increased physical activity and either a meal-replacement regimen or a low calorie diet.. 90 overweight or obese subjects (age 47 +/- 7.5 years, weight 90.6 +/- 11.3 kg, BMI 31.5 +/- 2.3) were included in this randomized controlled clinical trial. Subjects in the fat-restricted low-calorie-diet group (LCD-G; n = 30) received 2 dietary counseling sessions and instructions on how to increase physical activity. Subjects in the meal-replacement-diet group (MRD-G; n = 60) received the same lifestyle education and were instructed to replace 2 daily meals by a low-calorie high soy-protein drink.. Subjects in the MRD-G lost significantly more weight (6.4 vs. 3.1 kg, p < 0.01) and fat mass (5.1 vs. 2.8 kg, p < 0.01) than the LCD-G. Most metabolic risk parameters were reduced in both the MRD-G and the LCD-G; however, subjects in the MRD-G showed a higher reduction in waist circumference (6.1 vs. 1.8 cm, p < 0.01) and a larger decrease in triglycerides (-19.6 vs. +12.5 mg/dl, p < 0.01). The prevalence of the metabolic syndrome was reduced in subjects in the MRD-G only (-12%, p < 0.05) compared to an unchanged risk score in the LCD-G. The reductions in leptin (18.2 vs. 6.97 ng/ml) and insulin (4.92 vs. 0.58 microU/ml) were only significant in the MRD-G (p < 0.01).. Our data suggest that even over a short period of time, a meal-replacement diet is more effective in reducing metabolic risk factors, insulin, and leptin, and in improving anthropometric measures than a fat-restricted low-calorie diet.

Topics: Blood Glucose; Body Composition; Body Mass Index; Diet, Reducing; Energy Metabolism; Exercise; Female; Food, Formulated; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Soybean Proteins; Weight Loss

Obese patients have high plasma leptin concentrations that do not induce the expected responses on weight regulation, suggesting a leptin resistance in obesity. Elevated leptin levels are also thought to be related to a high sympathetic nervous system (SNS) activity. This effect could be preserved, lowered, or even abolished in obesity. We planned to investigate the possible association in a longitudinal study. Ninety-five normotensive healthy women, aged 40.4 +/- 11.4 years and body mass index of 33.2 +/- 2.3 kg/m(2), were studied. Baseline leptin, fat mass, and heart rate variability were measured and included in a 6-month longitudinal study. Body composition was measured by dual-energy x-ray absorption. Time domain heart rate variability, QT dynamicity, and spectral components on ambulatory electrocardiographs were analyzed. Dietary advice was given by a dietitian to the patient (maximum caloric reduction of 30%), and subjects were randomized in 3 treatment groups: sibutramine 10 mg, sibutramine 20 mg, or placebo. At baseline, low frequencies (LF) and the LF-high frequencies (HF) ratio, mainly related to the SNS, were negatively correlated to leptin concentration (r = -0.30, P = .002 and r = -0.36, P < .001) and to the leptin-fat mass ratio (r = -0.28, P = .004 and r = - 0.33, P = .0007), thus explaining 38% of the LF variance and 33% of the LF/HF variance. Diastolic blood pressure was also negatively correlated to leptin concentrations (-0.20, P = .04) and to the leptin-fat mass ratio (-0.22, P = .022). In contrast, no consistent correlations between leptin and the time domain components related to vagal activity were observed. At 6 months, after completion of the weight loss program, LF significantly decreased (-7.7% +/- 7.9%, P < .001), whereas HF was higher than the initial value (+20% +/- 5.2%). The leptin-fat mass ratio remained negatively correlated to the LF (r = -0.34, P = .030) and to LF/HF (r = -0.35, P = .021) values, explaining 21% of the LF variation. None of the pairwise comparisons between the 2 sibutramine groups and the placebo group were statistically significant for heart rate variability. High leptin concentration is associated with low indexes of cardiac SNS activity and with a lower diastolic blood pressure in normotensive obese women. Our results imply therefore that the relationship between leptin and the autonomic nervous system is disturbed in normotensive obese subjects.

Topics: Adult; Appetite Depressants; Blood Pressure; Body Composition; Cyclobutanes; Female; Heart Rate; Humans; Leptin; Middle Aged; Obesity; Regression Analysis; Sympathetic Nervous System; Weight Loss

Adiponectin increases insulin sensitivity, protects arterial walls against atherosclerosis, and regulates glucose metabolism, and is decreased in obese, insulin resistant, and type 2 diabetic patients. Adiponectin circulates in plasma as high, medium, and low molecular weight forms (HMW, MMW, and LMW). The HMW form was suggested to be closely associated with insulin sensitivity. This study investigated whether diet-induced changes in insulin sensitivity were associated with changes in adiponectin multimeric complexes.. Twenty obese women with highest and twenty obese women with lowest diet induced changes in insulin sensitivity (responders and non-responders respectively), matched for weight loss (body mass index (BMI)=34.5 (s.d. 2.9) resp. 36.5 kg/m(2) (s.d. 4.0) for responders and non-responders), were selected from 292 women who underwent a 10-week low-caloric diet (LCD; 600 kcal/d less than energy requirements). Plasma HMW, MMW, and LMW forms of adiponectin were quantified using Western blot method.. LCD induced comparable weight reduction in responders and non-responders by 8.2 and 7.6 kg. Homeostasis model assessment insulin resistance index decreased by 48.1% in responders and remained unchanged in non-responders. Total plasma adiponectin and the quantity of HMW and MMW remained unchanged in both groups, while LMW increased by 16.3% in non-responders. No differences between both groups were observed at baseline and after the study. Total plasma adiponectin, MMW, and LMW were negatively associated with fasting insulin levels at baseline.. No differences in total plasma adiponectin, HMW, MMW, and LMW forms were observed between responders and non-responders following 10-week LCD, suggesting that adiponectin is not a major determinant of weight loss-induced improvements in insulin sensitivity.

Topics: Adiponectin; Body Weights and Measures; Caloric Restriction; Diet, Fat-Restricted; Dimerization; Europe; Female; Humans; Insulin Resistance; Leptin; Lipids; Molecular Weight; Obesity; Weight Loss

To investigate cross-sectional and longitudinal relationships among exercise, sleep, ghrelin and leptin.. We randomly assigned 173 post-menopausal sedentary overweight (body mass index >or=24.0 kg/m(2) and >33% body fat) women aged 50-75 years living in western Washington State to either a facility- and home-based moderate-intensity physical activity intervention or a stretching control group. Fasting plasma ghrelin, leptin, measured height, weight and self-reported sleep were assessed at baseline and 12 months.. There were no consistent cross-sectional patterns between self-reported sleep measures and ghrelin or leptin at baseline. The weight loss differences between exercisers and stretchers were greater for those who slept less at follow-up than at baseline compared to those whose sleep duration did not change (-3.2 kg, 95% confidence interval (CI) -5.8, -0.5). Improvements in sleep quality were associated with significantly greater differences between exercisers and stretchers for ghrelin increases (improved vs same sleep quality: +115 pg/ml, 95% CI +25, +206) and leptin decreases (improved vs worsened sleep quality: -5.7 ng/ml, 95% CI -9.5, -1.5).. There was only limited evidence that changes in sleep duration or quality modified exercise-induced changes in weight, ghrelin or leptin. Moreover, the observed differences were not in the directions hypothesized. Future longitudinal studies including population-based samples using objective measures of sleep and long follow-up may help to clarify these relationships.

Topics: Aged; Body Mass Index; Cross-Sectional Studies; Exercise Therapy; Female; Ghrelin; Humans; Leptin; Longitudinal Studies; Middle Aged; Obesity; Peptide Hormones; Sleep; Weight Loss

Obese subjects have functional growth hormone deficiency (GHD). Recombinant human GH (rhGH) treatment of pituitary GHD improves serum levels of leptin, adiponectin and C-reactive protein (CRP). This study was undertaken to determine whether these rhGH-induced changes occur in obese subjects during rhGH supplementation.. Randomized double-blind placebo-controlled trial of low-dose rhGH (200 microg/day for the first month, then 400 microg/day for men and 600 microg/day for women thereafter) or placebo supplementation as an adjuvant to a standard weight loss program.. Forty healthy obese subjects, 28 premenopausal menstruating women (35+/-7 SD years) and 12 men (37+/-6 years).. Body weight, BMI, body composition (assessed by dual energy X-ray absorptiometry [DEXA]), and serum levels of glucose, insulin, IGF-I, IGFBP-3, insulin resistance index (homeostasis modal assessment [HOMA]), leptin, CRP and adiponectin were performed at baseline and at 6 months.. For similar entry BMI values, women when compared with men had higher percent body fat (BF) (43.5+/-4.6% vs. 29.8+/-4.0%, p<0.001), higher leptin levels (16.9+/-8.4 microg/L vs. 4.2+/-3.0 microg/L, p<0.001), and higher CRP levels (13.8+/-16.8 mg/L vs. 2.4+/-3.2mg/L, p=0.04). Serum levels of leptin and CRP, but not adiponectin, correlated significantly with BF in both sexes. Recombinant human GH treatment increased levels of IGF-I Z-Score between baseline and 6 months (from -0.7+/-0.9 SD to 0.1+/-1.1 SD, p=0.01) and modestly decreased BF (from 38.4+/-7.8% to 35.6+/-7.5%, p=0.046). Despite increased IGF-I, there were no differences between rhGH and placebo with regard to changes in leptin, CRP, or adiponectin.. It is concluded that in obesity, although rhGH treatment significantly increases IGF-I and modestly reduces body fat, the lack of significant changes in serum leptin, adiponectin or CRP levels suggests that rhGH treatment does not have a significant effect on these serum markers of adiposity.

Topics: Adiponectin; C-Reactive Protein; Combined Modality Therapy; Double-Blind Method; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Leptin; Obesity; Placebos; Recombinant Proteins; Weight Loss

The aim of the study was to investigate the effects of energy restriction with or without pegylated recombinant leptin (PEG-leptin) treatment on ghrelin, adiponectin, insulin and glucose concentrations. A randomized double-blind placebo-controlled trial was performed in 24 moderately overweight/obese men. PEG-leptin or placebo was administered weekly for 6 weeks, combined with a restricted energy intake of 2.1 MJ/d. At days 1, 25, and 46 a blood sample was taken and body-weight (BW) was measured. Days 1-25 was named phase 1, and days 25-46 phase 2. During phase 1 the rate of BW loss was significantly higher in the PEG-leptin compared to the placebo group (0.38+/-0.07 vs 0.32+/-0.06 kg/d, p<0.05). The rate of BW loss during phase 2 was 0.24+/-0.08 and 0.18+/-0.09 kg/d, respectively (p=0.07). In both groups the rate of BW loss during phase 1 was significantly higher than during phase 2 (p<0.001). Energy balance (EB) was significantly more negative during phase 1 than during phase 2 in both groups (p<0.0005). During phase 1 insulin, glucose and adiponectin decreased significantly in both groups. Adiponectin and ghrelin concentrations changed in the opposite direction between phase 1 and phase 2 (p<0.05). Initial BW loss due to a considerable negative EB induced decreased ghrelin, adiponectin, insulin and glucose levels. However, when EB became less negative and the rate of BW loss decreased, these changes were reversed for adiponectin and ghrelin. The PEG-leptin injections did not have an effect on the changes in insulin, glucose and adiponectin, but had an effect on the changes in ghrelin concentrations.

Topics: Adiponectin; Adolescent; Adult; Analysis of Variance; Blood Glucose; Caloric Restriction; Double-Blind Method; Energy Metabolism; Ghrelin; Humans; Insulin; Leptin; Male; Matched-Pair Analysis; Obesity; Peptide Hormones; Polyethylene Glycols; Recombinant Proteins; Weight Loss

The aim of the present study was to examine the effect of exercise training on adipokines, inflammatory markers, and oxidative stress in overweight children. Nineteen overweight children were randomly assigned to an aerobic exercise training or sedentary control group for 8 weeks. Measurements included peak oxygen uptake (V o(2)max), body weight and composition, adipokines (C-reactive protein, interleukin 6, tumor necrosis factor alpha, adiponectin, leptin, and resistin), and oxidative stress (8-isoprostane). There were no differences between groups for change in body weight or composition over the 8 weeks. Exercise training improved V o(2)max (exercise group, 1.64 +/- 0.13 to 1.85 +/- 0.17L/min vs control group, 1.83 +/- 0.12 to 1.60 +/- 0.13 L/min, P < .05) but did not change any of the measured adipokines or the marker of systemic oxidative stress, 8-isoprostane. These data suggest that in the absence of weight loss, exercise training alone does not improve the adipokine profile or levels of oxidative stress in overweight children.

Topics: C-Reactive Protein; Child; Exercise; Female; Humans; Immunohistochemistry; Interleukin-6; Leptin; Male; Overweight; Oxidative Stress; Oxygen Consumption; Tumor Necrosis Factor-alpha; Weight Loss

Carbohydrate-restricted diets have been shown to enhance satiation- and other homeostatic-signaling pathways controlling food intake and energy balance, which may serve to reduce the incidence of obesity and metabolic syndrome. This study was designed as a correlational, observational investigation of the effects of a carbohydrate-restricted diet on weight loss and body fat reduction and associated changes in circulating leptin, insulin, ghrelin, and cholecystokinin (CCK) concentrations in overweight/obese patients (4 men and 16 women) with metabolic syndrome. Subjects received clinical instruction on the initiation and maintenance of the commercial South Beach Diet, consisting of 2 phases: Phase I (initial 2 wk of the study) and Phase II (remaining 10 wk). Participants showed a decrease (P < 0.05) in body weight (93.5 +/- 3.6 kg vs. 88.3 +/- 3.4 kg), BMI (33.9 +/- 1.3 kg/m(2) vs. 32.0 +/- 1.3 kg/m(2)), waist circumference (112.8 +/- 2.8 cm vs. 107.7 +/- 3.0 cm), and total percent body fat (40.2 +/- 1.5% vs. 39.2 +/- 1.5%) by study completion. Plasma fasting insulin and leptin concentrations decreased significantly from baseline concentrations (139.1 +/- 12.2 pmol/L and 44.1 +/- 4.5 microg/L, respectively) by the end of Phase I (98.6 +/- 2.6 pmol/L and 33.3 +/- 4.1 microg/L, respectively). Plasma fasting ghrelin concentrations significantly increased from baseline (836.7 +/- 66.7 ng/L) by Phase II (939.9 +/- 56.8 ng/L). The postprandial increase in plasma CCK concentrations (difference in plasma CCK concentrations from fasting to postprandial) after Phase I (2.4 +/- 0.3 pmol/L) and Phase II (2.5 +/- 0.4 pmol/L) was significantly greater than the postprandial increase at baseline (1.1 +/- 0.5 pmol/L). Collectively, these results suggest that in patients with metabolic syndrome, improved adiposity signaling and increased postprandial CCK concentrations may act together as a possible compensatory control mechanism to maintain low intakes and facilitate weight loss, despite an increase in fasting ghrelin concentrations and subjective measures of hunger.

Topics: Adiposity; Adult; Diet; Dietary Carbohydrates; Dietary Proteins; Eating; Female; Gastrointestinal Tract; Ghrelin; Humans; Insulin; Leptin; Male; Middle Aged; Nutritional Physiological Phenomena; Peptide Hormones; Peptides; Signal Transduction; Weight Loss

Forty-four patients with the metabolic syndrome were placed on a reduced-calorie and reduced-fat regimen to lose weight throughout a 56-week period. The patients were treated in a crossover fashion with placebo and the angiotensin-converting enzyme inhibitor quinapril for 24 weeks each. The study measured endothelial-dependent flow-mediated dilation plus serum obesity markers of adiponectin and leptin. Metabolic parameters improved after 56 weeks. Serum adiponectin level increased by 18% (P<.05 vs baseline) and serum leptin level decreased by 16% with placebo (P<.05 vs baseline). These findings were potentiated further in the quinapril group. In comparison with baseline, flow-mediated dilation was increased by 13% in the placebo group (P=.055 vs baseline) and by 43% in the quinapril group (P<.001 vs baseline and placebo). These findings suggest that weight loss therapy improves endothelial function and markers of obesity. These results are potentiated with quinapril and are independent of changes in metabolic parameters.

Topics: Adiponectin; Adult; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Double-Blind Method; Endothelium, Vascular; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Prognosis; Quinapril; Tetrahydroisoquinolines; Vasodilation; Weight Loss

Obese individuals are frequently hyperleptinemic and insulin resistant. Chronic exercise is associated with improvements in plasma leptin level and insulin sensitivity; however, little is known about the acute effect of exercise on these parameters. The aim of this study was to evaluate the acute effect of aerobic exercise on plasma leptin and insulin sensitivity in obese women with stable caloric intake.. Twenty-three obese women (age 41.2 +/- 10.3 years, body mass index 40.7 +/- 6.7 kg/m2) were included to the study. All subjects were admitted to an exercise program (45-minute walking sessions at 60-80% of maximum heart rate) every day except weekends for four weeks (total 20 exercise sessions). Insulin resistance was evaluated by HOMA model. Plasma glucose, insulin and leptin levels were determined at baseline and at the end of the first, seventh, and twentieth exercise session.. Baseline and at the end of the first, seventh, and twentieth exercise session plasma leptin levels were 59.1 +/- 20.1, 58.5 +/- 21.0, 53.4 +/- 21.9, and 51.2 +/- 20.5 ng/ml and HOMA-r were 2.75 +/- 1.47, 1.77 +/- 0.71, 1.73 +/- 0.89, 1.62 +/- 0. 70, respectively. Compared to baseline, at the end of the seventh (p = 0.021) and twentieth exercise session (p = 0.003), plasma leptin levels were significantly low. Plasma leptin level did not change significantly at the end of the first exercise session (p > 0.05). At the end of the first exercise session (p = 0.005), end of the seventh (p = 0.003) and twentieth exercise session (p = 0.007) HOMA-r was lower than baseline. There was no correlation between weight loss during exercise period and the change of leptin, and HOMA-r. Fasting plasma glucose, insulin and leptin levels were determined at baseline and at the end of the first, seventh, and twentieth exercise session.. Our study suggests that acute exercise decreases insulin resistance at the first exercise session with no effect on leptin levels. Significant leptin decrement was evident at the first week and lasted during the entire four weeks exercise session.

Topics: Adult; Blood Glucose; Energy Intake; Exercise Therapy; Female; Humans; Insulin; Insulin Resistance; Leptin; Middle Aged; Obesity; Time Factors; Weight Loss

The effect of ingestion of green tea (GT) extract along with a low-energy diet (LED) on health-related blood parameters, and the relationships among changes in metabolic parameters and phases of weight loss were assessed. A double-blind, placebo-controlled, parallel design was used. 46 female subjects (BMI 27.7+/-1.8 kg/m(2)) were fed in energy balance from days 1 to 3, followed by a LED with GT (n=23) or placebo (PLAC, n=23) from days 4 to 87. The LED-period consisted of a phase 1 of 4 weeks (days 4-32) followed by a phase 2 of 8 weeks (days 32-87). Body composition and fasting blood samples were determined on days 4, 32 and 87. No significant differences were observed between the blood parameters of the PLAC and GT group. In phase 1 compared to phase 2 the rate of weight loss was 0.09+/-0.05 kg/day vs. 0.03+/-0.03 kg/day (p<0.001); Fat free mass (FFM) was 21% of weight loss in phase 1 vs. 7% in phase 2 (ns). Surprisingly, favourable changes in free fatty acids, triacylglycerol, beta-hydroxybutyrate, glucose and total cholesterol in phase 1 were reversed in phase 2 (p<0.01). Taken together, GT supplementation during a LED had no effect on health-related blood parameters. Initial improvements in several blood measures at day 32 were reversed by day 87, despite continued weight loss. Modest weight loss improved HDL cholesterol and blood pressure.

Topics: Administration, Oral; Adult; Analysis of Variance; Anthropometry; Body Mass Index; Body Weight; Camellia sinensis; Catechin; Double-Blind Method; Energy Intake; Energy Metabolism; Female; Humans; Leptin; Middle Aged; Plant Extracts; Reference Values; Regression Analysis; Tea; Triglycerides; Weight Loss

This study aims to investigate the role of changes in leptin and beta endorphin (BE) levels in weight loss following electroacupuncture (EA) application in obesity treatment. EA was applied to 20 females who were 41.45 +/- 4.71 years old and had a body mass index of 36.00 +/- 2.66; and a diet program was applied to 20 females who were 42.30 +/- 4.35 years old and had a body mass index of 34.90 +/- 3.21. There was a 4.5% weight reduction in the patients with EA application, whereas patients on diet restriction had a 3.1% weight reduction. A decrease of loss of body weight was observed in the EA group (p < 0.000) when compared against the diet restricted group. A decrease of serum leptin levels (p < 0.000) and an increase in the serum BE (p < 0.05) levels were observed in the EA group compared to the diet restricted group. In this study, reduced serum leptin levels paralleling to weight loss were observed in the EA group. Furthermore, it is thought that in the EA applied group, increasing serum BE level probably enhanced the lipolitic activity which may have caused weight loss in obese people by mobilizing energy stores. It may be considered that the EA application with diet restriction in obesity treatment is more effective than the diet restriction alone.

Topics: Adult; beta-Endorphin; Body Mass Index; Diet, Reducing; Electroacupuncture; Female; Humans; Leptin; Obesity; Weight Loss

Many formulas have been proposed to calculate insulin sensitivity and studies have shown their effectiveness. However, few studies have been done to compare formulas.. Seventy-two obese participants completed a randomized weight loss study. Weight loss, change in body fat and change in waist circumference were used as surrogates for change in insulin sensitivity. Correlation coefficients were calculated for each of these surrogates with proposed formulas for insulin sensitivity found in the literature.. The change in insulin sensitivity using the formula proposed by McAuley (exp(2.63-0.28 x ln(fasting insulin)-0.31 x ln(fasting triglyceride in mmol/l)) showed the greatest correlation with weight loss (r=-0.59, p<0.0001) and was statistically superior to change in fasting glucose, fasting insulin and homeostasis model assessment (HOMA).. The insulin sensitivity formula proposed by McAuley provides an accurate means of detecting insulin resistance. As it does not require a glucose tolerance test, it is also easier and less expensive than most other formulas. Use of this formula rather than fasting glucose would detect many more patients with insulin resistance who are at risk for subsequent diabetes and other complications.

Topics: Adipose Tissue; Blood Glucose; Body Mass Index; Body Size; Body Weight; C-Reactive Protein; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Obesity; Weight Loss

Decreased levels of GH and total IGF-I have been reported in obesity. It has been hypothesized that increased free (biologically active) IGF-I levels generated from IGF-binding protein (IGFBP) protease activity could be the mechanism for the low GH release in dieting obese subjects. However, no published data exist on free IGF-I levels, acid labile subunit (ALS), or IGFBP protease activity in relation to GH release during a hypocaloric diet. The main purpose of this study was to determine free IGF-I, ALS, IGFBPs-1-4, and IGFBPs-1-3 protease activity in relation to 24-h GH release before and after a short-term very low-calorie diet (VLCD).. Six obese subjects before weight loss, five after an average weight loss of 36.1 kg, and five age-and sex-matched lean controls underwent a 4-day VLCD. All subjects were studied on two occasions, once during normal basic diet and again during the last day of the VLCD (1.6 MJ).. Free IGF-I was determined by a non-competitive immunoradiometric assay.. Free IGF-I levels decreased in concert with increased ALS and unchanged blunted GH release after a VLCD in the obese subjects. IGFBPs-1-3 proteolytic activity was found to be unchanged by hypocaloric diet in all groups.. We conclude that free IGF-I decreases after a short-term hypocaloric diet in obese subjects with no concomitant change in 24-h GH release. Circulating free IGF-I per se cannot be the main mechanism of the attenuated GH release in dieting obese subjects.

Topics: Adult; Body Mass Index; Body Weight; Caloric Restriction; Carrier Proteins; Diet, Reducing; Endopeptidases; Female; Glycoproteins; Human Growth Hormone; Humans; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Protein 4; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Male; Obesity; Protein Denaturation; Thinness; Time Factors; Weight Loss

Ghrelin is postulated to be an orexigenic signal that promotes weight regain after weight loss (WL). However, it is not known whether this putative effect of ghrelin is sustained after weight stabilization. The objective of this study was to investigate the relationship of plasma ghrelin concentrations to active WL and weight maintenance in obese subjects.. This study was a randomized clinical trial, with a 12-month follow-up period. Obese Mexican-American women matched for age and BMI were randomized to a 12-month WL program (n = 25) or no intervention (controls, n = 23). Interventions included diet, exercise, and orlistat. Body weight and fasting ghrelin, leptin, insulin, and glucose concentrations were measured at baseline and 6 and 12 months.. The WL group lost 8.5% of body weight after 6 months and maintained the new weight for the next 6 months. Ghrelin concentrations increased significantly at 6 months but returned to baseline at 12 months. Baseline ghrelin concentrations were directly related to the degree of WL achieved after 12 months. Controls experienced no change in BMI or ghrelin levels. There were no associations between plasma ghrelin and leptin or insulin concentrations.. Consistent with previous results, ghrelin rises in response to WL, perhaps as a counterregulatory mechanism. However, the present results indicate that ghrelin concentrations return to baseline with sustained weight maintenance, suggesting that its effects are unlikely to regulate long-term energy balance. Baseline ghrelin concentrations are related to the degree of WL that can be achieved by active weight reduction.

Topics: Adult; Analysis of Variance; Body Mass Index; Body Weight; Female; Follow-Up Studies; Ghrelin; Health Promotion; Humans; Insulin; Insulin Resistance; Leptin; Mexican Americans; Middle Aged; Obesity; Peptide Hormones; Radioimmunoassay; Time Factors; Waist-Hip Ratio; Weight Loss

Strength training is usually associated with a reduction in fat mass and with muscle hypertrophy. The aim of the present study was to examine whether the serum free leptin index (FLI), measured by the molar excess of soluble leptin receptor (sOB-R) over leptin, is increased by 6 weeks of strength training. Eighteen male, physical education students were randomly assigned to two groups: a strength-training (n 12) and a control group (n 6). Body composition (lean body mass and body fat) determined by dual-energy X-ray absorptiometry (DXA), muscle performance and leptin, sOB-R, total testosterone and free testosterone concentrations were determined before and after training. Fat mass was reduced by 1 kg with strength training (P<0.05). Lean body mass of trained extremities was increased by 3% (P<0.05), while the concentration of free testosterone in serum was reduced by 17% (P<0.05) after training. However, despite the reduction in fat mass and free testosterone, serum leptin concentration was not significantly affected by strength training, even after accounting for the differences in body fat. By contrast, for a given fat mass, the sOB-R was increased by 13% (P<0.05) at the end of the strength-training programme, although the molar excess of sOB-R over leptin remained unchanged. Therefore, the quantity of free leptin available to bind to the target tissues was not significantly affected by the short strength-training programme, which elicited a 7% reduction in fat mass.

Topics: Absorptiometry, Photon; Adiposity; Adult; Analysis of Variance; Humans; Leptin; Male; Muscle Strength; Physical Education and Training; Receptors, Cell Surface; Receptors, Leptin; Testosterone; Time Factors; Weight Loss

We investigated the effects of different weight loss protocols on leptin levels in obese females with the aim of addressing the leptin resistance which has been found to be an aggravating factor in obesity. Twenty-four obese females enrolled to one of three 12-week weight loss protocols: orlistat-induced weight loss (OWL, n=8), exercise-induced weight loss (EWL, n=8) and orlistat plus exercise-induced weight loss (OEWL, n=8). Serum leptin levels were measured in duplicate by radioimmunoassay. There were significant reductions (P<0.01) in body weight and fat mass after the 12 week period in all groups: -11.4+/-0.5 kg and -9.8+/-0.5 kg (OEWL), -8.3+/-0.8 kg and -5.7+/-0.9 kg (OWL), -8.9+/-1.2 kg and -7.4+/-1.2 kg (EWL), respectively. Serum leptin levels were also decreased markedly in all groups: -59.2 % (OEWL1), -37.8 % (OWL) and -48.6 % (EWL) (P<0.01 all). In addition, there were marked decreases in leptin levels for each kilogram of fat mass after the 12 week period: -48.2+/-7.2 % (OEWL), -27.8+/-4.8 % (OWL) and -39.3+/-4.3 % (EWL) (P<0.01 all). Decreases in serum leptin levels expressed per kilogram of fat mass were significantly higher in the OEWL group compared to the OWL group (P=0.03). Consequently, an exercise training program in adjunct to pharmacotherapy provides higher weight reduction and fat mass loss in obesity treatment. It also seems to have further beneficial effects on leptin resistance, as indicated by decreases in leptin levels expressed per kilogram of fat mass.

Topics: Adult; Anti-Obesity Agents; Combined Modality Therapy; Exercise Therapy; Female; Humans; Lactones; Leptin; Obesity; Orlistat; Treatment Outcome; Weight Loss

The objective of this study is to assess the effects of sibutramine on body weight, body fat distribution, insulin resistance, plasma leptin, lipid profile and blood pressure profiles in hypertensive obese patients.. Eighty-six central obese hypertensive patients (BMI = 39 +/- 5 kg/m(2), 84% of women, 48 +/- 8.5 years old) were placed on a hypocaloric diet and placebo therapy for 4 weeks. They were then randomized to receive sibutramine (10 mg) or placebo for 24 weeks. Both, before therapy and at the end of the study, the waist and hip circumferences were measured and the waist/hip ratio (WHR) was calculated; abdominal ultrasonography was performed in order to estimate the amount of subcutaneous fat (SF) and visceral fat (VF), and the visceral/subcutaneous ratio. Beyond HOMA-r, another insulin resistance index (IRIp) was calculated by means of the formula: peak of blood glucose after oral glucose load x plasma insulin level/10(4). Fasting plasma leptin and lipid levels were also determined.. Sibutramine induced greater weight reduction than placebo (6.7 vs. 2.5%, p < 0.001). Reductions in WHR (0.97 +/- 0.08 vs. 0.94 +/- 0.07, p < 0.01), IRIp (0.11 +/- 0.07 vs. 0.09 +/- 0.06 mmol mu/l(2)) and VF (6.4 +/- 2.4-6.0 +/- 2.4 cm, p < 0.01) were observed only with sibutramine. Plasma leptin decreased with placebo (24 +/- 15 vs. 18 +/- 10 UI/l, p < 0.01), but not with sibutramine (18.8 +/- 8.4 vs. 18.2 +/- 13.2 UI/l). No clinically significant change in lipid profile was observed in both groups. Moreover, office and 24-h blood pressure values did not change during placebo or sibutramine therapy, whereas a significant increase in office heart rate, from 78.3 +/- 7.3-82 +/- 7.9 b.p.m., p = 0.02, was observed with sibutramine.. Sibutramine therapy induced greater body weight loss than placebo in hypertensive obese patients. This was associated with WHR reduction, decreases in VF and insulin resistance. The maintenance of leptin levels during sibutramine therapy may be important to avoid weight recovery, although this finding must be confirmed by other prospective studies.

Topics: Adult; Antihypertensive Agents; Appetite Depressants; Chi-Square Distribution; Cyclobutanes; Drug Therapy, Combination; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin Resistance; Leptin; Lipids; Male; Middle Aged; Obesity; Waist-Hip Ratio; Weight Loss

Previous clinical studies concerning the impact of body weight loss on single plasma TSH concentration measurements or the TSH response to TRH in obese humans have shown variable results.. The objective of this study was to investigate the effect of weight loss induced by caloric restriction on diurnal TSH concentrations and secretion in obese humans.. This was a clinical, prospective, crossover study.. The study was conducted at the Clinical Research Center of Leiden University Medical Center.. Eleven obese premenopausal women (body mass index, 33.3 +/- 0.7 kg/m2) were studied.. The study intervention was weight loss (50% reduction overweight by caloric restriction).. Twenty-four-hour plasma TSH concentrations (10-min intervals) and the 24-h TSH secretion rate, calculated by a waveform-independent deconvolution technique (Pulse), were determined.. The 24-h TSH secretion rate was significantly higher in obese women than in normal weight controls, and weight loss was accompanied by diminished TSH release (before weight loss, 43.4 +/- 6.4 mU/liter.24 h; after weight loss, 34.4 +/- 5.9 mU/liter.24 h; P = 0.02). Circulating free T3 levels decreased after weight loss from 4.3 +/- 0.19 to 3.8 +/- 0.14 pmol/liter (P = 0.04). Differences in 24-h TSH release correlated positively with the decline of circulating leptin (r2 = 0.62; P < 0.01).. Elevated TSH secretion in obese women is significantly reduced by diet-induced weight loss. Among various physiological cues, leptin may be involved in this phenomenon. The decreases in TSH and free T3 may blunt energy expenditure in response to long-term calorie restriction, thereby frustrating weight loss attempts of obese individuals.

Topics: Adult; Caloric Restriction; Circadian Rhythm; Cross-Over Studies; Diet, Reducing; Female; Humans; Leptin; Obesity; Prospective Studies; Thyrotropin; Weight Loss

This study investigated the effect of subcutaneously administered oxyntomodulin on body weight in healthy overweight and obese volunteers. Participants self-administered saline or oxyntomodulin subcutaneously in a randomized, double-blind, parallel-group protocol. Injections were self-administered for 4 weeks, three times daily, 30 min before each meal. The volunteers were asked to maintain their regular diet and level of physical exercise during the study period. Subjects' body weight, energy intake, and levels of adipose hormones were assessed at the start and end of the study. Body weight was reduced by 2.3 +/- 0.4 kg in the treatment group over the study period compared with 0.5 +/- 0.5 kg in the control group (P = 0.0106). On average, the treatment group had an additional 0.45-kg weight loss per week. The treatment group demonstrated a reduction in leptin and an increase in adiponectin. Energy intake by the treatment group was significantly reduced by 170 +/- 37 kcal (25 +/- 5%) at the initial study meal (P = 0.0007) and by 250 +/- 63 kcal (35 +/- 9%) at the final study meal (P = 0.0023), with no change in subjective food palatability. Oxyntomodulin treatment resulted in weight loss and a change in the levels of adipose hormones consistent with a loss of adipose tissue. The anorectic effect was maintained over the 4-week period. Oxyntomodulin represents a potential therapy for obesity.

Topics: Adiponectin; Adipose Tissue; Adolescent; Adult; Blood Glucose; Body Composition; Diet; Double-Blind Method; Eating; Energy Intake; Exercise; Female; Glucagon-Like Peptides; Humans; Injections, Subcutaneous; Insulin; Intercellular Signaling Peptides and Proteins; Kinetics; Leptin; Male; Middle Aged; Obesity; Oxyntomodulin; Self Administration; Weight Loss

Investigation of the effect of a green tea-caffeine mixture on weight maintenance after body weight loss in moderately obese subjects in relation to habitual caffeine intake.. A randomized placebo-controlled double blind parallel trial in 76 overweight and moderately obese subjects, (BMI, 27.5 +/- 2.7 kg/m2) matched for sex, age, BMI, height, body mass, and habitual caffeine intake was conducted. A very low energy diet intervention during 4 weeks was followed by 3 months of weight maintenance (WM); during the WM period, the subjects received a green tea-caffeine mixture (270 mg epigallocatechin gallate + 150 mg caffeine per day) or placebo.. Subjects lost 5.9 +/-1.8 (SD) kg (7.0 +/- 2.1%) of body weight (p < 0.001). At baseline, satiety was positively, and in women, leptin was inversely, related to subjects' habitual caffeine consumption (p < 0.01). High caffeine consumers reduced weight, fat mass, and waist circumference more than low caffeine consumers; resting energy expenditure was reduced less and respiratory quotient was reduced more during weight loss (p < 0.01). In the low caffeine consumers, during WM, green tea still reduced body weight, waist, respiratory quotient and body fat, whereas resting energy expenditure was increased compared with a restoration of these variables with placebo (p < 0.01). In the high caffeine consumers, no effects of the green tea-caffeine mixture were observed during WM.. High caffeine intake was associated with weight loss through thermogenesis and fat oxidation and with suppressed leptin in women. In habitual low caffeine consumers, the green tea-caffeine mixture improved WM, partly through thermogenesis and fat oxidation.

Topics: Adipose Tissue; Adolescent; Adult; Basal Metabolism; Caffeine; Diet, Reducing; Double-Blind Method; Energy Metabolism; Feeding Behavior; Female; Humans; Leptin; Male; Middle Aged; Obesity; Oxidation-Reduction; Oxygen Consumption; Satiation; Tea; Thermogenesis; Weight Loss

The aim of this study was to evaluate the effect on body weight and safety of subcutaneously administered recombinant leptin in obese adults and to evaluate whether the timing of recombinant leptin administration influences efficacy.. A randomized, double-blind, placebo-controlled, multicentre study was designed, comprising of a 3-week dietary lead-in followed by a 12-week leptin or placebo treatment period. A total of 284 overweight and obese (body mass index 27-37.0 kg/m(2)) predominantly white (98%) women (66%) and men (34%) with a mean (+/-s.d.) 46.8+/-10.4 years of age were randomized into three treatment groups with three matching placebo groups. Recombinant leptin was administered by subcutaneous injection [10 mg/morning, 10 mg/evening or 20 mg/day (10 mg twice daily)]. Patients were counselled at baseline to reduce dietary intake by 2,100 kJ/day (500 kcal/day), and dietary advice was reinforced every 2-4 weeks.. No statistically significant change in body weight occurred with recombinant leptin treatment compared with placebo treatment in any treatment group. No clinically significant adverse effects were observed with the exception of an increase in injection-site reactions in patients treated with recombinant leptin (83%) vs. placebo (36%).. Administration of recombinant leptin to an overweight and obese population, in addition to a mildly energy-restricted diet, was not efficacious in terms of weight loss at the doses and schedules studied. The hypothesis that nocturnal administration of recombinant leptin might have a specific effect on weight loss was not supported.

Topics: Adult; Anti-Obesity Agents; Double-Blind Method; Drug Administration Schedule; Energy Intake; Female; Humans; Hunger; Injections, Subcutaneous; Leptin; Lipids; Male; Middle Aged; Obesity; Weight Loss

A traditional Korean herbal formula (KH), which is based on Taeumjowi-tang, is currently the most widely used herbal formula in Korea. In this study, KH was administered to obese children for 30 days, and was found to be clinically safe and effective. The subjects were children admitted to hospital to be treated for obesity with relative body weights (%RBW) of 20% or more. Originally, there were 31 subjects, but nine dropped out during the experiment. There were eight girls and 14 boys, whose average age was 11.00 +/- 2.62 years, average weight was 53.37 +/- 17.29 kg, and average period (30-day amount) of KH dosage was 51.18 +/- 22.58 days. The short-term effects of KH on obese children were the reduction of their BMI from 24.34 +/- 3.10 to 23.26 +/- 3.00 kg/m2, of %RBW from 34.41 +/- 10.90 to 25.94 +/- 11.18% (p < 0.01), of body fat mass from 17.99 +/- 5.37 to 16.50 +/- 4.82 kg, and of body fat from 34.16 +/- 3.75 to 32.08 +/- 3.15% (p < 0.01). Concerning anthropometrical measurements, abdominal skin-fold decreased from 26.16 +/- 9.08 to 22.90 +/- 8.35 mm, as did subscapular skin-fold from 20.86 +/- 5.20 to 18.46 +/- 5.31 mm (p < 0.01). In terms of serum lipid levels, which are indices of heart disease, their total cholesterol decreased from 195.38 +/- 31.39 to 183.25 +/- 33.27 mg/dl, the arteriosclerosis index from 4.100 +/- 0.81 to 3.84 +/- 0.64 mg/dl (p < 0.05), and serum leptin level from 14.91 +/- 6.59 to 12.24 +/- 4.98 ng/ml (p < 0.01). Concerning the safety of KH, there were no significant changes in the subjects' livers, hearts, or kidneys. Nor were there any short-term signs of clinically serious side effects or withdrawal symptoms observed. The short-term effects of KH on obese children are weight loss and a decrease in obesity.

Topics: Adolescent; Body Fat Distribution; Body Mass Index; Child; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Female; Humans; Korea; Leptin; Lipids; Male; Obesity; Phytotherapy; Skinfold Thickness; Thyrotropin; Weight Loss

Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been shown to reduce body weight and improve cardiovascular risk factors in obese patients. The Rimonabant in Obesity-Lipids (RIO-Lipids) study examined the effects of rimonabant on metabolic risk factors, including adiponectin levels, in high-risk patients who are overweight or obese and have dyslipidemia.. We randomly assigned 1036 overweight or obese patients (body-mass index [the weight in kilograms divided by the square of the height in meters], 27 to 40) with untreated dyslipidemia (triglyceride levels >1.69 to 7.90 mmol per liter, or a ratio of cholesterol to high-density lipoprotein [HDL] cholesterol of >4.5 among women and >5 among men) to double-blinded therapy with either placebo or rimonabant at a dose of 5 mg or 20 mg daily for 12 months in addition to a hypocaloric diet.. The rates of completion of the study were 62.6 percent, 60.3 percent, and 63.9 percent in the placebo group, the group receiving 5 mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively. The most frequent adverse events resulting in discontinuation of the drug were depression, anxiety, and nausea. As compared with placebo, rimonabant at a dose of 20 mg was associated with a significant (P<0.001) mean weight loss (repeated-measures method, -6.7+/-0.5 kg, and last-observation-carried-forward analyses, -5.4+/-0.4 kg), reduction in waist circumference (repeated-measures method, -5.8+/-0.5 cm, and last-observation-carried-forward analyses, -4.7+/-0.5 cm), increase in HDL cholesterol (repeated-measures method, +10.0+/-1.6 percent, and last-observation-carried-forward analyses, +8.1+/-1.5 percent), and reduction in triglycerides (repeated-measures method, -13.0+/-3.5 percent, and last-observation-carried-forward analyses, -12.4+/-3.2 percent). Rimonabant at a dose of 20 mg also resulted in an increase in plasma adiponectin levels (repeated-measures method, 57.7 percent, and last-observation-carried-forward analyses, 46.2 percent; P<0.001), for a change that was partly independent of weight loss alone.. Selective CB1-receptor blockade with rimonabant significantly reduces body weight and waist circumference and improves the profile of several metabolic risk factors in high-risk patients who are overweight or obese and have an atherogenic dyslipidemia.

Topics: Adiponectin; Adult; Aged; Anti-Obesity Agents; Blood Glucose; Cannabinoid Receptor Antagonists; Cholesterol; Double-Blind Method; Dyslipidemias; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Piperidines; Pyrazoles; Rimonabant; Risk Factors; Triglycerides; Weight Loss

To determine the effects of a weight loss program, including dietary modifications, increased physical activity and dietary supplement (L-carnitine or placebo) on anthropometrics, leptin, insulin, the metabolic syndrome (MS) and insulin resistance in overweight /obese premenopausal women.. Participants consumed a hypocaloric diet; 30% protein, 30% fat and 40% carbohydrate in addition to increasing number of steps/day. Carnitine supplementation followed a randomized double blind protocol. Protocol lasted for 10 weeks. Seventy subjects (35 in the control and 35 in the carnitine group) completed the intervention. Anthropometrics, plasma insulin and leptin concentrations and body composition were measured. The number of subjects with the MetSyn and insulin resistance, were assessed at baseline and post-intervention.. Because there were no significant differences between the carnitine and the placebo groups for all measured parameters, participants were grouped together for all analysis. Subjects decreased total energy (-26.6%, p < 0.01) and energy from carbohydrate (-17.3%, p < 0.01) and increased energy from protein by 67% (p < 0.01) and number of steps/day (42.6%, p < 0.01). Body weight (-4.6%, p < 0.001), body mass index (-4.5%, p < 0.01), waist circumference (-6.5%, p < 0.01), total fat mass (-1.7%, p < 0.01), trunk fat mass (-2.0%, p < 0.01), insulin (- 17.9%, p < 0.01) and leptin (-5.9%, p < 0.05) decreased after the intervention. Ten of 19 participants with insulin resistance became insulin sensitive and 7 of 8 participants with the MetSyn no longer had the syndrome after the intervention.. Moderate increases in physical activity and a hypocaloric/high protein diet resulted in multiple beneficial effects on body anthropometrics and insulin sensitivity. Realistic dietary and physical activity goals must be the focus of intervention strategies for overweight and obese individuals.

Topics: Adult; Anthropometry; Body Composition; Carnitine; Diet, Reducing; Dietary Proteins; Dietary Supplements; Double-Blind Method; Exercise; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Obesity; Premenopause; Vitamin B Complex; Weight Loss

A relatively high percentage of energy intake as protein has been shown to increase satiety and decrease energy efficiency during overfeeding.. To investigate whether addition of protein may improve weight maintenance by preventing or limiting weight regain after weight loss of 5-10% in moderately obese subjects.. In a randomized parallel design, 148 male and female subjects (age 44.2 +/- 10.1 y; body mass index (BMI) 29.5 +/- 2.5 kg/m2; body fat 37.2 +/- 5.0%) followed a very low-energy diet (2.1 MJ/day) during 4 weeks. For subsequent 3 months weight-maintenance assessment, they were stratified according to age, BMI, body weight, restrained eating, and resting energy expenditure (REE), and randomized over two groups. Both groups visited the University with the same frequency, receiving the same counseling on demand by the dietitian. One group (n=73) received 48.2 g/day additional protein to their diet. Measurements at baseline, after weight loss, and after 3 months weight maintenance were body weight, body composition, metabolic measurements, appetite profile, eating attitude, and relevant blood parameters.. Changes in body mass, waist circumference, REE, respiratory quotient (RQ), total energy expenditure (TEE), dietary restraint, fasting blood-glucose, insulin, triacylglycerol, leptin, beta-hydroxybutyrate, glycerol, and free fatty acids were significant during weight loss and did not differ between groups. During weight maintenance, the 'additional-protein group' showed in comparison to the nonadditional-protein group 18 vs 15 en% protein intake, a 50% lower body weight regain only consisting of fat-free mass, a 50% decreased energy efficiency, increased satiety while energy intake did not differ, and a lower increase in triacylglycerol and in leptin; REE, RQ, TEE, and increases in other blood parameters measured did not differ.. A 20% higher protein intake, that is, 18% of energy vs 15% of energy during weight maintenance after weight loss, resulted in a 50% lower body weight regain, only consisting of fat-free mass, and related to increased satiety and decreased energy efficiency.

Topics: Adolescent; Adult; Attitude to Health; Body Mass Index; Body Weight; Dietary Proteins; Energy Metabolism; Exercise; Female; Humans; Leptin; Male; Middle Aged; Obesity; Satiation; Secondary Prevention; Weight Loss

To compare the efficacy of different weight loss regimens on body weight loss and metabolic improvement in breast cancer survivors.. Forty-eight obese breast cancer survivors were randomly divided into four groups and were followed for 1 year: 1) the Control group (subjects did not receive specific nutrition counseling); 2) the Weight Watchers group (subjects were given free coupons to attend weekly Weight Watchers meetings); 3) the Individualized group (a registered dietitian provided one-on-one nutritional counseling); and 4) the Comprehensive group (subjects received individualized dietary counseling and free coupons for the weekly Weight Watchers meetings). At baseline and 3-, 6-, and 12-month data collection visits, a fasting blood sample was obtained for assays. A three-day dietary record was kept during the week before these visits and dietary intake was analyzed.. Subjects in the three intervention groups lost weight (Control: 1.1 +/- 1.7 kg; Weight Watchers: -2.7 +/- 2.1 kg; Individualized: -8.0 +/- 1.9 kg; Comprehensive: -9.5 +/- 2.7 kg) and percentage body fat, but only the Individualized and Comprehensive groups had significant losses. Subjects in the Comprehensive group showed the most improvement in cholesterol levels and had reductions in blood leptin levels.. Because insulin resistance and high blood leptin levels are associated with breast cancer, losing weight to improve these parameters may reduce the risk of recurrence. Only subjects in the Comprehensive group showed significant reductions in body weight and fat, energy intake, and leptin levels. For breast cancer survivors, different weight loss strategies should be considered to assist them in losing weight.

Topics: Adolescent; Adult; Aged; Breast Neoplasms; Counseling; Diet, Reducing; Dietetics; Female; Humans; Insulin; Leptin; Middle Aged; Neoplasm Recurrence, Local; Obesity; Self-Help Groups; Survivors; Weight Loss

The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels.. A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking.. At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C.. The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.

Topics: Adult; Appetite; Biomarkers; Body Mass Index; Chromium; Citrates; Double-Blind Method; Drug Therapy, Combination; Fats; Female; Gymnema sylvestre; Humans; Leptin; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Middle Aged; Niacin; Obesity; Plant Extracts; Weight Loss

It has been suggested that elevated leptin levels underlie the low grade proinflammatory state in human obesity. We reasoned that if elevated leptin levels are an important factor in the proinflammatory state in obesity, then exogenous leptin administration during weight loss should counteract the concurrent beneficial effects of weight loss on the proinflammatory state. We therefore determined whether long-acting pegylated recombinant leptin (PEG-OB) prevents the decrease in cellular and humoral inflammation parameters during a very low calorie diet in healthy overweight young men. Except for B cells, PEG-OB treatment did not influence the decline in total leukocyte count and mononuclear subfractions during the diet. Weight loss decreased the humoral inflammation parameters TNFalpha, tissue plasminogen activator, and von Willebrand factor (P < 0.05), but in combination with PEG-OB treatment, a significant decrease was shown for inflammation markers as a whole (P < 0.014) and that of the individual parameters tissue plasminogen activator, von Willebrand factor, plasminogen activator inhibitor type 1, and intercellular adhesion molecule-1 (P < 0.05). The increase in C-reactive protein levels (P < 0.05) was the sole indication for a humoral proinflammatory action of leptin. Although PEG-OB treatment significantly increased weight loss (P < 0.03), the data do not support a proinflammatory role of leptin in human obesity.

Topics: Adult; Diet, Reducing; Humans; Inflammation; Injections, Subcutaneous; Intercellular Adhesion Molecule-1; Leptin; Leukocyte Count; Male; Monocytes; Obesity; Plasminogen Activator Inhibitor 1; Polyethylene Glycols; Recombinant Proteins; Tissue Plasminogen Activator; Tumor Necrosis Factor-alpha; von Willebrand Factor; Weight Loss

Increasing 1,25-dihydroxyvitamin D in response to low-calcium diets stimulates adipocyte Ca2+ influx and, as a consequence, stimulates lipogenesis, suppresses lipolysis, and increases lipid accumulation, whereas increasing dietary calcium inhibits these effects and markedly accelerates fat loss in mice subjected to caloric restriction. Our objective was to determine the effects of increasing dietary calcium in the face of caloric restriction in humans.. We performed a randomized, placebo-controlled trial in 32 obese adults. Patients were maintained for 24 weeks on balanced deficit diets (500 kcal/d deficit) and randomized to a standard diet (400 to 500 mg of dietary calcium/d supplemented with placebo), a high-calcium diet (standard diet supplemented with 800 mg of calcium/d), or high-dairy diet (1200 to 1300 mg of dietary calcium/d supplemented with placebo).. Patients assigned to the standard diet lost 6.4 +/- 2.5% of their body weight, which was increased by 26% (to 8.6 +/- 1.1%) on the high-calcium diet and 70% (to 10.9 +/- 1.6% of body weight) on the high-dairy diet (p < 0.01). Fat loss was similarly augmented by the high-calcium and high-dairy diets, by 38% and 64%, respectively (p < 0.01). Moreover, fat loss from the trunk region represented 19.0 +/- 7.9% of total fat loss on the low-calcium diet, and this fraction was increased to 50.1 +/- 6.4% and 66.2 +/- 3.0% on the high-calcium and high-dairy diets, respectively (p < 0.001).. Increasing dietary calcium significantly augmented weight and fat loss secondary to caloric restriction and increased the percentage of fat lost from the trunk region, whereas dairy products exerted a substantially greater effect.

Topics: Adipose Tissue; Adolescent; Adult; Blood Glucose; Body Composition; Calcium, Dietary; Dairy Products; Diet, Reducing; Energy Intake; Female; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Placebos; Weight Loss

It has repeatedly been shown that high serum leptin levels at target weight ensue from therapeutically induced weight gain in patients with anorexia nervosa (AN). It was hypothesized that elevated leptin levels may be an important factor underlying the difficulties of maintaining the target-weight in AN patients after re-feeding. The aim of this study was to examine if serum leptin levels at discharge from inpatient treatment predict renewed weight loss within 2 months after discharge and upon a 1 yr follow-up. Univariate variance analysis (ANOVA) revealed that 60% (cor. R2=0.60, P=0.002) of the variance in the BMI standard deviation score (BMI-SDS) 2 months after discharge was explained by the model consisting of the independent variables lg10 leptin levels at discharge (P=0.019) and at admission (P=0.069) and BMI-SDS at admission (P=0.002) and delta BMI between admission and discharge (P=0.047). Similarly, 60% (cor. R2=0.60, P=0.005) of the variance in BMI-SDS 1 yr after discharge was explained by lg10 leptin levels at discharge (P=0.046) and at admission (P=0.052) and BMI-SDS at admission (P=0.008) and 2 months after discharge (P=0.007) and delta BMI between admission and discharge (P=0.933). Patients with a poor outcome after 1 yr (n=9, ANCOVA, group: descriptive P=0.041), but not recovered patients (n=9, P=0.649), had lg10 leptin levels at discharge higher than those of controls when adjusted for BMI and % body fat at discharge. In conclusion, high serum leptin levels at discharge from inpatient treatment may indicate a risk for renewed weight loss and an unfavorable 1 yr outcome in AN.

Topics: Adolescent; Anorexia Nervosa; Body Mass Index; Female; Follow-Up Studies; Humans; Inpatients; Leptin; Patient Discharge; Predictive Value of Tests; Recurrence; Reference Values; Treatment Failure; Weight Gain; Weight Loss

Adiponectin influences insulin sensitivity and lipid metabolism, but it is not clear whether these effects are correlated with fat mass or distribution. We studied the relationship between plasma adiponectin and leptin levels, insulin sensitivity, and serum lipids by a cross-sectional study (n = 242 subjects) and by an intervention study (95 of 242) to evaluate the effect of weight loss (WL). Considering all subjects both together and subdivided into nonobese (n = 107) and obese (n = 135) groups, plasma adiponectin, but not plasma leptin, was significantly (P < 0.01) correlated with insulin sensitivity [homeostasis model assessment of insulin-resistance index (HOMAIR), insulin sensitivity index (ISI) at oral glucose tolerance test, and clamp in 115 of 242 individuals], high-density lipoprotein cholesterol, and triglycerides. These relationships were still significant (P < 0.01) after adjusting for age, gender, body mass index (BMI), and ISI. After WL (-16.8 +/- 0.8%), plasma adiponectin increased, and plasma leptin decreased (P < 0.0001 for both). Their changes (Delta) were significantly correlated with Delta-BMI (P < 0.05 for both). Delta-Adiponectin, but not Delta-leptin, significantly (P < 0.001) correlated with Delta-high-density lipoprotein cholesterol and Delta-triglycerides; these correlations were independent of age, gender, Delta-BMI, and Delta-ISI (P < 0.005). In conclusion, both cross-sectional and intervention studies indicate that plasma adiponectin level correlates with serum lipids independently of fat mass. The intervention study also suggests that adiponectin increase after WL is correlated with serum lipid improvement independently of insulin sensitivity changes.

Topics: Adiponectin; Adipose Tissue; Adolescent; Adult; Age Factors; Aged; Body Composition; Body Weight; Cholesterol, HDL; Cross-Sectional Studies; Female; Glucose Clamp Technique; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Obesity; Proteins; Triglycerides; Weight Loss

Weight reduction after gastric bypass surgery has been attributed to a decrease of the orexigenic peptide ghrelin, which may be regulated by insulin and leptin. This study examined effects of long-term weight loss after laparoscopical adjustable gastric banding on plasma ghrelin and leptin concentrations and their relationship with insulin action. Severely obese patients (15 women, three men, 36 +/- 12 yr) underwent clinical examinations every 3 months and modified oral glucose tolerance tests to assess parameters of insulin sensitivity and secretion every 6 months. After surgery, body mass index fell from 45.3 +/- 5.3 to 37.2 +/- 5.3 and 33.6 +/- 5.5 kg/m(2) at 6 and 12 months, respectively (P < 0.0001). This was associated with lower (P < 0.0001) plasma glucose, insulin, insulin resistance, waist circumference, and blood pressure. Plasma leptin decreased from 27.6 +/- 9.5 to 17.7 +/- 9.8 (P = 0.0005) and 12.7 +/- 5.1 ng/ml (P < 0.0001). Plasma ghrelin was comparable before and at 6 months (234 +/- 53; 232 +/- 53 pmol/liter) but increased at 12 months (261 +/- 72 pmol/liter; P = 0.05 vs. 6 months). At 6 and 12 months, ghrelin levels correlated negatively with fasting plasma insulin levels and hepatic insulin extraction but not with body mass or insulin action. In conclusion, prolonged weight loss results in a rise of fasting ghrelin concentrations that correlates with fasting insulin concentrations but not improvement of insulin sensitivity.

Topics: Adult; Body Mass Index; Female; Gastric Bypass; Gastroplasty; Ghrelin; Glucose Intolerance; Glucose Tolerance Test; Hormones; Humans; Insulin; Insulin Resistance; Leptin; Liver; Longitudinal Studies; Male; Middle Aged; Obesity, Morbid; Osmolar Concentration; Peptide Hormones; Postoperative Period; Weight Loss

To determine the effect of weight loss and exercise interventions on serum leptin and to investigate the relationship of physical function and osteoarthritis (OA) severity with serum leptin in older overweight and obese adults with knee OA. In addition, the study examined if serum leptin predicts weight loss.. Longitudinal, controlled clinical trial of weight loss and exercise interventions.. Community dwelling, older, overweight and obese adults (n=316; >60 years of age; body mass index >/=28.0 kg m(-2)) with symptomatic knee OA and self-reported difficulty in performing selected physical activities were recruited.. Participants were randomized into one of four groups for the 18-month study duration: Healthy Lifestyle Controls, Dietary Weight Loss (Diet), Exercise Training (Exercise), and a combination of Dietary Weight Loss and Exercise Training (Diet+Exercise). The weight loss goal for the two Diet groups was 5% from baseline at 18 months. Participants in the Exercise groups were trained for 3 days week(-1), 60 min day(-1).. Body weight, body mass index, serum leptin, physical function, and OA severity were measured at baseline, 6 months, and 18 months.. Diet and Diet+Exercise groups lost 5.3 and 6.1% of their weight, respectively, at 18 months with the Exercise group losing 2.9%. There was a significant main effect of weight loss on serum leptin with a decrease in serum leptin averaged across the 6- and 18-month time points for the Diet and Diet+Exercise groups compared to the other two groups (beta=0.245; P<0.01). No main effect for exercise training was observed. Serum leptin was related to self-reported physical function. In all participants, a mixed model analysis demonstrated that lower levels of baseline serum leptin predict larger weight loss (beta=-2.779; P=0.048).. Decreases in serum leptin may be one mechanism by which weight loss improves physical function and symptoms in OA patients.

Topics: Aged; Biomarkers; Body Mass Index; Diet, Reducing; Exercise Therapy; Exercise Tolerance; Female; Follow-Up Studies; Humans; Leptin; Logistic Models; Male; Middle Aged; Osteoarthritis, Knee; Weight Loss

Leptin resistance is a hallmark of obesity, but its etiology is unknown, and its clinical measurement is elusive. Leptin-sensitive subjects have normal resting energy expenditure (REE) at a low leptin concentration, while leptin-resistant subjects have a normal REE at a higher leptin concentration; thus, the ratio of REE:Leptin may provide a surrogate index of leptin sensitivity. We examined changes in REE and leptin in a cohort of 17 obese subjects during experimental weight loss therapy with the insulin-suppressive agent octreotide-LAR, 40 mg i.m. q28d for 6 months. Six subjects lost significant weight (>10%) and BMI (>-3 kg/m(2)) with a 34% decline in leptin and a 46% decrease in insulin area under the curve (IAUC) to oral glucose tolerance testing. These subjects maintained their pretreatment REE, and thus exhibited a rise in REE:Leptin, while the other 11 showed minimal changes in each of these parameters. For the entire cohort, the change in IAUC correlated negatively with the change in REE:Leptin. These results suggest that the REE:Leptin ratio, while derivative, may serve as a useful clinical indicator of changes in leptin sensitivity within obese subjects. They also support the possibilities that hyperinsulinemia may be a proximate cause of leptin resistance, and that reduction of insulinemia may promote weight loss by improving leptin sensitivity.

Topics: Adult; Blood Glucose; Body Mass Index; Energy Metabolism; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Leptin; Obesity; Octreotide; Weight Loss

Leptin, a circulating hormone secreted from adipocytes, is an index of adiposity and is reduced by caloric restriction and weight loss. A recent population study suggested that dietary-derived omega3 fatty acids lower leptin levels independent of body fat.. To examine whether dietary fish enhanced the effects of weight loss on serum leptin levels, in 69 overweight, treated hypertensive men and women.. Participants were randomized to a daily fish meal, a weight-reduction regimen, the two regimens combined or a control group for 16 weeks.. A total of 63 individuals completed the study. Weight fell 5.6 +/- 0.8 kg with energy-restriction. Blood pressure (BP) reductions in the combined fish-weight loss group were twice that seen with either intervention alone. At baseline, in all groups combined, serum leptin levels correlated with serum insulin (r = 0.307, P = 0.014), but not with body weight. The greatest change in serum leptin occurred in the fish-weight loss group (control, 0.60 +/- 0.76 ng/ml; fish, 1.20 +/- 0.79 ng/ml; weight loss, -1.40 +/- 1.05 ng/ml; fish-weight loss, -5.08 +/- 1.64 ng/ml). In the fish-weight loss group, the change in serum leptin was predicted by changes in serum insulin (r = 0.488, P = 0.038), 24-h BP (systolic BP (SBP): r = 0.435, P = 0.060; diastolic BP (DBP): r = 0.563, P = 0.018) and 24-h heart rate (0.584, P = 0.028). Using general linear models, there was a significant fish x weight-loss interaction (P = 0.008) on post-intervention serum leptin after adjustment for baseline levels, independent of post-intervention insulin.. A daily fish meal as part of a weight-reducing regimen was more effective than either measure alone at reducing leptin levels. Reductions in leptin may be related to the substantial fall in BP seen with the fish-weight loss program.

Topics: Animals; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Body Weight; Diet; Diet, Reducing; Energy Intake; Fatty Acids; Female; Fishes; Heart Rate; Humans; Hypertension; Insulin; Leptin; Lipids; Male; Middle Aged; Obesity; Phospholipids; Weight Loss

The aim of the study was an attempt to answer following questions: 1. Is extensive, non-pharmacological obesity treatment programme effective and is reduced body weight likely to be maintained in the long term? 2. What is the influence of the programme on some components of metabolic syndrome? 3. What is the effect of the programme on levels of leptin and insulin as indexes of weight reduction effectiveness? An informed consent to participate in the treatment was given by 37 women (GB) aged 19-47 yrs. (mean 36 +/- 7.7); with BMI 36 +/- 4.9 kg/m2. Control group (GK) was composed of 16 women aged 21-40 yrs. A 3-month extensive, ambulatory, non-pharmacological obesity treatment programme was offered to study subjects. Anthropometric, biochemical and hormonal assessment was performed before treatment (0), after 3 months--at the end of treatment (3), and after one year (R). After 3 months a reduction of body weight was observed in 34 persons (92%) whereas in 1 person (2.7%) body weight was stable and in 2 (5.4%) body weight increased. Body weight reduction was accompanied by beneficial changes in metabolic parameters. After one-year follow-up reduced body weight was maintained in 33 persons (89%), however, insulin and leptin levels and HOMA index increased significantly when compared to those observed during active treatment and were comparable with initial values. In the control group a significant increase in BMI, insulin and leptin levels and HOMA index was observed after one-year follow-up.. 1. The extensive, non-pharmacological obesity treatment programme is effective because enables the reduction of body weight by 10% and patients are likely to maintain reduced body weight for one year. 2. The programme brings out metabolic benefits and enables to maintain them after its discontinuance. 3. The rebound increase in leptin and insulin levels after 9 months since active treatment has been discontinued may be an unfavourable prognostic factor in terms of maintenance of reduced body weight and indicates that the programme should be repeated in some patients groups.

Topics: Adult; Ambulatory Care; Body Mass Index; Female; Humans; Insulin; Leptin; Middle Aged; Obesity; Time Factors; Treatment Outcome; Weight Gain; Weight Loss

Increasing evidence suggests that falling leptin concentrations observed during fasting act as a peripheral signal of starvation, which serves to conserve energy in the face of limited reserves. An extension of this hypothesis is that exogenous leptin should affect energy regulation during severe energy restriction.. To explore this hypothesis, we assessed whether elevated leptin concentrations achieved with the use of long-acting pegylated human recombinant leptin [polyethylene glycol-OB protein (PEG-OB)] affected weight loss and changes in body composition, energy expenditure, appetite, and metabolic variables during semistarvation in healthy overweight men.. A randomized, double-blind, placebo-controlled study was executed in overweight men with a mean (+/- SEM) age of 34.8 +/- 1.3 y and body mass index (in kg/m2) of 28.8 +/- 0.5. All subjects received weekly treatment with 80 mg PEG-OB (n = 12) or matching placebo (n = 10) for 46 d while their energy intake was reduced to 2.1 MJ/d by means of a very-low-energy diet. Body composition (hydrodensitometry and deuterium dilution), energy expenditure (ventilated hood), and appetite (visual analogue scales) were evaluated at the start and the end of the study. Metabolic variables were measured throughout the study period.. Compared with placebo treatment, treatment with PEG-OB led to significant (P < 0.03) additional weight loss (14.6 +/- 0.8 compared with 11.8 +/- 0.9 kg) and a reduction in appetite (P < 0.05) after 46 d, but the 2 treatment groups did not differ significantly in changes in body composition, energy expenditure, and metabolic variables.. Our observations support the hypothesis that the decrease in leptin concentrations during starvation increases appetite in humans.

Topics: Adolescent; Adult; Body Composition; Body Mass Index; Diet, Reducing; Double-Blind Method; Energy Intake; Energy Metabolism; Humans; Leptin; Male; Middle Aged; Obesity; Placebos; Polyethylene Glycols; Weight Loss

We examined predictors of weight loss with topiramate, an anticonvulsant associated with weight loss in adults.. In this uncontrolled, prospective clinical trial, topiramate was added to existing anticonvulsants in adults (40 to 110 kg) with partial-onset seizures. Primary measurements were change from baseline weight after 3 months and 1 year in patients completing 1 year of topiramate treatment (N = 38). Physiological and metabolic measures were analyzed for correlation with weight loss during topiramate treatment.. In patients who completed 1 year of topiramate treatment, baseline weight was reduced in 82% at 3 months and in 86% at 1 year. Mean body weight was reduced 3.0 kg (3.9% of baseline) at 3 months and 5.9 kg (7.3%) at 1 year. In obese patients [body mass index (BMI) >/= 30 kg/m(2)], mean weight loss was 4.2 kg (4.3%) at 3 months and 10.9 kg (11.0%) at 1 year. Weight loss was primarily caused by reduction in body fat mass. For all patients, weight loss at 3 months correlated most strongly with reduced caloric intake (p = 0.02). At 1 year, caloric intake had returned to baseline levels; weight loss correlated most strongly with higher baseline BMI (p = 0.0007).. Our results suggest that weight loss occurs in most adults treated with topiramate and is sustained for at least 1 year. Reduced caloric intake may account, in part, for weight loss during early treatment. The pattern of weight loss differs according to baseline BMI, with obese patients experiencing greater weight loss during continued therapy.

Topics: Adult; Anticonvulsants; Blood Glucose; Body Composition; Body Mass Index; Cholesterol; Energy Intake; Epilepsy; Female; Fructose; Glucose Tolerance Test; Humans; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Regression Analysis; Topiramate; Weight Loss

Starvation induces a complex neuroendocrine response in humans thought to have evolved to defend against reduced energy intake. The drop in leptin levels observed during fasting has been implicated as a factor that triggers this adaptive response. To explore this hypothesis, we executed a randomized, double-blind, placebo-controlled study to investigate whether elevated leptin levels using long-acting pegylated human recombinant leptin (PEG-OB) influenced the neuroendocrine responses to semi-starvation in human subjects.. Twenty-four overweight male subjects (mean+/-s.e.m.; 34.8+/-1.3 yrs; 28.8+/-0.5 kg/m(2)) were prescribed a very low energy diet (2.1 MJ/day) to induce a state of semi-starvation for the next 46 days. In addition, all subjects received a weekly treatment of 80 mg PEG-OB or matching placebo. Hormone measurements were performed throughout the study period and included 5-h frequent hormone samplings and 24-h urine collections.. Weekly subcutaneous administration of PEG-OB led to significant additional weight loss (2.8 kg) but it did not reverse the fasting-induced changes in the thyroid, corticotropic, somatotropic axes and sympathetic nervous system activity. However, after adjustment for weight loss, the drop in mean luteinizing hormone levels was attenuated in the PEG-OB group compared with the placebo group.. These results suggest that a reduced level of leptin accompanying food restriction might be a component of the fasting-induced neuroendocrine inhibition of the human reproductive axis.

Topics: Adaptation, Physiological; Adolescent; Adult; Energy Intake; Energy Metabolism; Hormones; Humans; Leptin; Linear Models; Male; Middle Aged; Obesity; Polyethylene Glycols; Recombinant Proteins; Starvation; Weight Loss

To study the impact of a weight-loss program on sex hormones and sexual function among 38 middle-aged obese men (BMI >or=35 kg/m(2)).. A randomized controlled clinical trial was conducted. The treatment group (n = 19) participated in a 4-month weight-loss program including 10 weeks on a very-low-energy diet (VLED) and 17 behavior modification visits. There was no intervention in the control group (n = 19). Both groups were followed for 8 months, i.e., 22 weeks after the active weight loss in the treatment group. The outcome measures (weight, sex hormones, sexual function, leptin, and metabolic variables) were obtained at baseline and at three time-points during follow-up.. The mean weight loss in the treatment group was 21 kg at the end of the 10-week VLED. At the end of follow-up, the maintained weight loss was 17 kg of baseline weight. The control group was weight stable throughout the study. In the treatment group, increases in sex hormone-binding globulin, testosterone, and high-density lipoprotein-cholesterol, as well as decreases in insulin and leptin, were maintained until the end of follow-up, although with VLED, the level of several hormones and metabolic variables improved transiently during the rapid weight loss. There were no significant changes in the questionnaire scores on sexual function in either group.. We conclude that obese men lose weight and increase their serum testosterone level on a weight-loss program with VLED and behavior modification. However, they do not change their sexual function scores.

Topics: Behavior Therapy; Body Mass Index; Cholesterol, HDL; Diet, Reducing; Energy Intake; Gonadal Steroid Hormones; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Orgasm; Penile Erection; Sex Hormone-Binding Globulin; Sexual Behavior; Testosterone; Weight Loss

This study compared the relative effectiveness of two means of energy deficit, food restriction (FR) and increased physical activity (EX), on body weight, body composition and concentrations of serum leptin, insulin, glucose, and lipids in female subjects. Thirteen adult female volunteers participated in a two-phase crossover-treatment study. Each phase involved a 9-day energy deficit period and a 5-day follow up energy repletion period. A 25% energy deficit was achieved by either FR or EX. Baseline values were established prior to phase one. Results showed that FR had greater body weight loss, but less body fat loss compared to EX. FR and EX both reduced serum leptin, insulin, total triacylglycerol, LDL-C and VLDL-C concentrations. However, only EX elevated HDL-C. These effects were reversed during follow up energy repletion. Results suggest that under iso-caloric energy deficit conditions FR is more effective in reducing body weight but EX is more effective in reducing body fat and maintaining lean body mass. EX can lead to a more desirable blood lipid profile than can FR. Thus, it is desirable to include exercise in a weight reduction program.

Topics: Adipose Tissue; Adult; Blood Glucose; Body Composition; Body Mass Index; Cross-Over Studies; Diet, Reducing; Energy Intake; Energy Metabolism; Exercise; Female; Humans; Insulin; Leptin; Lipids; Middle Aged; Weight Loss

To compare the effects of a standard American diet, a traditional low-fat diet, and a low-fat diet containing the fat substitute olestra on risk factors for heart disease and diabetes.. A 9-month, double-blind, randomized, parallel-arm, feeding study comparing three diets: (1). control (33% fat), (2). fat-reduced (FR; 25% fat), and (3). fat-substituted (FS) where olestra replaced 1/3 of dietary fat (33% lipid and 25% digestible fat). Subjects were allowed to adjust their total energy intake as desired, allowing weight to fluctuate.. A total of 37 healthy, obese men (age 36.7+/-1.3 y; body mass index 30.8+/-0.4 kg/m(2)).. Body weight and composition by dual-energy X-ray absorptiometry, blood pressure, serum lipids, lipoproteins, hemostatic factors, glucose, insulin, and leptin at baseline and every 3 months.. The FS group lost 6.27 kg of body weight by 9 months vs 4.0 kg in the control and 1.79 kg in the FR groups. There was a significant diet main effect on cholesterol (P=0.002), low-density lipoprotein cholesterol (P=0.003), and triglycerides (P=0.01), all of which decreased in the FS group but not the other groups by 9 months. Apolipoprotein B (ApoB) increased in the FR and control groups but was unchanged in the FS group (diet main effect P=0.04). High-density lipoprotein (HDL) cholesterol increased in all groups over 9 months (time main effect P=0.0001). Time main effects were also observed for cholesterol, ApoA1, ApoB, Factor VII, diastolic blood pressure, and glucose. After adjustment for % fat loss at 9 months, the effects of diet on change in risk factors remained significant only for triglycerides.. Consumption of a low-fat diet containing olestra for 9 months produced significant improvement in cardiovascular risk factors, an effect largely explained by weight loss. Long-term low-fat diet consumption with or without olestra does not decrease HDL cholesterol.

Topics: Adult; Apolipoproteins; Blood Glucose; Cholesterol; Cholesterol, LDL; Diet, Fat-Restricted; Dietary Fats, Unsaturated; Double-Blind Method; Fat Substitutes; Fatty Acids; Humans; Insulin; Leptin; Male; Obesity; Risk Factors; Sucrose; Triglycerides; Weight Loss

We investigated the effect of an intensive training program on fasting leptin and adiponectin levels.. Sixteen middle-aged men with type 2 diabetes were randomly assigned to either a training or control group. The training program consisted of 8 weeks of supervised endurance exercise (75% VO(2peak), 45 min) twice a week, with intermittent exercise (five 2 min exercises at 85% VO(2peak) separated by 3 min exercises at 50% VO(2peak)) once a week, on an ergocycle.. Training decreased abdominal fat by 44%, increased mid-thigh muscle cross-sectional area by 24%, and improved insulin sensitivity by 58% without significant change in body weight. Compared with controls, no significant variation in leptin or adiponectin levels was observed. However, in the trained group, change in adiponectin correlated with change in body weight (Spearman rank correlation, r(s):-0.76, P=0.03) but not with insulin sensitivity or abdominal adiposity variations.. An 8 week intensive training program inducing a marked reduction in abdominal fat and increase in insulin sensitivity does not affect adiponectin and leptin levels in men with type 2 diabetes.

Topics: Abdomen; Adiponectin; Adipose Tissue; Adult; Diabetes Mellitus, Type 2; Exercise; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Physical Endurance; Proteins; Weight Loss

To examine the effect of dietary restraint during and following pegylated recombinant leptin (PEG-OB protein) treatment in overweight men.. A randomized double-blind placebo-controlled trial in 24 overweight men (BMI: 28.8+/-0.3 kg/m(2); age: 34.8+/-0.9 y). PEG-OB protein (80 mg) or placebo was administered subcutaneously weekly for 6 weeks, combined with a 2.1 MJ/day energy restriction program. Dietary restraint was determined by the Three-Factor Eating Questionnaire before and after treatment, and after 8 weeks follow-up.. During treatment dietary restraint increased, and general hunger, resting energy expenditure and respiratory quotient decreased similarly in the PEG-OB and the placebo group. With PEG-OB treatment, additional weight loss (P<0.03) was observed. During 8 weeks follow-up, body weight increase was larger in the PEG-OB group compared to placebo (P<0.05), and body weight regain was faster. Body weight regain was inversely correlated with the increase in cognitive dietary restraint during treatment (PEG-OB group: r(2)=0.49, P<0.02; placebo group: r(2)=0.60, P=0.01).. Although treatment with PEG-OB protein led to a greater body weight loss relative to placebo, weight maintenance thereafter was mainly supported by dietary restraint, which was more effective in the placebo-treated group, resulting in a slower regain of body weight.

Topics: Adolescent; Adult; Combined Modality Therapy; Diet, Reducing; Double-Blind Method; Follow-Up Studies; Humans; Leptin; Male; Obesity; Polyethylene Glycols; Prospective Studies; Recombinant Proteins; Weight Gain; Weight Loss

Ghrelin, the endogenous ligand of GH-secretagogue receptors, has been implicated in the regulation of feeding behavior and energy balance. Aim of the study was to investigate ghrelin levels in fasting conditions and after a standard meal test in obese subjects before and after a 3-week integrated body weight reduction (BWR) program (consisting of energy-restricted diet, exercise training, psychological counselling and nutritional education). Weight, height, fat mass, fat free mass (by impedentiometry), circulating ghrelin, insulin and leptin levels were evaluated in 10 obese subjects (3 male, 7 female; mean age: 35 +/- 9.3 yr; body mass index BMI: 45.2 +/- 10.6 kg/m2) before and after weight reduction. At baseline, obese subjects showed significantly lower ghrelin levels than controls, which were negatively correlated with BMI, weight, insulin and leptin levels. Fasting ghrelin levels were not modified by standard meal test in obese subjects (from 110.8 +/- 69.7 to 91.8 +/- 70.2 pmol/l p=ns), while a significant reduction was observed in controls (from 352.4 +/- 176.7 to 199.0 +/- 105.2 pmol/l; p<0.01). After a 3-week integrated BWR program obese subjects significantly reduced weight, BMI and leptin levels, while no significant changes were found both in fasting ghrelin and in ghrelin response after the meal. In conclusion, 5% weight loss obtained after a short-term period of integrated BWR program is not sufficient to normalize fasting ghrelin levels nor to restore the normal ghrelin suppression after a meal in severely obese subjects.

Topics: Adult; Area Under Curve; Caloric Restriction; Diet; Energy Metabolism; Fasting; Female; Ghrelin; Health Education; Humans; Insulin; Leptin; Lipids; Male; Middle Aged; Obesity; Peptide Hormones; Physical Fitness; Psychotherapy; Weight Loss

Energy restriction is a common therapeutic approach for weight reduction, but the most effective macronutrient distribution of the hypoenergetic diet as well as the role of the metabolic processes involved require further investigations.. To study the effect of a high protein (HP) hypoenergetic diet compared with a high carbohydrate (HC) hypoenergetic diet on fuel utilisation changes during the weight loss process in obese women.. Eleven obese (BMI>30) women were randomly assigned to a 10w dietary intervention study comparing HP (30% protein) or HC (55% carbohydrate) energy restricted diets providing 30% energy fat content. Substrate utilisation was evaluated by indirect calorimetry. Body weight and composition (Bod Pod) and blood measurements were performed before and after weight loss.. On average, the individuals on the HP dietary group lost 4.4 kg more than those in the HC program (p<0.50), which was mainly due to a fat mass loss (3.7 kg, p<0.05) with no statistical differences in lean body mass reduction. These losses were accompanied by a significant decrease in fasting leptin in the HP group (-52%; P<0.05). On the other hand post-absorptive lipid oxidation decreased in the HC group (-48%) and remained unchanged in the HP groups.. The replacement of some dietary carbohydrate by protein in energy restricted diets, improves weight and fat losses and specifically promotes lipid oxidation in the fasting state, without major different in lean body mass depletion.

Topics: Adipose Tissue; Adult; Body Composition; Diet, Reducing; Dietary Carbohydrates; Dietary Proteins; Energy Metabolism; Female; Humans; Leptin; Middle Aged; Obesity; Treatment Outcome; Weight Loss

One of the main goals of weight reduction in morbidly obese subjects is its benefit on coronary heart disease (CHD) risk. A cross-sectional study was designed to randomly assign 79 morbidly obese subjects (27 men and 52 women; age: 30-45 years) either to a diet protocol (20 kcal per kg fat-free mass (FFM); 55% carbohydrates, 30% fat, and 15% proteins) or to malabsorptive surgery (biliopancreatic diversion). Fatness parameters, measured by dual-energy X-ray absorptiometry, lipid profile, insulin, leptin, sex steroid hormones and sex hormone-binding globulin (SHBG) levels were compared at baseline and 1 year after the beginning of the study. The data showed that plasma SHBG levels, but not testosterone levels, correlated negatively to fasting insulin levels and positively to HDL-cholesterol in both men and women. Total leptin levels were significantly lower (P<0.0001) in post-BPD subjects of both sexes compared to dietary treated obese subjects. The logarithm of plasma leptin correlated significantly and positively with insulin but negatively with SHBG.A step-down regression analysis showed that FFM and SHBG, but not insulin levels, were the most powerful independent variables for predicting HDL-cholesterol levels in morbidly obese patients. The negative relationship between SHBG levels and CHD risk appears to be mediated by a concomitant variation in body fatness. Finally, in obese patients, SHBG levels seem to be an indicator of total adiposity rather than an index of an altered insulin/glucose homeostasis.

Topics: Adult; Biomarkers; Body Composition; Cardiovascular Diseases; Cholesterol, HDL; Cohort Studies; Cross-Sectional Studies; Diet, Fat-Restricted; Female; Gastroplasty; Humans; Incidence; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity, Morbid; Probability; Regression Analysis; Risk Factors; Sensitivity and Specificity; Sex Hormone-Binding Globulin; Weight Loss

The aim of the present study was to evaluate the cerebrospinal fluid (CSF)/serum leptin ratio during pharmacological therapy for obesity with centrally and peripherally acting drugs. Thirty-one obese women (mean age, 32.3 +/- 10 yr; body mass index, 38.2 +/- 5.2 kg/m(2); body fat, 43.3 +/- 5.4%) were studied before and 2 months after a weight loss program consisting of a balanced diet (1200 kcal/d) plus drug therapy. The patients were randomly assigned into three study groups: group I, fenproporex 25 mg/d (n = 10); group II, sibutramine 10 mg/d (n = 10); and group III, orlistat 120 mg tid (n = 11). Body fat, measured by dual-energy x-ray absorptiometry, and serum and CSF concentrations of leptin were examined at baseline and 2 months after therapy. At baseline, clinical and biochemical characteristics of the groups were similar. All of the women lost weight, approximately 7.0% of their initial body weight, and the reduction was not different among the groups. Serum leptin fell significantly after 2 months in all groups, and the decline was proportional to the reduction in body fat, because leptin levels adjusted for body fat did not change after treatment. CSF leptin levels showed a significant decrease after 2 months in all groups, and this decline was higher on group III compared with group I (P = 0.006). After therapy, the CSF/serum leptin ratio did not change in group I (1.57 +/- 0.3 to 1.72 +/- 0.62%) and group II (1.78 +/- 1.01 to 1.69 +/- 1.27%), whereas it declined significantly in group III (1.65 +/- 0.43 to 1.09 +/- 0.47%; P < 0.01), corresponding to a decrease of 33.3 +/- 22.5% for the CSF/serum leptin ratio. The percentage change in group III was significantly different from the positive variation on group I (11.9 +/- 42.1%; P = 0.006) and close to the statistical significance compared with the negative variation seen in group II (-7.6 +/- 27.8%; P = 0.06). Our results showed that the CSF/serum leptin ratio decreased after weight loss in obese women treated during 2 months with orlistat, whereas this ratio did not change in this period of time in obese women treated with fenproporex and sibutramine.

Topics: Adolescent; Adult; Amphetamines; Anti-Obesity Agents; Appetite Depressants; Cyclobutanes; Humans; Lactones; Leptin; Middle Aged; Obesity; Orlistat; Weight Loss

To investigate whether weekly subcutaneous administration of 60 mg of long-acting pegylated human leptin (PEG-OB) for 8 weeks was able to influence weight loss, metabolic profile and inflammatory status of obese subjects on a mildly hypoenergetic diet (deficit: 3.2 MJ/day).. A prospective, randomized, double-blind and placebo-controlled single-center trial.. Twenty-eight healthy, obese subjects (16 women, 12 men; age 22-65 y; body mass index 27.7-38.7 kg/m2).. Bodyweight, metabolic profile (including lipids), C-reactive protein (CRP) and soluble TNF alpha-receptor (sTNF-R) 55 and 75 levels.. At the end of the study no significant differences in the delta or percentage weight loss between the placebo (n = 14) and PEG-OB (n = 14) groups was observed. Also the changes in metabolic profile, CRP, sTNF-R55 and R75 concentrations between the two groups after 8 weeks of treatment did not differ.. Weekly injection of 60 mg PEG-OB did not lead to additional weight loss after 8 weeks of treatment. Furthermore, PEG-OB administration did not affect the changes in metabolic profile and the inflammatory status of obese subjects.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Mass Index; Body Weight; C-Reactive Protein; Double-Blind Method; Female; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Placebos; Prospective Studies; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Weight Loss

Although it is known that plasma leptin concentrations correlate with the amount of adipose tissue in the body, little information is available on the long-term effects on leptin concentrations of changes in diet and exercise.. We wanted to examine whether changes in dietary energy sources and exercise-mediated energy expenditure, alone or in combination, affect plasma leptin concentrations.. In a randomized, 2 x 2 factorial trial, 186 men with metabolic syndrome were divided into 4 groups: diet, exercise, a combination of diet and exercise, and control. Data on dietary intake, physical fitness, and demographics were collected and plasma leptin concentrations were measured before and after a 1-y intervention period.. Plasma leptin concentrations, body mass index, and fat mass decreased in association with long-term reductions in food intake as well as increased physical activity. By adjusting for either body mass index or fat mass, we observed a highly significant reduction in plasma leptin concentration after both the diet and the exercise interventions. There was no interaction between the interventions, suggesting a direct and additive effect of changes in diet and physical activity on plasma leptin concentrations.. Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass.

Topics: Adipose Tissue; Adult; Body Mass Index; Cardiovascular Diseases; Diet; Dietary Fats; Exercise; Health Behavior; Humans; Insulin Resistance; Leptin; Longitudinal Studies; Male; Middle Aged; Risk Factors; Smoking; Weight Loss

Weight reduction reduces bone mineral density (BMD) and increases the risk of osteoporosis.. We investigated whether bone is mobilized in postmenopausal women during energy restriction and whether hormones regulate bone turnover and mass.. Twenty-seven obese postmenopausal women with a mean (+/-SD) age of 55.9 +/- 7.9 y and body mass index (in kg/m(2)) of 33.0 +/- 3.8 completed the 6-mo study. Fourteen women followed a moderate energy-restricted diet (WL group) and 13 control subjects maintained their body weight (WM group). Body weight, bone turnover markers, serum parathyroid hormone (PTH), and dietary intake were measured throughout the study. Total-body BMD, sex hormone binding globulin, leptin, and estrone were measured at baseline and at week 25.. In the WL group, body weight decreased by 10.2 +/- 5.5% (P < 0.001), body fat mass decreased by 18.7 +/- 11.3% (P < 0.001), and total-body BMD decreased by 1.2 +/- 1.2%; these changes were significantly different from those in the WM group (P < 0.05). Serial measurements showed chronically elevated rates of bone resorption and formation during energy restriction that were greater than in the WM group (P < 0.05). Serum sex hormone binding globulin increased and leptin decreased with weight loss (P < 0.05). Serum PTH tended to increase in the WL group but not in the WM group (P < 0.06). The reduction in fat mass with weight loss was directly associated with a decrease in serum estrone (P < 0.01, R(2) = 0.50).. Moderate energy restriction increases bone turnover in obese postmenopausal women and may be regulated in part by alterations in serum PTH and estrone.

Topics: Absorptiometry, Photon; Adipose Tissue; Body Composition; Bone Density; Bone Resorption; Diet, Reducing; Energy Intake; Estrone; Female; Humans; Leptin; Middle Aged; Obesity; Osteoporosis, Postmenopausal; Parathyroid Hormone; Postmenopause; Sex Hormone-Binding Globulin; Time Factors; Weight Loss

The control of body fat is a prominent factor in human health. Animal studies have indicated a homeostatic central nervous system regulation of body fat with particular involvement of the melanocortin receptor pathway. This study provides evidence for a similar role for melanocortins in the long-term control of fat stores in humans. Thirty-six normal weight humans were assigned to one of three experimental groups. After a 4-week baseline, one group was treated with MSH/ACTH(4-10) (MSH/ACTH(4-10)) representing the core sequence of all melanocortins. Another group received desacetyl-alphaMSH, a selective agonist of the brain melanocortin-4 receptor, which shares the 4-10 sequence with MSH/ACTH(4-10). The third group received placebo. Treatments were given intranasally twice daily for 6 weeks, at equimolar doses (MSH/ACTH(4-10), 0.5 mg; desacetyl-alphaMSH, 0.84 mg). Body weight, body composition, and plasma hormone concentrations were measured before and after treatment. MSH/ACTH(4-10) reduced body fat, on the average, by 1.68 kg (P < 0.05) and body weight by 0.79 kg (P < 0.001). Concurrently, plasma leptin levels were decreased by 24% (P < 0.02), and insulin levels were decreased by 20% (P< 0.05) after MSH/ACTH(4-10). Changes after desacetyl-alphaMSH remained nonsignificant. The finding of reduced body adiposity after MSH/ACTH(4-10) confirms and extends to the human the findings of animal models indicating an essential role of the hypothalamic melanocortin system in body weight control.

Topics: Adipose Tissue; Adrenocorticotropic Hormone; Adult; alpha-MSH; Body Composition; Humans; Insulin; Leptin; Melanocyte-Stimulating Hormones; Peptide Fragments; Placebos; Receptor, Melanocortin, Type 4; Receptors, Peptide; Thyroid Hormones; Thyrotropin; Weight Loss

Adipose tissue influences steroid conversion by paracrine and autocrine mechanisms. Leptin is secreted by adipocytes and influenced by sex hormones and adiposity. Short-term weight loss in the treatment of childhood obesity reduces leptin and adipose tissue. We therefore asked, Do alterations in sex hormones occur owing to weight loss? and can these alterations be explained by changes in fat mass or sc fat and are alterations in sex hormones directly related to the fall in leptin? Twenty obese boys and 40 obese girls were studied before and after 3 wk of low-calorie diet and physical activity. The weight loss program significantly lowered fat mass, abdominal fat distribution, sc fat (all p < 0.0001), leptin, insulin, and estradiol (all p < 0.0001) but not testosterone. Changes in leptin were related to changes in body mass and to changes in fat mass in boys. In girls, changes in leptin were related to changes in sc fatness and also to changes in insulin. In boys, the reduction in sc fat was positively correlated to changes in testosterone (r = 0.54; p < 0.01) and inversely related to the fall in estradiol (r = -0.41; p < 0.05). In girls, changes in testosterone (r = 0.33; p < 0.05) and in estradiol (r = 0.40; p < 0.01) were related to changes in insulin. Stepwise regression showed that initial leptin was the best determinant for the fall in leptin (adjusted R2 = 0.87; p < 0.0001). The results show that alterations in sex hormones are related to changes in certain fat depots in boys whereas in girls changes in insulin might participate in changes in sex hormones. A greater fall in leptin owing to short-term weight loss is not associated with greater alterations in sex hormones and initial leptin is the best determinant to explain the variability in changes in leptin. The possibility of sex differences in changes in sex hormones secondary to the reduction in fatness warrants further study.

Topics: Adipose Tissue; Adolescent; Body Composition; Child; Diet, Reducing; Estradiol; Exercise; Female; Gonadal Steroid Hormones; Humans; Leptin; Male; Obesity; Testosterone; Weight Loss

The relation between insulin-leptin-visceral fat axis during weight loss has not been studied previously.. To evaluate the insulin, leptin, and abdominal adiposity relation during weight loss in patients with upper body obesity.. Twenty volunteers (7 men, 13 women) with mean age 50.6+/-6.3 (SD) and upper body obesity (weight 105.4+/-12.3 kg, BMI 35.9+/-2.5 kg/m2) were recruited. Participants were enrolled in a one-arm clinical study using a calorie-deficient diet and an escalating dose regimen of sibutramine, starting with 5 mg daily and increasing in 5-mg increments to 20 mg per day. Body weight, insulin, leptin, glucose, lipids, abdominal computed tomography (CT), and total body electrical conductance (TOBEC) were measured serially at weeks 0, 4, 8, 12, and 24.. Eighteen patients completed the 6-month study: one man and one woman discontinued because of adverse events. With diet and sibutramine, body weight was significantly and continuously reduced throughout the 6-month study. There was a 16.0% (p = 0.0001) reduction in body weight (p < 0.001) and 22.5% (p = 0.0001) decrease in total body fat mass. Abdominal CT scans showed a 28.3% (p = 0.0001) reduction in total abdominal fat, a 26.0% (p = 0.0001) reduction in subcutaneous fat (p < 0.001), and a 31.0% (p = 0.0003) reduction in visceral fat (p < 0.001). There was a 32.0% (p = 0.0008) reduction in leptin levels and 37.9% (p = 0.0001) reduction in insulin levels between baseline and week 4, but no further significant reduction in leptin and insulin levels was observed for the duration of the study. There was a significant correlation between insulin and leptin concentrations throughout the study (p = 0.0001). Leptin was presented as a function of insulin measured at the same time. Significant associations between visceral abdominal fat, subcutaneous fat, and leptin were also observed.. In this study, we found that leptin and insulin were related in weight loss. The data suggest that insulin may act as a strong regulator of leptin secretion during weight loss and that circulating leptin levels can be predicted by insulin level. Using sibutramine in conjunction with hypocaloric diet reduced body weight and decreased fat mass significantly. Visceral and subcutaneous abdominal fat depots were shown to decrease. Whether sibutramine exerts any selective reduction of visceral abdominal fat as opposed to total body fat mass will require further clinical investigation.

Topics: Adipose Tissue; Adult; Appetite Depressants; Cyclobutanes; Diet, Reducing; Female; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Time Factors; Viscera; Weight Loss

Hyperinsulinemia and insulin resistance are common features of obesity in humans and experimental animals. It has been demonstrated that metformin, an antihyperglycemic agent, decreases hyperinsulinemia and insulin resistance leading to decreased adiposity in obese and non-insulin-dependent diabetes mellitus (NIDDM) adults. To evaluate the antiobesity effect of metformin, we conducted a randomized double-blind placebo controlled trial in 24 hyperinsulinemic nondiabetic obese adolescents (body mass index [BMI] >30 kg/m(2)). All subjects were placed on a low-calorie (1,500 kcal for women and 1,800 kcal for men) meal plan. After an initial 1-week lead-in period, 12 subjects (mean +/- SE for age and BMI, 15.6 +/- 0.4 and 41.2 +/- 1.8, respectively) received metformin (850 mg twice daily) for 8 weeks, and 12 subjects (mean +/- SE for age and BMI, 15.7 +/- 0.5 and 40.8 +/- 1.4, respectively) received placebo. Compared to the placebo group, the metformin group had greater weight loss (6.5% +/- 0.8% v 3.8 +/- 0.4%, P <.01), greater decrease in body fat (P <.001), greater increase in fat-free mass to body fat ratio (P <.005), and greater attenuation of area under the curve (AUC) insulin response to an oral glucose tolerance test (P <.001). This was associated with enhanced insulin sensitivity, as determined by the fasting plasma glucose:insulin, 2-hour glucose:insulin, and AUC glucose:AUC insulin ratios, in the metformin group compared to controls (P <.01). This corresponded to a significant reduction in plasma leptin (P <.005), cholesterol, triglycerides, and free fatty acid (FFA) levels (P <.05) only in the metformin-treated subjects. Combined metformin treatment and low-calorie diet had a significant antiobesity effect in hyperinsulinemic obese adolescents compared to a low-calorie diet alone.

Topics: Adipose Tissue; Adolescent; Blood Glucose; Body Composition; Body Mass Index; Cholesterol; Diet, Reducing; Double-Blind Method; Energy Intake; Fasting; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypoglycemic Agents; Kinetics; Leptin; Male; Metformin; Obesity, Morbid; Placebos; Triglycerides; Weight Loss

The aim of the present study was to determine the impact of weight loss and its related metabolic and hormonal changes on resting energy expenditure (REE) and substrate oxidation. Forty subjects (16 men and 24 women) took part in a 15-week weight loss program that consisted of drug therapy (fenfluramine, 60 mg/day) or placebo coupled to an energy restriction (-700 Cal/day). Subjects were asked to come to the laboratory after an overnight fast for an indirect calorimetry measurement before and after weight loss. Fasting blood samples were also drawn and were analyzed for plasma glucose, insulin, leptin, and free fatty acid determinations. This program reduced body weight by 11% and 9% (P < 0.01) in men and women, respectively. Fat mass (FM) and fat-free mass (FFM) were also significantly reduced in both sexes. A significant decrease in REE (13%; P < 0.01) and fat oxidation (11%; P = 0.08) was observed in men in response to this program, whereas no significant differences were noted for these variables in women. In men, positive correlations were found between changes in FFM and energy-related variables, whereas the best predictor of changes in REE and substrate oxidation was the change in FM in women. The most important finding of this study is that in men, the association between changes in fasting plasma leptin and changes in REE (r = 0.50; P < 0.01) and fat oxidation (r = 0.63; P < 0.01) persist after correction for changes in body composition. These results suggest that a comparable weight loss is accompanied by a greater decrease in REE and substrate oxidation in men than in women, and that these changes are better explained by changes in leptinemia in men and by changes in FM in women.

Topics: Adult; Basal Metabolism; Blood Glucose; Body Mass Index; Diet, Reducing; Energy Intake; Energy Metabolism; Fatty Acids, Nonesterified; Female; Fenfluramine; Humans; Insulin; Leptin; Male; Obesity; Regression Analysis; Weight Loss

The independent effects of weight loss and exercise on plasma leptin and total (AT), subcutaneous (SAT), and visceral (VAT) adipose tissue were investigated in 52 obese men. Subjects were randomly assigned to four 12-wk protocols: 1) control (C, n = 8), 2) diet-induced weight loss (DWL, n = 14), 3) exercise-induced weight loss (EWL, n = 14), and 4) exercise with weight maintenance (EWS, n = 16). Plasma leptin was unchanged in C (from 7.8 +/- 1.3 to 7.7 +/- 1.0 ng/ml). Equivalent weight loss (7.5 kg) decreased leptin significantly but similarly (DWL, from 8.5 +/- 1.0 to 4.8 +/- 0.6 ng/ml; EWL, from 10.1 +/- 1.0 to 5.0 +/- 0.6 ng/ml). Exercise in the absence of weight loss did not alter leptin levels (from 10.1 +/- 1. 3 to 9.2 +/- 1.2 ng/ml). Changes in leptin correlated with changes in AT and SAT (both P < 0.05) but not in VAT. We conclude that reduction in adipose tissue after weight loss results in a collateral decrease in circulating leptin, and exercise, independent of its effects on weight loss, has no profound influence on leptin secretion.

Topics: Adipose Tissue; Adult; Anthropometry; Body Composition; Diet, Reducing; Exercise; Humans; Leptin; Magnetic Resonance Imaging; Male; Middle Aged; Obesity; Weight Loss

Controversial effects of weight reduction on gonadotropin secretion in obesity have been reported. As a result of pulsatility, single serum samples or frequent sampling studies are somewhat limited with regard to monitoring LH and FSH concentrations. We studied follicular phase nocturnal urinary (nu) LH and FSH secretion and glucose metabolism (150-min euglycemic hyperinsulinemic clamp) during 1 menstrual cycle/30-day period before and after weight reduction in 10 severely overweight infertility patients (age, 29 +/- 3.1 yr; body mass index, 37.1 +/- 3.3 kg/m2; +/-SEM). A 6-week very low calorie diet was followed by a 4-week normocaloric period. The urinary LH and FSH results reported represent samples taken 12 to 2 days before the LH surge, or 10 consecutive samples in the case of amenorrhea. We observed a decrease of 8% (P < 0.001) in percent body fat mass and a 5% (P < 0.005) reduction in waist to hip ratio. Mean nu-LH decreased by 45% [6.06 +/- 1.05 (+/-SEM) to 3.22 +/- 0.71 IU/L], whereas mean nu-FSH remained unchanged. Insulin-stimulated glucose uptake increased by 41% (P < 0.01), which was accounted for by a significant increase in nonoxidative glucose disposal (P = 0.003). Serum sex hormone-binding globulin concentrations increased by 39% (P < 0.01), and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) levels increased by 46% (P < 0.05). Fasting serum insulin concentrations decreased by 38%, those of leptin by 37%, those of androstenedione by 32%, those of testosterone by 20% (all P < 0.01), and those of dehydroepiandrosterone sulfate by 13% (P < 0.05). The percent change in nu-LH correlated negatively with glucose uptake (r = -0.76; P < 0.01) and the increase in serum sex hormone-binding globulin (r = -0.85; P < 0.005) and positively with the percent change in waist to hip ratio (r = 0.79; P < 0.01). The absolute nu-LH levels after weight reduction correlated significantly with fasting insulin concentrations (r = 0.88; P < 0.001) and negatively with glucose uptake (r = -0.67; P < 0.05). No significant relationships were found between absolute levels or changes in nu-LH concentrations and leptin, IGF-I, IGFBP-3, or IGFBP-1 concentrations. Our findings suggest that weight reduction with a very low calorie diet results in a decrease in nu-LH concentrations, a reduction in the LH/FSH ratio, and FSH predominance favoring folliculogenesis. The decrease in LH concentrations is inversely related to the severity of insulin resistance. It is po

Topics: Adult; Blood Glucose; Body Composition; Female; Follicle Stimulating Hormone; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Luteinizing Hormone; Obesity; Steroids; Weight Loss

The aim of this study was to investigate the potential role of adipose cytokines in the obesity-associated insulin resistance. To that end, we compared: 1) serum concentrations of interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), and leptin in eight healthy lean control females and in android obese female without (n = 14) and with (n = 7) type 2 diabetes; and 2) the levels of these cytokines both in serum and in sc adipose tissue in the 14 obese nondiabetic women before and after 3 weeks of a very low-calorie diet (VLCD). As compared with lean controls, obese nondiabetic and diabetic patients were more insulin resistant and presented increased values for leptin, IL-6, TNFalpha, and C-reactive protein. In the whole group, IL-6 values were more closely related to the parameters evaluating insulin resistance than leptin or TNFalpha values. VLCD resulted in weight loss and decreased body fat mass (approximately 3 kg). Insulin sensitivity was improved with no significant change in both serum and adipose tissue TNFalpha levels. In contrast, VLCD induced significant decreases in IL-6 and leptin levels in both adipose tissue and serum. These results suggest that, as for leptin, circulating IL-6 concentrations reflect, at least in part, adipose tissue production. The reduced production and serum concentrations after weight loss could play a role in the improved sensitivity to insulin observed in these patients.

Topics: Adipose Tissue; Adult; Aged; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Humans; Interleukin-6; Leptin; Middle Aged; Obesity; Tumor Necrosis Factor-alpha; Weight Loss

The aim of the present investigation was to determine whether leptinemia is only a reflection of the status of fat stores or if insulinemia has a significant influence over leptin levels. Study 1 focused on the association between fasting plasma insulin and leptin in subjects of the Quebec Family Study who were first classified as either high- or low-insulin individuals and were then individually matched on the basis of fat mass (FM). In Study 2, 19 men and 23 women took part in a 15-week weight loss program that consisted of drug therapy (fenfluramine, 60 mg/day) or placebo coupled to an energy-restricted diet (-2930 kJ/day). Body weight, FM, and fat-free mass (assessed by underwater weighing) as well as visceral and sc abdominal and mid-thigh adipose tissue measured by computed tomography were assessed before and after weight loss. Blood samples were drawn and analyzed for fasting plasma insulin and leptin before and after weight loss. In Study 1, significant positive associations were noted between log10 transformed fasting insulin and leptin in both men (r = 0.55, P < 0.0001) and women (r = 0.48, P < 0.0001). Moreover, after having carefully matched high-insulin to low-insulin individuals on the basis of FM, significantly lower leptin levels were observed in the low-insulin groups, in men (5.5 vs. 8.1 ng/mL, P < 0.05) as well as in women (18.7 vs. 24 ng/mL, P < 0.05). Results from Study 2 showed significant reductions of body weight, FM, fat-free mass, visceral abdominal tissue, sc abdominal tissue, and mid-thigh adipose tissue levels in men and women in response to the weight loss protocol. Moreover, the decrease in fasting plasma insulin was the only significant correlate of changes in fasting plasma leptin levels during weight loss, even after corrections for changes in FM in both men (r = 0.50, P < 0.05) and women (r = 0.46, P < 0.05). These results suggest that in a population characterized by a wide range of adiposity hyperinsulinemia has the potential to modulate leptin levels beyond what can be explained by total adiposity. Moreover, this relation also seems to exist in a dynamic setting (i.e. during weight loss) because changes in insulin were independent predictors of the changes in leptinemia in both men and women after correction for changes in FM.

Topics: Adipose Tissue; Adult; Body Composition; Body Weight; Cross-Sectional Studies; Diet, Reducing; Energy Intake; Fasting; Female; Fenfluramine; Humans; Insulin; Leptin; Male; Multivariate Analysis; Placebos; Quebec; Regression Analysis; Selective Serotonin Reuptake Inhibitors; Sex Characteristics; Tomography, X-Ray Computed; Weight Loss; White People

To identify variables associated with leptin change in subjects with type 2 diabetes after 3 weeks and 20 weeks of weight loss.. Subjects with type 2 diabetes treated with diet or sulfonylureas (n = 54) were enrolled in a 20-week behavioral weight control program. Sulfonylureas were stopped > or =2 weeks before study entry. Seven subjects who restarted sulfonylureas after week 3 had their data analyzed separately after this point.. Leptin, fasting plasma glucose, and insulin levels were measured at baseline and at 3, 10, and 20 weeks. After 3 weeks, subjects lost 2.7+/-2.0 kg (p<0.001), and had significant decreases in leptin (5.2+/-7.0 ng/mL, p<0.001), fasting plasma glucose (1.8+/-1.8 mmol/L, p<0.001), and insulin (23+/-60 pmol/L, p<0.03). Between week 3 and week 20, subjects lost an additional 6.3+/-4.4 kg (p<0.001), but had no further changes in leptin. The primary determinants of leptin change at all time-points were weight loss and initial leptin level. Changes in insulin were not related to changes in leptin after controlling for the effects of weight loss. At week 20, more recent weight loss (week 10 to week 20) was as strong a predictor of overall change in leptin as overall weight loss (baseline to 20 week). Subjects who restarted sulfonylureas had an increase in both leptin levels (+1.9+/-9.0 ng/mL, p<0.05) and insulin levels (+23+/-65 pmol/L, p<0.05), despite significant overall weight loss (-7.4+/-4.0 kg, p<0.01). Initial changes in leptin (0 weeks to 3 weeks) did not affect subsequent ability to lose weight.. Both short- and long-term changes in weight had an effect on leptin changes in individuals with type 2 diabetes. Although physiological insulin changes did not independently influence changes in leptin concentration with weight loss, increases in insulin levels with sulfonylurea therapy were associated with increases in leptin levels despite weight loss.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Diet, Reducing; Energy Intake; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Leptin; Male; Middle Aged; Proteins; Sex Characteristics; Sulfonylurea Compounds; Weight Loss

The aim of the study was to examine the effects of weight reduction by exercise and diet on metabolic control in obese subjects with insulin resistance, particularly investigating if changes in serum leptin concentrations were directly associated with improvements in metabolic control. Twenty obese men (48 +/- 8 yr; body mass index 32. 1 +/- 3.9 kg/m(2)) with previously diagnosed type II diabetes mellitus were assigned to a 4-wk intervention program of exercise (2, 200 kcal/wk) and diet (1,000 kcal/day; 50% carbohydrates, 25% protein, 25% fat; polyunsaturated-to-saturated fatty acid ratio 1.0). Intervention induced significant reductions in body weight and serum leptin levels, and improvements in lipoprotein profile and glucose control. Reductions in leptin levels were directly associated with reductions in serum triglycerides and cholesterol, a finding that was independent of improvements in glucose control. These data show that serum leptin concentrations can be reduced with caloric restriction and exercise in male patients with type II diabetes, and they suggest a direct relationship between leptin and lipoprotein metabolism that is not solely due to weight reduction.

Topics: Adult; Blood Glucose; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Reducing; Exercise Therapy; Humans; Leptin; Lipids; Lipoproteins; Longitudinal Studies; Male; Middle Aged; Obesity; Prospective Studies; Proteins; Triglycerides; Weight Loss

The protein hormone leptin is important to the homeostatic regulation of body weight. Treatment with exogenous leptin may affect weight loss.. To determine the relationship between increasing doses of exogenous leptin administration and weight loss in both lean and obese adults.. A randomized, double-blind, placebo-controlled, multicenter, escalating dose cohort trial conducted from April 1997 to October 1998.. Four university nutrition and obesity clinics and 2 contract clinical research clinics.. Fifty-four lean (body mass index, 20.0-27.5 kg/m2; mean [SD] body weight, 72.0 [9.7] kg) and 73 obese (body mass index, 27.6-36.0 kg/m2; mean [SD] body weight, 89.8 [11.4] kg) predominantly white (80%) men (n = 67) and women (n = 60) with mean (SD) age of 39 (10.3) years.. Recombinant methionyl human leptin self-administered by daily morning subcutaneous injection (0 [placebo], 0.01, 0.03, 0.10, or 0.30 mg/kg). In part A, lean and obese subjects were treated for 4 weeks; in part B, obese subjects were treated for an additional 20 weeks. Lean subjects consumed a eucaloric diet to maintain body weight at the current value, and obese subjects were prescribed a diet that reduced their daily energy intake by 2100 kJ/d (500-kcal/d) from the amount needed to maintain a stable weight.. Body weight, body fat, and incidence of adverse events.. Weight loss from baseline increased with increasing dose of leptin among all subjects at 4 weeks (P = .02) and among obese subjects at 24 weeks (P = .01) of treatment. Mean (SD) weight changes at 4 weeks ranged from -0.4 (2.0) kg for placebo (n = 36) to -1.9 kg (1.6) kg for the 0.1 mg/kg dose (n = 29). Mean (SD) weight changes at 24 weeks ranged from -0.7 (5.4) kg for the 0.01 mg/kg dose (n = 6) to -7.1 (8.5) kg for the 0.30 mg/kg dose (n = 8). Fat mass declined from baseline as dose increased among all subjects at 4 weeks (P = .002) and among obese subjects at 24 weeks of treatment (P = .004); more than 95% of weight loss was fat loss in the 2 highest dose cohorts at 24 weeks. Baseline serum leptin concentrations were not related to weight loss at week 4 (P = .88) or at week 24 (P = .76). No clinically significant adverse effects were observed on major organ systems. Mild-to-moderate reactions at the injection site were the most commonly reported adverse effects.. A dose-response relationship with weight and fat loss was observed with subcutaneous recombinant leptin injections in both lean and obese subjects. Based on this study, administration of exogenous leptin appears to induce weight loss in some obese subjects with elevated endogenous serum leptin concentrations. Additional research into the potential role for leptin and related hormones in the treatment of human obesity is warranted.

Topics: Adult; Antibodies; Body Composition; Body Mass Index; Double-Blind Method; Drug Administration Schedule; Energy Intake; Female; Humans; Leptin; Linear Models; Male; Obesity; Recombinant Proteins; Weight Loss

The difficulty in maintaining weight loss during obesity treatment may be caused by a counteracting neuroendocrine response. It has been proposed that leptin could be a regulator of this response. We examined the relations between leptin levels during an initial very low calorie diet, other simultaneous endocrine changes, and the 1-yr weight reduction. Sixty-nine obese (24 men and 45 women) were treated with very low calorie diet for 16 weeks, followed by a hypocaloric diet for 32 weeks. Serum levels of leptin, insulin, cortisol, and thyroid hormones were measured at weeks 0, 8, and 18. The relative weight reductions after 18 and 48 weeks were 20.1% and 14.4% in men and 15.4% and 11.8% in women. Low initial leptin levels and large declines in serum leptin were associated with a large 1-yr weight loss in both genders. Leptin levels (baseline or changes) were not independently associated with the changes in insulin, cortisol, or thyroid hormones. Our results may indicate that leptin by itself could be of minor importance for the neuroendocrine response to severe caloric restriction in humans.

Topics: Adolescent; Adult; Body Mass Index; Diet, Reducing; Energy Intake; Female; Humans; Hydrocortisone; Insulin; Leptin; Male; Middle Aged; Obesity; Thyrotropin; Thyroxine; Triiodothyronine; Weight Loss

Leptin is believed to play a role in regulating food intake and body weight. The aim of this study was to examine the influence of parental history of obesity on the association between baseline serum leptin concentrations and subsequent 4-y weight changes. Changes in food intake were also considered in the analysis. Middle-aged, obese women with no obese parent (n = 25) or at least one obese parent (n = 24) were included in the analysis. At baseline, women with no parental history of obesity and women with a parental history of obesity did not differ in body mass index (in kg/m2: 41.2 and 40.2, respectively) or median leptin concentrations (40.8 and 38.8 microg/L, respectively). Four-year weight changes varied widely in both groups combined (from -30 to 24 kg). Stratified regression analysis, adjusted for age, weight, and height, revealed that high leptin concentrations predicted less weight gain (or more weight loss) in women with no obese parent (beta = -21.2, P = 0.0006) but played no significant role in predicting weight gain in women with at least one obese parent (beta = -3.8, P = 0.41). Adding changes in energy and fat intakes to the model reduced the association between leptin and weight change to nonsignificance in the women with no obese parent, indicating that the effect of leptin could be explained largely by dietary changes. In conclusion, serum leptin concentrations predict long-term weight change in obese women with no history of parental obesity, an association largely mediated by changes in food intake.

Topics: Adult; Diet; Female; Humans; Leptin; Middle Aged; Obesity; Predictive Value of Tests; Proteins; Radioimmunoassay; Regression Analysis; Weight Gain; Weight Loss

Leptin is a hormone that regulates fat metabolism and appetite. The secretion of leptin is regulated by adiposity and, in the rodent, by factors such as insulin, beta-adrenergic agonists, and glucocorticoids (GCs). Increased secretion of the endogenous human GC, cortisol, occurs during stress and in disorders such as major depression. Pharmacological GCs can robustly increase plasma leptin concentrations in humans, leading us to hypothesize that cortisol may serve as a physiological regulator of human leptin secretion.. A randomized double-blind placebo-controlled comparison of 2 fixed oral dosages of cortisol (40 mg/d and 160 mg/d), given for 4 days to matched groups of healthy subjects (n=47). Low-dose treatment approximated GC output during mild stress, while high-dose treatment approximated GC output during maximal stress, spanning a range of GC secretion relevant to physiological stress.. Cortisol produced dose-dependent and time-dependent increases in plasma leptin concentrations (time x treatment condition x body mass index; F6,123=10.73; P<.001). Initial treatment-induced increases in plasma leptin concentration returned toward baseline values during 4 treatment days, suggesting tolerance to this GC effect in these healthy subjects.. The results indicate an important role for GCs in the short-term regulation of human leptin secretion. Glucocorticoid-induced increases in leptin secretion suggest a mechanism that may contribute to anorexia and weight loss during stress and disease states such as major depression, if these conditions are associated with sustained increases in plasma leptin concentrations.

Topics: Adipose Tissue; Adult; Anorexia; Body Mass Index; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hydrocortisone; Leptin; Male; Placebos; Proteins; Stress, Physiological; Weight Loss

Obesity, strongly associated with the risk for coronary heart disease (CHD), is becoming increasingly prevalent. This study was designed to establish first whether systemic arterial compliance (SAC), an index of arterial function, is improved with weight loss and second, whether cardiovascular risk factors that improve with weight loss are reduced equally with lean meat or with an equivalent amount of plant protein in the diet. Thirty-six women, mostly overweight or obese, aged 40+/-9 years, were allocated nonrandomly to a 16-week parallel-design trial of two equienergetic diets designed to lead to weight loss, with one arm of the study emphasizing red meat and the other soybeans as the major protein source. Body weight, waist and hip circumference, and plasma lipids, glucose, insulin, and leptin levels were measured, and SAC was calculated from ultrasound measurement of aortic flow velocity and aortic root driving pressure. Subjects lost weight (9% of body weight in 16 weeks) and showed decreased plasma total and low-density lipoprotein (LDL) cholesterol (12% and 14%, P < .0001, respectively), triacylglycerol (17%, P < .05), and leptin (24%, P < .01) concentrations. However, lipoprotein(a) [Lp(a)] levels did not change significantly. Mean arterial pressure (MAP) decreased 7% and SAC increased 28% (P < .001 for both). However, only the decrease in arterial pressure correlated significantly with the reduction in the waist to hip ratio (WHR), and the improvement in SAC correlated inversely with the blood pressure reduction (P < .001 for both). Further, weight loss and the metabolic benefits of weight loss occurred equally with the meat-based and plant-based diets. We conclude that moderate weight loss in women leads to a substantial reduction in the cardiovascular risk, including SAC.

Topics: Adult; Arteries; Blood Glucose; Blood Pressure; Compliance; Dietary Proteins; Female; Humans; Insulin; Leptin; Lipids; Meat; Middle Aged; Obesity; Proteins; Soybean Proteins; Weight Loss

Animal research suggests that leptin may have an important role in the regulation of energy balance. The role of leptin in the progressive involuntary weight loss associated with cancer in humans is of considerable interest. However, such studies are limited. In this study, we compared circulating leptin concentrations in gastrointestinal cancer patients and weight loss (n = 27) with those of healthy subjects (n = 27). The effect of the presence of an inflammatory response on leptin concentrations was also examined. There were significantly lower leptin concentrations in male (median, 2.4 microg/liter; range, <0.5-6.0 microg/liter) and female (median, 3.4 microg/liter; range, <0.5-9.8 microg/liter) cancer patients than there were in male (median, 6.5 microg/liter; range, 3.1-10.9 microg/liter) and female (median, 18.7 microg/liter; range, 8.0-31.5 mcirog/liter) healthy subjects (P < 0.001). However, the leptin concentrations in both patients and normal subjects were related to the predicted percentage of body fat (r = 0.731; P < 0.001). Circulating leptin concentrations in the cancer patients were not altered by the presence of an inflammatory response. These results suggest that cancer anorexia/cachexia is not due to a simple dysregulation of leptin production.

Topics: Adult; Aged; Case-Control Studies; Energy Metabolism; Female; Gastrointestinal Neoplasms; Humans; Inflammation; Leptin; Male; Middle Aged; Proteins; Weight Loss

Correlations between serum leptin (LEP) and BMI and the percentage of fat mass (FM), as well as differences between male and female serum levels and their behaviour during weight loss have already been extensively described in adult obesity, whereas few cases have been examined in child and adolescent obesity. There are also few studies of the alterations in NPY in peripheral blood in obese subjects during weight loss.. This study aimed to evaluate the correlations between LEP and BMI, FM% and NPY in 72 obese subjects, with BMI > 35 (29 males and 43 females) aged between 9.6 and 19.8 years old, during weight loss together with any differences between the sexes.. LEP was positively correlated in both sexes with BMI and FM%, whereas no correlation emerged with NPY; LEP levels decreased gradually during weight loss, whereas no changes were observed in NPY except during the first phases of weight loss in males when the decrease was significant. LEP concentrations were significantly higher in females, who also showed a higher FM% with equal BMI. No difference was observed between NPY levels in both sexes.. The authors conclude that: 1) the behaviour of LEP in child-adolescent obesity is broadly comparable to that described in adult obesity; 2) the highest LEP concentrations with equal BMI in females appear to reflect the different body composition of the two sexes given that females have a higher FM%; 3) the control exerted by LEP on hypothalamic NPY cannot be seen in peripheral blood and no differences emerged between the two sexes.

Topics: Adolescent; Adult; Child; Female; Humans; Leptin; Male; Neuropeptide Y; Obesity; Proteins; Sex Factors; Weight Loss

The aim of this study was to determine whether serum leptin concentrations are reduced in response to short-term energy restriction in centrally obese individuals with impaired glucose tolerance or non-insulin-dependent diabetes mellitus. Twenty African Americans [16 females and 4 males, 44 +/- 7 y (x +/- SD), 107.2 +/- 23.8 kg, 39 +/- 7% body fat] consumed a 7-d energy-restricted diet (4.03 +/- 0.72 MJ/d) of whole foods. Oral-glucose-tolerance tests (OGTTs) were performed before and immediately after the diet to assess changes in serum leptin, glucose, and insulin concentrations. Baseline leptin concentration correlated significantly with percentage body fat (r = 0.80), body mass index (r = 0.72), fat mass (4 = 0.64), waist-height ratio (r = 0.6), body weight (r = 0.59, all P < 0.01), waist circumference (r = 0.49), and basal insulin concentration (r = 0.48, both P < 0.05). Seven days of energy restriction resulted in significant reductions (P < 0.005) in leptin (-6.1 +/- 8.4 micrograms/L), basal glucose (-0.9 +/- 0.8 mmol/L), OGTT glucose area under the curve (-158 +/- 164 mmol/L), and basal insulin concentration (-34 +/- 69 pmol/L, P < 0.05). In addition, there was a trend for a reduction in OGTT insulin area under the curve (-15,567 +/- 3,658 pmol/L, P = 0.05), and a tendency for basal insulin and leptin to change together (r = 0.41, P = 0.07). Despite the weight loss of 3.1 +/- 1.3 kg (P < 0.0001), the loss of fat mass was calculated to be only -1.0 +/- 0.1 kg. These results suggest that negative energy balance or improved insulin action was responsible for the changes in leptin, glucose, and insulin concentrations. In summary, short-term energy restriction effectively reduced serum leptin concentrations and improved glucose tolerance and insulin action in obese individuals with impaired or diabetic glucose tolerance.

Topics: Adult; Area Under Curve; Black People; Blood Glucose; Diabetes Mellitus, Type 2; Energy Intake; Female; Glucose Intolerance; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Proteins; Weight Loss

Leptin is likely to be involved in the homeostasis of body weight. Insulin is suggested to regulate both short-term and long-term circulating leptin levels. The present study aims to assess the relation between insulin and leptin levels in obese humans.. Some 53 obese subjects (body mass index 35.1 +/- 3.9 kg m-2 (mean +/- SD)) were prescribed a hypocaloric diet and randomized to either a placebo or the intestinal lipase inhibitor orlistat for 2 years. Serum leptin and insulin levels were determined repeatedly during these 2 years (5 times in the fasting condition and twice after an oral glucose load).. Leptin concentrations appeared to be regulated at a specific level for each individual throughout the weight-loss period. The BMI explained 39.7% of the total variance in leptin levels, the body-fat distribution 17.2%, individual characteristics 30.3%; and the fasting serum insulin concentration 1.0%. After a mean weight loss of 7.7 +/- 4.9 kg, the time-integrated insulin response to an oral glucose load was significantly lower but the leptin response remained unchanged.. The BMI is the main determinant of the circulating leptin concentration in obese humans. Individual characteristics seem to determine the leptin level, given the BMI. In a short-term observational study in obese humans, changes of insulin levels do not appear to be correlated to changes in leptin levels.

Topics: Adult; Biomarkers; Body Mass Index; Diet; Double-Blind Method; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Insulin; Lactones; Leptin; Lipase; Male; Middle Aged; Obesity; Orlistat; Proteins; Single-Blind Method; Weight Loss

In some recent studies, glucocorticoid treatment was associated with rapid induction of obese (ob) gene expression in adipose tissue of normal rats and in isolated adipocytes. We studied the effect of acute stimulation of the corticotropic axis on plasma leptin, the ob gene product, in 7 women of normal weight and 12 women with obesity. Under double-blind, placebo-controlled conditions, a single 12.5-mg dose of clomipramine, a serotonin uptake inhibitor, was administered intravenously in 15 minutes. Mean basal plasma leptin was increased more than 3-fold in subjects with obesity compared with subjects of normal weight (35.1 +/- 4.9 ng/mL vs. 8.9 +/- 1.4 ng/mL, p = 0.001). Whereas corticotropin (ACTH) and cortisol responses were increased in women who were obese compared with women who were lean, no significant effect of clomipramine infusion was found on plasma leptin concentrations measured during the following 150 minutes in both groups. There was a strong positive correlation between basal plasma leptin concentrations and body mass index (r = 0.92, p < 0.0001). In six subjects with obesity studied after a moderate weight loss, mean basal plasma leptin was significantly decreased (43.7 +/- 6.4 ng/mL before vs. 28.0 +/- 8.1 ng/mL after, p = 0.04), but the hormonal response pattern to clomipramine administration was unchanged. We conclude that, at least in the short term, an acute stimulation of the corticotropic axis does not seem to increase leptin secretion in humans, as shown by the response to the serotoninergic agent clomipramine.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Body Mass Index; Clomipramine; Double-Blind Method; Female; Humans; Hydrocortisone; Kinetics; Leptin; Obesity; Placebos; Proteins; Selective Serotonin Reuptake Inhibitors; Weight Loss

Altitude exposure may suppress appetite and hence provide a viable weight-loss strategy. While changes in food intake and availability as well as physical activity may contribute to altered appetite at altitude, herein we aimed to investigate the isolated effects of hypobaric hypoxia on appetite regulation and sensation. Twelve healthy women (age: 24.0 ± 4.2 years, body mass: 60.6 ± 7.0 kg) completed two 4-day sojourns in a hypobaric chamber, one in normoxia [P

Topics: Adult; Altitude; Appetite; Energy Intake; Female; Ghrelin; Humans; Hypoxia; Leptin; Sensation; Weight Loss; Young Adult

Leptin acts on hypothalamic neurons expressing agouti-related protein (AgRP) or pro-opiomelanocortin (POMC) to suppress appetite and increase energy expenditure, but the intracellular mechanisms that modulate central leptin signalling are not fully understood. Here we show that growth factor receptor-bound protein 10 (Grb10), an adaptor protein that binds to the insulin receptor and negatively regulates its signalling pathway, can interact with the leptin receptor and enhance leptin signalling. Ablation of Grb10 in AgRP neurons promotes weight gain, while overexpression of Grb10 in AgRP neurons reduces body weight in male and female mice. In parallel, deletion or overexpression of Grb10 in POMC neurons exacerbates or attenuates diet-induced obesity, respectively. Consistent with its role in leptin signalling, Grb10 in AgRP and POMC neurons enhances the anorexic and weight-reducing actions of leptin. Grb10 also exaggerates the inhibitory effects of leptin on AgRP neurons via ATP-sensitive potassium channel-mediated currents while facilitating the excitatory drive of leptin on POMC neurons through transient receptor potential channels. Our study identifies Grb10 as a potent leptin sensitizer that contributes to the maintenance of energy homeostasis by enhancing the response of AgRP and POMC neurons to leptin.

Topics: Agouti-Related Protein; Animals; Female; GRB10 Adaptor Protein; Leptin; Male; Mice; Pro-Opiomelanocortin; Weight Loss

Physique athletes lose substantial weight preparing for competitions, potentially altering systemic metabolism. We investigated sex differences in body composition, resting energy expenditure (REE), and appetite-regulating and thyroid hormone changes during a competition preparation among drug-free physique athletes. The participants were female (10 competing (COMP) and 10 nondieting controls (CTRL)) and male (13 COMP and 10 CTRL) physique athletes. COMP were tested before they started their diet 23 weeks before competing (PRE), during their diet one week before competing (MID), and 23 weeks after competing (POST), whereas CTRL were tested at similar intervals but did not diet. Measurements included body composition by dual-energy X-ray absorptiometry, muscle size, and subcutaneous fat thickness (SFA) by ultrasound, REE by indirect calorimetry, circulating ghrelin, leptin T3, and T4 hormone analysis. Fat mass (FM) and SFA decreased in both sexes (

Topics: Athletes; Basal Metabolism; Body Composition; Energy Metabolism; Female; Humans; Leptin; Male; Thermogenesis; Weight Loss

Canine obesity negatively influences health and well-being, but can be managed by altering diet composition and caloric intake. Restricted feeding, dietary intervention, and consequent weight loss may be used to improve health and modify gastrointestinal microbiota. In this study, we aimed to determine the effects of restricted feeding of specially formulated foods on weight loss, body composition, voluntary physical activity, serum hormones and oxidative stress markers, and fecal metabolites and microbiota populations of obese dogs. Twenty-four obese dogs [body weight (BW) = 15.2 ± 1.7 kg; body condition score (BCS) = 8.7 ± 0.4; muscle condition score (MCS) = 3.5 ± 0.3; age = 7.2 ± 1.6 yr] were used in a 24-wk study. A control (OR) food was fed during a 4-wk baseline to identify intake needed to maintain BW. After baseline, dogs were allotted to one of two diets: OR or test (FT), and then fed to lose 1.5% BW/wk. Food intake, BW, BCS, and MCS were measured, blood and fecal samples were collected, DEXA scans were performed, and voluntary physical activity was measured over time. Microbiota data were evaluated using QIIME2 and change from baseline data from other measures were evaluated using the Mixed Models procedure of SAS, with P < 0.05 being significant. Restricted feeding led to reduced BW, BCS, fat mass, and blood cholesterol, triglyceride, glucose, and leptin concentrations, and increased MCS and lean body mass percentage. Blood cholesterol reduction was greater in dogs fed FT vs. OR. Fecal metabolites and bacterial alpha-diversity were affected by diet and weight loss. Dogs fed FT had greater reductions in fecal short-chain fatty acid, branched-chain fatty acid, and ammonia concentrations than those fed OR. Dogs fed OR had a higher alpha-diversity than those fed FT. Weight loss increased alpha-diversity (weeks 16, 20, and 24 > weeks 0 and 4). Beta-diversity showed separation between dietary groups and between week 0 and all other time points after week 8. Weight loss increased fecal Allobaculum and Ruminococcus torques. Weight loss also increased fecal Bifidobacterium, Faecalibaculum, and Parasutterella, but were greater in dogs fed OR. Weight loss decreased fecal Collinsella, Turicibacter, Blautia, Ruminococcus gnavus, Faecalibacterium, and Peptoclostridium, but were greater in dogs fed OR. In summary, restricted feeding promoted safe weight and fat loss, reduced blood lipid and leptin concentrations, and altered fecal microbiota of obese dogs.. In this study, we aimed to determine the effects of restricted feeding of specially formulated foods on weight loss, body composition, voluntary physical activity, serum hormones and oxidative stress markers, and fecal metabolites and microbiota populations of obese dogs. A control (OR) food was fed during a 4-wk baseline to identify intake needed to maintain the body weight (BW). After baseline, dogs were allotted to one of two diets: OR or test (FT) and then fed to lose 1.5% BW per week for 24 wk. Restricted feeding and weight loss led to reduced BW, body condition score, fat mass, and blood cholesterol, triglyceride, glucose and leptin concentrations and increased muscle condition score and lean body mass percentage. The reduction in blood cholesterol was greater in dogs fed FT vs. OR. Fecal metabolites and bacterial alpha-diversity were affected by diet and weight loss, with dogs fed with OR having a higher alpha-diversity than those fed with FT. Restricted feeding and weight loss increased alpha-diversity, affected beta-diversity, and impacted the relative abundances of nearly 20 bacterial genera. In summary, restricted feeding with high-protein, low-starch kibble diets promoted safe weight and fat loss, reduced blood lipid and leptin concentrations, and altered fecal microbiota of obese dogs.

Topics: Animal Feed; Animals; Body Composition; Cholesterol; Diet; Dog Diseases; Dogs; Feces; Leptin; Microbiota; Obesity; Physical Conditioning, Animal; Weight Loss

Topics: Gastrectomy; Humans; Leptin; Obesity, Morbid; Retrospective Studies; Treatment Outcome; Weight Loss

Patients with psoriatic arthritis (PsA) are frequently obese. We have previously shown decreased disease activity in patients with PsA with a body mass index (BMI) ≥ 33 kg/m. VLED (640 kcal/day) during 12 or 16 weeks, depending on BL BMI < 40 or ≥ 40 kg/m. Serum interleukin (IL)-23, (median (interquartile range) 0.40 (0.17-0.54) ng/mL vs. 0.18 (0.10-0.30) ng/mL, p < 0.001) and leptin (26.28 (14.35-48.73) ng/mL vs. 9.25 (4.40-16.24) ng/mL, p < 0.001) was significantly decreased in patients with PsA. Serum total (tot)-adiponectin and high molecular weight (HMW) adiponectin increased significantly. Similar findings were found in controls. Also, in patients with PsA, ∆BMI was positively correlated with ∆IL-23 (r. Weight loss was associated with decreased levels of leptin and cytokines, in particular IL-23. These findings may partly explain the anti-inflammatory effect of weight reduction in PsA.. ClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016, retrospectively registered.

Topics: Adipokines; Adiponectin; Arthritis, Psoriatic; Cytokines; Humans; Interleukin-23; Leptin; Obesity; Tumor Necrosis Factor-alpha; Weight Loss

Fundectomy, shown as an alternative to restrictive techniques, causes absorption restriction and metabolic changes. This study aimed to examine the histopathological changes caused by the fundectomy as a technique applied to rats by hormones that affect stomach and obesity metabolism and its effect on weight loss.. 2randomly selected Winstar-Hannover rat groups were evaluated by measuring their pre-and postoperative weights and biochemically measuring Gastrin, Ghrelin, and Leptin levels on day 30. After sacrification, the stomachs were taken for histopathological examination.. Significant weight loss was observed in the fundectomy group in the 1stmonth postoperatively. Biochemically, Gastrin means in the fundectomy group were statistically significantly higher than in the control group. The mean Ghrelin and Leptin levels of the Fundectomy Group were statistically significantly lower (p=0.005). Immunohistochemically, Gastrin means ™at the antrum and proximal stomach parts of the Fundectomy Group were significantly higher than in the control group. As Ghrelin, a significant decrease was observed in all 3regions of the Fundectomy Group compared to the control group. Leptin results were significantly lower at the antrum and proximal stomach parts of the Fundectomy Group. Histopathologically, in the Fundectomy Group, cystic glandular hyperplasia was moderate at the proximal stomach, foveolar hyperplasia was mild at the antrum, fibrosis was moderate at the antrum and corpus, and high at the proximal stomach.. Fundectomy is an effective method in terms of weight loss. This animal experiment, conducted as a pilot study, will be an essential step in elucidating metabolic and histopathological changes.. Bariatric surgery, Fundectomy, Obesity.. La resezione del fondo gastrico, indicata come alternativa alle tecniche restrittive, provoca restrizione dell’assorbimento e alterazioni metaboliche. Questo studio mirava a esaminare i cambiamenti istopatologici causati da questo intervento eseguito su ratti ad opera di ormoni che influenzano il metabolismo dello stomaco e dell’obesità e il suo effetto sulla perdita di peso. Sono stati utilizzati 2 Gruppi di ratti Winstar-Hannover, selezionati casualmente, valutando il loro peso pre e postoperatorio e misurando biochimicamente i livelli di gastrina, grelina e leptina al giorno 30. Dopo il sacrificio, gli stomaci sono stati sottoposti ad esame istopatologico. RISULTATI: È stata osservata nel 1° mese dopo l’intervento una significativa perdita di peso nel gruppo dei resecati del fondo gastrico. Dal punto di vista biochimico, i livelli medi della Gastrina è risultato statisticamente e significativamente più elevato nel gruppo dei gastroresecati rispetto al gruppo di controllo. I livelli medi di grelina e leptina sono risultati statisticamente e significativamente più bassi (p=0,005) nel gruppo dei gastroresecati. Dal punto di vista immuno-istochimico i livelli medi della Gastrina sono risultati significativamente più elevati nelle parti dell’antro e dello stomaco prossimale nel gruppo dei gastro-resecati rispetto al gruppo di controllo. Per quanto riguarda la Grelina, è stata osservata una diminuzione significativa in tutte e 3 le regioni del gruppo della fundectomia rispetto al gruppo di controllo. I risultati della leptina sono risultati significativamente più bassi nelle parti dell’antro e dello stomaco prossimale del gruppo dei fundectomizzati. Dal punto di vista istologico nel gruppo della fundectomia, l’iperplasia ghiandolare cistica era moderata nello stomaco prossimale, l’iperplasia foveolare era lieve all’antro, la fibrosi era moderata all’antro e al corpo ed elevata nello stomaco prossimale. CONCLUSIONE: la fundectomia si è dimostrata un metodo efficace ai fini della riduzione del peso. Questo studio sperimentale sugli animali, condotto come studio pilota, potrà rappresentare un passaggio essenziale per chiarire i cambiamenti metabolici e istopatologici della resezione del fondo gastrico.

Topics: Animals; Gastrins; Ghrelin; Hyperplasia; Leptin; Obesity; Pilot Projects; Rats; Weight Loss

Adipocyte dysregulation is one mechanism linking overweight and breast cancer recurrence. Exercise and weight loss are associated with a decreased risk of breast cancer recurrence in breast cancer survivors with overweight or obesity, which may be mediated through reduced leptin levels, increased adiponectin levels, and an elevated adiponectin to leptin (A:L) ratio. The four-arm randomized controlled WISER Survivor trial examined the 12-month intervention effects of exercise, weight loss, and the combination of exercise and weight loss on adipokine levels among breast cancer survivors (

Topics: Adipokines; Adiponectin; Breast Neoplasms; Cancer Survivors; Female; Humans; Leptin; Neoplasm Recurrence, Local; Obesity; Overweight; Survivors; Weight Loss

Feline obesity is a common and preventable disease, posing a myriad of health risks and detriments. Specially formulated diets and restricted feeding may serve as an intervention strategy to promote weight loss and improve feline health. In this study, our objective was to determine the effects of restricted feeding and weight loss on body composition, voluntary physical activity, blood hormones and metabolites, and fecal microbiota of overweight cats. Twenty-two overweight adult spayed female and neutered male cats [body weight (BW) = 5.70 ± 1.0 kg; body condition score (BCS) = 7.68 ± 0.6; age = 4 ± 0.4 yr] were used in a weight loss study. A control diet (OR) was fed during a 4-wk baseline to identify intake needed to maintain BW. After baseline (week 0), cats were allotted to OR or a test diet (FT) and fed to lose ~1.0% BW/wk for 24 wk. At baseline and 6, 12, 18, and 24 wk after weight loss, dual-energy x-ray absorptiometry scans were performed and blood samples were collected. Voluntary physical activity was measured at weeks 0, 8, 16, and 24. Fecal samples were collected at weeks 0, 4, 8, 12, 16, 20, and 24. Change from baseline data were analyzed statistically using the Mixed Models procedure of SAS, with P < 0.05 considered significant. Restricted feeding of both diets led to weight and fat mass loss, lower BCS, and lower blood triglyceride and leptin concentrations. Cats fed the FT diet had a greater reduction in blood triglycerides and cholesterol than cats fed the OR diet. Restricted feeding and weight loss reduced fecal short-chain fatty acid, branched-chain fatty acid, phenol, and indole concentrations. Fecal valerate concentrations were affected by diet, with cats fed the OR diet having a greater reduction than those fed the FT diet. Fecal bacterial alpha diversity was not affected, but fecal bacterial beta diversity analysis showed clustering by diet. Restricted feeding and weight loss affected relative abundances of 7 fecal bacterial genera, while dietary intervention affected change from baseline relative abundances of 2 fecal bacterial phyla and 20 fecal bacterial genera. Our data demonstrate that restricted feeding promoted controlled and safe weight and fat loss, reduced blood lipids and leptin concentrations, and shifted fecal metabolites and microbiota. Some changes were also impacted by diet, highlighting the importance of ingredient and nutrient composition in weight loss diets.. The objective of this study was to determine the effects of diet, restricted feeding and weight loss on body composition, voluntary physical activity, blood hormones and metabolites, and fecal metabolites and microbiota of overweight cats. Overweight cats were allotted to a control diet (OR) or weight loss diet (FT) and fed to lose ~1.0% body weight/week for 24 wk. Body weight, body composition, and voluntary physical activity were measured, while fecal and blood samples were collected over time. Restricted feeding led to weight and fat mass loss, and lower blood triglyceride and leptin concentrations. Cats fed FT had a greater reduction in blood triglycerides and cholesterol than cats fed OR. Restricted feeding reduced fecal metabolite concentrations and affected relative abundances of 7 fecal bacterial genera. Fecal bacterial beta diversity analysis showed clustering by diet. Dietary intervention affected change from baseline relative abundances of 2 fecal bacterial phyla and 20 fecal bacterial genera. Our data demonstrate that restricted feeding promoted controlled and safe weight and fat loss, reduced blood lipids and leptin concentrations, and shifted fecal metabolites and microbiota. Some dietary differences were noted, highlighting the importance of ingredient and nutrient composition in weight loss diets.

Topics: Animal Feed; Animals; Bacteria; Body Composition; Body Weight; Cat Diseases; Cats; Diet; Feces; Female; Leptin; Male; Microbiota; Overweight; Weight Loss

Laparoscopic sleeve gastrectomy (LSG) for morbid obesity may improve gut microbiota balance and decrease chronic inflammation. This study examines the changes in gut microbiota and immune environment, including mucosal-associated invariant T cells (MAIT cells) and regulatory T cells (Treg cells) caused by LSG.. Ten morbidly obese patients underwent LSG at our institution between December 2018 and March 2020. Flow cytometry for Th1/Th2/Th17 cells, Treg cells and MAIT cells in peripheral blood and colonic mucosa and 16S rRNA analysis of gut microbiota were performed preoperatively and then 12 months postoperatively.. Twelve months after LSG, the median percent total weight loss was 30.3% and the median percent excess weight loss was 66.9%. According to laboratory data, adiponectin increased, leptin decreased, and chronic inflammation improved after LSG. In the gut microbiota, Bacteroidetes and Fusobacteria increased after LSG, and indices of alpha diversity increased after LSG. In colonic mucosa, the frequency of MAIT cells increased after LSG. In peripheral blood, the frequency of Th1 cells and effector Treg cells decreased after LSG.. After LSG for morbid obesity, improvement in chronic inflammation in obesity is suggested by change in the constituent bacterial species, increase in the diversity of gut microbiota, increase in MAIT cells in the colonic mucosa, and decrease in effector Treg cells in the peripheral blood.

Topics: Adiponectin; Gastrectomy; Gastrointestinal Microbiome; Humans; Inflammation; Laparoscopy; Leptin; Mucosal-Associated Invariant T Cells; Obesity, Morbid; RNA, Ribosomal, 16S; T-Lymphocytes, Regulatory; Treatment Outcome; Weight Loss

The aim of this study was to determine whether the hormone changes following weight loss are proportional to the degree of weight loss and to starting BMI.. A very low-energy diet was used to achieve 15% weight loss. Fasting and postprandial gut hormones and leptin were measured during a meal test at baseline and at 5% (1%), 10% (2%), and 15% (2.5%) weight loss. Linear mixed-effects models were used to analyze hormone changes.. From baseline to 5% weight loss, decreases were seen in fasting concentrations of leptin (-8.25 ng/mL; p < 0.001), amylin (-21.3 pg/mL; p < 0.001), and glucagon-like peptide 1 (-59.55 pg/mL; p < 0.001). There was a small further reduction in leptin between 5% and 15% weight loss (-1.88 ng/mL; p = 0.019) but not in glucagon-like peptide 1 and amylin. Fasting ghrelin showed a significant increase at 10% weight loss (41.64 pg/mL; p = 0.002), with a nonsignificant increase from 10% to 15% loss (26.03 pg/mL; p = 0.065). Postprandial changes in hormone levels were variable. There was no correlation between baseline weight and the degree of hormone changes.. The majority of changes in fasting gut hormones and leptin occurred in early weight loss, with minor further changes up to 15% weight loss. Starting weight did not affect the degree of hormone change.

Topics: Appetite; Body Mass Index; Fasting; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Islet Amyloid Polypeptide; Leptin; Weight Loss

Heterozygous variants in the leptin-melanocortin pathway are associated with obesity. However, their effect on the long-term outcomes after Roux-en-Y gastric bypass (RYGB) is still unknown.. In this matched case-control study, 701 participants from the Mayo Clinic Biobank with a history of RYGB were genotyped. Sixty-three patients had a heterozygous variant in the leptin-melanocortin pathway. After excluding patients with potential confounders, carriers were randomly matched (on sex, age, body mass index [BMI], and years since surgery) with two non-carrier controls. The electronic medical record of carriers and matched non-carriers was reviewed for up to 15 years after RYGB.. A total of 50 carriers and 100 matched non-carriers with a history of RYGB were included in the study. Seven different genes (LEPR, PCSK1, POMC, SH2B1, SRC1, MC4R, and SIM1) in the leptin-melanocortin pathway were identified. At the time of surgery, the mean age was 50.8 ± 10.6 years, BMI 45.6 ± 7.3 kg/m. Carriers of a heterozygous variant in the leptin-melanocortin pathway have a progressive and significant weight regain in the mid- and long-term after RYGB. Genotyping patients experiencing significant weight regain after RYGB could help implement multidisciplinary and individualized weight loss interventions to improve weight maintenance after surgery.

Topics: Adaptor Proteins, Signal Transducing; Adult; Case-Control Studies; Female; Gastric Bypass; Humans; Leptin; Male; Melanocortins; Middle Aged; Obesity, Morbid; Weight Gain; Weight Loss

(1) Objective: The aim of this study was to clarify the role of adipokines in the regulation of glucose metabolism in middle-aged obese subjects with impaired glucose tolerance in response to a long-term exercise and dietary intervention. (2) Methods: Skeletal muscle, plasma and serum samples were examined in 22 subjects from an exercise−diet intervention study aiming to prevent type 2 diabetes. The subjects were further divided into two subgroups (non-responders n = 9 and responders n = 13) based on their achievement in losing at least 3 kg. (3) Results: The two-year exercise−diet intervention reduced leptin levels and increased adiponectin levels in responders; the changes in leptin levels were significantly associated with changes in their weights (r = 0.662, p < 0.01). In responders, insulin sensitivity (Bennett and McAuley index) increased and was associated with changes in maximal oxygen uptake (VO2peak) (r = 0.831, p < 0.010 and r = 0.890, p < 0.01). In addition, the VO2peak and oxidative capacity of skeletal muscle improved in responders, but not in non-responders. However, there were no changes between the two groups in expressions of the glucose transporter protein-4 (GLUT-4) gene or of AMP-activated protein kinase (AMPK)-α1 or AMPK-α2 proteins. (4) Conclusions: The exercise−diet intervention decreased serum leptin and increased serum adiponectin concentrations, improved glucose control without affecting GLUT-4 gene expression in the skeletal muscle in responders.

Topics: Adipokines; Adiponectin; AMP-Activated Protein Kinases; Blood Glucose; Diabetes Mellitus, Type 2; Gene Expression; Glucose Intolerance; Glucose Transporter Type 4; Glycemic Control; Humans; Insulin Resistance; Leptin; Middle Aged; Muscle, Skeletal; Weight Loss

Fibroblast growth factor 21 (FGF21) is a peripherally-derived endocrine hormone that acts on the central nervous system (CNS) to regulate whole body energy homeostasis. Pharmacological administration of FGF21 promotes weight loss in obese animal models and human subjects with obesity. However, the central targets mediating these effects are incompletely defined.. To explore the mechanism for FGF21's effects to lower body weight, we pharmacologically administer FGF21 to genetic animal models lacking the obligate FGF21 co-receptor, β-klotho (KLB), in either glutamatergic (Vglut2-Cre) or GABAergic (Vgat-Cre) neurons. In addition, we abolish FGF21 signaling to leptin receptor (LepR-Cre) positive cells. Finally, we examine the synergistic effects of FGF21 and leptin to lower body weight and explore the importance of physiological leptin levels in FGF21-mediated regulation of body weight.. Here we show that FGF21 signaling to glutamatergic neurons is required for FGF21 to modulate energy expenditure and promote weight loss. In addition, we demonstrate that FGF21 signals to leptin receptor-expressing cells to regulate body weight, and that central leptin signaling is required for FGF21 to fully stimulate body weight loss during obesity. Interestingly, co-administration of FGF21 and leptin synergistically leads to robust weight loss.. These data reveal an important endocrine crosstalk between liver- and adipose-derived signals which integrate in the CNS to modulate energy homeostasis and body weight regulation.

Topics: Animals; Body Weight; Fibroblast Growth Factors; Humans; Leptin; Neurons; Obesity; Receptors, Leptin; Weight Loss

Many cytokines have been proposed to regulate reproduction due to their actions on hypothalamic kisspeptin cells, the main modulators of gonadotropin-releasing hormone (GnRH) neurons. Hormones such as leptin, prolactin and growth hormone are good examples of cytokines that lead to Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation, consequently exerting effects in kisspeptin neurons. Different studies have investigated how specific components of the JAK/STAT signaling pathway affect the functions of kisspeptin cells, but the role of the suppressor of cytokine signaling 3 (SOCS3) in mediating cytokine actions in kisspeptin cells remains unknown. Cre-Loxp technology was used in the present study to ablate Socs3 expression in kisspeptin cells (Kiss1/Socs3-KO). Then, male and female control and Kiss1/Socs3-KO mice were evaluated for sexual maturation, energy homeostasis features, and fertility. It was found that hypothalamic Kiss1 mRNA expression is significantly downregulated in Kiss1/Socs3-KO mice. Despite reduced hypothalamic Kiss1 mRNA content, these mice did not present any sexual maturation or fertility impairments. Additionally, body weight gain, leptin sensitivity and glucose homeostasis were similar to control mice. Interestingly, Kiss1/Socs3-KO mice were partially protected against lipopolysaccharide (LPS)-induced body weight loss. Our results suggest that Socs3 ablation in kisspeptin cells partially prevents the sickness behavior induced by LPS, suggesting that kisspeptin cells can modulate energy metabolism in mice in certain situations.

Topics: Animals; Body Weight; Cytokines; Female; Kisspeptins; Leptin; Lipopolysaccharides; Male; Mice; RNA, Messenger; Suppressor of Cytokine Signaling 3 Protein; Weight Loss

Biliopancreatic diversion with duodenal switch (BPD/DS) results in lifelong changes in gastrointestinal physiology with unclear associations with appetite perception.. To explore mixed meal-induced changes in glucose homeostasis and gut hormones and their correlations with appetite perception.. University hospital.. Of 28 patients studied preoperatively (age: 38.4 ± 11.3 years; body mass index [BMI]: 56.5 ± 5.1 kg/m. BPD/DS resulted in 66.1% ± 23.3% excess BMI loss. Leptin was halved. Glucose and insulin levels were reduced, blunting a preoperative peak at 30 minutes, giving a lower homeostasis model assessment for insulin resistance (HOMA-IR; 13.9 versus 4.8). In contrast, reduced ghrelin and motilin concentrations were accompanied by pronounced peaks 20-30 minutes prior to meal responses. GIP was reduced, whereas GLP-1 and PYY responses were markedly increased, with an early postprandial peak (P < .05, for all). HOMA-IR correlated with insulin (r = .72) and GIP (r = .57). Postoperatively, satiety correlated with GLP-1 (r = .56), whereas the gastric motility index correlated with the desire to eat (r = .60), percentage excess BMI loss (r = -.55), and percentage total weight loss (r = -.49). Delta insulin, GLP-1, and leptin correlated positively with percentage total weight loss (r = .51, r = .48, and r = .58, respectively).. BPD/DS reduces leptin, HOMA-IR, and GIP while markedly increasing GLP-1 and PYY. This study marks the magnitude change in GLP-1 with additional effects of PYY as important factors for weight loss.

Topics: Adult; Appetite; Biliopancreatic Diversion; Female; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Glucose; Homeostasis; Humans; Insulin; Leptin; Male; Middle Aged; Motilin; Peptide YY; Weight Loss

The study is aimed at investigating the curative effect of acupuncture on simple obesity and its influence on serum levels of prostaglandin E and leptin in Sprague-Dawley (SD) rats.. In the study, there are 50 male SD rats. We took 10 as healthy controls and fed 40 with a diet of high fat for 8 weeks. After the 40 rat model was established successfully, we fed 10 rats in the model group with a normal diet and treated 10 rats in the acupuncture group by acupuncture. During the experiment, the body fat and body length of rats were measured weekly, and Lee's index was calculated. After the treatment, the levels of leptin, prostaglandin E, C-reactive protein (CRP), triacylglycerol (TG), cholesterol (CHO), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were detected, and the liver fat morphology was observed by electron microscope.. Acupuncture significantly downregulated the serum levels of CRP, TG, CHO, LDL, leptin, and prostaglandin E and upregulated the serum levels of HDL in rats with simple obesity.. On basis of these results, it was found that acupuncture could boost fat metabolism and weight loss by inhibiting the production of leptin and prostaglandin E.

Topics: Acupuncture Therapy; Adipose Tissue; Animals; C-Reactive Protein; Computational Biology; Disease Models, Animal; Leptin; Lipids; Liver; Male; Obesity; Prostaglandins E; Rats; Rats, Sprague-Dawley; Weight Loss

Dietary intervention is a common tactic employed to curtail the current obesity epidemic. Changes in nutritional status alter metabolic hormones such as insulin or leptin, as well as the insulin-like growth factor (IGF) system, but little is known about restoration of these parameters after weight loss in obese subjects and if this differs between the sexes, especially regarding the IGF system. Here male and female mice received a high fat diet (HFD) or chow for 8 weeks, then half of the HFD mice were changed to chow (HFDCH) for 4 weeks. Both sexes gained weight (p < 0.001) and increased their energy intake (p < 0.001) and basal glycemia (p < 0.5) on the HFD, with these parameters normalizing after switching to chow but at different rates in males and females. In both sexes HFD decreased hypothalamic NPY and AgRP (p < 0.001) and increased POMC (p < 0.001) mRNA levels, with all normalizing in HFDCH mice, whereas the HFD-induced decrease in ObR did not normalize (p < 0.05). All HFD mice had abnormal glucose tolerance tests (p < 0.001), with males clearly more affected, that normalized when returned to chow. HFD increased insulin levels and HOMA index (p < 0.01) in both sexes, but only HFDCH males normalized this parameter. Returning to chow normalized the HFD-induced increase in circulating leptin (p < 0.001), total IGF1 (p < 0.001), IGF2 (p < 0.001, only in females) and IGFBP3 (p < 0.001), whereas free IGF1 levels remained elevated (p < 0.01). In males IGFBP2 decreased with HFD and normalized with chow (p < 0.001), with no changes in females. Although returning to a healthy diet improved of most metabolic parameters analyzed, fIGF1 levels remained elevated and hypothalamic ObR decreased in both sexes. Moreover, there was sex differences in both the response to HFD and the switch to chow including circulating levels of IGF2 and IGFBP2, factors previously reported to be involved in glucose metabolism. Indeed, glucose metabolism was also differentially modified in males and females, suggesting that these observations could be related.

Topics: Animals; Blood Glucose; Diet, High-Fat; Energy Intake; Female; Hypothalamus; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Sex Characteristics; Weight Loss

Excess fat mass (FM) contributes to poor prostate cancer (PCa) prognosis and comorbidity. However, FM gain is a common side effect of androgen deprivation therapy (ADT). We examined the efficacy of a 12-wk weight loss intervention to reduce FM and maintain lean mass (LM) in ADT-treated obese PCa patients.. Fourteen ADT-treated obese PCa patients (72 ± 9 yr, 39.7% ± 5.4% body fat) were recruited for a self-controlled prospective study, with 11 completing the 6-wk control period, followed by a 12-wk intervention comprising 300 min·wk-1 of exercise including supervised resistance training and home-based aerobic exercise, and dietitian consultations advising a daily energy deficit (2100-4200 kJ) and protein supplementation. Body composition was assessed by dual x-ray absorptiometry. Secondary outcomes included muscle strength (one-repetition maximum), cardiorespiratory fitness (maximal oxygen consumption), and blood biomarkers.. There were no significant changes during the control period. Patients attended 89% of supervised exercise sessions and 100% of dietitian consultations. No changes in physical activity or energy intake were observed. During the intervention, patients experienced significant reductions in weight (-2.8 ± 3.2 kg, P = 0.016), FM (-2.8 ± 2.6 kg, P < 0.001), and trunk FM (-1.8 ± 1.4 kg, P < 0.001), with LM preserved (-0.05 ± 1.6 kg, P = 0.805). Muscle strength (4.6%-24.7%, P < 0.010) and maximal oxygen consumption (3.5 ± 4.7 mL·min-1·kg-1, P = 0.041) significantly improved. Leptin significantly decreased (-2.2 (-2.7 to 0.5) ng·mL-1, P = 0.016) with no other changes in blood biomarkers such as testosterone and lipids (P = 0.051-0.765); however, C-reactive protein (rs = -0.670, P = 0.024) and triglycerides (r = -0.667, P = 0.025) were associated with individual changes in LM.. This study shows preliminary efficacy for an exercise and nutrition weight loss intervention to reduce FM, maintain LM, and improve muscle strength and cardiorespiratory fitness in ADT-treated obese PCa patients. The change in body composition may affect blood biomarkers associated with obesity and PCa progression; however, further research is required.

Topics: Absorptiometry, Photon; Adipose Tissue; Adiposity; Aged; Aged, 80 and over; Androgen Antagonists; Biomarkers; Cardiorespiratory Fitness; Energy Intake; Exercise; Humans; Leptin; Male; Middle Aged; Muscle Strength; Obesity; Oxygen Consumption; Prospective Studies; Prostatic Neoplasms; Resistance Training; Testosterone; Time Factors; Weight Loss

This study was conducted as part of a larger study of East Tyrolean health tourism, and investigates the effects of an active seven-day vacation on metabolic parameters and adipokines. Fifty-two healthy vacationers participated in two types of vacation activities (golf vs. Nordic walking or e-biking [nw&eb]). In the former group, 30 subjects played golf for a mean duration of 33.5 h per week; in the NW&EB group, 22 persons performed Nordic walking or e-biking for a mean duration of 14.2 h per week. Metabolic parameters and adipokines, such as leptin, adiponectin, GF-21, irisin, omentin-1, betatrophin, and resistin, were measured one day before and one day after the stay. After one week, only the NW&EB group experienced a significant decrease of 1.0 kg in body weight. Significant changes in HDL-C, FGF-21, irisin, and omentin-1 were seen in the golf group; and in triglycerides, HbA1c, leptin and adiponectin in the NW&EB group. No significant changes in betatrophin or resistin were registered in either group. A seven-day vacation with an activity program for several hours per week causes favorable changes in metabolic parameters and adipokines known to be involved in the pathophysiology of the metabolic syndrome. The changes differed in their magnitude and significance, depending on the type of activity.

Topics: Adipokines; Adiponectin; Angiopoietin-Like Protein 8; Angiopoietin-like Proteins; Bicycling; Blood Pressure; Cardiometabolic Risk Factors; Cholesterol, HDL; Cytokines; Female; Fibroblast Growth Factors; Fibronectins; Germany; Glycated Hemoglobin; Golf; GPI-Linked Proteins; Heart Rate; Holidays; Humans; Lectins; Leptin; Male; Metabolic Syndrome; Metabolism; Middle Aged; Peptide Hormones; Resistin; Time Factors; Triglycerides; Walking; Weight Loss

Several studies have demonstrated that heavy metals disrupt energy homeostasis. Leptin inhibits food intake and decreases body weight through activation of its receptor in the hypothalamus. The impact of heavy metals on leptin signaling in the hypothalamus is unclear. Here, we show that the environmental pollutant, methylmercury (MeHg), favors an anorexigenic profile in wild-type males. C57BL/6J mice were exposed to MeHg via drinking water (5 ppm) up to 30 days. Our data shows that MeHg exposure was associated with changes in leptin induced activation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in the hypothalamus. In males, the activation of JAK2/STAT3 signaling pathway was sustained by an increase in SOCS3 protein levels. In females, MeHg-activated STAT3 was inhibited by a concomitant increase in PTP1B. Taken together, our data suggest that MeHg enhanced leptin effects in males, favoring an anorexigenic profile in males, which notably, have been shown to be more sensitive to the neurological effects of this organometal than females. A better understanding of MeHg-induced molecular mechanism alterations in the hypothalamus advances the understanding of its neurotoxicity and provides molecular sites for novel therapies.

Topics: Animals; Appetite; Drug Administration Schedule; Drug Synergism; Feeding Behavior; Female; Leptin; Male; Methylmercury Compounds; Mice; Mice, Inbred C57BL; Weight Loss

We aimed to determine whether the sodium/glucose cotransporter family member SGLT3, a proposed glucose sensor, is expressed in the intestine and/or kidney, and if its expression is altered in mouse models of obesity and in humans before and after weight-loss surgery.. We used in-situ hybridization and quantitative PCR to determine whether the Sglt3 isoforms 3a and 3b were expressed in the intestine and kidney of C57, leptin-deficient ob/ob, and diabetic BTBR ob/ob mice. Western blotting and immunohistochemistry were also used to assess SGLT3 protein levels in jejunal biopsies from obese patients before and after weight-loss Roux-en-Y gastric bypass surgery (RYGB), and in lean healthy controls.. Sglt3a/3b mRNA was detected in the small intestine (duodenum, jejunum and ileum), but not in the large intestine or kidneys of mice. Both isoforms were detected in epithelial cells (confirmed using intestinal organoids). Expression of Sglt3a/3b mRNA in duodenum and jejunum was significantly lower in ob/ob and BTBR ob/ob mice than in normal-weight littermates. Jejunal SGLT3 protein levels in aged obese patients before RYGB were lower than in lean individuals, but substantially upregulated 6 months post-RYGB.. Our study shows that Sglt3a/3b is expressed primarily in epithelial cells of the small intestine in mice. Furthermore, we observed an association between intestinal mRNA Sglt3a/3b expression and obesity in mice, and between jejunal SGLT3 protein levels and obesity in humans. Further studies are required to determine the possible role of SGLT3 in obesity.

Topics: Adult; Animals; Disease Models, Animal; Down-Regulation; Female; Gastric Bypass; Gene Expression; Humans; Insulin; Insulin Resistance; Intestinal Mucosa; Intestine, Small; Jejunum; Leptin; Male; Mice; Mice, Inbred C57BL; Middle Aged; Obesity; Protein Isoforms; RNA, Messenger; Sodium-Glucose Transport Proteins; Transcriptome; Weight Loss

Previous studies indicate that oxytocin (OT) administration reduces body weight in high-fat diet (HFD)-induced obese (DIO) rodents through both reductions in food intake and increases in energy expenditure. We recently demonstrated that chronic hindbrain [fourth ventricular (4V)] infusions of OT evoke weight loss in DIO rats. Based on these findings, we hypothesized that chronic 4V OT would elicit weight loss in DIO mice. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle over 28 days on body weight, food intake, and body composition. OT reduced body weight by approximately 4.5% ± 1.4% in DIO mice relative to OT pretreatment body weight (

Topics: Adipocytes, Brown; Adipocytes, White; Adiposity; Animals; Anti-Obesity Agents; Diet, High-Fat; Disease Models, Animal; Eating; Energy Intake; Infusions, Intraventricular; Leptin; Male; Mice, Inbred C57BL; Obesity; Oxytocin; Rhombencephalon; Thermogenesis; Uncoupling Protein 1; Weight Loss

Beinaglutide has been approved for glucose lowering in type 2 diabetes mellitus (T2DM) in China. In addition to glycemic control, significant weight loss is observed from real world data. This study is designed to investigate the pharmacological and pharmacokinetic profiles of beinaglutide in different models.. The pharmacological efficacy of beinaglutide was evaluated in C57BL/6 and ob/ob mice after single administration. Pharmacokinetic profiles in mice were investigated after single or multiple administration. Sub-chronic pharmacological efficacy was investigated in ob/ob mice for two weeks treatment and diet-induced ob/ob mice model of nonalcoholic steatohepatitis (NASH) for four weeks treatment.. Beinaglutide could dose-dependently reduce the glucose levels and improve insulin secretion in glucose tolerance tests, inhibit food intake and gastric emptying after single administration. At higher doses, beinaglutide could inhibit food intake over 4 h, which results in weight loss in ob/ob mice after about two weeks treatment. No tachyphylaxis is observed for beinaglutide in food intake with repeated administration. In NASH model, beinaglutide could reduce liver weight and hepatic steatosis and improve insulin sensitivity. Signiant changes of gene levels were observed in fatty acid β-oxidation (Ppara, Acadl, Acox1), mitochondrial function (Mfn1, Mfn2), antioxidation (Sod2), Sirt1, and et al. SIGNIFICANCE: Our results characterize the pharmacological and pharmacokinetic profiles of beinaglutide in mice and supported that chronic use of beinaglutde could lead to weight loss and reduce hepatic steatosis, which suggest beinaglutide may be effective therapy for the treatment of obesity and NASH.

Topics: Animals; Antioxidants; Diabetes Complications; Diabetes Mellitus; Glucagon-Like Peptide 1; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Liraglutide; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Oxidation-Reduction; Peptide Fragments; PPAR alpha; Weight Loss

The impact of diet and fibre fractions on adipocytokines in obese subjects with a risk of diabetes has not been investigated in detail yet. The purpose of the study is to evaluate the effects of a 12-month lifestyle intervention with different fibre profiles (resistant starch (RS)-rich fibre, or ordinary food fibre profiles) on adipocytokine levels. Fifty participants are divided into two groups (RS group and Fibre group). The groups differ only in the percentage of the recommended level of the RS consumed as a fraction of the same total fibre amount. The applied dietary intervention includes intake of 7531 KJ/daywith a total fibre portion of 25-35 g/dayfor both groups that includes 15 g/day of RS for the RS group only. The levels of leptin, adiponectin, apelin, resistin, tumor necrosis factor (TNF)-alpha and C-reactive protein (CRP) are measured, and their relationship to anthropometric and biochemical parameters is estimated. Along with significant body weight loss, only leptin is significantly reduced by 13% in the RS group while in the Fibre group, apelin levels are significant (-21%). Polynomial regression shows a negative correlation between RS intake and adiponectin (R2 = 0.145) and resistin level (R2 = 0.461) in the RS group. This study indicates the possibility that fibre fractions differently influence the outcome of lifestyle interventions, as well as their adipocytokine levels, in obese prediabetic adults.

Topics: Adipokines; Adiponectin; Aged; Apelin; Biomarkers; Diet; Dietary Fiber; Exercise; Humans; Inflammation; Leptin; Life Style; Male; Middle Aged; Obesity; Prediabetic State; Resistant Starch; Resistin; Weight Loss

The protein leverage hypothesis predicts that low dietary protein should increase energy intake and cause adiposity. We designed 10 diets varying from 1% to 20% protein combined with either 60% or 20% fat. Contrasting the expectation, very low protein did not cause increased food intake. Although these mice had activated hunger signaling, they ate less food, resulting in decreased body weight and improved glucose tolerance but not increased frailty, even under 60% fat. Moreover, they did not show hyperphagia when returned to a 20% protein diet, which could be mimicked by treatment with rapamycin. Intracerebroventricular injection of AAV-S6K1 significantly blunted the decrease in both food intake and body weight in mice fed 1% protein, an effect not observed with inhibition of eIF2a, TRPML1, and Fgf21 signaling. Hence, the 1% protein diet induced decreased food intake and body weight via a mechanism partially dependent on hypothalamic mTOR signaling.

Topics: Activating Transcription Factor 4; Adipose Tissue, White; Animals; Diet, Protein-Restricted; Eating; Energy Metabolism; Fibroblast Growth Factors; Gene Expression; Glucose Tolerance Test; Hyperphagia; Hypothalamus; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases; Weight Loss

Hypothalamic inflammation and endoplasmic reticulum (ER) stress are extensively linked to leptin resistance and overnutrition-related diseases. Surgical intervention remains the most efficient long-term weight-loss strategy for morbid obesity, but mechanisms underlying sustained feeding suppression remain largely elusive. This study investigated whether Roux-en-Y gastric bypass (RYGB) interacts with obesity-associated hypothalamic inflammation to restore central leptin signaling as a mechanistic account for post-operative appetite suppression.. RYGB or sham surgery was performed in high-fat diet-induced obese Wistar rats. Sham-operated rats were fed ad libitum or by weight matching to RYGB via calorie restriction (CR) before hypothalamic leptin signaling, microglia reactivity, and the inflammatory pathways were examined to be under the control of gut microbiota-derived circulating signaling.. RYGB, other than CR-induced adiposity reduction, ameliorates hypothalamic gliosis, inflammatory signaling, and ER stress, which are linked to enhanced hypothalamic leptin signaling and responsiveness. Mechanistically, we demonstrate that RYGB interferes with hypothalamic ER stress and toll-like receptor 4 (TLR4) signaling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the altered gut microbial environment upon RYGB surgery.. Our data demonstrate that RYGB interferes with hypothalamic TLR4 signaling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the post-surgical altered gut microbial environment.

Topics: Animals; Caloric Restriction; Diet, High-Fat; Disease Models, Animal; Gastric Bypass; Gastrointestinal Microbiome; Hypothalamus; Inflammation; Leptin; Male; Microglia; Neurons; Obesity, Morbid; Rats; Rats, Wistar; Signal Transduction; Treatment Outcome; Weight Loss

Predictive values of acute phase metabolic abnormalities of anorexia nervosa (AN) have seldom been studied. As early postrestoration weight loss is associated with poor outcome, discharge biologic parameters were assessed to detect an association with 2-month follow-up weight loss as a proxy to poor outcome.. Fasting plasma levels of leptin, acyl-ghrelin, obestatin, PYY, oxytocin and BDNF were measured in 26 inpatients, at inclusion, at discharge and 2 months later. A body mass index less than 18 2-month postdischarge was considered a poor outcome.. Nineteen patients (73%) had a fair outcome and seven (27%) had a poor one with a mean loss of 0.69 versus 4.54 kg, respectively. Only discharge leptin levels were significantly higher in fair versus poor outcome patients (14.1 vs. 7.0 ng/ml, p = 0.006). The logistic regression model using discharge leptin, acyl-ghrelin, obestatin, oxytocin, PYY and BDNF levels as predictors of outcome disclosed a nearly significant effect of leptin (p < 0.10). Receiver operating characteristic analysis showed 11.9 ng/ml was the best value of threshold. Neither clinical variables differed according to outcome.. Leptin level may be a biomarker of early weight relapse after acute inpatient treatment of AN. Its clinical usefulness in monitoring care in AN should further be determined.

Topics: Aftercare; Anorexia Nervosa; Body Mass Index; Humans; Leptin; Patient Discharge; Weight Loss

Glycosuria induced by sodium-glucose cotransporter 2 (SGLT2) inhibitors leads to weight loss and improved diabetes control, but a significant disparity exists between observed and expected weight loss with these medications, hindering clinical effects. This study investigated whether this discrepancy could be explained by compensatory increases in appetite and associated alterations in appetite-regulating hormones.. This was a prospective single-center observational pilot study. Adults 18-70 years old newly prescribed an SGLT2 inhibitor through usual care were invited to participate. Fasting and postprandial appetite was assessed immediately before, 1 week after, and 12 weeks after SGLT2 inhibitor initiation. Serum samples were collected at corresponding time points to measure ghrelin, leptin, and peptide tyrosine-tyrosine (PYY). Seven patients were included. At 1 and 12 weeks after SGLT2 inhibitor initiation, self-reported appetite did not change significantly and trended toward a decrease in appetite. There were no significant differences in fasting or postprandial ghrelin, leptin, or PYY.. Results suggest the discrepancy between expected and observed weight loss with SGLT2 inhibitors cannot be explained by increases in appetite or changes in appetite-regulating hormones. Further studies are needed to investigate alternative metabolic compensatory mechanisms to optimize weight loss with SGLT2 inhibitor use.

Topics: Aged; Appetite Regulation; Biomarkers; Diabetes Mellitus, Type 2; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Peptide YY; Pilot Projects; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Treatment Outcome; Weight Loss

Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (

Topics: Adiposity; Agouti-Related Protein; Animals; Caloric Restriction; Diet, Fat-Restricted; Diet, High-Fat; Dietary Fats; Disease Models, Animal; Eating; Ghrelin; Hypothalamus; Leptin; Male; Metabolic Diseases; Neuropeptide Y; Neuropeptides; Obesity; Pro-Opiomelanocortin; Rats; Rats, Wistar; Weight Loss

The pathogenesis of consumptive syndrome of tuberculosis (TB) is largely unknown. Leptin concentrations may be high because of the host's inflammatory response, contributing to weight loss in patients with TB. The receptor for advanced glycation end products (RAGE) is also associated with weight loss in patients with TB and is related to enhanced mortality. The objective of this study was to evaluate the association between leptin and AGE/RAGE.. Case-control study. Leptin, AGE (carboxymethyl lysine, CML) and soluble RAGE (sRAGE) were measured from blood samples by ELISA.. We included in the study 34 patients with TB and 34 controls. We found an inverse correlation between serum leptin levels and sRAGE, only in cases (r = -0.609, p < 0.0001). sRAGE levels were lower in patients with TB who died as compared with patients who survive (21.90 ± 4.24 pg/mL vs 66.14 ± 29.49 pg/mL; p = 0.045). Leptin levels were higher in patients with TB who died as compared with patients who survive (14.11 [7.48-14.11] ng/mL vs 3.08 [0.54-6.34] ng/mL; p = 0.028).. We identified lower sRAGE levels and higher leptin levels in patients with TB who died as compared with patients who survive. In addition, an inverse and significant correlation between serum leptin and sRAGE levels was demonstrated. Future studies, with a larger sample size and in different settings, including not only hospitalized patients, are needed to confirm these findings.

Topics: Adult; Antigens, Neoplasm; Case-Control Studies; Female; Humans; Leptin; Male; Mitogen-Activated Protein Kinases; Prospective Studies; Tuberculosis; Weight Loss

Although bariatric surgery is approved for a woman of child-bearing age with an interest in subsequent pregnancy, reports of in utero growth issues during pregnancy have garnered a closer look at the impact of maternal surgical weight loss on the pre- and postpartum periods. Offspring of dams having received vertical sleeve gastrectomy (VSG) are born small-for-gestational age and have increased risk for metabolic syndrome later in life. Here, we aimed to determine whether the postnatal catch-up growth trajectory of bariatric offspring may be affected by milk composition. Milk samples were collected at postnatal day 15/16 from dams having received VSG surgery and fed a high-fat diet (HFD) (H-VSG), Sham surgery and fed chow (C-Sham), or Sham surgery and fed HFD (H-Sham). Milk obtained from H-VSG dams had elevated glucose (P < 0.05) and significantly reduced triglyceride content (P < 0.01). Milk from H-Sham dams had the lowest amount of milk protein (P < 0.05). Fatty acid composition measured by fractionation was largely not affected by surgery but rather maternal diet. No difference was observed in milk leptin levels; however, insulin, adiponectin, and growth hormone levels were significantly increased in milk from H-VSG animals. H-Sham had the lowest level of immunoglobulin (Ig)A, whereas IgG was significantly reduced in H-VSG. Taken together, the quality of milk from H-VSG dams suggests that milk composition could be a factor in reducing the rate of growth during the lactation period.

Topics: Adiponectin; Animals; Animals, Suckling; Bariatric Surgery; Diet, High-Fat; Disease Models, Animal; Female; Gastrectomy; Glucose; Growth Disorders; Growth Hormone; Humans; Insulin; Lactation; Leptin; Male; Milk; Nutrients; Obesity; Postoperative Period; Rats; Rats, Long-Evans; Weight Loss

Repetitive physical activity is a well-established intervention to reduce obesity and to prevent weight regain. Besides increased energy expenditure, reduced caloric intake may contribute to exercise-induced weight loss in obesity. Using adipocyte-specific glycoprotein 130 knockout (gp130. gp130. Repetitive physical activity reduced food intake and HFD-induced weight gain in gp130. Adipocyte-specific IL-6 signalling is involved in exercise-mediated regulation of food intake and weight reduction in HFD-fed mice.

Topics: Adipocytes; Animals; Body Weight; Cytokine Receptor gp130; Diet, High-Fat; Eating; Energy Metabolism; Insulin; Leptin; Male; Mice; Mice, Knockout; Obesity; Physical Conditioning, Animal; Signal Transduction; Weight Loss

Published reports showed conflicting results regarding the sustained alterations in leptin, chemerin, and ghrelin concenratios after metabolic surgery. Therefore, we performed the present work to contrast the alterations in leptin, chemerin, and ghrelin levels one year after Roux-en-Y gastric bypass (RYGB) versus laparoscopic sleeve gastrectomy (LSG).. The present research is a prospective, comparative one that followed 100 cases for whom RYGB or LSG was done. We assessed the serum values of adiposity-associated mediators, including adipokcytokines (leptin and active chemerin) and gastrointestinal hormones (total ghrelin). The primary outcome in the present study was the alterations in leptin, chemerin, and ghrelin values at 12 months after RYGB and LSG.. The serum leptin level decreased significantly in the LSG group with a mean change of - 170.8 ± 29.4 ng/mL (p < 0.001). Similarly, the serum leptin concentration decreased significantly in the RYGB group, with a mean change of - 165.42 ± 53.4 (p < 0.001). In addition, the mean reduction in baseline chemerin levels 12 months after the operation was considerable in the LSG cohort (- 23.24 ± 9.5 ng/mL) and RYGB group (- 22.12 ± 15.9 ng/mL). The ghrelin values demonstrated a notable reduction in the LSG cohort (- 0.083 ± 0.11 pg/mL) and RYGB group (- 0.068 ± 0.097 pg/mL). However, the changes in the three hormones were not substantially different between both groups (p > 0.05).. Both RYGB and LSG result in a considerable, comparable decrease in the postoperative serum concentrations of leptin, chemerin, and ghrelin.

Topics: Chemokines; Gastrectomy; Gastric Bypass; Ghrelin; Humans; Laparoscopy; Leptin; Obesity, Morbid; Prospective Studies; Weight Loss

The medium-term impact of gastric bypass (GB) surgery on the inflammatory state and endothelial function of patients has yet to be confirmed.. This study aims to elucidate the inflammatory profile and endothelial dysfunction response of adults with obesity 6 and 24 months after undergoing GB surgery.. The anthropometric and biochemical markers of 32 adults with obesity (two men and 30 females) were collected preoperatively, and 6 and 24 months postoperatively.. Our results demonstrated that after GB there was an improvement in the inflammatory profile, identified by a reduction in pro-inflammatory markers (CRP, IL-6, leptin) and an increase in anti-inflammatory markers (adiponectin, IL-10). The decrease in PAI-1 and ICAM-1 levels may suggest improvement in endothelial function. These findings provide clear evidence of the medium-term impact of GB on inflammation state and a number of endothelial markers, and a consequent reduction in the risk of cardiovascular diseases.

Topics: Adiponectin; Adult; Biomarkers; Female; Follow-Up Studies; Gastric Bypass; Humans; Inflammation; Leptin; Male; Obesity; Obesity, Morbid; Weight Loss

Background: obesity is a chronic disease associated with inadequate eating habits and reduced levels of physical activity. Because of obesity, the risk for comorbidities is increased, especially for cardiovascular diseases, insulin resistance, and increased pro-inflammatory factors. The aim of the present investigation was to analyze potential correlations between pro/anti-inflammatory adipokines, glycemic index, and other markers of diet quality using a metabolic profile in women undergoing interdisciplinary weight loss therapy. Methods: thirty-two women with obesity were enrolled in a 12-week program of interdisciplinary therapy combining a clinical, nutritional, and physical exercise approach. Body composition, quality of diet, metabolic profile, and pro/anti-inflammatory adipokines were analyzed. Results: the therapy showed to be effective in reducing body weight, body mass index, and body fat. There was also an improvement in lipid profile, including total cholesterol, non-HDL-cholesterol, VLDL-cholesterol, triglycerides and glucose metabolism, including glucose, and insulin. As for food intake, there was a decrease in calorie consumption, carbohydrates, lipids, and glycemic load, and an increased consumption of proteins. Positive correlations were demonstrated between insulin concentration and waist circumference; leptin and body fat and abdominal circumference; and LDL-cholesterol fraction and total cholesterol consumption. Negative correlations were demonstrated between leptin and monosaturated fat consumption; and adiponectin and liver enzyme GGT levels. Conclusions: interdisciplinary therapy had positive effects on inflammatory state, mediated by leptin, adiponectin, and quality of diet. Our findings suggest the effectiveness and clinical relevance of the interdisciplinary clinical therapy applied for obesity.. Introducción: la obesidad es una enfermedad crónica asociada con hábitos alimentarios inadecuados y niveles reducidos de actividad física. Debido a la obesidad, el riesgo de comorbilidad aumenta, especialmente el de las enfermedades cardiovasculares, la resistencia a la insulina y el aumento de los factores proinflamatorios. El objetivo investigación fue analizar las posibles correlaciones entre las adipocinas pro/antiinflamatorias, el índice glucémico y otros marcadores de calidad de la dieta con el perfil metabólico en mujeres sometidas a terapia interdisciplinaria para perder peso. Métodos: treinta y dos mujeres con obesidad participaron en 12 semanas de terapia interdisciplinaria en la que se combinaron los enfoques clínico, nutricional y de ejercicio físico. Se analizaron la composición corporal, la calidad de la dieta, el perfil metabólico y las adipocinas pro/antiinflamatorias. Resultados: la terapia demostró ser efectiva para reducir el peso corporal, el índice de masa corporal y la grasa corporal. También hubo una mejora del perfil lipídico, incluidos el colesterol total, el colesterol no HDL, el VLDL-colesterol , y el metabolismo de la glucosa, incluyendo la glucosa y la insulina. En cuanto a la ingesta de alimentos, hubo disminución en el consumo de calorías, carbohidratos, lípidos y carga glucémica, y aumento del consumo de proteínas. Se demostraron correlaciones positivas entre la concentración de insulina y la circunferencia de la cintura ; la leptina, la grasa corporal y la circunferencia abdominal, y la fracción de colesterol LDL y el consumo total de colesterol. Se demostraron correlaciones negativas entre la leptina y el consumo de grasa monosaturada, y la adiponectina y la enzima hepática GGT. Conclusiones: la terapia interdisciplinaria tuvo efectos positivos sobre el estado inflamatorio, mediado por la leptina, la adiponectina, y la calidad de la dieta. Nuestros hallazgos sugieren la efectividad y la relevancia clínica de la terapia clínica interdisciplinaria aplicada a la obesidad.

Topics: Adiponectin; Adiposity; Adult; Blood Glucose; Body Composition; Body Mass Index; Diet; Energy Intake; Exercise Therapy; Female; Humans; Inflammation Mediators; Internet; Leptin; Lipids; Obesity; Patient Care Team; Treatment Outcome; Weight Loss

Obesity is characterized by a resistance to appetite-regulating hormones, leading to a misalignment between the physiological signals and the perceived hunger/satiety signal. A disruption of the synthesis rhythm may explain this situation. The aim of this study was to evaluate the effect of dietary-induced weight loss on the daily rhythms of leptin and ghrelin and its influence on the daily variability of the appetite sensations of patients with obesity. Twenty subjects with obesity underwent a hypocaloric dietary intervention for 12 weeks. Plasma leptin and ghrelin were analyzed at baseline and at the end of the intervention and in 13 normal-weight controls. Appetite ratings were analyzed. Weight loss decreased leptin synthesis (

Topics: Adult; Appetite; Blood Glucose; Circadian Rhythm; Female; Ghrelin; Humans; Hunger; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity; Satiety Response; Weight Loss

Dietary polyphenols including anthocyanins target multiple organs.. We aimed to assess the involvement of glucagon-like peptide 1 (GLP-1), leptin, insulin and fibroblast growth factor 21 (FGF21) in mediating metabolic beneficial effects of purified anthocyanin cyanidin-3-glucoside (Cy3G).. Intestinal proglucagon gene (Gcg; encoding GLP-1) and liver Fgf21 expression were assessed in 6-wk-old male C57BL-6J mice fed a low-fat-diet (LFD; 10% of energy from fat), alone or with 1.6 mg Cy3G/L in drinking water for 3 wk [experiment (Exp.) 1; n = 5/group]. Similar mice were fed the LFD or a high-fat diet (HFD; 60% energy from fat) with or without Cy3G for 20 wk. Half of the mice administered Cy3G also received 4 broad-spectrum antibiotics (ABs) in drinking water between weeks 11 and 14, for a total of 6 groups (n = 8/group). Metabolic tolerance tests were conducted between weeks 2 and 16. Relevant hormone gene expression and plasma hormone concentrations were assessed mainly at the end of 20 wk (Exp. 2).. In Exp. 1, Cy3G administration increased ileal but not colonic Gcg level by 2-fold (P < 0.05). In Exp. 2, Cy3G attenuated HFD-induced body-weight gain (20.3% at week 16), and improved glucose tolerance (26.5% at week 15) but not insulin tolerance. Although Cy3G had no effect on glucose tolerance in LFD mice, LFD/Cy3G/AB mice showed better glucose tolerance than LFD/Cy3G mice (23%). In contrast, HFD/Cy3G/AB mice showed worse glucose tolerance compared with HFD/Cy3G mice (15%). Beneficial effects of Cy3G in HFD mice were not associated with changes in plasma leptin, insulin or GLP-1 concentrations. However, Cy3G increased hepatic Fgf21 expression in mice in Exp. 1 by 4-fold and attenuated Fgf21 overexpression in HFD mice (Exp. 2, 22%), associated with increased expression of genes that encode FGFR1 and β-klotho (>3-fold, P < 0.05).. Dietary Cy3G may reduce body weight and exert metabolic homeostatic effects in mice via changes in hepatic FGF21.

Topics: Animals; Anthocyanins; Diet, High-Fat; Dietary Fats; Fibroblast Growth Factors; Gene Expression Regulation; Glucagon-Like Peptide 1; Glucose Intolerance; Glucosides; Incretins; Leptin; Liver; Male; Mice; Random Allocation; Weight Gain; Weight Loss

The effect of weight reduction following bariatric surgery is already well known.. To investigate the effects of abdominoplasty on metabolic markers indicative of weight loss.. The authors prospectively enrolled consecutive obese patients after laparoscopic sleeve gastrectomy. They were candidates for post-bariatric surgery abdominoplasty. The authors measured metabolic markers one day prior to surgery, 24 hours after, and 3 months following surgery. They recorded medical and demographic parameters.. Sixteen patients were recruited for participation in the study. Mean age was 47 years and 88% of the patients were female. Bariatric surgery achieved a mean decline in body mass index of 13.8 kg/m2. All patients underwent abdominoplasty. Leptin and insulin levels were slightly increased at 3 months postoperative. No significant changes were observed in glucose, hemoglobin, or triglycerides throughout the study.. In a cohort of obese patients undergoing laparoscopic sleeve gastrectomy followed by abdominoplasty, no significant changes were noted in a patient's metabolic profiles. The results suggest that abdominoplasty has no effect on the metabolic markers tested in contrast to other reports; however, the cosmetic, behavioral, and psychological advantages of abdominoplasty are well established.

Topics: Abdominoplasty; Adult; Bariatric Surgery; Cohort Studies; Female; Gastrectomy; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Weight Loss

Topics: Adiponectin; Adult; Body Mass Index; Female; Fibronectins; Humans; Hypnosis; Leptin; Male; Middle Aged; Obesity; Treatment Outcome; Weight Loss

Bariatric surgery is a first-line treatment for patients with obesity and diabetes. It is uncertain whether leptin has an influence on glycemia in the postoperative period.. A cohort study of thirty-eight individuals with obesity and diabetes who underwent laparoscopic Roux-en-Y gastric bypass was undertaken. The levels of leptin, glucose, and glycosylated hemoglobin were verified in the preoperative period and in the first and third postoperative months.. The search for factors that influence diabetes control after bariatric surgery is of major importance in clinical practice. Our study reported a level of leptin that can predict the prognosis of glycemic control after the intervention. This finding still needs to be validated and confirmed in other populations.

Topics: Bariatric Surgery; Blood Glucose; Body Mass Index; Cohort Studies; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Glycemic Control; Humans; Leptin; Middle Aged; Obesity, Morbid; Treatment Outcome; Weight Loss

Although genetic predisposition influences the onset and progression of insulin resistance and diabetes, dietary nutrients are critical. In general, protein is beneficial relative to carbohydrate and fat but dependent on protein source. Our recent study demonstrated that 70% replacement of dietary casein protein with the equivalent quantity of protein derived from herring milt protein hydrolysate (HMPH; herring milt with proteins being enzymatically hydrolyzed) significantly improved insulin resistance and glucose homeostasis in high-fat diet-induced obese mice. As production of protein hydrolysate increases the cost of the product, it is important to determine whether a simply dried and ground herring milt product possesses similar benefits. Therefore, the current study was conducted to investigate the effect of herring milt dry powder (HMDP) on glucose control and the associated metabolic phenotypes and further to compare its efficacy with HMPH. Male C57BL/6J mice on a high-fat diet for 7 weeks were randomized based on body weight and blood glucose into three groups. One group continued on the high-fat diet and was used as the insulin-resistant/diabetic control and the other two groups were given the high-fat diet modified to have 70% of casein protein being replaced with the same amount of protein from HMDP or HMPH. A group of mice on a low-fat diet all the time was used as the normal control. The results demonstrated that mice on the high-fat diet increased weight gain and showed higher blood concentrations of glucose, insulin, and leptin, as well as impaired glucose tolerance and pancreatic β-cell function relative to those on the normal control diet. In comparison with the high-fat diet, the replacement of 70% dietary casein protein with the same amount of HMDP or HMPH protein decreased weight gain and significantly improved the aforementioned biomarkers, insulin sensitivity or resistance, and β-cell function. The HMDP and HMPH showed similar effects on every parameter except blood lipids where HMDP decreased total cholesterol and non-HDL-cholesterol levels while the effect of HMPH was not significant. The results demonstrate that substituting 70% of dietary casein protein with the equivalent amount of HMDP or HMPH protein protects against obesity and diabetes, and HMDP is also beneficial to cholesterol homeostasis.

Topics: Animal Feed; Animals; Biomarkers; Blood Glucose; Diet, High-Fat; Disease Models, Animal; Energy Intake; Fatty Acids, Nonesterified; Fish Proteins, Dietary; Glycemic Control; Insulin; Insulin Resistance; Insulin-Secreting Cells; Leptin; Male; Mice, Inbred C57BL; Obesity; Protein Hydrolysates; Weight Loss

Topics: Adiposity; Adult; Anthropometry; Body Mass Index; Female; Gastric Balloon; Health Status Indicators; Humans; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Obesity; Subcutaneous Fat; Waist-Height Ratio; Weight Loss

Developing effective treatments for obesity and related metabolic disease remains a challenge. One logical strategy targets the appetite-regulating actions of gut hormones such as incretins. One of these incretins, glucose-dependent insulinotropic polypeptide (GIP), has garnered much attention as a potential target: however, whether it is beneficial to boost or block the action of GIP to promote weight loss remains an unresolved question. In this issue of the JCI, Kaneko and colleagues show that antagonizing GIP signaling in the CNS enhances the weight-reducing effects of leptin in rodents with diet-induced obesity. The authors posit that an increase in circulating intestinally derived GIP, as a consequence of overnutrition, acts in the brain to impair hypothalamic leptin action, resulting in increased food intake and body weight gain. This research advances the idea that multiple GIP signaling pathways and mechanisms exist in the obese state and offers intriguing new insights into the antiobesogenic consequences of antagonizing brain GIP action.

Topics: Gastric Inhibitory Polypeptide; Humans; Incretins; Leptin; Obesity; Weight Loss

Body weight has been shown to be a predictor of clinical progression in Huntington's disease (HD). Alongside widespread neuronal pathology, both HD patients and the R6/2 mouse model of HD exhibit weight loss and increased energy expenditure, providing a rationale for targeting whole-body energy metabolism in HD. Leptin-deficient mice display low energy expenditure and increased body weight. We therefore hypothesized that normalizing energy metabolism in R6/2 mice, utilizing leptin- deficiency, would lead to a slower disease progression in the R6/2 mouse. In this study, we show that R6/2 mice on a leptin-deficient genetic background display increased body weight and increased fat mass compared to R6/2 mice, as well as wild type littermates. The increased body weight was accompanied by low energy expenditure, illustrated by a reduction in respiratory exchange rate. Leptin-deficient R6/2 mice had large white adipocytes with white adipocyte gene expression characteristics, in contrast to white adipose tissue in R6/2 mice, where white adipose tissue showed signs of browning. Leptin-deficient R6/2 mice did not exhibit improved neuropathological measures. Our results indicate that lowering energy metabolism in HD, by increasing fat mass and reducing respiratory exchange rate, is not sufficient to affect neuropathology. Further studies targeting energy metabolism in HD are warranted.

Topics: Animals; Disease Models, Animal; Energy Metabolism; Female; Huntington Disease; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Obese; Mice, Transgenic; Weight Loss

Numerous studies associate adipokines with colorectal malignancy, but few data deal with patients suffering exclusively of rectal carcinoma (RC).. We evaluated leptin and adiponectin levels in RC patients compared to healthy population and their dynamics after surgery.. Serum leptin and adiponectin were evaluated before surgery in 59 RC consecutive patients (38 males and 21 females), and in age and weight matched healthy controls. Measurements were repeated at 24, 72 hours and 7 days after surgery.. Adipokine levels were higher in women. Controls had higher leptin (32.±4.34 vs 9.51±1.73 ng/ml in women and 11±2.66 vs 2.54±0.39 ng/ml in men, p = 0.00048 and 0.0032) and lower adiponectin (9±0.64 vs 11.85±1.02 μg/ml in women and 7.39±0.51 vs 8.5±0.62 μg/ml in men, p = 0.017 and 0.019) than RC patients. Surgery caused an increase of leptin from 5.11±0.8 to 18.7±2.42 ng/ml, p = 6.85 x 10¨8, and a decrease of adiponectin from 9.71±0.58 to 7.87±0.47 μg/ml, p = 1.4 x 10¨10 for all RC patients and returned thereafter to the initial range at 7 days. Adipokines were correlated with body weight (BW). The significance of correlation persisted after surgery only in males, but disappeared in females. Adipokines were not modified by tumor position, presurgical chemoradiotherapy or surgical technique. Women with RC experiencing weight loss had higher adiponectin than women without weight modifications (p<0.05 at all time points).. Adipokine levels of patients with RC differ from the healthy population, possibly reflecting an adaptation to disease. Adipokine modifications after surgery may be related to acute surgical stress. Whether leptin and adiponectin directly interact is not clear. Women have higher adipokine levels, more so after significant weight loss, but the strength of their correlation with BW decreases after surgery. These data suggest gender differences in the adipokine profile of RC patients which may find clinical applications.

Topics: Adiponectin; Aged; Biomarkers, Tumor; Body Weight; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Rectal Neoplasms; Sex Factors; Stress, Physiological; Weight Loss

The physiological role of leptin is thought to be a driving force to reduce food intake and increase energy expenditure. However, leptin therapies in the clinic have failed to effectively treat obesity, predominantly due to a phenomenon referred to as leptin resistance. The mechanisms linking obesity and the associated leptin resistance remain largely unclear. With various mouse models and a leptin neutralizing antibody, we demonstrated that hyperleptinemia is a driving force for metabolic disorders. A partial reduction of plasma leptin levels in the context of obesity restores hypothalamic leptin sensitivity and effectively reduces weight gain and enhances insulin sensitivity. These results highlight that a partial reduction in plasma leptin levels leads to improved leptin sensitivity, while pointing to a new avenue for therapeutic interventions in the treatment of obesity and its associated comorbidities.

Topics: Animals; Antibodies, Neutralizing; Eating; Energy Metabolism; Insulin; Insulin Resistance; Leptin; Mice; Mice, Inbred Strains; Obesity; Weight Loss; Weight Reduction Programs

The importance of hypothalamic leptin and insulin resistance in the development and maintenance of obesity remains unclear. The tyrosine phosphatases protein tyrosine phosphatase 1B (PTP1B) and T cell protein tyrosine phosphatase (TCPTP) attenuate leptin and insulin signaling and are elevated in the hypothalami of obese mice. We report that elevated PTP1B and TCPTP antagonize hypothalamic leptin and insulin signaling and contribute to the maintenance of obesity. Deletion of PTP1B and TCPTP in the hypothalami of obese mice enhances CNS leptin and insulin sensitivity, represses feeding, and increases browning, to decrease adiposity and improve glucose metabolism. The daily intranasal administration of a PTP1B inhibitor, plus the glucocorticoid antagonist RU486 that decreases TCPTP expression, represses feeding, increases browning, promotes weight loss, and improves glucose metabolism in obese mice. Our findings causally link heightened hypothalamic PTP1B and TCPTP with leptin and insulin resistance and the maintenance of obesity and define a viable pharmacological approach by which to promote weight loss in obesity.

Topics: Adipose Tissue, White; Administration, Intranasal; Animals; Blood-Brain Barrier; Cholestanes; Diet, High-Fat; Feeding Behavior; Gliosis; Glucocorticoids; Hypothalamus; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mifepristone; Obesity; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatase, Non-Receptor Type 2; Spermine; Weight Loss

Topics: Humans; Insulin; Leptin; Obesity; Weight Loss

The clinical use of the hormone leptin, a key regulator of food intake, to treat the most common instances of obesity has so far failed. In this issue, Zhao et al. (2019) report that, paradoxically, reducing leptin levels in obese mice increases their sensitivity to the concentrations that remain, and leads to reductions in weight gain, thus suggesting why these earlier trials may have failed and possibly a new approach to treating obesity.

Topics: Animals; Insulin; Leptin; Mice; Neurobiology; Obesity; Weight Loss

Birth weight and leptin seem to be the factors responsible for early programming of body weight in later life. A marker for leptin action is free leptin index (FLI), which depends on soluble leptin receptor (Ob-Re) (FLI = leptin/Ob-Re). In the present article, we suggest that FLI is modulated partly by cortisol variations observed in newborns in the first days of life and is connected with their postnatal weight loss.. The study group consisted of 44 full-term newborns. Leptin, cortisol and Ob-Re concentrations were determined in the umbilical cord blood (UCB) and in the newborns' blood (NB) on the fourth day of life, free leptin index (FLI = leptin/Ob-Re) was calculated. Correlations between the assessed parameters and the somatic features of the newborns were examined.. Birth weight, length and chest circumference of newborns were positively correlated with leptin concentration in the UCB but not with FLI in the UCB. Cortisol and leptin concentrations, as well as FLI values declined concomitantly with body weight, and were lower on the fourth day of life than on the first one; however, Ob-Re concentration increased (p < 0.0001). There was a positive correlation between the newborns' birth weight loss percentage evaluated on the fourth day of life and FLI in newborns (R = 0.39; p < 0.01). Positive correlations between cortisol and Ob-Re in UCB (R = 0.35; p < 0.02) and in NB (R = 0.36; p < 0.01), as well as a negative correlation between cortisol and FLI (R = -0.32; p < 0.03) in NB were noted.. Our data suggest a possible relationship between cortisol and a soluble leptin receptor (Ob-Re), which changes free leptin index (FLI) and is connected with birth weight loss in newborns. Whether these observations are important for programming of future body weight of children requires further research.

Topics: Age Factors; Body Weight; Female; Fetal Blood; Humans; Infant, Newborn; Leptin; Male; Receptors, Leptin; Weight Loss

Insufficient responses to hypocaloric diets have been attributed to hormonal adaptations that override self-control of food intake. We tested this hypothesis by measuring circulating energy-balance hormones and brain functional magnetic resonance imaging reactivity to food cues in 24 overweight/obese participants before, and 1 and 3 months after starting a calorie restriction diet. Increased activity and functional connectivity in prefrontal regions at month 1 correlated with weight loss at months 1 and 3. Weight loss was also correlated with increased plasma ghrelin and decreased leptin, and these changes were associated with food cue reactivity in reward-related brain regions. However, the reduction in leptin did not counteract weight loss; indeed, it was correlated with further weight loss at month 3. Activation in prefrontal regions associated with self-control could contribute to successful weight loss and maintenance. This work supports the role of higher-level cognitive brain function in body-weight regulation in humans.

Topics: Adult; Brain; Caloric Restriction; Cognition; Female; Ghrelin; Humans; Leptin; Male; Obesity; Weight Loss

Topics: Adolescent; Adult; Blood Pressure; Body Mass Index; Diabetes Mellitus; Dyslipidemias; Female; Follow-Up Studies; Gastrectomy; Ghrelin; Humans; Hypertension; Laparoscopy; Leptin; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Preoperative Period; Prospective Studies; Sleep Apnea, Obstructive; Time Factors; Treatment Outcome; Weight Loss; Young Adult

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve blood glucose control, as well as reducing bodyweight by promoting urinary glucose excretion. The weight loss is less than expected from urinary glucose loss, however, likely because of an increase in food intake. To investigate whether SGLT-2 inhibitors might increase appetite by affecting related hormones, we examined the effects of the SGLT-2 inhibitor, ipragliflozin, including those on appetite-regulating hormones, in individuals with suboptimally controlled type 2 diabetes.. Both glycated hemoglobin level (from 7.9 ± 0.8 to 7.1 ± 0.7%) and bodyweight (from 75.2 ± 12.6 to 72.6 ± 12.4 kg) were significantly decreased after treatment for 16 weeks. The fasting serum leptin level was significantly decreased after 2 weeks (from 19.5 ± 13.1 to 18.1 ± 12.4 ng/mL) and remained decreased up to 16 weeks, even after adjustment for bodyweight, whereas the plasma active ghrelin level showed no significant change. The visual analog scale score for hunger was significantly increased at 2 and 8 weeks.. The present results suggest that ipragliflozin improved glycemic control and reduced bodyweight, but also reduced serum leptin levels and might thereby have increased appetite.

Topics: Appetite; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Eating; Female; Follow-Up Studies; Ghrelin; Glucosides; Glycated Hemoglobin; Glycemic Index; Humans; Leptin; Male; Middle Aged; Prognosis; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes; Weight Loss

To investigate the association between visceral adipose tissue loss and insulin resistance and hyperleptinemia in adolescents with obesity submitted to interdisciplinary weight-loss therapy.. A total of 172 post-pubertal adolescents (body mass index greater than the 95th percentile of the Centers for Disease Control and Prevention reference growth charts) were recruited for the study. The adolescents were assigned to long-term weight-loss therapy. Body composition, visceral and subcutaneous fat, glucose metabolism, lipid profile, hepatic enzymes and leptin concentration were measured. After the therapy, the adolescents were allocated to three different groups according to the tertile of visceral fat reduction.. Positive effects on body composition were observed in all analysed groups independent of visceral fat reduction. It was found that visceral fat was an independent predictor of insulin resistance in the investigated population. Obese adolescents who lost a higher proportion of visceral adipose tissue (>1.8 cm) demonstrated improved metabolic and inflammatory parameters twice as much than those who presented smaller losses. Positive correlations between visceral fat reduction and glucose metabolism, lipid profile, hepatic enzymes and homeostasis model assessment of insulin resistance index were demonstrated.. The magnitude of the reduction in visceral fat was an independent predictor of insulin resistance, hyperleptinemia and metabolic disorders related to obese adolescents.

Topics: Adiposity; Adolescent; Age Factors; Biomarkers; Blood Glucose; Female; Health Status; Humans; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipids; Male; Metabolic Syndrome; Pediatric Obesity; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Loss; Young Adult

Weight loss triggers important metabolic responses to conserve energy, especially via the fall in leptin levels. Consequently, weight loss becomes increasingly difficult with weight regain commonly occurring in most dieters. Here we show that central growth hormone (GH) signaling also promotes neuroendocrine adaptations during food deprivation. GH activates agouti-related protein (AgRP) neurons and GH receptor (GHR) ablation in AgRP cells mitigates highly characteristic hypothalamic and metabolic adaptations induced by weight loss. Thus, the capacity of mice carrying an AgRP-specific GHR ablation to save energy during food deprivation is impaired, leading to increased fat loss. Additionally, administration of a clinically available GHR antagonist (pegvisomant) attenuates the fall of whole-body energy expenditure of food-deprived mice, similarly as seen by leptin treatment. Our findings indicate GH as a starvation signal that alerts the brain about energy deficiency, triggering key adaptive responses to conserve limited fuel stores.

Topics: Agouti-Related Protein; Animals; Body Weight; Brain; Energy Metabolism; Female; Growth Hormone; Human Growth Hormone; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Somatotropin; Weight Loss

Food restriction (FR) has been commonly used to decrease body fat, reducing the risk of overweight in humans and animals. However, the lost weight has been shown to be followed by overweight when food restriction ends. It remains uncertain whether the weight loss drives the overweight, or not. In the present study, striped hamsters were restricted by 15%, 30% and 40% of ad libitum food intake for 2 weeks, followed by high-fat refeeding for 6 weeks (FR15%-Re, FR30%-Re and FR40%-Re). The hamsters in FR15%, FR30% and FR40% groups decreased by 21.1%, 37.8% and 50.0% in fat mass (P < 0.01), and 16.8%, 42.8% and 53.4% in leptin levels (P < 0.01) compared with the hamsters fed ad libitum. The FR15%-Re, FR30%-Re and FR40%-Re groups showed 77.0%, 37.2% and 23.7% more body fat than ad libitum group (P < 0.01). The FR15%-Re group showed considerable decreases in gene expression of arcuate nucleus co-expressing proopiomelanocortin (POMC), cocaine - and amphetamineregulated transcript (CART) and the long isoform of leptin receptor (LepRb) in the hypothalamus and of several genes associated with fatty acid transport to mitochondria and β-oxidation in brown adipose tissue and liver. It suggests that less weight loss is likely to drive more fat accumulation when food restriction ends, in which the impaired function of LepRb, POMC and CART in the brain and fatty acid oxidation in brown adipose tissue and liver may be involved.

Topics: Adipose Tissue; Animals; Cricetinae; Diet, High-Fat; Feeding Behavior; Food Deprivation; Hypothalamus; Leptin; Lipid Metabolism; Male; Overweight; Pro-Opiomelanocortin; Receptors, Leptin; Weight Loss

The ketogenic diet (KD) is being increasingly promoted as a strategy to fight obesity. Although the KD is effective for weight loss and weight control, comprehensive determination of its relationship with biochemical, physiological and psychological changes is still largely unexplored. We hypothesized that a 12-week KD (12KD) would significantly affect body weight, physical performance, cognitive function, eating behaviors, the metabolic and hormonal profile in obese adults, although differently in men and women. In an uncontrolled intervention, 35 sedentary obese adults (13 men, 25 women), aged 37 ± 7 years with a BMI 36.1 ± 5.6 kg/m

Topics: Adult; Blood Glucose; Cholesterol, LDL; Cognition; Diet, Ketogenic; Feeding Behavior; Female; Humans; Insulin; Leptin; Male; Obesity; Physical Functional Performance; Weight Loss

The prevalence of obesity increases with age in humans and in rodents. Age-related obesity is characterized by leptin resistance and associated with heightened risk of metabolic disorders. However, the effect of leptin resistance per se has been difficult to disentangle from other effects of aging. Here we demonstrate that celastrol, a natural phytochemical that was previously shown to act as a leptin sensitizer, induces weight loss in aged animals, but not in young controls. Celastrol reduces food intake and lowers fasting glucose without affecting energy expenditure. Unexpectedly, administration of celastrol just before the dark period disrupted circadian rhythms of sleep and activity. This regimen was also associated with loss of lean mass an outcome that would not be desirable in elderly patients. Adjusting the timing of celastrol administration by 12 hr, to the beginning of the light period, avoided interference with circadian rhythms while retaining the reductions in body weight and adiposity. Thus, targeting leptin signaling is an effective strategy to ameliorate age-associated weight gain, and can profoundly impact circadian rhythms.

Topics: Aging; Animals; Behavior, Animal; Body Weight; Circadian Rhythm; Eating; Energy Metabolism; Glucose Tolerance Test; Injections, Intraperitoneal; Leptin; Male; Mice; Obesity; Pentacyclic Triterpenes; Triterpenes; Weight Loss

To assess the differences in the parameters that are metabolically related to cardiovascular diseases after weight loss in obese people with coronary artery diseases (CADs).. This study was conducted on 184 patients who were diagnosed with CADs in Istanbul University Cardiology Institute Hospital, Istanbul, Turkey. The levels of leptin, fibrinogen, homocysteine, high-sensitivity C-reactive protein (hs-CRP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), fasting blood glucose and insulin, glycated hemoglobin, and uric acid of the obese patients who were put on calorie restricted diet were evaluated retrospectively and compared before and after weight loss. For comparison, non-obese control patients were also studied. Student's t-test and Chi-square test were used for the statistical analysis. Results: Levels of homocysteine, glycated hemoglobin, and leptin were significantly higher in the obese patients than in the non-obese patients. Diabetic obese patients with CADs lost (11.1%) and non-diabetic obese patients with CADs lost (10.5%) of their body weight in 6 months. The levels of cholesterol, LDL-C, and fibrinogen were significantly improved in both groups. Conclusion: The obese patients lost weight after being on calorie-restricted diets and showed significant improvement in the levels of cholesterol, LDL-C, fibrinogen. There was no significant difference in the levels of homocysteine, hs-CRP, and leptin before and after weight loss in both diabetic and non-diabetic obese patients.

Topics: Adult; Aged; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Chi-Square Distribution; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet, Reducing; Female; Fibrinogen; Glycated Hemoglobin; Homocysteine; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Triglycerides; Uric Acid; Weight Loss

Leptin has been shown to stimulate the hypothalamus-pituitary-thyroid (HPT) axis in vivo and vitro. Its role in thyroid axis regulation after weight loss induced by bariatric surgery is still unknown. The aim of this study was to evaluate the influence of leptin on weight loss and thyroid function variation induced by Roux-en-Y gastric bypass (RYGB) surgery in euthyroid individuals with obesity and type 2 diabetes mellitus (T2DM).. 65 Chinese individuals with obesity and T2DM who underwent RYGB, and 27 healthy volunteers were enrolled in this retrospective study. Participants were evaluated for changes in anthropometric parameters, metabolic indexes, thyroid function, and leptin levels before and 12 months after surgery.. After RYGB, all of these patients experienced significant weight reduction and improved glucose control. Metabolic parameters were significantly ameliorated after surgery compared with baseline. Thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) declined in parallel. Median (IQR) plasma leptin levels decreased from 33.7 ng/mL (17.9-63.1) to 10.3 ng/mL (4.0-18.5). Pearson correlation analysis showed that TSH was significantly positively correlated with body mass index, C-reactive protein (CRP), and leptin. Multiple stepwise linear regression indicated that leptin and CRP were independent factors affecting TSH. The β coefficients were 0.38 (p = 0.001) and 0.32 (p = 0.004), respectively. There was a significant positive correlation between ΔTSH and Δleptin (r = 0.33, p = 0.01).. Decreased or normalized TSH levels after weight loss induced by RYGB might be mediated by the decline in leptin. There could be cross talk between adipose tissue and the HPT axis.

Topics: Adult; Bariatric Surgery; Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Humans; Leptin; Male; Middle Aged; Obesity; Retrospective Studies; Thyroid Gland; Thyrotropin; Weight Loss

We studied the effects of multiple cycles of weight loss and regain on the defended body weight in rats. Thirty-six male Wistar rats were divided into three weight-matched groups: weight cyclers (

Topics: Adiposity; Animals; Body Composition; Body Weight; Caloric Restriction; Diet, Reducing; Ghrelin; Glucose Tolerance Test; Insulin; Leptin; Male; Rats; Rats, Wistar; Weight Loss

Hyperleptinemia is supposed to play a causal role in the development of obesity-associated hypertension, possibly via increased sympathetic tone. Hence patients with congenital leptin deficiency should be hypotensive and their low blood pressure should increase under leptin substitution.. To test this assumption, we examined ambulatory blood pressure, resting heart rate, Schellong test results, cold pressor test results, heart rate variability, catecholamine metabolites, and aldosterone levels in 6 patients with congenital leptin deficiency before as well as 2-7 days and 7-14 months after the start of leptin substitution. Ambulatory blood pressure was also examined in 3 patients with biallelic disease-causing variants in the leptin receptor gene.. Contrary to our expectations, even before leptin substitution, 1 patient with biallelic leptin receptor gene variants and 4 patients with leptin deficiency had been suffering from hypertension. Short-term substitution with leptin increased blood pressure further in 3 out of 4 patients (from 127.0 ± 11.7 to 133.8 ± 10.6 mm Hg), concomitant with an increase in resting heart rate as well as in heart rate during the Schellong test in all patients (from 87.6 ± 7.7 to 99.9 ± 11.0 bpm, p = 0.031, and from 102.9 ± 13.5 to 115.6 ± 11.3 bpm, p = 0.031, respectively). Furthermore, the systolic blood pressure response during the cold pressor test increased in 4 out of 6 patients. Unexpectedly, catecholamine metabolites and aldosterone levels did not increase. After long-term leptin substitution and weight loss, the resting heart rate decreased in 4 out of 6 patients compared to baseline, and in all patients below the heart rate seen immediately after the start of therapy (from 99.9 ± 11.0 to 81.7 ± 5.4 bpm; p = 0.031).. These results show that obesity-associated hypertension does not depend on the presence of leptin. However, short-term leptin substitution can increase the blood pressure and heart rate in obese humans with leptin deficiency, indicating that leptin plays at least an additive role in obesity-associated hypertension. The mechanisms behind this are not clear but might include an increase in regional sympathetic tone.

Topics: Adolescent; Adult; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Child; Cohort Studies; Female; Heart Rate; Hormone Replacement Therapy; Humans; Hypertension; Leptin; Male; Metabolism, Inborn Errors; Obesity; Receptors, Leptin; Weight Loss; Young Adult

Leptin administration into the hindbrain, and specifically the nucleus of the solitary tract, increases phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin receptor activation, in hypothalamic nuclei known to express leptin receptors. The ventromedial nucleus of the hypothalamus (VMH) shows the greatest response, with a threefold increase in pSTAT3. This experiment tested the importance of VMH leptin receptor-expressing neurons in mediating weight loss caused by fourth ventricle (4V) leptin infusion. Male Sprague-Dawley rats received bilateral VMH 75-nL injections of 260 ng/μL of leptin-conjugated saporin (Lep-Sap) or blank-saporin (Blk-Sap). After 23 days they were fitted with 4V infusion cannulas and 1 wk later adapted to housing in a calorimeter before they were infused with 0.9 μg leptin/day for 14 days. There was no effect of VMH Lep-Sap on weight gain or glucose clearance before leptin infusion. Leptin inhibited food intake and respiratory exchange ratio in Blk-Sap but not Lep-Sap rats. Leptin had no effect on energy expenditure or brown adipose tissue temperature of either group. Inguinal and epididymal fat were significantly reduced in leptin-treated Blk-Sap rats, but the response was greatly attenuated in Lep-Sap rats. VMH pSTAT3 was increased in leptin-treated Blk-Sap but not Lep-Sap rats. These results support the concept that leptin-induced weight loss results from an integrated response across different brain areas. They also support previous reports that VMH leptin receptors do not play a significant role in maintaining energy balance in basal conditions but limit weight gain during positive energy balance.

Topics: Adipose Tissue; Animals; Body Temperature; Eating; Fourth Ventricle; Glucose; Infusions, Intraventricular; Leptin; Male; Neurons; Rats; Rats, Sprague-Dawley; Receptors, Leptin; Saporins; STAT3 Transcription Factor; Ventromedial Hypothalamic Nucleus; Weight Loss

We monitored changes in serum leptin, adiponectin, and resistin concentrations in obese cats during weight loss. Six naturally developed obese cats were fed low-fat, high-fiber dry food during a 9-week experimental period. Serum leptin, adiponectin, and resistin concentrations were measured at week 0, 4, 8, and 9. Body weight became significantly lower week 4 onward than that at week 0 (P<0.05 or 0.01). At week 9, serum leptin concentrations were significantly lower than those at week 0 (P<0.05). Contrarily, serum adiponectin and resistin concentrations did not significantly differ within the 9 weeks. While serum leptin levels were strongly positively correlated with body weight (r=0.923, P<0.001), serum adiponectin levels were moderately negatively correlated with it (r=-0.529, P<0.01), with serum resistin having a no correlation with body weight. Serum leptin levels might be more closely related with pathogenesis of adiposity than serum adiponectin or resistin in cats.

Topics: Adiponectin; Animals; Cat Diseases; Cats; Diet; Female; Leptin; Obesity; Resistin; Weight Loss

Topics: Adipose Tissue; alpha-MSH; AMP-Activated Protein Kinases; Animals; Appetite; Blood Glucose; Body Weight; Brain; Carrier Proteins; Eating; Heat-Shock Proteins; Hypothalamus; Insulin; Leptin; Male; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Pro-Opiomelanocortin; Weight Loss

Loss of white adipose tissue (WAT), associated with type 1 diabetes (DM1), contributes to increased chronic systemic inflammation.. The aim of this study was to investigate the effects of leucine supplementation and resistance training (RT) in attenuating WAT loss and improving inflammatory parameters and glucose metabolism in DM1 rats.. Thirty-two male Wistar rats were distributed into four groups: DA (sedentary and supplemented with non-essential amino acids (NEAA)), DL (sedentary and supplemented with leucine), DTA (submitted to RT and supplemented with NEAA) and DTL (submitted to RT and supplemented with leucine). DM1 was induced by streptozotocin (STZ). An 8-week period of RT consisted of climbing a ladder with a progressively increased load, and supplementation was offered in the feed.. Glycemia, polyphagia and polydipsia were lower in DL, DTA and DTL groups compared with the DA group by approximately 20% ( p<.0001), 28% ( p=.004) and 64% ( p<.0001), respectively. Weight of total WAT and retroperitoneal adipose tissue (RPAT) were higher by approximately 21% ( p=.01) and 54% ( p=.0004), respectively, in DL, DTA and DTL groups compared with DA. However, gene expression of adiponectin and leptin in RPAT was only increased by RT (DTA and DTL) compared with DA and DL by approximately 93% ( p<.0001) and 78% ( p=.0002), respectively. Similarly, the levels of adiponectin in the serum, tissue IL-10 (RPAT) and serum IL-10 were only increased in DTA and DTL compared with DA and DL by approximately 31% ( p=.03), 45% ( p=.0009) and 35% ( p=.003), respectively.. Both interventions, isolated or together, reduced hyperglycemia and excessive loss of WAT, but RT was the main factor responsible for attenuating inflammation.

Topics: Adiponectin; Adipose Tissue, White; Adiposity; Animals; Anti-Inflammatory Agents, Non-Steroidal; Combined Modality Therapy; Diabetes Mellitus, Type 1; Dietary Supplements; Gene Expression Regulation; Hyperglycemia; Inflammation Mediators; Insulin Resistance; Intra-Abdominal Fat; Leptin; Leucine; Male; Random Allocation; Rats, Wistar; Resistance Training; Weight Loss

We evaluated the contribution of brown adipose tissue (BAT) sympathetic innervation on central leptin-mediated weight loss. In a short- and long-term study, F344BN rats were submitted to either a denervation of interscapular BAT (Denervated) or a sham operation (Sham). Animals from each group received the Ob (Leptin) or green fluorescent protein (GFP; Control) gene through a single injection of recombinant adeno-associated virus delivered centrally. Changes in body weight were recorded for 14 or 35 days, after which adipose tissues and skeletal muscles were weighed. In both studies, hypothalamic phosphorylated STAT3 (P-STAT3) was significantly higher in Sham-Leptin and Denervated-Leptin groups compared with their respective Control groups ( P < 0.01), indicating that leptin signaling was enhanced at the end point. We measured uncoupling protein 1 (UCP1), a marker of BAT thermogenic activity, and found a significant induction in Leptin in Sham animals ( P < 0.001) but not in Denervated animals, demonstrating that BAT UCP1 protein was only induced in Sham rats. Both Sham-Leptin and Denervated-Leptin rats lost ~15% of their initial body weight ( P < 0.001) by day 14 and reached a maximum of 18% body weight loss that stabilized over week 3 of treatment, indicating that sympathetic outflow to BAT is not required for leptin-mediated weight loss. In summary, interscapular BAT (iBAT) denervation did not prevent body weight loss following central leptin gene delivery. The present data show that sympathetic innervation of iBAT is not essential for leptin-induced body weight loss.

Topics: Adipose Tissue, Brown; Animals; Body Weight; Denervation; Dependovirus; Gene Expression Regulation; Gene Transfer Techniques; Infusions, Intraventricular; Leptin; Male; Rats; Rats, Inbred F344; Rats, Transgenic; Sympathetic Nervous System; Thermogenesis; Uncoupling Protein 1; Weight Loss

Body fat distribution has been shown to be a predictor of adhesion molecule and inflammatory marker expression albeit the effect of modest weight change on concentrations of adhesion molecules and inflammatory markers in postmenopausal women are not fully understood. The primary aim was to investigate the effects of weight change on adhesion molecules and inflammatory markers over 24 months in postmenopausal women.. Body composition was assessed in 254 healthy postmenopausal women using dual-energy X-ray absorptiometry (DXA). Adhesion molecules and inflammatory markers were analysed by multiplex ELISA. Participants weight gain/loss at 24 months was defined as any value that was either above/below the weight value recorded at baseline.. Postmenopausal women with an average weight loss of 3% had significantly decreased leptin concentrations by 18% at 24 months (P < 0.01). A 4% increase in body weight or a 9% increase in FMI significantly increased intercellular adhesion molecule-1 (ICAM-1), tumour necrosis factor-α (TNF-α) and leptin concentrations in postmenopausal women at 24 months (P < 0.01).. Modest weight loss in postmenopausal women has a lowering effect on leptin concentrations over 24 months which may improve inflammatory status whilst modest weight gain increases ICAM-1, leptin and TNF-α, markers which are associated with a pro-inflammatory state and vascular complications.

Topics: Aged; Biomarkers; Body Weight; Cohort Studies; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leptin; Middle Aged; Postmenopause; Tumor Necrosis Factor-alpha; Weight Gain; Weight Loss

Increased parathyroid hormone (PTH) is commonly associated with obesity, and its role in the pathogenesis of obesity-related glucometabolic abnormalities is uncertain. We aimed to explore the relationships of PTH with glucose/insulin homeostasis parameters before and after bariatric surgery-induced weight loss, and whether they depend or not on 25-hydroxyvitamin D (25OHD) status.. We included 42 subjects (27 women, aged 40 ± 5 years, BMI 48.5 ± 7.3 kg/m. Weight loss was accompanied by significant reduction of PTH levels (77.9 ± 19.1 vs. 60.5 ± 13.4 pg/ml; p = 0.005), without concomitant modification of 25OHD status. Both baseline PTH and its postoperative percent change resulted associated, with baseline fat mass (β = 0.615, p = 0.003) and its concurrent postoperative reduction (r = 0.419; p = 0.006), but neither with glucose homeostasis parameters nor their respective variations after weight loss. Interestingly, leptin reduction after weight loss was independently related to PTH change (β = 0.396, p = 0.015) and IGF-1 levels (β = 0.176, p = 0.059).. Circulating PTH decreases with fat mass reduction independent of 25OHD status, but it  is not associated with improvement of insulin resistance and related metabolic parameters. Leptin and PTH may mediate the cross-talk between adipose tissue and parathyroid glands, which possibly contributes to bone adaptation to excess body weight.

Topics: Adult; Bariatric Surgery; Blood Glucose; Body Mass Index; Calcium; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity, Morbid; Parathyroid Hormone; Vitamin D; Weight Loss

Purpose/Aim: The influence of weight loss on bone turnover and bone quality in childhood remains controversial, but it may implicate interactions between adiposity and bone metabolism. Therefore, we studied the relationships between bone markers and adipokines during weight loss in obese children.. We determined serum leptin, soluble leptin receptor, adiponectin, bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), sclerostin, body composition, and bone mineral density (BMD) in 40 obese prepubertal children before and after therapy. The control group, matched for sex and age, consisted of 40 non-obese children.. We found that values of the total body less head-bone mineral content (TBLH-BMC) and TBLH-BMD were significantly increased, but TBLH-BMD Z-score was decreased by 25% (p = 0.002) in obese children with weight loss after therapy. We observed increases of CTX-I to OC ratio (p = 0.009), and Gla-OC concentrations (p = 0.049). Changes in TBLH-BMD Z-score in patients were positively correlated with changes in BMI Z-score (p = 0.001), percentage of fat mass (p = 0.004), and BALP activity (p = 0.01). Changes in BALP activity were negatively correlated (p < 0.001) with changes in adiponectin concentrations, while changes in sclerostin levels were positively correlated (p = 0.001) with leptin changes.. We suggest that alterations in adipokines metabolism were associated with a lower rate of bone mineral accrual as a result of decreased bone formation rather than increased bone resorption. The lower rate of bone mass accrual in weight losing children may be an effect of reduced BALP levels related to increase in adiponectin levels.

Topics: Adaptor Proteins, Signal Transducing; Adipokines; Adiponectin; Behavior Therapy; Body Composition; Body Mass Index; Bone Density; Bone Morphogenetic Proteins; Bone Remodeling; Child; Child, Preschool; Diet Therapy; Exercise Therapy; Female; Genetic Markers; Humans; Leptin; Male; Pediatric Obesity; Receptors, Leptin; Weight Loss

Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.

Topics: Adipose Tissue; Animals; Body Weight; Diet, High-Fat; Energy Intake; Energy Metabolism; Gene Expression Regulation; Homeostasis; Leptin; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Obesity; Osteocytes; Rats, Sprague-Dawley; Weight Loss

Investigations into the relationship between dietary carbohydrate restriction and health are mixed. Current guidelines for nutrition promote low-fat foods and higher carbohydrate consumption for optimal health and weight loss. However, high-fat, low-carbohydrate diets are revealing both intra- and extracellular adaptations that have been shown to elicit favorable cardiometabolic changes associated with obesity. Moreover, dietary fat is associated with higher satiety levels from the hormones adiponectin, leptin, and cholecystokinin. Additionally, insulin responses from high-glycemic carbohydrates are known to alter these pathways, potentially leading to an increase in energy consumption and a possible mechanism for obesity.. There is convincing evidence of beneficial effects of controlled trials implementing high-fat, low-carbohydrate diets in both sedentary and obese individuals, but longer duration clinical trials are required to confirm this hypothesis.

Topics: Adiponectin; Cholecystokinin; Diet, Carbohydrate-Restricted; Diet, High-Fat; Energy Intake; Humans; Insulin; Leptin; Nutrition Policy; Obesity; Satiation; Weight Loss

Food restriction (FR) is the most commonly used intervention to prevent the overweight. However, the lost weight is usually followed by "compensatory growth" when FR ends, resulting in overweight. The present study was aimed to examining the behavior patterns and hormones mechanisms underpinning the over-weight. Energy budget and body fat content, and several endocrine markers related to leptin signals were examined in the striped hamsters under 20% FR refed by either low-fat diet (LF group) or high-fat diet (HF group). Body mass and fat content significantly regained when FR ended, and the hamsters in HF group showed 49.1% more body fat than in LF group (P < 0.01). Digestive energy intake was higher by 20.1% in HF than LF group, while metabolic thermogenesis and behavior patterns did not differed between the two groups. Gene expression of leptin receptor and anorexigenic peptides of pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript in hypothalamus were significantly up-regulated in LF group, but down-regulated in HF group. It suggests that effective leptin signals to the brain were involved in attenuation of hyperphagia in hamsters refed with LF. However, "leptin resistance" probably occurred in hamsters refed with HF, which impaired the control of hyperphagia, resulting in development of over-weight.

Topics: Adipose Tissue; Animals; Body Weight; Cricetinae; Diet, High-Fat; Dietary Fats; Down-Regulation; Eating; Energy Intake; Hyperphagia; Hypothalamus; Leptin; Male; Overweight; Pro-Opiomelanocortin; Receptors, Leptin; Thermogenesis; Up-Regulation; Weight Loss

Human obesity is associated with impaired central insulin signaling, and in very rare cases, severe obesity can be caused by congenital leptin deficiency. In such patients, leptin replacement results in substantial weight loss and improvement in peripheral metabolism.. In a leptin-deficient patient, we investigated the impact of leptin substitution on central insulin action, as quantified by changes in neuronal activity after intranasal insulin application. This was assessed before and during the first year of metreleptin substitution.. After only 1 year, treatment with metreleptin reestablishes brain insulin sensitivity, particularly in the hypothalamus and, to a lesser degree, in the prefrontal cortex. Results are depicted in comparison with a control group. In our patient, brain activation changes were accompanied by substantial weight loss, reduced visceral adipose tissue, reduced intrahepatic lipid content, and improved whole-body insulin sensitivity.. Leptin replacement and weight loss improved homeostatic insulin action in the patient in question.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Hormone Replacement Therapy; Humans; Hypothalamus; Insulin; Insulin Resistance; Leptin; Pakistan; Prefrontal Cortex; Weight Loss; Young Adult

Endoscopic sleeve gastroplasty is a safe and feasible treatment for obesity. This study is focused on our technique modification which suggests a different suturing pattern in order to distribute suture tension more evenly.. A retrospective study of 148 patients (121 women) who underwent this procedure and were monitored for 12 months was conducted. The average age was 41.53 ± 10 years. The average BMI was 35.11 ± 5.5 kg/m. %TWL was 17.53 ± 7.57 in 12 months and 18.5 ± 9% in 18 months indicating durability of the procedure. Patients with a BMI < 35 benefited most from an endoscopic gastroplasty. Leptin did not predict a response to endoscopic gastroplasty and decreased in all patients. In just one case there was a mild bleeding (0.67%) at the insertion point of the helix, which was resolved by sclerotherapy.. Endoscopic gastroplasty offers a real choice for obese patients. This single-center experience with a modified suturing pattern provides a successful technique for weight loss.

Topics: Adult; Body Mass Index; Endoscopy; Female; Gastroplasty; Humans; Leptin; Male; Obesity; Retrospective Studies; Suture Techniques; Weight Loss

Topics: Adiponectin; Adult; alpha-MSH; Energy Metabolism; Female; Gastric Bypass; Humans; Leptin; Male; Middle Aged; Obesity; Peptide YY; Prospective Studies; Treatment Outcome; Weight Loss

Obesity is a multifactorial disease characterized by the presence of the pro-inflammatory state associated with the development of many comorbidities, including bone turnover marker alterations. This study aimed to investigate the role of the inflammatory state on bone turnover markers in obese adolescents undergoing interdisciplinary weight loss treatment for one year.. Thirty four post-pubescent obese adolescents with primary obesity, a body mass index (BMI) greater than > 95th percentile of the CDC reference growth charts, participated in the present investigation. Measurements of body composition, bone turnover markers, inflammatory biomarkers and visceral and subcutaneous fat were taken. Adolescents were submitted to one year of interdisciplinary treatment (clinical approach, physical exercise, physiotherapy intervention, nutritional and psychological counseling).. Reduction in body mass, body fat mass, visceral and subcutaneous fat, as well as, an increase in the body lean mass and bone mineral content was observed. An improvement in inflammatory markers was seen with an increase in adiponectin, adiponectin/leptin ratio and inteleukin-15. Moreover, a positive correlation between the adiponectin/leptin ratio and osteocalcin was demonstrated. Further, both lean and body fat mass were predictors of osteocalcin. Negative associations between leptin with osteocalcin, adiponectin with Beta CTX-collagen, and visceral fat with adiponectin were observed.. It is possible to conclude that the inflammatory state can negatively influence the bone turnover markers in obese adolescents. In addition, the interdisciplinary weight loss treatment improved the inflammatory state and body composition in obese adolescents. Therefore, the present findings should be considered in clinical practice.

Topics: Adiponectin; Adolescent; Adult; Biomarkers; Body Mass Index; Bone Density; Bone Remodeling; Combined Modality Therapy; Diet, Reducing; Exercise Therapy; Female; Humans; Leptin; Male; Obesity; Osteocalcin; Resistance Training; Weight Loss; Young Adult

Pathophysiological links between inflammation, obesity, and adipokines can be used for the treatment of metabolic dysregulation.. To examine the influence of duodenal-jejunal omega switch surgery in combination with different diet patterns on plasma concentrations of fatty acid-binding protein 4 (FABP4), C-reactive protein (CRP), leptin, and chemerin.. After 8 weeks on a high-fat diet (HF) or control diet (CD), rats underwent surgery. Duodenal-jejunal omega switch (DJOS) with an exclusion of one-third of intestinal length and SHAM surgery were performed. For the next 8 weeks, 50% of DJOS/SHAM animals were kept on the same diet as before (HF/DJOS/HF, HF/SHAM/HF, CD/DJOS/CD, and CD/SHAM/CD), and 50% had a changed diet (HF/DJOS/CD, HF/SHAM/CD, CD/DJOS/HF, and CD/SHAM/HF). FABP4, CRP, leptin, and chemerin were assessed using ELISA kits.. FABP4: significant differences between DJOS and SHAM were observed in animals maintained on CD/CD; CRP: varied between DJOS and SHAM groups maintained on HF/HF, CD/CD, and CD/HF; leptin and chemerin levels: DJOS lowered leptin and chemerin plasma levels versus SHAM, while HF/HF, CD/HF, and HF/CD significantly increased leptin and chemerin plasma levels when compared to CD/CD.. The beneficial effect of DJOS surgery is stronger than proinflammatory conditions caused by an HF obesogenic diet.

Topics: Animals; Bariatric Surgery; C-Reactive Protein; Chemokines; Dietary Fats; Duodenum; Fatty Acid-Binding Proteins; Intercellular Signaling Peptides and Proteins; Jejunum; Leptin; Male; Rats; Rats, Sprague-Dawley; Weight Loss

Bariatric surgery is considered the most efficient treatment for morbid obesity and its related diseases. However, its role as a metabolic modifier is not well understood. We aimed to determine biosignatures of response to bariatric surgery and elucidate short-term metabolic adaptations.. We used a LC- and FIA-ESI-MS/MS approach to quantify acylcarnitines, (lyso)phosphatidylcholines, sphingomyelins, amino acids, biogenic amines and hexoses in serum samples of subjects with morbid obesity (n = 39) before and 1, 3 and 6 months after bariatric surgery. K-means cluster analysis allowed to distinguish metabotypes of response to bariatric surgery.. For the first time, global metabolic changes following bariatric surgery independent of the baseline health status of the subjects have been revealed. We identify two metabolic phenotypes (metabotypes) at the interval 6 months-baseline after surgery, which presented differences in the levels of compounds of urea metabolism, gluconeogenic precursors and (lyso)phospholipid particles. Clinically, metabotypes were different in terms of the degree of improvement in insulin resistance, cholesterol, low-density lipoproteins and uric acid independent of the magnitude of weight loss.. This study opens new perspectives and new hypotheses on the metabolic benefits of bariatric surgery and understanding of the biology of obesity and its associated diseases.

Topics: Adult; Anthropometry; Bariatric Surgery; C-Reactive Protein; Chromatography, Liquid; Female; Follow-Up Studies; Gluconeogenesis; Humans; Insulin Resistance; Leptin; Lipids; Lipoproteins, LDL; Male; Metabolome; Middle Aged; Obesity, Morbid; Phenotype; Tandem Mass Spectrometry; Treatment Outcome; Urea; Weight Loss; Young Adult

Weight is defended so that increases or decreases in body mass elicit responses that favor restoration of one's previous weight. While much is known about the signals that respond to weight loss and the central role that leptin plays, the lack of experimental systems studying the overfed state has meant little is known about pathways defending against weight gain. We developed a system to study this physiology and found that overfed mice defend against increased weight gain with graded anorexia but, unlike weight loss, this response is independent of circulating leptin concentration. In overfed mice that are unresponsive to orexigenic stimuli, adipose tissue is transcriptionally and immunologically distinct from fat of ad libitum-fed obese animals. These findings provide evidence that overfeeding-induced obesity alters adipose tissue and central responses in ways that are distinct from ad libitum obesity and activates a non-leptin system to defend against weight gain.

Topics: Adipose Tissue; Animals; Anorexia; Hyperphagia; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Weight Gain; Weight Loss

Appetite and weight changes are core symptoms of Major Depressive Disorder (MDD), and those with MDD are at increased risk of obesity, cardiovascular disease and metabolic disorders. Leptin promotes satiety, with leptin dysregulation and resistance noted in obesity. However, the role of leptin in weight changes in MDD is not established. This study investigates leptin levels in relation to appetite and weight changes and problematic eating behaviours in MDD.. Plasma leptin levels, psychopathology and biometrics were compared between participants meeting DSM-5 diagnostic criteria for MDD (n = 63) and healthy controls (n = 60). Depressed participants were also sub-categorised according to increased, decreased or unchanged appetite and weight. The Dutch Eating Behaviour Questionnaire and Yale Food Addiction Scale were examined in a subset of participants with MDD.. Females with increased appetite/weight had higher leptin levels than those with stable or reduced appetite/weight, however males showed the opposite effect. Leptin levels were positively correlated with problematic eating behaviours. One quarter of the depressed subset, all females, met the Yale criteria for food addiction, approximately double the rates reported in general community samples.. The study is limited by a cross sectional design and a small sample size in the subset analysis of eating behaviours.. The results provide new information about associations between leptin, sex-specific weight and appetite changes and problematic eating behaviours, which may be risk factors for cardiovascular and metabolic diseases in MDD, particularly in females. Future longitudinal research investigating leptin as a risk factor for weight gain in MDD is warranted, and may lead to early interventions aimed at preventing weight gain in at-risk individuals.

Topics: Adult; Appetite; Case-Control Studies; Cross-Sectional Studies; Depressive Disorder, Major; Feeding and Eating Disorders; Female; Humans; Leptin; Male; Middle Aged; Sex Characteristics; Weight Gain; Weight Loss

Spexin is a novel peptide predominantly produced in human white adipose tissue and has recently been implicated as a potential signal in the regulation of body weight, energy homeostasis, and satiety. The effect of bariatric surgery on spexin is unknown.. To study the effect of Roux-en-Y gastric bypass (RYGB) surgery on endogenous spexin concentration and various risk factors of type 2 diabetes and cardiovascular disease in youth with severe obesity.. University hospital, United States METHODS: Spexin, body mass index (BMI), insulin, glucose, total and high molecular weight adiponectin, leptin, and high sensitivity C- reactive protein were measured longitudinally (baseline, 6 mo, and 12 mo) after RYGB surgery in girls with severe obesity (n = 12; age = 16.7 ± 1.5 years; BMI = 51.6 ± 2.9 kg/m. Serum spexin concentration increased (P = .01) at 6 months after surgery and stabilized afterward. Spexin level correlated negatively with homeostatic model assessment insulin resistance, HOMA-IR (Spearman correlation r = -.796, P < .001) and positively with high molecular weight adiponectin (Spearman correlation r = .691, P = .011). The change in spexin concentration, from baseline to 6 months after surgery, was inversely correlated with the corresponding change in BMI (Spearman correlation r = -.573, P = .051). Furthermore, the 6-month changes in spexin and HOMA-IR were inversely correlated (slope [standard error, SE] = -.0084 (.0019), P = .001)], even after adjusting for the change in BMI.. The enhancement of circulating spexin concentration in response to RYGB and correlations with beneficial postoperative changes in various adipokines in youth are novel findings that require further validation.

Topics: Adiponectin; Adolescent; Body Mass Index; C-Reactive Protein; Female; Gastric Bypass; Humans; Insulin Resistance; Leptin; Obesity, Morbid; Pediatric Obesity; Peptide Hormones; Pilot Projects; Prospective Studies; Weight Loss

The objectives of this study were to verify effects of step-aerobic exercise (SAE) and jogging-walking exercise (JWE) program on myokines and adipokines levels in overweight sedentary females.. Volunteer subjects (N.=25) were assigned to two exercise groups: steps aerobics and jogging-walking. The exercise program given to them was for five days a week and for twelve weeks period. Serum samples were collected from venous blood before and immediately after Cardio-Respiratory Fitness Test (CRF) by Bruce protocol and stored at -80 °C until they were assayed before 12 weeks exercise program. After 12-weeks training program this procedure was repeated. Serum TNF-α, IL-6, IL-15, IL-17, IL-18, leptin, resistin and adiponectin levels were assayed by ELISA.. Leptin and IL-15 levels were increased whereas resistin levels were decreased after CRF Test in JWE training group following 12-weeks exercise program. TNF-α, IL-15 and IL-18 levels were higher and leptin levels were lower in SAE group than JWE group after 12-weeks exercise period. However, both SAE and JWE did not lead to significant change in serum levels of IL-17, IL-6 and adiponectin levels.. This study has added to existing knowledge that both SAE and JWE may cause weight loss especially in fat mass. But, the effect of SAE and JWE on myokines and adipokines levels may be the different. Further studies are needed to find out clinical importance of these findings.

Topics: Adipokines; Adiponectin; Adult; Exercise Therapy; Female; Humans; Interleukin-15; Interleukin-17; Interleukin-18; Interleukin-6; Jogging; Leptin; Overweight; Tumor Necrosis Factor-alpha; Walking; Weight Loss

Topics: Adiponectin; Adult; Blood Glucose; Body Mass Index; Female; Gastrectomy; Humans; Insulin; Insulin Resistance; Japan; Leptin; Lipids; Male; Middle Aged; Obesity, Morbid; Organ Size; Pancreas; Retrospective Studies; Spleen; Tomography, X-Ray Computed; Treatment Outcome; Weight Loss

BACKGROUND Ligation of the left gastric artery (LLGA), which supplies the fundus of the stomach, may reduce the appetite hormone ghrelin, resulting in weight control. The aim of this study was to compare LLGA and sleeve gastrectomy (SG) in terms of postoperative outcomes in a rat model. MATERIAL AND METHODS Fifteen male Wistar albino rats, weighing >350 grams (range 350-525 grams), were enrolled in LLGA (N=5), SG (N=5), and control (N=5) groups. Blood samples were drawn preoperatively and also during the first and fourth week postoperatively to assay ghrelin and leptin hormone levels. Body weight was measured in each group. RESULTS The maximum reduction in ghrelin level (41.5%) was found in the LLGA group. Considerable% total weight loss (TWL) (mean 24.1%) was observed in the SG group, and slight%TWL was noted in the control and LLGA groups (means of 0.1% and 2.1%, respectively). There was no significant difference in mean percent weight change between the LLGA and the SG groups (p=0.08). Blood sample analysis revealed no statistically significant changes in ghrelin or leptin levels between the groups (p=0.9 and p=0.3, respectively). CONCLUSIONS We present evidence that LLGA causes the same reduction in ghrelin hormone levels as SG at 4 weeks after surgery in a rat model. However, LLGA did not cause the same%TWL as SG. The mechanism of weight loss in SG is most likely due to restriction and to the effects of the procedure, rather than due to neurohormonal changes.

Topics: Animals; Arteries; Bariatric Surgery; Blood Glucose; Gastrectomy; Ghrelin; Leptin; Ligation; Male; Models, Animal; Obesity; Obesity, Morbid; Rats; Rats, Wistar; Stomach; Weight Loss

Food structure contributes to the induction of satiation and the maintenance of satiety following intake of a meal. There is evidence from human studies that protein-crosslinking of a milk-protein based meal may enhance satiety, but the mechanism underpinning this effect is unknown. We investigated whether a rat model would respond in a similar manner and might provide mechanistic insight into enhanced satiety by structural modification of a food source. Rats were schedule fed a modified AIN-93M based diet in a liquid form or protein-crosslinked to produce a soft-solid form. This was compared to a modified AIN-93M solid diet. Average daily caloric intake was in the order solid > liquid > crosslinked. Body composition was unaltered in the solid group, but there was a loss of fat in the liquid group and a loss of lean and fat tissue in the crosslinked group. Compared to rats fed a solid diet, acute responses in circulating GLP-1, leptin and insulin were eliminated or attenuated in rats fed a liquid or crosslinked diet. Quantification of homeostatic neuropeptide expression in the hypothalamus showed elevated levels of Npy and Agrp in rats fed the liquid diet. Measurement of food intake after a scheduled meal indicated that reduced energy intake of liquid and crosslinked diets is not due to enhancement of satiety. When continuously available ad-libitum, rats fed a liquid diet showed reduced weight gain despite greater 24 h caloric intake. During the dark phase, caloric intake was reduced, but compensated for during the light phase. We conclude that structural modification from a liquid to a solidified state is beneficial for satiation, with less of a detrimental effect on metabolic parameters and homeostatic neuropeptides.

Topics: Agouti-Related Protein; Animals; Diet, Reducing; Energy Intake; Food Handling; Gene Expression Regulation; Glucagon-Like Peptide 1; Hypothalamus; Insulin; Insulin Secretion; Leptin; Male; Milk Proteins; Neurons; Neuropeptide Y; Overweight; Rats, Sprague-Dawley; Satiety Response; Transglutaminases; Weight Gain; Weight Loss

We examined the effect of restriction of foods with high fructose content in obese school children.. In a clinical study, we selected 54 obese children 6 to 11 years old with high fructose consumption (>70 g/day) in order indicate dietary fructose restriction (<20 g/day) for 6 weeks. Anthropometry, liver ultrasound as well as glucose, insulin, lipids, leptin, IGFBP1, and RBP4 serum levels were collected.. The group of children had 80% adherence and reported decreased fructose consumption (110 ± 38.6 to 11.4 ± 12.0 g/day) and also a significant decrease in caloric (2,384 ± 568 to 1,757 ± 387 kcal/day) and carbohydrate consumption (302 ± 80.4 to 203 ± 56.0 g/day). The severity of steatosis improved significantly after fructose restriction (p < 0.000001). However, no changes in BMI, systolic blood pressure, or diastolic blood pressure were found. Only triglyceride levels decreased (1.44 ± 0.43 to 1.31 ± 0.38 mmol/l), High-densitiy lipoprotein cholesterol showed a marginal increase (1.45 ± 0.19 to 1.56 ± 0.44 mmol/l). Insulin resistance and RBP4 did not change.. In school children, the restriction of high fructose foods with a decrease of caloric and carbohydrate intake at 6 weeks did not induce weight loss; however, triglyceride levels and hepatic steatosis decreased. Differences with other studies in regard to weight loss may be explained by adaptive changes on metabolic expenditure.

Topics: Blood Pressure; Body Mass Index; Child; Dietary Carbohydrates; Energy Intake; Fatty Liver; Female; Fructose; High Fructose Corn Syrup; Humans; Insulin; Insulin Resistance; Leptin; Male; Pediatric Obesity; Triglycerides; Weight Loss

Leptin is an adipokine released mainly by adipose tissue, with many functions including regulation of energy balance. However, little is known about the effect of LEPR polymorphism on orexigenic and anorexigenic neuropeptides. Thus, the aim of the present study is to verify the influence of LEPR polymorphism (rs2767485) on serum orexigenic (NPY, MCH and AgRP) and anorexigenic (Leptin and α-MSH) neuropeptides levels among obese adolescents submitted to 1year of multicomponent weight loss therapy.. Seventy-six adolescents with obesity were enrolled in 1year of weight loss therapy including clinical, nutritional, psychological and exercise-related. Blood samples were collected to analyze neuropeptides (NPY, MCH, AgRP and leptin) and LEPR genotyping. Visceral fat was measured by ultrasound and body composition was measured by plethysmography. The parameters were measured at baseline and after one year. Adolescents were grouped according to genotype (TT or CT+CC group). Effect of the weight loss therapy was analyzed through ANOVA and Wilcox, according to normality. Statistic value was set at <0.05.. C-allele carriers have the orexigenic neuropeptides (NPY, AgRP and MCH) levels statistically higher when compared with TT group, at baseline. Furthermore, TT group seems to respond better to the therapy by a greater delta on BMI. Indeed, the data suggest a concomitant increased of AgRP levels in CT+CC genotypes, after weight loss therapy.. Both groups responded to the weight loss intervention, however wildtypes (TT) appear to respond to the intervention most optimally with C carries, where post intervention reduction in BMI was significantly greater in wildtypes. The leptin receptor polymorphism seems to affect neuroendocrine regulation of energy balance among adolescents with obesity.

Topics: Adiposity; Adolescent; Agouti-Related Protein; Brazil; Energy Metabolism; Female; Humans; Leptin; Male; Neuropeptide Y; Obesity; Polymorphism, Single Nucleotide; Receptors, Leptin; Ultrasonography; Weight Loss

Longitudinal studies support a prospective relationship between weight suppression (WS) and bulimic syndrome (BN-S) maintenance. Although biobehavioral mechanisms have been proposed to explain this link, such mechanisms have yet to be identified. Given that weight loss would reduce leptin levels which may influence eating, this study examined whether reduced leptin levels mediate the link between greater WS and longer illness duration.. Women (N = 53), ages 18-45 years, were recruited from the community if they met criteria for a BN-S, including either DSM-5 bulimia nervosa (BN; n = 33) or purging disorder (PD: n = 20), and fell within a healthy weight range (18.5-26.5 kg/m. Significant associations were found among greater WS, lower leptin concentrations, and longer duration of illness. Mediation analyses using bootstrapping procedures indicated all paths were significant and that leptin mediated the link between WS and illness duration. An alternative model in which longer illness duration contributed to leptin, via greater WS, was not supported.. Longitudinal research is needed to support temporal associations and explore behavioral mechanisms linking leptin to illness trajectory.

Topics: Adolescent; Adult; Bulimia Nervosa; Female; Humans; Leptin; Middle Aged; Weight Loss; Young Adult

The aim of our study was to evaluate the influence of lifestyle factors and molecular biomarkers on the maintenance of the weight lost after a hypocaloric Mediterranean diet.. After 3 months on a diet, patients (n = 335) remained with no controlled diet during 3 years and they were revaluated.. Using linear regression, in the group of responders, we detected that a positive weight loss at 3 months, serum levels of leptin at 3 months, and each 30 min per week of physical activity were associated with weight loss maintenance. In the model with reduced weight (RW) as dependent variable, a positive weight loss at 3 months was associated with 2.4% RW (95% CI 1.31-8.11; p = 0.015), each unit of serum leptin levels at 3 months with -0.44% RW (95% CI -0.59 to -0.020; p = 0.007), each basal unit homeostasis model assessment for insulin resistance (HOMA-IR) level with -2.32% (95% CI -13.01 to -0.17; p = 0.040), and each 30 min per week of physical activity with 1.58% RW (95% CI 1.08-2.94; p = 0.020).. Obese subjects who are on maintenance weight loss after a dietary intervention appear to have a better initial response during the 3 months intervention, more physical activity at 3 years, and lower basal HOMA-IR and leptin after weight loss than those who regain weight.

Topics: Adult; Anthropometry; Biomarkers; Body Weight Maintenance; Diet, Mediterranean; Diet, Reducing; Exercise; Female; Humans; Leptin; Life Style; Male; Middle Aged; Obesity; Prospective Studies; Weight Loss

Endothelial cell dysfunction in obesity can be reduced by calorie restriction (CR), however it is unclear whether this benefit requires a concomitant weight loss or is it simply related to the reduced calorie intake per se. In our study serum was drawn from 41 obese women who were undergoing an 8-week dietary intervention with 15 - 30% energy deficit, and from 48 age- and sex-matched controls of normal weight. Serum was analysed for biomarkers of endothelial cell function, oxidative stress and inflammation. Compared with non-obese individuals, the obese patients had lower serum levels of nitric oxide (NO), adiponectin, and decreased serum antioxidant status. They also had significantly higher levels of adhesive molecules, thrombomodulin (TM), von Wilebrand factor (vWF), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and leptin. To further characterize the effect of moderate CR, the patients were ranked into two comparable groups according to the extent of weight loss - below and above the median (-5.8 kg). A moderate dietary intervention did not correct adiponectin, antioxidant status, vWF, TM, and plasminogen activator inhibitor-1 (PAI-1) but ameliorated changes in other parameters. Only changes in NO and - to a lesser degree - in sE-selectin showed a clear relationship with the magnitude of weight reduction. By contrast, a beneficial reduction in TNF-α occurred equally in patients who lost more or less weight after caloric restriction. We concluded that moderate calorie restriction could still improve several parameters of endothelial cell function irrespective of whether it was accompanied by changes in body mass. However, a significant improvement in nitric oxide, a key mediator of endothelial well-being, requires a substantial reduction in body weight.

Topics: Adiponectin; Adult; Antioxidants; Biomarkers; Body Weight; Caloric Restriction; Endothelial Cells; Endothelium, Vascular; Female; Humans; Inflammation; Leptin; Nitric Oxide; Obesity; Oxidative Stress; Weight Loss

Insulin action in the hypothalamus plays a critical role in the regulation of energy homeostasis, yet the intracellular signaling mechanisms mediating insulin action are incompletely understood. Although phosphodiesterase 3B (PDE3B) mediates insulin action in the adipose tissue and it is highly expressed in the hypothalamic areas implicated in energy homeostasis, its role, if any, in mediating insulin action in the hypothalamus is unknown. We tested the hypothesis that insulin action in the hypothalamus is mediated by PDE3B.. Using enzymatic assay, we examined the effects of peripheral or central administration of insulin on hypothalamic PDE3B activity in adult mice. Western blotting and immunohistochemistry also examined p-Akt and p-STAT3 levels in the hypothalamus. Effects of leptin on these parameters were also compared. We injected cilostamide, a PDE3 inhibitor, prior to central injection of insulin and examined the 12- to 24-hour food intake and 24-hour body weight. Finally, we examined the effect of cilostamide on insulin-induced proopiomelanocortin (Pomc), neurotensin (Nt), neuropeptide Y (Npy) and agouti-related peptide (Agrp) gene expression in the hypothalamus by qPCR.. Peripheral or central injection of insulin significantly increased PDE3B activity in the hypothalamus in association with increased p-Akt levels but without any change in p-STAT3 levels. However, leptin-induced increase in PDE3B activity was associated with an increase in both p-Akt and p-STAT3 levels in the hypothalamus. Prior administration of cilostamide reversed the anorectic and body weight-reducing effects as well as stimulatory effect of insulin on hypothalamic Pomc mRNA levels. Insulin did not alter Nt, Npy and Agrp mRNA levels.. Insulin induction of hypothalamic PDE3B activity and the reversal of the anorectic and body weight-reducing effects and stimulatory effect of insulin on hypothalamic Pomc gene expression by cilostamide suggest that activation of PDE3B is a novel mechanism of insulin signaling in the hypothalamus.

Topics: Animals; Body Weight; Cyclic Nucleotide Phosphodiesterases, Type 3; Eating; Gene Expression; Hypothalamus; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Phosphodiesterase Inhibitors; Phosphorylation; Pro-Opiomelanocortin; Proto-Oncogene Proteins c-akt; Quinolones; Signal Transduction; STAT3 Transcription Factor; Weight Loss

The effect of rapid weight loss program on adipocytokines is not yet clear. Therefore the aim of the present study was the effect of rapid weight loss (4%) on leptin, adiponectin, and insulin resistance in elite free style wrestlers.. For this purpose, fifteen young freestyle wrestlers (weight 67.6±0.8, BMI 22.5±0.21 kg/m², body fat percent 6.12±0.18, waist to hip circumference ratio 0.82±0.08) in two weight categories (60 and 66 kg) were randomly selected. Caloric intake (mean 7 days measured by Food analyzer software) measured at 1 week before weight loss program by standard methods. Wrestlers performed a week rapid weight loss (average of 4% of body weight loss) protocol by caloric and water restriction by 60% (600-700 kcal per day), under the supervision of their coach. Anthropometric characteristics, leptin, adiponectin and insulin resistance were measured before and 12 and 36 hours after rapid weight loss program.. Rapid weight loss program with 4% of weight loss had a significantly reduced impact on anthropometric factors; leptin level, insulin resistance, and increased beta cell function, while the changes of adiponectin were not significant after rapid weight loss.. Findings of this study shows that rapid weight loss program significantly decreased leptin, L/A ratio and HOMA-IR, without significant changes on adiponectin levels. These changes may have harmful physiological effects on wrestlers' bodies but they can be useful to regulate of fatty acid, glucose metabolism, and insulin resistance.

Topics: Adiponectin; Anthropometry; Body Mass Index; Body Weight; Humans; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Weight Loss; Weight Reduction Programs; Wrestling; Young Adult

Mammals of the Neotropics are characterized by a marked annual cycle of activity, which is accompanied by several physiological changes at the levels of the whole organism, organs and tissues. The physiological characterization of these cycles is important, as it gives insight on the mechanisms by which animals adjust adaptively to seasonality. Here we studied the seasonal changes in blood biochemical parameters in the relict South American marsupial Dromiciops gliroides ("monito del monte" or "little mountain monkey"), under semi-natural conditions. We manipulated thermal conditions in order to characterize the effects of temperature and season on a battery of biochemical parameters, body mass and adiposity. Our results indicate that monitos experience an annual cycle in body mass and adiposity (measured as leptin levels), reaching a maximum in winter and a minimum in summer. Blood biochemistry confirms that the nutritional condition of animals is reduced in summer instead of winter (as generally reported). This was coincident with a reduction of several biochemical parameters in summer, such as betahydroxybutyrate, cholesterol, total protein concentration and globulins. Monitos seem to initiate winter preparation during autumn and reach maximum body reserves in winter. Hibernation lasts until spring, at which time they use fat reserves and become reproductively active. Sexual maturation during summer would be the strongest energetic bottleneck, which explains the reductions in body mass and other parameters in this season. Overall, this study suggests that monitos anticipate the cold season by a complex interaction of photoperiodic and thermal cues.

Topics: 3-Hydroxybutyric Acid; Acclimatization; Adiposity; Animals; Chile; Cholesterol; Hibernation; Leptin; Marsupialia; Nutritional Status; Photoperiod; Seasons; Serum Globulins; Weight Gain; Weight Loss

Combatting overweight or obesity can lead to large fluctuations in an individual's body weight, often referred to as weight cycling or 'yo-yo' dieting. Current evidence regarding the potentially damaging effects of these changes is conflicting.. Here, we assess the metabolic effects of weight cycling in a murine model, comprising three dietary switches to normal or high-fat diets at 6 week intervals; male C57BL/6 mice were fed either a control (C) or high-fat (F) diet for 6 weeks (n=140/group). C and F groups were then either maintained on their initial diet (CC and FF, respectively) or switched to a high-fat (CF) or control (FC) diet (n=35/group). For the final 6 week interval, CC and CF groups were returned to the control diet (CCC and CFC groups), while FC and FF groups were placed on a high-fat diet (FCF and FFF) (n=28/group).. For the majority of metabolic outcomes changes aligned with dietary switches; however, assessment of neuropeptides and receptors involved in appetite regulation and reward signalling pathways reveal variable patterns of expression. Furthermore, we demonstrate that multiple cycling events leads to a significant increase in internal fat deposition, even when compared with animals maintained on a high-fat diet (internal fat: FCF: 7.4±0.2 g vs FFF: 5.6±0.2 g; P<0.01).. Increased internal adipose tissue is strongly linked to the development of metabolic syndrome associated conditions such as type 2 diabetes, cardiovascular disease and hypertension. Although further work will be required to elucidate the mechanisms underlying the neuronal control of energy homoeostasis, these studies provide a causative link between weight cycling and adverse health.

Topics: Adipose Tissue; Animals; Diet, Fat-Restricted; Diet, High-Fat; Disease Models, Animal; Energy Intake; Energy Metabolism; Gastric Inhibitory Polypeptide; Insulin; Interleukin-6; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Weight Gain; Weight Loss

This study was established a model of obesity to estimate the impact of fennel and cumin as anti-obesity extracts on body weight, body mass index (BMI), food consumption, leptin concentration, sperm quality and testis architecture to determine the reversibility of reproductive function of obese animals. Male rats were randomly assigned to either a normal or high-fat diet for 8 weeks. Then, we divided 56 adult rats into seven groups: control (CO); obesity (OB); fennel 100 and 200 mg/kg; cumin 50 and 100 mg/kg; and fennel 100 mg/kg plus cumin 50 mg/kg. From weeks 9-16, the animals treated extracts by gavages daily. We analysed leptin concentration, sperm quality and apoptosis of testis along with evaluating changes in body weight. Body weight of animals increased 25% at week 8. However, body weight, BMI, leptin concentration and apoptosis indices of OB rats increased at the end of study. However, the relative sperm parameters decreased. Nevertheless, fennel and cumin treatment improved sperm quality, and spermatogenic cells apoptosis following weight loss. Concomitant with weight loss, leptin concentration and food consumption decreased. In conclusion, fennel and cumin as supplements may ameliorate sperm quality of obese animals following weight loss and reduction in leptin concentration.

Topics: Animals; Apoptosis; Body Weight; Cuminum; Diet, High-Fat; Foeniculum; Leptin; Male; Obesity; Plant Extracts; Rats; Rats, Wistar; Semen Analysis; Spermatogenesis; Spermatozoa; Testis; Weight Loss

The role for c-Jun N-terminal Kinase (JNK) in the control of feeding and energy balance is not well understood. Here, by use of novel and highly selective JNK inhibitors, we investigated the actions of JNK in the control of feeding and body weight homeostasis. In lean mice, intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of SR-3306, a brain-penetrant and selective pan-JNK (JNK1/2/3) inhibitor, reduced food intake and body weight. Moreover, i.p. and i.c.v. administrations of SR11935, a brain-penetrant and JNK2/3 isoform-selective inhibitor, exerted similar anorectic effects as SR3306, which suggests JNK2 or JNK3 mediates aspect of the anorectic effect by pan-JNK inhibition. Furthermore, daily i.p. injection of SR3306 (7 days) prevented the increases in food intake and weight gain in lean mice upon high-fat diet feeding, and this injection paradigm reduced high-fat intake and obesity in diet-induced obese (DIO) mice. In the DIO mice, JNK inhibition sensitized leptin's anorectic effect, and enhanced leptin-induced STAT3 activation in the hypothalamus. The underlying mechanisms likely involve the downregulation of SOCS3 by JNK inhibition. Collectively, our data suggest that JNK activity promotes positive energy balance, and the therapeutic intervention inhibiting JNK activities represents a promising approach to ameliorate diet-induced obesity and leptin resistance.

Topics: Animals; Diet, High-Fat; Eating; Energy Metabolism; Hypothalamus; JNK Mitogen-Activated Protein Kinases; Leptin; Mice; Mitogen-Activated Protein Kinase 10; Mitogen-Activated Protein Kinase 9; Obesity; Protein Kinase Inhibitors; Signal Transduction; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Weight Loss

Roux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured a real bone mineral density at the hip and spine by dual-energy X-ray absorptiometry, and volumetric BMD (vBMD) and bone microarchitecture at the distal radius and tibia by high-resolution peripheral quantitative CT in 25 morbidly obese subjects (15 females, 10 males) at 0, 12 and 24 months after RYGB. Bone turnover markers (BTMs), calciotropic and gut hormones and adipokines were measured at the same time points.. After a 24.1% mean weight loss from baseline to month 12 (. Despite weight stabilization and maintenance of metabolic parameters, bone loss and deterioration in bone strength continued and were substantial in the second year. The clinical importance of these changes in terms of increased risk of developing osteoporosis and fragility fractures remain an important concern.

Topics: Absorptiometry, Photon; Adiponectin; Adult; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Collagen Type I; Female; Follicle Stimulating Hormone; Gastric Bypass; Hip Joint; Humans; Insulin; Leptin; Longitudinal Studies; Lumbar Vertebrae; Luteinizing Hormone; Male; Middle Aged; Obesity, Morbid; Osteoporosis; Parathyroid Hormone; Peptide Fragments; Peptides; Postoperative Complications; Procollagen; Radius; Tibia; Tomography, X-Ray Computed; Vitamin D; Weight Loss

The SNP 3'UTR C/T (rs10401670), it is a polymorphism that has been associated with diabetes mellitus and it has been scarcely studied before. As far as we know, no studies on interaction among diet intervention, rs10401670 variant of RETN and metabolic response has been realized.. Our aim was to analyze the effects of the rs10401670 RETN gene polymorphism on insulin resistance response and metabolic changes secondary to weight loss after 3 months of a hypocaloric diet in adults obese patients without diabetes mellitus.. A Caucasian population of 135 obese patients without diabetes mellitus was analyzed. Before and after 3 months on a low fat hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. The statistical analysis was performed for the combined CT and TT as a group (minor allele group) and wild type CC as second group (major allele group) (dominant model).. Forty nine patients (36.3%) had the genotype CC (major allele group) and 86 (63.7%) patients had the next genotypes; CT (67 patients, 49.6%) or TT (19 patients, 14.1%) (minor allele group). After dietary treatment and in major allele group, weight, BMI, fat mass, systolic blood pressure and waist circumference decreases were similar than minor allele group. In T allele carriers, fasting plasma glucose, insulin, HOMA-IR, total cholesterol and LDL cholesterol levels decreased significantly. In non T allele carriers and after dietary treatment, only LDL cholesterol and total cholesterol decreased. In non T Allele carriers, the decrease in total cholesterol was -15.1 ± 18.3 mg/dl (decrease in T Allele carriers -18.3 ± 15.7 mg/dl: p > 0.05), LDL-cholesterol was -14.3 ± 18.5 mg/dl (decrease in T Allele carriers -17.3 ± 10.1 mg/dl:p > 0.05), fasting glucose plasma -2.2 ± 1.5 mg/dL (decrease in T Allele carriers -4.8 ± 1.2 mg/dL: p = 0.02), insulin -1.1 ± 2.0 mUI/L (decrease in T Allele carriers -6.3 ± 1.9 mUI/L: p = 0.001) and HOMA-IR -0.2 ± 1.0 (decrease in T Allele carriers -1.8 ± 1.4: p = 0.005). Leptin levels decrease in both genotypes after dietary treatment (-21.1 ± 8.5 ng/dL in nonT Allele carriers vs -16.2 ± 10.2 ng/dL in T Allele carriers:p > 0.05). Resistin remained unchanged in both groups.. In our study in non-diabetic obese subjects, we describe an association of rs10401670T allele with a better metabolic response (glucose, insulin and HOMA-IR) secondary to weight loss with a hypocaloric diet.

Topics: Adult; Alleles; Anthropometry; Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Diabetes Complications; Diabetes Mellitus; Diet, Reducing; Female; Genotype; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Resistin; Waist Circumference; Weight Loss

Gastric electrical stimulation (GES) has great potential for the treatment of obesity. We investigated the impact of chronic GES on the alteration of adipose tissue and the regulation of neuropeptide Y (NPY), orexin (OX), α-melanocyte-stimulating hormone (α-MSH) and oxytocin (OXT), and their receptors in several tissues.. Most of the experiments included three groups of diet-induced obesity rats: (1) sham-GES (SGES); (2) GL-6mA (GES with 6 mA, 4 ms, 40 Hz, 2 s on, 3 s off at lesser curvature); and (3) SGES-PF (SGES rats receiving pair feeding to match the consumption of GL-6mA rats). Chronic GES was applied for 2 h every day for 4 weeks. During treatment with GES, food intake and body weight were monitored weekly. The alteration of epididymal fat weight, gastric emptying, and expression of peptides and their receptors in several tissues were determined.. GL-6mA was more potent than SGES-PF in decreasing body weight gain, epididymal fat tissue weight, adipocyte size and gastric emptying. Chronic GES significantly altered NPY, OX, α-MSH and OXT and their receptors in the hypothalamus, adipose tissue and stomach.. Chronic GES effectively leads to weight loss by reducing food intake, fat tissue weight and gastric emptying. NPY, α-MSH, orexin and OXT, and their receptors in the hypothalamus, adipose tissue and stomach appear to be involved in the anti-obesity effects of chronic GES.

Topics: Adipocytes; alpha-MSH; Animals; Disease Models, Animal; Eating; Electric Stimulation Therapy; Electrodes, Implanted; Epididymis; Gastric Emptying; Gastric Mucosa; Ghrelin; Hypothalamus; Intra-Abdominal Fat; Leptin; Male; Neuropeptide Y; Obesity; Orexin Receptors; Orexins; Oxytocin; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Receptor, Melanocortin, Type 3; Receptors, G-Protein-Coupled; Receptors, Melanocortin; Receptors, Neuropeptide; Receptors, Neuropeptide Y; Receptors, Oxytocin; RNA, Messenger; Weight Loss

Body weight loss of Lep(ob/ob) mice in response to leptin is larger than expected from the reduction in energy intake alone, suggesting a thermogenic action of unknown magnitude. We exploited the superior pharmacological properties of a novel long-acting leptin prepared via PASylation to study the contribution of its anorexigenic and thermogenic effects. PASylation, the genetic fusion of leptin with a conformationally disordered polypeptide comprising 600 Pro/Ala/Ser (PAS) residues, provides a superior way to increase the hydrodynamic volume of the fusion protein, thus retarding kidney filtration and extending plasma half-life. Here a single PAS(600)-leptin injection (300 pmol/g) resulted in a maximal weight reduction of 21% 6 days after application. The negative energy balance of 300 kJ/(4 d) was driven by a decrease in energy intake, whereas energy expenditure remained stable. Mice that were food restricted to the same extent showed an energy deficit of only 220 kJ/(4 d) owing to recurring torpor bouts. Therefore, the anorexigenic effect of PAS(600)-leptin contributes 75% to weight loss, whereas the thermogenic action accounts for 25% by preventing hypometabolism. In a second experiment, just four injections of PAS(600)-leptin (100 pmol/g) administered in 5- to 6-day intervals rectified the Lep(ob/ob) phenotype. In total, 16 nmol of PAS(600)-leptin per mouse triggered a weight loss of 43% within 20 days and normalized hypothermia and glucose homeostasis as well as hepatic steatosis. The beneficial properties of PAS(600)-leptin are substantiated by a comparison with previous studies in which approximately 400 nmol (∼25-fold) unmodified leptin was mandatory to achieve similar improvements.

Topics: Amino Acid Motifs; Animals; Appetite Depressants; Dose-Response Relationship, Drug; Energy Intake; Energy Metabolism; Female; Hypothalamus; Injections, Subcutaneous; Leptin; Liver; Male; Mice, Mutant Strains; Molecular Weight; Motor Activity; Obesity; Peptides; Recombinant Fusion Proteins; Satiety Response; Specific Pathogen-Free Organisms; Thermogenesis; Weight Loss

Thyroid hormone and leptin are essential regulators of energy homeostasis. Both hormones stimulate energy expenditure but have opposite effects on appetite. The mechanisms behind food intake regulation in thyroid dysfunctions are poorly understood. It has been shown that hypothyroid rats exhibited impaired leptin anorexigenic effect and signaling in total hypothalamus, even though they were hypophagic. It was hypothesized that hypothyroidism modulates the expression of neuropeptides: orexigenic neuropeptide Y (NPY) and anorexigenic proopiomelanocortin (POMC), independently of inducing nuclei-specific changes in hypothalamic leptin signaling.. Adult male rats were rendered hypothyroid by administration of 0.03% methimazole in the drinking water for 21 days. Protein content of NPY, POMC, and leptin signaling (the signal transducer and activator of transcription 3 [STAT3] pathway) were evaluated by Western blot, and mRNA levels by real time reverse transcription polymerase chain reaction in arcuate (ARC), ventromedial (VMN), and paraventricular (PVN) hypothalamic nuclei isolated from euthyroid (eu) and hypothyroid (hypo) rats. Leptin anorexigenic effect was tested by recording food intake for two hours after intracerebroventricular (i.c.v.) administration of leptin. Statistical differences were considered significant at p ≤ 0.05.. Hypothyroidism was confirmed by decreased serum triiodothyronine, thyroxine, and increased thyrotropin, in addition to increased levels of pro-TRH mRNA in PVN and Dio2 mRNA in the ARC of hypo rats. Hypothyroidism decreased body weight and food intake associated with decreased protein content of NPY and increased content of POMC in the ARC. Conversely, hypothyroidism induced central resistance to the acute anorexigenic effect of leptin, since while euthyroid rats displayed reduced food intake after leptin i.c.v. injection, hypothyroid rats showed no response. Hypothyroid rats exhibited decreased leptin receptor (ObRb) protein content in ARC and VMN but not in PVN nucleus. ObRb protein changes were concomitant with decreased phosphorylated STAT3 in the ARC, and decreased total STAT3 in VMN and PVN. However, hypothyroidism did not affect mRNA levels of Lepr or Stat3 in the hypothalamic nuclei.. Experimental hypothyroidism induced a negative energy balance accompanied by decreased NPY and increased POMC protein content in the ARC, resulting in predominance of anorexigenic pathways, despite central leptin resistance and impairment of the leptin signaling cascade in a nuclei-specific manner.

Topics: Animals; Appetite Regulation; Arcuate Nucleus of Hypothalamus; Disease Models, Animal; Eating; Energy Metabolism; Feeding Behavior; Hypothyroidism; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Leptin; Male; Methimazole; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Phosphorylation; Pro-Opiomelanocortin; Rats, Wistar; Receptors, Leptin; Signal Transduction; STAT3 Transcription Factor; Thyrotropin-Releasing Hormone; Ventromedial Hypothalamic Nucleus; Weight Loss

Beneficial clinical effects of weight reduction following bariatric therapies is not fully understood and maybe related to the complex interactions between leptin, adiponectin, visfatin, omentin, and ghrelin. The aim of study was to investigate their timeline changes associated with weight reduction and their profile in relation to the type of treatment and its efficacy.. Circulating hormones levels were analyzed before and after endoscopic and surgical procedures in 67 obese patients and compared to non-obese healthy controls.. Obese patients had higher leptin levels and lower levels of adiponectin, visfatin, omentin, and ghrelin than non-obese controls. During the consecutive follow-up visits after treatment, there was a gradual decrease in leptin levels and an increase in adiponectin levels to the levels observed in non-obese. At 50-54weeks, the ghrelin levels were lower and the levels of adiponectin and visfatin, but not omentin, were higher compared to their baseline values. BMI correlated with ghrelin and leptin levels. The percentage of total weight loss correlated positively with adiponectin levels and negatively with leptin levels. Patients with adequate weight loss had a significantly lower leptin concentration than those with treatment failure. There were timeline variations in hormone levels between endoscopic and bariatric therapies, however there were no significant differences in the median their concentration at 50-54weeks after therapy.. Our study supports observations that weight loss itself, rather than the procedure type, is responsible for hormonal variation. The leptin levels reflect the best the body weight changes after bariatric therapies.

Topics: Adiponectin; Adult; Bariatric Surgery; Cytokines; Endoscopy; Female; Ghrelin; GPI-Linked Proteins; Hormones; Humans; Lectins; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity; Prospective Studies; Time Factors; Treatment Outcome; Weight Loss

Weight re-gain within 2 y after Roux-en-Y gastric bypass (RYGB) is significantly associated with increased intake of and cravings for sweet foods. Here we describe a novel model of this late increase in sweet appetite. Ovariectomized RYGB and Sham-operated rats, with or without estradiol treatment, were maintained on Ensure liquid diet and offered a low-energy, artificially sweetened diet (ASD) 2 h/d. First, we tested rats more than six months after RYGB. ASD meals were larger in RYGB than Sham rats, whereas Ensure meals were smaller. General physical activity increased during ASD meals in RYGB rats, but not during Ensure meals. Second, new rats were adapted to ASD before surgery, and were then offered ASD again during 4-10 wk following surgery. Estradiol-treated RYGB rats lost the most weight and progressively increased ASD intake to >20 g/2 h in wk 9-10 vs. ∼3 g/2 h in Sham rats. Finally, the same rats were then treated with leptin or saline for 8 d. Leptin did not affect body weight, Ensure intake, or activity during meals, but slightly reduced ASD intake in estradiol-treated RYGB rats. Food-anticipatory activity was increased in estradiol-treated RYGB rats during the saline-injection tests. Because increased meal-related physical activity together with larger meals is evidence of hunger in rats, these data suggest that (1) RYGB can increase hunger for a low-energy sweet food in rats and (2) low leptin levels contribute to this hunger, but are not its only cause. This provides a unique rat model for the increased avidity for sweets that is significantly associated with weight recidivism late after RYGB.

Topics: Animals; Body Weight; Dietary Sucrose; Energy Intake; Female; Food, Formulated; Gastric Bypass; Hunger; Leptin; Motor Activity; Non-Nutritive Sweeteners; Ovariectomy; Rats; Rats, Long-Evans; Weight Gain; Weight Loss

Seasonal Weight Loss (SWL) is an important constraint, limiting animal production in the Tropics and the Mediterranean. As a result, the study of physiological and biochemical mechanisms by which domestic animal breeds respond to SWL is important to those interested in animal breeding and the improvement thereof. To that end, the study of the proteome has been instrumental in gathering important information on physiological mechanisms, including those underlying SWL. In spite of that, little information is available concerning physiological mechanisms of SWL in production animals. The objective of this study was to determine differential protein expression in the muscle of three different breeds of sheep, the Australian Merino, the Dorper and the Damara, each showing different levels of tolerance to weight loss (low, medium and high, respectively). Per breed, two experimental groups were established, one labeled "Growth" and the other labeled "Restricted." After forty-two days of dietary treatment, all animals were euthanized. Muscle samples were then taken. Total protein was extracted from the muscle, then quantified and two-dimensional gel electrophoresis were conducted using 24 cm pH 3-10 immobiline dry strips and colloidal coomassie staining. Gels were analyzed using Samespots® software and spots of interest were in-gel digested with trypsin. The isolated proteins were identified using MALDI-TOF/TOF. Results indicated relevant differences between breeds; several proteins are suggested as putative biomarkers of tolerance to weight loss: Desmin, Troponin T, Phosphoglucomutase and the Histidine Triad nucleotide-binding protein 1. This information is of relevance to and of possible use in selection programs aiming towards ruminant animal production in regions prone to droughts and weight loss.

Topics: Animals; Breeding; Diet; Electrophoresis, Gel, Two-Dimensional; Insulin; Leptin; Muscle Proteins; Muscles; Proteome; Sheep; Weight Loss

Confined space, limited exercise equipment, rotating shift work and reduced sleep may affect cardiometabolic health in submariners. To test this hypothesis, 53 male U.S. Submariners (20-39 years) were studied before and after a 3-month routine submarine patrol. Measures included anthropometrics, dietary and physical activity, biomarkers of cardiometabolic health, energy and appetite regulation, and inflammation. Before deployment, 62% of submariners had a body fat % (BF%) ≥ 25% (obesity), and of this group, 30% met the criteria for metabolic syndrome. In obese volunteers, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), leptin, the leptin/adiponectin ratio, and pro-inflammatory chemokines growth-related oncogene and macrophage-derived chemokine were significantly higher compared to non-obese submariners. Following the patrol, a significant mean reduction in body mass (5%) and fat-mass (11%) occurred in the obese group as a result of reduced energy intake (~2000 kJ) during the patrol; and, independent of group, modest improvements in serum lipids and a mean reduction in interferon γ-induced protein 10 and monocyte chemotactic protein 1 were observed. Since 43% of the submariners remained obese, and 18% continued to meet the criteria for metabolic syndrome following the patrol, the magnitude of weight loss was insufficient to completely abolish metabolic dysfunction. Submergence up to 3-months, however, does not appear to be the cause of obesity, which is similar to that of the general population.

Topics: Adiponectin; Adipose Tissue; Adult; Blood Glucose; Body Mass Index; Chemokines; Energy Intake; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Military Personnel; Obesity; Sedentary Behavior; Ships; Sleep; Weight Loss; Work; Young Adult

Fibroblast growth factor 21 (FGF-21) is a hepatic protein that plays a critical role in liver, adipose tissue, and bone metabolism. Animal models reported an increase of FGF-21 and associated growth disturbances in undernutrition. Therefore, we studied the impact of weight loss in obese children on growth, FGF-21, and insulin-like factor 1 (IGF-1) concentrations.. We analyzed height, serum concentrations of FGF-21, IGF-1, IGFBP-3, leptin, and insulin at baseline and 1 year later in 30 obese children with substantial weight loss (reduction >0.5 BMI-SDS) and in 30 obese children of similar age, gender, and pubertal stage with stable BMI-SDS. All children participated in a 1-year lifestyle intervention. Height and IGF-1 was transformed to standard deviation score (SDS). Multiple linear regression analyses adjusted for age, gender, and pubertal stage were performed.. At baseline, height-SDS was significantly related to IGF-1-SDS (β-coefficient 0.68 95% confidence interval (95% CI)±0.49; p=0.008) and leptin (β-coefficient 0.042 95% CI±0.030; p=0.008), but not to FGF-21 or insulin. FGF-21 was not significantly associated with IGF-1 or IGFBP-3. In longitudinal analysis, changes of FGF-21 were not significantly related to changes of height, IGF-1-SDS or IGFBP-3. However, in the subgroup of 30 children with substantial BMI-SDS reduction, FGF-21, leptin, insulin, and HOMA decreased significantly.. As there was no significant association between FGF-21 and growth or IGF-1 both in cross-sectional and longitudinal analyses, these findings do not support the hypothesis that FGF-21 is involved in growth of obese children. Further studies are necessary to understand the multiple alterations in the growth hormone (GH) axis in obese children.

Topics: Adolescent; Body Height; Body Mass Index; Child; Cross-Sectional Studies; Female; Fibroblast Growth Factors; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Longitudinal Studies; Male; Obesity; Weight Loss

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of non-alcoholic fatty liver disease (NAFLD) related to obesity and insulin resistance. Currently, medical interventions for NAFLD have focused on diet control and exercise to reduce body weight, and there is a requirement for effective pharmacological therapies. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote the urinary excretion of glucose by blocking its reabsorption in renal proximal tubules. SGLT2 inhibitors lower blood glucose independent of insulin action and are expected to reduce body weight because of urinary calorie loss. Here we show that an SGLT2 inhibitor ipragliflozin improves hepatic steatosis in high-fat diet-induced and leptin-deficient (ob/ob) obese mice irrespective of body weight reduction. In the obese mice, ipragliflozin-induced hyperphagia occurred to increase energy intake, attenuating body weight reduction with increased epididymal fat mass. There is an inverse correlation between weights of liver and epididymal fat in ipragliflozin-treated obese mice, suggesting that ipragliflozin treatment promotes normotopic fat accumulation in the epididymal fat and prevents ectopic fat accumulation in the liver. Despite increased adiposity, ipragliflozin ameliorates obesity-associated inflammation and insulin resistance in epididymal fat. Clinically, ipragliflozin improves liver dysfunction in patients with T2DM irrespective of body weight reduction. These findings provide new insight into the effects of SGLT2 inhibitors on energy homeostasis and fat accumulation and indicate their potential therapeutic efficacy in T2DM-associated hepatic steatosis.

Topics: Adipose Tissue; Adult; Animals; Body Weight; Diabetes Mellitus, Type 2; Diet, High-Fat; Drug Evaluation, Preclinical; Energy Intake; Epididymis; Glucose; Glucosides; Humans; Hyperphagia; Hypoglycemic Agents; Insulin Resistance; Leptin; Lipids; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Organ Size; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes; Weight Loss

C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has beneficial metabolic and cardiovascular effects in various animal models. Alterations in circulating CTRP9 have also been observed in patients with cardiovascular disease and diabetes, but little is known about the impact of obesity and bariatric surgery on CTRP9 concentrations.. The aim of this study was to compare CTRP9 levels in obese and lean subjects and to determine whether circulating CTRP9 levels in morbidly obese patients are altered by bariatric surgery.. Fifty-nine obese bariatric surgical patients and 62 lean controls were recruited to participate in a cross-sectional study at an academic medical center. The obese patients were further invited to participate in a cohort study, and 21 returned for analysis at 3 and 6 months postsurgery.. Bariatric surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy) was the intervention for this study.. Fasting serum was obtained from all subjects on entry to the study and was analyzed in the core laboratory for hemoglobin A1c, glucose, aspartate aminotransferase, alanine aminotransferase, total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides; CTRP9, insulin, adiponectin, and leptin were measured by ELISA. Serum from the patients in the cohort study was also analyzed at 3 and 6 months.. Serum CTRP9 was significantly higher in the obese group compared to the lean group. CTRP9 was associated with obesity, even after controlling for age, gender, and ethnicity. Following bariatric surgery, there was a significant decrease in weight at 3 and 6 months postprocedure, accompanied by decreases in CTRP9, hemoglobin A1c and leptin, and an increase in serum adiponectin.. CTRP9 levels are elevated in obesity and significantly decrease following weight loss surgery. Our data suggest that CTRP9 may play a compensatory role in obesity, similar to that of insulin, and is down-regulated following weight loss surgery.

Topics: Adiponectin; Adult; Aged; Bariatric Surgery; Cross-Sectional Studies; Female; Glycoproteins; Humans; Leptin; Lipids; Male; Middle Aged; Obesity, Morbid; Treatment Outcome; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; Weight Loss; Young Adult

Chronic kidney disease (CKD) leading to kidney failure and end stage renal disease (ESRD) is a common health problem associated with wasting syndrome characterized by inadequate nutrient intake and decrease tissue anabolism and/or catabolism. In CKD adipokines, especially leptin and adiponectin (ADPN), accumulate in serum due to reduced renal clearance. Although, rapidly growing, knowledge of adipocytokines is limited and much is still unknown of the altered adipocytokine pattern in patients with impaired renal function. The aim of this study is to assess the adipocytokines, leptin, and adiponectin in relation to weight loss in pediatric patients with CKD stage-5 treated conservatively (CT) or undergoing maintenance hemodialysis (MHD).. 41 CKD stage-5 patients and 20 healthy controls were included in this study. Serum levels of leptin and adiponectin were determined by ELISA. Leptin gene expression was analyzed using quantitative real time-polymerase chain reactions (QPCR).. Patients had significantly elevated ADPN levels and non significantly elevated serum leptin levels as compared to controls (p < 0.001, p = 0.354, respectively). Leptin gene expression and body mass index (BMI) were highly significantly reduced in CKD stage-5 compared to controls (p < 0.001 for each). There were no significant differences between patients treated conservatively and those undergoing MHD with respect to all studied parameters. Finally, univariate logistic regression analysis revealed no association between leptin, ADPN, and weight loss in CKD stage-5 patients.. The present study showed non significantly elevated or even normalized serum leptin levels, elevated serum adiponectin level and reduced leptin gene expression in CKD stage-5 patients as compared to healthy controls. Patients had significantly lower weight than healthy controls but there was no association between leptin, adiponectin, and weight loss in CKD stage-5 studied patients so, further studies are needed to clarify the role of the two adipokines in body weight loss in those patients.

Topics: Adipokines; Adiponectin; Adolescent; Age Factors; Biomarkers; Body Mass Index; Case-Control Studies; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Logistic Models; Male; Nutritional Status; Predictive Value of Tests; Real-Time Polymerase Chain Reaction; Renal Dialysis; Renal Insufficiency, Chronic; Severity of Illness Index; Treatment Outcome; Weight Loss

In several studies reduced striatal dopamine D2/3 receptor (D2/3R) availability was reported in obese subjects compared to lean controls. Whether this is a reversible phenomenon remained uncertain. We previously determined the short-term effect of Roux-en-Y gastric bypass surgery (RYGB) on striatal D2/3R availability (using [(123)I]IBZM SPECT) in 20 morbidly obese women. Striatal D2/3R availability was lower compared to controls at baseline, and remained unaltered after 6 weeks, despite significant weight loss. To determine whether long-term bariatric surgery-induced weight loss normalizes striatal D2/3R binding, we repeated striatal D2/3R binding measurements at least 2 years after RYGB in 14 subjects of the original cohort. In addition, we assessed long-term changes in body composition, eating behavior and fasting plasma levels of leptin, ghrelin, insulin and glucose. Mean body mass index declined from 46±7kg/m(2) to 32±6kg/m(2), which was accompanied by a significant increase in striatal D2/3R availability (p=0.031). Striatal D2/3R availability remained significantly reduced compared to the age-matched controls (BMI 22±2kg/m(2); p=0.01). Changes in striatal D2/3R availability did not correlate with changes in body weight/fat, insulin sensitivity, ghrelin or leptin levels. Scores on eating behavior questionnaires improved and changes in the General Food Craving Questionnaire-State showed a borderline significant correlation with changes in striatal D2/3R availability. These findings show that striatal D2/3R availability increases after long-term bariatric-surgery induced weight loss, suggesting that reduced D2/3R availability in obesity is a reversible phenomenon.

Topics: Adult; Benzamides; Blood Glucose; Body Mass Index; Corpus Striatum; Feeding Behavior; Female; Follow-Up Studies; Gastric Bypass; Ghrelin; Humans; Leptin; Obesity, Morbid; Pyrrolidines; Radiopharmaceuticals; Receptors, Dopamine D2; Receptors, Dopamine D3; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Weight Loss

Body weight varies depending on the prevailing direction of environmental pressures; however, physiological factors also play a significant role in the control of body weight. The aim of the present study was to assess the impact of Roux-en-Y gastric bypass (RYGB) on hormones and peptides involved in the control of energy balance and their possible implications in appetite/satiety.. The sample included 39 individuals with extreme obesity (37 women and two men) who underwent RYGB. Anthropometric and biochemical markers were collected before surgery and 6 months after RYGB.. The BMI decreased from 44.3±6.4 to 31.7±5.7 kg/m (P<0.001) at the sixth month. Percentage of excess weight lost was 63.2±25.0%. Leptin and glucose levels decreased significantly 6 months after RYGB (P<0.001). Interestingly, a significant correlation was confirmed between the anorexigenic gut hormone peptide YY (PYY) and the central anorexigenic mediator α-melanocyte-stimulating hormone after 6 months of RYGB (r=0.35, P=0.004). In contrast, PYY concentrations were correlated negatively with BMI (r=-0.34, P=0.002).. In the present investigation, it was found that there is a relationship between α-melanocyte-stimulating hormone and PYY concentrations, and it supports the role of the PYY to POMC signal in appetite regulation after RYGB.

Topics: Adult; alpha-MSH; Appetite Regulation; Blood Glucose; Body Mass Index; Energy Metabolism; Gastric Bypass; Gastric Mucosa; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Peptide Hormones; Peptide YY; Stomach; Time Factors; Treatment Outcome; Weight Loss; Young Adult

Early anthropometric and metabolic changes during a caloric-restricted diet in obese postmenopausal women and correlations between these factors with activity in brain areas involved in processing of visual food related stimuli were investigated.. An 8-week prospective intervention study of 18 healthy postmenopausal women, with a body mass index of 30-35 kg m. A mean weight loss of 4.2±0.5 kg (4.8%) and a 4.2±0.4 cm decline in waist circumference were achieved. In the first week of caloric restriction, triglyceride, leptin, resistin and adiponectin levels as well as systolic blood pressure decreased and insulin-like growth factor-binding protein 1 levels increased. During and after weight loss, a significant increase in ghrelin levels was observed. Before weight loss, increased activation of the right amygdala was seen in response to food stimuli, and free fatty acids and glucose correlated with activity in various areas involved in food reward processing. After weight loss, fasting ghrelin and sated leptin levels correlated with activity in these areas.. Already in the first week of caloric restriction in obese postmenopausal women, various favourable metabolic changes occur before clinically relevant weight loss is achieved. Activity in the amygdala region and correlations of metabolic factors with activity in brain areas involved in food reward processing differ substantially before and after weight loss.

Topics: Adiponectin; Aged; Anthropometry; Body Mass Index; Brain; Caloric Restriction; Female; Ghrelin; Humans; Leptin; Middle Aged; Netherlands; Obesity; Postmenopause; Prospective Studies; Weight Loss

poco se conoce sobre el impacto de orlistat en el sistema leptina. Estudiamos la respuesta de la leptina plasmática y la sensación de saciedad tras dos días de tratamiento con orlistat sin dieta hipocalórica ni pérdida de peso.. reclutamos veinte mujeres obesas en nuestras consultas externas de medicina. Habían recibido restricción dietética y modificación del estilo de vida, pero se habían mantenido obesas con peso corporal estable durante seis meses antes de su inclusión en el estudio.. las pacientes tomaron 120 mg de orlistat 3 veces al día y mantuvieron su dieta habitual. Al inicio y dos días después del tratamiento con orlistat se repitieron el examen físico, la sensación de hambre y la analítica. No hubo diferencias significativas en el consumo de energía de la dieta, el peso corporal y la relación cintura-cadera, así como en glucosa sérica, insulina y péptido C. Solamente las concentraciones de leptina y triglicéridos en suero disminuyeron (p: 0,0001 y 0,01, respectivamente). La disminución de la concentración de leptina en suero se correlacionó positivamente con cambios en la concentración de triglicéridos (p: 0.01, r2: 0,45). La sensación de hambre aumento antes de la cena y se correlacionó negativamente con la disminución de la leptina (p: 0,0001, r2: 0,74) y triglicéridos (p: 0,02, r2: 0.59).. estos datos sugieren que la malabsorción parcial de grasas por el tratamiento con orlistat disminuye rápidamente los niveles plasmáticos de triglicéridos y leptina. Este descenso se asoció con aumento del apetito antes de la ingesta que sigue a la comida principal del día.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Dietary Fats; Female; Humans; Intestinal Absorption; Lactones; Leptin; Orlistat; Satiety Response; Triglycerides; Weight Loss

In obese individuals, weight loss might be affected by variants of the adipokine-encoding genes. We verified whether selected functional single nucleotide polymorphisms in LEP, LEPR and ADIPOQ are associated with changes in serum levels of the respective adipokines and weight loss in 100 prepubertal obese (SDS-BMI > 2) Caucasian children undergoing lifestyle intervention. Frequencies of the -2548G > A LEP, Q223R LEPR, K656N LEPR, -11377C > G and -11426A > G ADIPOQ polymorphisms were analyzed by restriction fragment length polymorphism. Serum adipokine and soluble leptin receptor (sOB-R) concentrations were measured using the ELISA method. Among the analyzed polymorphisms, only LEPR polymorphisms were associated with changes of SDS-BMI or sOB-R concentrations in children after therapy. Carriers of the wild-type K665N and at least one minor Q223R allele had the greatest likelihood of losing weight (OR = 5.09, p = 0.006), an increase in sOB-R (ptrend = 0.022) and decrease in SDS-BMI correlated with the decrease of fat mass (p < 0.001). In contrast, carrying of the wild-type Q223R and at least one minor K665N allele were associated with a decrease in sOB-R concentrations and a decrease in SDS-BMI correlated with a decrease in fat-free mass (p = 0.002). We suggest that the combination of different LEPR variants, not a single variant, might determine predisposition to weight loss in the prepubertal period.

Topics: Adiponectin; Adiposity; Alleles; Body Mass Index; Child; Child, Preschool; Combined Modality Therapy; Diet, Healthy; Diet, Reducing; Exercise; Female; Genetic Association Studies; Healthy Lifestyle; Heterozygote; Humans; Leptin; Male; Pediatric Obesity; Polymorphism, Single Nucleotide; Receptors, Leptin; Solubility; Weight Loss

Substantial weight loss through intense dietary regimens is thought to ameliorate endothelial dysfunction in obesity. It is less clear whether similar improvements can be achieved with modest dietary interventions. This study aimed to identify the parameters of endothelial cell status in obesity that are affected by mild calorie restriction.. Human umbilical vein endothelial cells (EA.hy926 line) in culture were exposed pairwise to serum from 57 individuals with simple obesity (BMI > 30 kg/m(2)) collected before and after 8-week dietary intervention with energy deficit of 300-500 kcal/day.. Analysis of endothelial transcriptome suggested that the intervention could impact on endothelial cell growth. Cell proliferation was measured with the MTT test and verified by [(3)H]-thymidine incorporation. The participants were categorized according to a change in proliferation over time. Significant decrease in endothelial cell proliferation correlated with the extent of weight loss in men, but not in women. This effect corresponded with changes in serum levels of leptin and adiponectin, but was not related to serum concentrations of several known angiogenic mediators (VEGF, MCP-1, TSP-1, MMP-9, angiopoietin-2).. Direction and magnitude of changes in serum-induced endothelial cell proliferation identifies patients with the greatest weight loss in response to modest calorie restriction.

Topics: Adiponectin; Adult; Aged; Angiogenic Proteins; Caloric Restriction; Cell Proliferation; Endothelial Cells; Female; Gene Expression Profiling; Human Umbilical Vein Endothelial Cells; Humans; Leptin; Male; Middle Aged; Obesity; Weight Loss; Young Adult

The aim of this study was to investigate the effect of a lifestyle intervention in obesity on the soluble form of the activated leukocyte cell adhesion molecule (sALCAM) and its association with metabolic parameters.. Twenty-nine obese subjects selected from the OPTIFAST®52 program. This program consisted into 2 crucial phases: an initial 12-week active weight reduction phase, followed by a 40-week weight maintenance phase. At baseline, after 12 weeks and at the end of the program, fasting glucose and insulin, total cholesterol, LDL-C, HDL-C, triglycerides, adiponectin, leptin, high sensitivity CRP, sALCAM, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and leptin-to-adiponectin-ratio were determined. Oral glucose tolerance test (OGTT) was performed when indicated.. At baseline, the serum concentration of sALCAM was increased and correlated positively with HOMA-IR and negatively with age. At the end of the program, sALCAM concentrations decreased significantly. Multivariate analysis showed that sALCAM significantly correlated with age, glucose concentration after 2 h OGTT and the HOMA-IR. A higher decrease of HOMA-IR during the study was observed in subjects with higher concentration of sALCAM at baseline.. sALCAM might be a novel biomarker in obesity that correlates and predicts insulin sensitivity improvement and that can be affected by lifestyle intervention.

Topics: Adiponectin; Adult; Age Factors; Antigens, CD; Biomarkers; Blood Glucose; Body Weight Maintenance; C-Reactive Protein; Cell Adhesion Molecules, Neuronal; Cholesterol; Female; Fetal Proteins; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Male; Multivariate Analysis; Obesity; Risk Reduction Behavior; Triglycerides; Weight Loss

Obesity is now recognized as a state of chronic low-grade inflammation and is called as metabolic inflammation. Delta-5 desaturase (D5D) is an enzyme that metabolizes dihomo-γ-linolenic acid (DGLA) to arachidonic acid (AA). Thus, D5D inhibition increases DGLA (precursor to anti-inflammatory eicosanoids) while decreasing AA (precursor to pro-inflammatory eicosanoids), and could result in synergistic improvement in the low-grade inflammatory state. Here, we demonstrate reduced insulin resistance and the anti-obesity effect of a D5D selective inhibitor (compound-326), an orally active small-molecule, in a high-fat diet-induced obese (DIO) mouse model. In vivo D5D inhibition was confirmed by determining changes in blood AA/DGLA profiles. In DIO mice, chronic treatment with compound-326 lowered insulin resistance and caused body weight loss without significant impact on cumulative calorie intake. Decreased macrophage infiltration into adipose tissue was expected from mRNA analysis. Increased daily energy expenditure was also observed following administration of compound-326, in line with sustained body weight loss. These data indicate that the novel D5D selective inhibitor, compound-326, will be a new class of drug for the treatment of obese and diabetic patients.

Topics: 8,11,14-Eicosatrienoic Acid; Adiponectin; Adipose Tissue; Animals; Arachidonic Acid; Body Weight; Delta-5 Fatty Acid Desaturase; Diet, High-Fat; Energy Metabolism; Enzyme Inhibitors; Fatty Acid Desaturases; Gene Expression; Hep G2 Cells; Humans; Inflammation; Insulin Resistance; Leptin; Macrophages; Male; Mice, Inbred C57BL; Obesity; Pyrimidinones; Pyrrolidinones; Reverse Transcriptase Polymerase Chain Reaction; Weight Loss

We examined 11 women aged 19-26 years (mean age 22.5±3.5 years) with secondary amenorrhea complaining frequent urination over 1.5 years and repeatedly, but unsuccessful treated for overactive bladder and chronic cystitis. The rare cause of sustained urination disorders in young female patients of reproductive age was established: development of secondary amenorrhea caused by weight loss ("cosmetic" amenorrhea) with subsequent estrogene deficit and urogenital atrophy. Morphological examination of the bladder mucosa, an important clue to the diagnosis, helps to identify the true cause of dysuria, urogenital atrophy of the bladder mucosa, in secondary ("cosmetic") amenorrhea, and determine future course of etiopathogenic treatment of sustained dysuria in young women. The treatment is often effective in case of proper and timely diagnosis and the absence of irreversible changes.

Topics: Adult; Amenorrhea; Case-Control Studies; Cystitis; Dysuria; Estradiol; Estrogens; Female; Follicle Stimulating Hormone; Humans; Leptin; Luteinizing Hormone; Mucous Membrane; Urinary Bladder; Urinary Bladder, Overactive; Weight Loss

Polymorphisms of a single nucleotide in RETN have been associated with indexes of insulin resistance. Our aim was to analyze the effects of the rs1862513 RETN gene polymorphism on insulin resistance, insulin levels, and resistin levels changes after 3 months of a low-fat hypocaloric diet.. A Caucasian population of 133 obese patients was analyzed before and after 3 months on a low-fat hypocaloric diet.. Fifty-six patients (42.1%) had the genotype GG (wild group) and 77 (57.9%) patients had the other genotypes; GC (59 patients, 44.4%) or CC (18 patients, 13.5%; mutant group). In wild and mutant genotype groups, weight, body mass index, fat mass, waist circumference, and systolic blood pressure decreased. In the wild genotype group, the decrease in total cholesterol was -13.1 ± 25.3 mg/dL (vs. -4.4 ± 13.7 mg/dL in mutant group: p = 0.004 for group deltas), low density lipoprotein (LDL)-cholesterol was -13.0 ± 21.5 mg/dL (-4.3 ± 10.5 mg/dL: p = 0.007), glucose -7.2 ± 3.5 mg/dL (-0.8 ± 0.2 mg/dL: p = 0.01), insulin -5.6 ± 2.5 mUI/L (-2.9 ± 1.2 mUI/L: p = 0.03) and homeostasis model assessment-insulin resistance (HOMA-IR) -2.5 ± 1.1 (-0.6 ± 1.4: p = 0.02). Leptin levels decreased in both genotypes (-10.1 ± 9.5 ng/dL in wild type group vs. -13.1 ± 0.2 ng/dL in mutant type group: p > 0.05).. The present study suggests that the G/G genotype of RETN rs1862513 could be a predictor of the reduction of HOMA-IR, insulin, fasting glucose and LDL cholesterol secondary to a hypocaloric diet in obese subjects.

Topics: Adult; Blood Glucose; Cholesterol; Cholesterol, LDL; Diet, Fat-Restricted; Diet, Reducing; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Resistin; Weight Loss; White People

To study the day-night variation of omentin-1 levels and assess whether leptin and/or short- and long-term energy deprivation alter circulating omentin-1 levels via cytokines.. Omentin-1 levels were measured hourly in serum samples from six healthy men to evaluate for day-night variation. To study effects of acute energy deprivation and of leptin administration, eight healthy subjects were studied in the fasting state for 72 h with administration of either placebo or metreleptin (recombinant human leptin) in physiologic replacement doses. We evaluated the effect of leptin in pharmacologic doses on serum omentin-1 and cytokine levels, as well as on omentin-1 levels in ex vivo omental adipose tissue, in 15 healthy volunteers. To study the effect of chronic energy deprivation and weight loss on omentin-1 levels, we followed 18 obese subjects for 12 months who underwent bariatric surgery.. There is no day-night variation in omentin-1 levels. Short-term and chronic energy deprivation, as well as ex vivo leptin administration and physiologic replacement doses of leptin, do not alter omentin-1 levels; pharmacologic doses of metreleptin reduce omentin-1 levels, whereas levels of tumor necrosis factor-α receptor II and interleukin-6 tend to increase.. Omentin-1 levels are reduced by pharmacologic doses of metreleptin independent of effects on cytokine levels.

Topics: Bariatric Surgery; Circadian Rhythm; Cytokines; Dose-Response Relationship, Drug; Energy Metabolism; Fasting; GPI-Linked Proteins; Humans; Interleukin-6; Lectins; Leptin; Obesity; Tumor Necrosis Factor-alpha; Weight Loss

Perturbations of energy balance induce compensatory processes that may alter expected weight loss. In obese patients, our aim was to investigate the relationships that occurred between fasting plasma concentrations of anorexigenic peptides and metabolic parameters, appetite, physical capacity, and weight loss in the 5 first days of a program associating exercise and caloric reduction. Thirteen obese women were monitored from day 1 to day 5 with 2 exercise sessions in day 2 and day 4. We measured, in a fasted state, changes in body weight, hunger ratings, and plasma concentrations of fatty acids, triglycerides, leptin, insulin, amylin, peptide YY, and insulin-resistance index. Physical performance was assessed by a 6-min walking test. The program resulted in significantly reduced body weight (0.75±0.4 kg; p=0.001), of plasma concentrations of triglycerides, insulin, amylin, peptide YY, and the insulin-resistance index, and also increased fatty acids (p<0.05). Hunger ratings were increased (p<0.05). Program-induced changes in fatty acids, leptin, and insulin concentrations were related to physical performance (r(2)=0.45, 0.59, and 0.52; p<0.05, respectively) and to weight loss (r(2)=0.65, 0.57, 0.55; p<0.05, respectively). Five days of diet and exercise induced weight loss, improved lipid profile, and decreased insulin resistance while hunger ratings increased. Subjects with higher physical capacity lost more weight, presented higher increases in fatty acids and lower changes of leptin and insulin concentrations suggesting a better metabolic flexibility. To reduce the compensatory responses that can occur with energy imbalances, our study supports to account for individual activity level before prescribing weight-loss program associating diet and exercise.

Topics: Adult; Body Weight; Diet, Reducing; Exercise; Female; Humans; Hunger; Insulin; Insulin Resistance; Leptin; Lipids; Middle Aged; Obesity; Weight Loss

BACKGROUND/OBJETIVES: Obese leptin-deficient ob/ob mice exhibit high adiposity and reduced muscle mass with leptin replacement promoting weight loss and inducing muscle accretion through PGC-1α-dependent mechanisms. Our aim was to analyze in vivo and in vitro the effect of leptin on FNDC5, a novel PGC-1α-dependent myokine that is synthesized and cleaved to form irisin that induces white adipose browning.. Twelve-week-old male wild-type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg kg(-1) day(-1)) and pair-fed. Leptin administration was associated with increased gastrocnemius weight and cell surface area, higher Pgc1a and Fndc5 transcript levels and a slight increase in circulating irisin. Leptin upregulated Fndc5 expression through nitric oxide (NO)-dependent mechanisms in murine C2C12 myocytes and stimulated both basal and irisin-stimulated myogenesis, as evidenced by increased myocyte cell proliferation, higher myogenin and myonectin transcript levels together with lower mRNA expression of myostatin and dystrophin and the muscle atrophy-related factors MuRF1 and MAFbx. Interestingly, leptin downregulated Fndc5 expression in a NO-independent manner in murine differentiated subcutaneous adipocytes. Furthermore, leptin prevented the irisin-induced upregulation of both brown (Ucp1 and Cidec) and beige (Tmem26) adipocyte-specific genes and the increase in uncoupling protein-1-positive cells.. Taken together, our results provide evidence for a regulatory role of leptin on FNDC5/irisin, favoring muscle accretion but reducing fat browning.

Topics: 3T3-L1 Cells; Adipose Tissue, Brown; Animals; Cells, Cultured; Fibronectins; Gene Expression; Leptin; Male; Mice; Muscle, Skeletal; Nitric Oxide; Obesity; Pigments, Biological; Subcutaneous Fat, Abdominal; Transcription Factors; Up-Regulation; Weight Loss

The aim of this study was to explore the changes in the adipokines leptin and adiponectin in obese patients with type 1 diabetes mellitus (T1DM) who underwent seven days of fasting and 21 days of low-calorie diet (LCD). The plasma leptin and adiponectin concentrations were measured in 14 obese patients with T1DM at baseline, immediately after 7 days of fasting, and after 21 days of LCD. 13 non-obese patients with T1DM were studied only after an overnight fasting. Bioimpedance technique was used for determination of body composition. Obese T1DM patients lost 6.0 kg (6.0; 6.8) (median, 25 %; 75 %) and decreased their fat tissue after fasting and LCD. Plasma leptin in obese T1DM was significantly higher than in non-obese T1DM patients: 9.10 (5.06; 25.89) vs. 1.71 (1.12; 7.08) microg . l(-1) and transiently decreased immediately after fasting: 3.45 microg . l(-1) (1.47; 7.00), (P<0.05). Adiponectin/leptin ratio in obese T1DM was significantly lower than in non-obese T1DM patients: 0.67 (0.57; 1.49) vs. 3.50 (2.46; 6.30) . 10(3) and transiently increased immediately after fasting: 2.22 (1.26; 3.24) . 10(3), (P<0.05). We conclude that obese patients with T1DM are characterized by hyperleptinemia that is reduced by prolonged fasting, but only slightly affected by low calorie diet.

Topics: Adiponectin; Adipose Tissue; Adult; Body Composition; Caloric Restriction; Diabetes Mellitus, Type 1; Fasting; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Humans; Leptin; Male; Middle Aged; Obesity; Weight Loss; Young Adult

The impact of nutritional status on outcome of allogeneic stem cell transplantation (alloSCT) is controversial. This study investigates the influence of pretransplant weight loss and serologic indicators of nutritional homeostasis on relapse and death of acute myeloid leukemia (AML) after alloSCT.. Pretransplant weight loss along with serum levels of total serum protein (TSP), albumin, C-reactive protein, and leptin were collected retrospectively in a training cohort (n = 149) and correlated with clinical outcome. Metabolic risk groups were defined and tested in an independent validation cohort (n = 167).. We identified pretransplant weight loss and TSP as strong independent predictors of relapse and death. Patients in the metabolic high-risk group (low TSP and weight loss) had an increased risk for relapse (P = 0.0002) and death (P = 0.002), but a similar risk for acute graft-versus-host disease. Weight loss coincided with reduced pretransplant serum leptin levels. The adverse influence of weight loss and high metabolic risk on relapse and overall survival could be confirmed in the validation cohort and similarly in patients with less than or more than 5% blasts before alloSCT. Multivariate analysis of both cohorts revealed a hazard ratio for relapse of 7.78 (2.59-23.36, P = 0.0003) in the metabolic high risk group.. Altered nutritional homeostasis before alloSCT correlates with recurrence of AML after transplantation. Studies addressing pretransplant nutritional interventions to reduce AML relapse rates are warranted.

Topics: Blood Proteins; Body Mass Index; Hematopoietic Stem Cell Transplantation; Humans; Leptin; Leukemia, Myeloid, Acute; Nutritional Status; Recurrence; Retrospective Studies; Transplantation, Homologous; Weight Loss

Weight regain contributes to the therapeutic failure in 15-20% of type 2 diabetic patients after Roux-en-Y gastric bypass surgery (RYGB), and the mechanism remains largely unknown. This study was conducted to explore the mechanism of weight regain.. Wild-type (WT) diet-induced obese (DIO) mice were used to mimic human obesity, and ob/ob mice were used for leptin deficiency-induced obesity. Two groups of mice were compared in weight regain for 10 months after RYGB. Weight loss, food intake, fecal energy loss and energy expenditure were monitored in the study of weight regain. Fasting insulin, insulin tolerance and homeostatic model assessment-insulin resistance were tested for insulin sensitivity under the weight regain. Weight loss from RYGB and calorie restriction was compared for the impact in insulin sensitivity.. In WT mice, RYGB induced a sustained weight loss and insulin sensitization over the sham operation in this 10-month study. However, RYGB failed to generate the same effects in leptin-deficient ob/ob mice, which suffered a weight regain over the pre-surgery level. In ob/ob mice, body weight was reduced by RYGB transiently in the first week, recovered in the second week and increased over the baseline thereafter. Weight loss was induced by RYGB relative to that of sham mice, but the loss was not sufficient to keep body weight below the pre-surgery levels. In addition, insulin sensitivity was not improved by the weight loss. The response to RYGB was improved in ob/ob mice by 2 weeks of leptin treatment. Weight loss from calorie restriction had an equivalent effect on insulin sensitization compared with that of RYGB.. Those data demonstrate that ob/ob mice and DIO mice responded differently to RYGB surgery, suggesting that leptin may be one of the factors required for RYGB to prevent weight regain and diabetes recurrence.

Topics: Animals; Diet, High-Fat; Disease Models, Animal; Gastric Bypass; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Reproducibility of Results; Weight Gain; Weight Loss

To ascertain the association between umbilical cord levels of adiponectin, leptin and resistin, and birth weight (BW) and newborn weight change (NWC) in the first 96 h of life.. 392 full-term singletons were recruited, in 2005/2006, at the five public units providing obstetrical and neonatal care in Porto. Information was collected by face-to-face interview and additionally from clinical records. Umbilical cord blood adipokines levels were determined and categorized using the 10th and 90th percentiles. Anthropometrics were obtained by trained examiners and NWC estimated as (weight - BW)/BW × 100, adjusted for newborn's age. Regression coefficients and 95% confidence intervals were calculated.. Low leptin levels (≤5.6 ng/ml) were associated with lower BW (β = -137.3 g 95%CI -268.6 g, -6.1 g) and high leptin levels (≥30.7 ng/ml) were associated with higher BW (β = 276.3 g 95%CI 145.8 g, 406.8 g) and higher NWC (β = 1.10% 95% CI 0.29%, 1.92%), comparing to newborns with normal leptin levels. Adiponectin and resistin were not associated with BW or NWC.. High umbilical cord blood leptin levels predicted higher BW and lower weight loss in the immediate postnatal period.

Topics: Adipokines; Adiponectin; Birth Weight; Body Weight; Female; Fetal Blood; Humans; Infant, Low Birth Weight; Infant, Newborn; Leptin; Male; Resistin; Weight Loss

The low-grade inflammatory state in obesity leads to insulin resistance and endothelial dysfunction, which promote cardiovascular diseases in individuals with obesity. The purpose of this study was to evaluate the early effects of weight loss achieved through bariatric surgery on the inflammatory and prothrombotic states. This study also aimed to identify the role of hyperleptinemia on the prothrombotic state.. The sample was composed of 41 extremely obese who underwent Roux-en-Y gastric bypass (RYGB). Anthropometric and clinical data, and biochemical markers of inflammation were collected prior to surgery and 6 months post-RYGB.. It was found that plasminogen activator inhibitor-1 (PAI-1) concentrations were higher among extremely obese individuals with hyperleptinemia than in those without hyperleptinemia (p < 0.01).In relation to the baseline, post-surgery body mass index (BMI) was reduced by 12.9 kg/m(2), corresponding to 63.50 % of excess weight loss. Additionally, waist circumference was found to decrease significantly from 126.2 to 101.4 cm. Plasma total cholesterol (p < 0.01), LDL cholesterol (p = 0.02), triglycerides (p < 0.01), and glucose (p = 0.01) were also found to decrease. Pro-inflammatory biomarkers were observed to decrease: PAI-1 by 55.9 ± 6.0 % (p < 0.01), C-reactive protein (CRP) by 18.8 ± 3.4 % (p < 0.01), intercellular adhesion molecule-1 (ICAM-1) by 89.9 ± 5.7 % (p < 0.01), leptin by 27.9 ± 3.2 % (p < 0.01), and resistin by 69.3 ± 5.8 % (p < 0.01). Additionally, significant decreases of tumor necrosis factor alpha (TNF-α) and leptin/adiponectin ratio were observed. Anti-inflammatory cytokines adiponectin and interleukin-10 (IL-10) were significantly increased (170.7 ± 82.5 %, p < 0.01; 122.7 ± 55.1 %, p = 0.02). CRP levels were predictive of ICAM-1 (p = 0.04), and changes in leptin concentrations were associated with decreased PAI-1 levels (p = 0.03).. We observed that individuals with obesity that have hyperleptinemia have higher circulating PAI-1 levels, which could indicate increased risk for cardiovascular disease. The biomarkers of inflammation and thrombosis measured in this study decreased after RYGB, suggesting that the surgery may be effective in reducing pro-inflammatory and thrombotic risk in individuals with extreme obesity.

Topics: Adiponectin; Adult; Biomarkers; Body Mass Index; C-Reactive Protein; Female; Gastric Bypass; Humans; Inflammation; Insulin Resistance; Intercellular Adhesion Molecule-1; Interleukin-10; Leptin; Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Treatment Outcome; Triglycerides; Weight Loss; Young Adult

We determined whether persistent nausea and vomiting (N/V) symptoms following Roux-en-Y gastric bypass surgery is due to elevated systemic glucagon-like peptide-1 (GLP-1) and leptin in female non-diabetic subjects. Subjects with N/V post-Roux-en-Y gastric bypass (RYGB) surgery had significantly elevated fasting GLP-1 levels compared to that with post-operative asymptomatic subjects and to morbidly obese, obese and lean subjects not undergoing surgery. Weight loss, glycaemia, insulin and post-prandial GLP-1 levels were similar in all post-operative subjects. Despite comparable BMI, leptin was significantly lower in symptomatic subjects. Furthermore, leptin secretion from subcutaneous adipose tissue was inhibited by GLP-1 (0.1-1.0 nM; n = 6). Persistent N/V following RYGB surgery is associated with elevated fasting GLP-1, but lower leptin levels. The latter may be a consequence of the direct GLP-1 inhibition of leptin secretion from adipose tissue.

Topics: Adipokines; Adult; Blood Glucose; Case-Control Studies; Female; Gastric Bypass; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Leptin; Middle Aged; Nausea; Obesity, Morbid; Postoperative Nausea and Vomiting; Postprandial Period; Vomiting; Weight Loss

To investigate the behavioural and intracellular mechanisms by which the glucagon like peptide-1 (GLP-1) receptor agonist, liraglutide, and leptin in combination enhance the food intake inhibitory and weight loss effects of either treatment alone.. We examined the effects of liraglutide (a long-acting GLP-1 analogue) and leptin co-treatment, delivered in low or moderate doses subcutaneously (s.c.) or to the third ventricle, respectively, on cumulative intake, meal patterns and hypothalamic expression of intracellular signalling proteins [phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein tyrosine phosphatase-1B (PTP1B)] in lean rats.. A low-dose combination of liraglutide (25 µg/kg) and leptin (0.75 µg) additively reduced cumulative food intake and body weight, a result mediated predominantly through a significant reduction in meal frequency that was not present with either drug alone. Liraglutide treatment alone also reduced meal size; an effect not enhanced with leptin co-administration. Moderate doses of liraglutide (75 µg/kg) and leptin (4 µg), examined separately, each reduced meal frequency, cumulative food intake and body weight; only liraglutide reduced meal size. In combination these doses did not further enhance the anorexigenic effects of either treatment alone. Ex vivo immunoblot analysis showed elevated pSTAT3 in the hypothalamic tissue after liraglutide-leptin co-treatment, an effect which was greater than that of leptin treatment alone. In addition, s.c. liraglutide reduced the expression of PTP1B (a negative regulator of leptin receptor signalling), revealing a potential mechanism for the enhanced pSTAT3 response after liraglutide-leptin co-administration.. Collectively, these results show novel behavioural and molecular mechanisms underlying the additive reduction in food intake and body weight after liraglutide-leptin combination treatment.

Topics: Animals; Appetite Depressants; Body Weight; Drug Therapy, Combination; Eating; Glucagon-Like Peptide 1; Hypothalamus; Incretins; Leptin; Liraglutide; Male; Obesity; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Rats; Rats, Sprague-Dawley; STAT3 Transcription Factor; Weight Loss

To determine (1) the effects of weight loss in obese subjects on six adipokines and joint biomarkers; and (2) the relationship between changes in these markers with changes in cartilage outcomes.. Plasma levels of adiponectin, leptin, IL-6, COMP, MMP-3 and urine levels of CTX-II were measured at baseline and 12 months from 75 obese subjects enrolled in two weight-loss programs. Magnetic resonance imaging (MRI) was used to assess cartilage volume and thickness. Associations between weight loss, cartilage outcomes and markers were adjusted for age, gender, baseline BMI, presence of clinical knee OA, with and without weight loss percent.. Mean weight loss was 13.0 ± 9.5%. Greater weight loss percentage was associated with an increase in adiponectin (β = 0.019, 95% CI 0.012 to 0.026,) and a decrease in leptin (β = -1.09, 95% CI -1.37 to -0.82). Multiple regression analysis saw an increase in adiponectin associated with reduced loss of medial tibial cartilage volume (β = 14.4, CI 2.6 to 26.3) and medial femoral cartilage volume (β = 18.1, 95% CI 4.4 to 31.8). Decrease in leptin was associated with reduced loss of medial femoral volume (β = -4.1, 95% CI -6.8 to -1.4) and lateral femoral volume (β = -1.8, 95% CI -3.7 to 0.0). When weight loss percent was included in the model, only the relationships between COMP and cartilage volume remained statistically significant.. Adiponectin and leptin may be associated with cartilage loss. Further work will determine the relative contributions of metabolic and mechanical factors in the obesity-related joint changes.

Topics: Adipokines; Adiponectin; Adult; Aged; Biomarkers; Cartilage Oligomeric Matrix Protein; Cartilage, Articular; Cohort Studies; Collagen Type II; Female; Humans; Interleukin-6; Knee Joint; Leptin; Magnetic Resonance Imaging; Male; Matrix Metalloproteinase 3; Middle Aged; Obesity; Organ Size; Osteoarthritis, Knee; Peptide Fragments; Prospective Studies; Regression Analysis; Treatment Outcome; Weight Loss

Fibroblast growth factor (FGF) 21 is an endocrine factor with an emerging role as a metabolic regulator. We previously reported the presence of a significant day/night variation of FGF-21 in energy-replete, healthy female subjects. However the day/night patterns of secretion in male subjects remain to be fully elucidated. To elucidate day/night pattern of FGF-21 levels in male subjects in the energy-replete state, its relationship to FFA and to investigate whether a sexual dimorphism exists in FGF-21 physiology.. Eight healthy lean male subjects were studied for up to 5 days while on an isocaloric diet. Blood samples were obtained for measurement of FGF-21 and free fatty acids (FFA) hourly from 0800 AM on day 4 till 0800AM on day 5.. FGF-21 did not exhibit any statistically significant day/night variation pattern of circulating FGF-21 levels during the isocaloric fed state in male subjects. FGF-21 levels in male subjects are closely cross-correlated with FFA levels, similar to female subjects.. A sexual dimorphism exists in FGF-21 physiology; that as opposed to female subjects, no significant day/night variation exists in FGF-21 rhythm in male subjects in the energy-replete state. Circulating pattern of FGF-21, similar to the female subjects, was highly cross-correlated to the FFA levels in the male subjects, signifying that the sexual dimorphism in FGF-21 physiology may be related to the differing lipid metabolism in both the genders.

Topics: Circadian Rhythm; Energy Metabolism; Fatty Acids, Nonesterified; Female; Fibroblast Growth Factors; Healthy Volunteers; Humans; Leptin; Male; Sex Characteristics; Signal Transduction; Weight Loss; Young Adult

Obesity is characterized by an increased production of inflammatory markers. High levels of circulating free fatty acids and chronic inflammation lead to increased oxidative stress, contributing to the development of insulin resistance (IR). Recent studies have focused on the potential use of flavonoids for obesity management due to their antioxidant and anti-inflammatory properties. This study was designed to investigate the antioxidant and anti-inflammatory effects of helichrysum and grapefruit extracts in overweight insulin-resistant rats. Thirty-eight male Wistar rats were randomly distributed in two groups: control group (n=8) and high-fat sucrose (HFS) group (n=30). After 22 days of ad libitum water and food access, the rats fed HFS diet changed to standard diet and were reassigned into three groups (n=10 each group): nonsupplemented, helichrysum extract (2 g/kg bw), and grapefruit extract (1 g/kg bw) administered for 5 weeks. Rats supplemented with both extracts gained less body weight during the 5-week period of treatment, showed lower serum insulin levels and liver TBARS levels. Leptin/adiponectin ratio, as an indicator of IR, was lower in both extract-administered groups. These results were accompanied by a reduction in TNFα gene expression in epididymal adipose tissue and intestinal mucosa, and TLR2 expression in intestinal mucosa. Helichrysum and grapefruit extracts might be used as complement hypocaloric diets in weight loss treatment. Both extracts helped to reduce weight gain, hyperinsulinemia, and IR, improved inflammation markers, and decreased the HFS diet-induced oxidative stress in insulin-resistant rats.

Topics: Adiponectin; Animals; Antioxidants; Blood Glucose; Body Weight; Citrus paradisi; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Helichrysum; Inflammation; Insulin; Insulin Resistance; Leptin; Male; Overweight; Plant Extracts; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Treatment Outcome; Weight Loss

Understanding the mechanisms that drive weight loss in a lean population may elucidate systems that regulate normal energy homeostasis. This prospective study of British military volunteers investigated the effects of a 6-month deployment to Afghanistan on energy balance and circulating concentrations of specific appetite-regulating hormones.. Measurements were obtained twice in the UK (during the Pre-deployment period) and once in Afghanistan, at Mid-deployment. Body mass, body composition, food intake, and appetite-regulatory hormones (leptin, active and total ghrelin, PYY, PP, GLP-1) were measured.. Repeated measures analysis of 105 volunteers showed body mass decreased by 4.9% ± 3.7% (P < 0.0001) during the first half of the deployment. Leptin concentrations were significantly correlated with percentage body fat at each time point. The reduction in percentage body fat between Pre-deployment and Mid-deployment was 8.6%, with a corresponding 48% decrease in mean circulating leptin. Pre-deployment leptin and total and active ghrelin levels correlated with subsequent change in body mass; however. no changes were observed in the anorectic gut hormones GLP-1, PP, or PYY.. These data suggest that changes in appetite-regulating hormones in front line military personnel occur in response to, but do not drive, reductions in body mass.

Topics: Adult; Afghan Campaign 2001-; Afghanistan; Body Composition; Eating; Energy Metabolism; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Male; Middle Aged; Military Personnel; Peptide YY; Prospective Studies; Weight Loss; Young Adult

The majority of weight loss studies fail to standardize conditions such as diet and exercise via a weight maintenance period prior to commencement of the trial. This study aimed to determine whether a weight stabilization period is necessary to establish stable baseline hormone concentrations. Fifty-one obese male participants with a body mass index of 30-40 kg m(-2) and aged 25-54 years underwent 4 weeks on an energy balance diet that was designed to achieve weight stability. Blood samples were collected in the fasting state at commencement and completion of the 4-week period, and circulating concentrations of 18 commonly measured hormones were determined. During the 4-week weight maintenance period, participants achieved weight stability within -1.5 ± 0.2 kg (-1.4 ± 0.2%) of their initial body weight. Significant reductions in serum insulin (by 18 ± 6.5%) and leptin (by 21 ± 6.0%) levels occurred, but no significant changes were observed for gut-derived appetite-regulating hormones (ghrelin and peptide YY), nor thyroid, adrenal, gonadal or somatotropic hormones. There were no significant correlations between the change in body weight and the change in circulating concentrations of insulin or leptin over the 4-week period, indicating that the observed changes were not due to weight loss, albeit significant negative correlations were observed between the changes in body weight and plasma ghrelin and peptide YY levels. This study demonstrates the need for baseline weight maintenance periods to stabilize serum levels of insulin and leptin in studies specifically investigating effects on these parameters in the obese. However, this does not apply to circulating levels of gut-derived appetite-regulating hormones (ghrelin and peptide YY), nor thyroid, adrenal, gonadal or somatotropic hormones.

Topics: Adult; Clinical Trials as Topic; Diet; Energy Metabolism; Ghrelin; Hormones; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Peptide YY; Research Design; Weight Loss

Predictors of weight loss (WL) or weight regain (WR) after Roux-en-Y gastric bypass (RYGBP) are not established. The aim of this study was to analyze the usefulness of some baseline peptides (leptin, insulin, and ghrelin) as biomarkers of WL and WR in morbid obese patients after RYGBP at long term.. Seventy-six morbid obese (47 women, age 41.6 ± 9.6 years, body mass index [BMI] 52.1 ± 8 kg/m(2)) patients were evaluated at baseline and at 1, 2, and 6 years after surgery.. Excess body weight loss after 6 years was of 63.9%. Age, BMI, and studied hormones at baseline or their changes over time did not predict long-term excess body weight loss. WR greater than 10% was observed in 36.8% of patients between 2 and 6 years of follow-up, but it was not correlated with BMI, age, or baseline peptide concentrations.. Measurement of ghrelin, insulin, and leptin before surgery is not useful as predictors of WL or WR at long term after RYGBP.

Topics: Adult; Biomarkers; Female; Gastric Bypass; Ghrelin; Humans; Insulin; Leptin; Male; Obesity, Morbid; Prognosis; Prospective Studies; Recurrence; Time Factors; Weight Gain; Weight Loss

Pharmacological administration of fibroblast growth factor 21 (FGF21) improves metabolic profile in preclinical species and humans. FGF21 exerts its metabolic effects through formation of beta-klotho (KLB)/FGF receptor 1c FGFR1c complex and subsequent signaling. Data from various in vitro systems demonstrate the intact C- and N-terminus of FGF21 is required for binding with KLB, and interaction with FGFR1c, respectively. However the relative roles of the termini for in vivo pharmacological effects are unclear. Here we report PF-05231023, a long-acting FGF21 analogue which is unique in that the half-life and subcutaneous (s.c.) bioavailability of the intact C-terminus are significantly different from those of the intact N-terminus (2 vs. 22 hr for half-life and 4~7 vs. ~50% SC bioavailability). Therefore, this molecule serves as a valuable tool to evaluate the relative roles of intact C-terminus vs. N-terminus in in vivo pharmacology studies in preclinical species. We determined the effects of PF-05231023 administration on body weight (BW) loss and glucose reduction during an oral glucose tolerance test (OGTT) following SC and intravenous (i.v.) administration in diet-induced obese (DIO) and leptin-deficient obese (ob/ob) mice, respectively. Our data show that the intact N-terminus of FGF21 in PF-05231023 appears to be sufficient to drive glucose lowering during OGTT and sustain BW loss in DIOs. Further, PK/PD modeling suggests that while the intact FGF21 C-terminus is not strictly required for glucose lowering during OGTT in ob/ob mice or for BW reduction in DIO mice, the higher potency conferred by intact C-terminus contributes to a rapid initiation of pharmacodynamic effects immediately following dosing. These results provide additional insight into the strategy of developing stabilized versions of FGF21 analogs to harness the full spectrum of its metabolic benefits.

Topics: Administration, Intravenous; Animals; Antibodies, Monoclonal, Humanized; Blood Glucose; Diet; Fibroblast Growth Factors; Glucose Tolerance Test; Injections, Subcutaneous; Leptin; Male; Mice, Obese; Models, Biological; Obesity; Time Factors; Weight Loss

Free fatty acid (FFA) levels are raised in obesity as a consequence of increased production and reduced clearance. They may link obesity with insulin resistance. Bariatric surgery can result in considerable weight loss and reduced insulin resistance, but the mechanism of action is not well understood. Although drugs such as metformin that lower insulin resistance can contribute to weight loss, a better understanding of the links between obesity, weight loss and changes in insulin resistance might lead to new approaches to patient management.. Variations in circulating levels of leptin, insulin and FFAs over 24 h were studied in severely obese (body mass index over 40 kg/m(2) ) women before and 6 months after biliopancreatic diversion (BPD). Body composition was measured by dual-energy X-ray absorptiometry. A euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Levels of insulin, leptin and FFAs were measured every 20 min for 24 h. Pulsatile hormone and FFA analyses were performed.. Among eight patients studied, insulin sensitivity more than doubled after BPD, from mean(s.d.) 39·78(7·74) to 96·66(27·01) mmol per kg fat-free mass per min, under plasma insulin concentrations of 102·29(9·60) and 93·61(9·95) µunits/ml respectively. The secretory patterns of leptin were significantly different from random but not statistically different before and after BPD, with the exception of the pulse height which was reduced after surgery. Both plasma insulin and FFA levels were significantly higher throughout the study day before BPD. Based on Granger statistical modelling, lowering of daily FFA levels was linked to decreased circulating leptin concentrations, which in turn were related to the lowering of daily insulin excursions. Multiple regression analysis indicated that FFA level was the only predictor of leptin level.. Lowering of circulating levels of FFAs after BPD may be responsible for the reduction in leptin secretion, which in turn can decrease circulating insulin levels. Surgical relevance Insulin resistance is a common feature of obesity and type II diabetes. These patients are also relatively insensitive to the biological effects of leptin, a satiety hormone produced mainly in subcutaneous fat. Biliopancreatic diversion, a malabsorptive bariatric operation that drastically reduces circulating lipid levels, improves insulin resistance independently of weight loss. The mechanism of action, however, has still to be elucidated. This study demonstrated that normalization of insulin sensitivity after bariatric surgery was associated with a reduction in 24-h free fatty acid concentrations and changes in the pattern of leptin peaks in plasma. Bariatric surgery improves the metabolic dysfunction of obesity, and this may be through a reduction in circulating free fatty acids and modification of leptin metabolism.

Topics: Adult; Biliopancreatic Diversion; Body Mass Index; Circadian Rhythm; Fatty Acids, Nonesterified; Female; Follow-Up Studies; Humans; Insulin; Leptin; Obesity, Morbid; Prognosis; Time Factors; Weight Loss

The combinatorial peptidergic therapy of islet amyloid polypeptide (IAPP) and leptin (LEP) analogues was once an optimistic option in treating obese animals and patients. However, the need for frequent administrations and its negative side effects prevent it from being a viable choice. Here, we developed a combinatorial gene therapy of IAPP and LEP, where two genes are inserted into a single plasmid with self-cleaving furin and 2A sites to treat diet-induced obese (DIO) mice. The developed plasmid DNA (pDNA) individually produced both IAPP and LEP peptides in vitro and in vivo. The pDNA was delivered with a non-viral polymeric carrier, and its once-a-week administrations demonstrated a synergistic loss of body weight and significant reductions of fat mass, blood glucose, and lipid levels in DIO mice. The results suggest that the combinatorial gene therapy would have higher potential than the peptidergic approach for future translation due to its improved practicability.

Topics: Adiposity; Animals; Blood Glucose; Diet, High-Fat; Disease Models, Animal; Eating; Gene Transfer Techniques; Genetic Therapy; HEK293 Cells; Humans; Islet Amyloid Polypeptide; Leptin; Lipids; Male; Mice, Inbred C57BL; Obesity; Plasmids; Polymers; Time Factors; Transfection; Weight Loss

Piper nigrum Linn (Piperaceae) (PnL) is used in traditional medicine to treat gastric ailments, dyslipidemia, diabetes, and hypertension.. The present study explores the possible protective effects of P. nigrum extracts on high-fat diet-induced obesity in rats.. High-fat diet-induced obese rats were treated orally with 200 mg/kg bw of different extracts (hexane, ethylacetate, ethanol, and aqueous extracts) of PnL for 42 d. The effects of PnL extracts on body composition, insulin resistance, biochemical parameters, leptin, adiponectin, lipid profile, liver marker enzymes, and antioxidants were studied.. The HFD control group rats showed a substantial raise in body weight (472.8 ± 9.3 g), fat% (20.8 ± 0.6%), and fat-free mass (165.9 ± 2.4 g) when compared with normal control rats whose body weight, fat%, and fat-free mass were 314.3 ± 4.4 g, 6.4 ± 1.4%, and 133.8 ± 2.2 g, respectively. Oral administration of ethyl acetate or aqueous extracts of PnL markedly reduced the body weight, fat%, and fat-free mass of HFD-fed rats. In contrast to the normal control group, a profound increase in plasma glucose, insulin resistance, lipid profile, leptin, thiobarbituric acid reactive substance (TBARS), and the activities of lipase and liver marker enzymes, and a decrease in adiponectin and antioxidant enzymes were noted in HFD control rats. Administration of PnL extracts to HFD-induced obese rats significantly (p < 0.05) restored the above profiles.. PnL extracts significantly reduced the body weight, fat%, and ameliorated HFD-induced hyperlipidemia and its constituents.

Topics: Adiponectin; Adiposity; Animals; Antioxidants; Biomarkers; Blood Glucose; Diet, High-Fat; Disease Models, Animal; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Insulin; Insulin Resistance; Leptin; Lipids; Male; Oxidative Stress; Phytotherapy; Piper nigrum; Plant Extracts; Plants, Medicinal; Rats, Sprague-Dawley; Solvents; Thiobarbituric Acid Reactive Substances; Weight Loss

Peripheral coadministration of amylin and leptin produces enhanced suppression of food intake and body weight, but the central nuclei mediating these effects remain unclear. Because each of these peptides controls feeding via actions at the ventral tegmental area (VTA), we tested the hypothesis that the VTA is a site of action for the cooperative effects of leptin and amylin on energy balance control. First, we show that intra-VTA injection of amylin and leptin at doses of each peptide that are effective in reducing food intake and body weight when administered separately produces an enhanced suppression of feeding when administered in combination. We also demonstrate that subthreshold doses of both amylin and leptin cause significant hypophagia and body weight loss when coadministered into the VTA. Additionally, we provide evidence that VTA amylin receptor blockade significantly attenuates the ability of intra-VTA leptin to reduce feeding and body weight gain. Together, these data provide the first evidence that the VTA mediates the interaction of amylin and leptin to cooperatively promote negative energy balance.

Topics: Animals; Appetite Regulation; Body Weight; Energy Metabolism; Islet Amyloid Polypeptide; Leptin; Male; Rats; Rats, Sprague-Dawley; Signal Transduction; Ventral Tegmental Area; Weight Loss

Angiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin-(1-7) is a metabolite of angiotensin I and of angiotensin II . As an agonist of Mas receptors, angiotensin-(1-7) has beneficial cardiovascular and metabolic effects.. We investigated the anti-obesity effects of transgenically overexpressed angiotensin-(1-7) in rats. We secondly examined whether weight loss due to telmisartan (8 mg·kg(-1) ·d(-1) ) in diet-induced obese Sprague Dawley (SD) rats can be blocked when the animals were co-treated with the Mas receptor antagonist A779 (24 or 72 μg·kg(-1) ·d(-1) ).. In contrast to wild-type controls, transgenic rats overexpressing angiotensin-(1-7) had 1.) diminished body weight when they were regularly fed with chow; 2.) were protected from developing obesity although they were fed with cafeteria diet (CD); 3.) showed a reduced energy intake that was mainly related to a lower CD intake; 5.) remained responsive to leptin despite chronic CD feeding; 6.) had a higher, strain-dependent energy expenditure, and 7.) were protected from developing insulin resistance despite CD feeding. Telmisartan-induced weight loss in SD rats was partially antagonized after a high, but not a low dose of A779.. Angiotensin-(1-7) regulated food intake and body weight and contributed to the weight loss after AT1 receptor blockade. Angiotensin-(1-7)-like agonists may be drug candidates for treating obesity.

Topics: Angiotensin I; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Animals, Genetically Modified; Benzimidazoles; Benzoates; Diet; Energy Intake; Energy Metabolism; Insulin Resistance; Leptin; Male; Obesity; Peptide Fragments; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rats; Receptors, G-Protein-Coupled; Signal Transduction; Telmisartan; Weight Gain; Weight Loss

To investigate the effect of ex-vivo leptin treatment before and after weight loss on key-molecules of intracellular leptin signaling in peripheral blood mononuclear cells (PBMCs) of obese women.. Five healthy obese women underwent a 12-week medical nutrition treatment aiming at inducing 10% weight loss. Isolated PBMCs at baseline, and at weeks 8 and 12 were treated with increasing leptin doses (0, 25 and 75 ng/ml) for 30 min. The phosphorylation of signal transducer and activator of transcription (STAT)3, extracellular-signal-regulated kinase (ERK), protein kinase B (Akt) and 5' adenosine monophosphate-activated protein kinase (AMPK) of PBMCs was analyzed using Western blotting.. Women lost 10 ± 1% and 13 ± 1% of weight at week 8 and 12, respectively. Circulating leptin and insulin significantly decreased from 39.5 ± 7.7 to 12.2 ± 2.4 ng/ml (p = 0.026) and from 13.0 ± 1.6 to 5.4 ± 0.9 μU/ml (p = 0.005) at week 12, respectively. In the ex vivo study, a significant decrease in STAT3 phosphorylation was observed in the control group after weight loss. Treatment of PBMCs with leptin 75 ng/ml increased significantly ERK, STAT3 and Akt phosphorylation, but no weight loss induced change was observed in response to leptin treatment ex vivo.. A 10%-15% weight loss decreases baseline STAT3 phosphorylation ex vivo, but does not alter the effect of increasing doses of leptin on the incremental intracellular phosphorylation of STAT3, ERK, Akt and AMPK. Supraphysiologic leptin doses (75 ng/ml) result in higher protein phosphorylation compared to either physiologic doses or no treatment, before and after weight loss.

Topics: Adult; Extracellular Signal-Regulated MAP Kinases; Female; Humans; Leptin; Obesity; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Leptin; Signal Transduction; STAT3 Transcription Factor; Weight Loss

Women who are obese at the time of breast cancer diagnosis have higher overall mortality than normal weight women and some evidence implicates adiponectin and leptin as contributing to prognostic disadvantage. While intentional weight loss is thought to improve prognosis, its impact on these adipokines is unclear. This study compared the pattern of change in plasma leptin and adiponectin in overweight-to-obese post-menopausal breast cancer survivors during weight loss. Given the controversies about what dietary pattern is most appropriate for breast cancer control and regulation of adipokine metabolism, the effect of a low fat versus a low carbohydrate pattern was evaluated using a non-randomized, controlled study design. Anthropometric data and fasted plasma were obtained monthly during the six-month weight loss intervention. While leptin was associated with fat mass, adiponectin was not, and the lack of correlation between leptin and adiponectin concentrations throughout weight loss implies independent mechanisms of regulation. The temporal pattern of change in leptin but not adiponectin was affected by magnitude of weight loss. Dietary pattern was without effect on either adipokine. Mechanisms not directly related to dietary pattern, weight loss, or fat mass appear to play dominant roles in the regulation of circulating levels of these adipokines.

Topics: Adiponectin; Anthropometry; Biomarkers; Body Mass Index; Breast Neoplasms; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Female; Humans; Leptin; Middle Aged; Overweight; Postmenopause; Prognosis; Survivors; Time Factors; Weight Loss

Feed restriction, and seasonal weight loss (SWL), are major setbacks for animal production in the tropics and the Mediterranean. They may be solved through the use of autochthonous breeds particularly well adapted to SWL. It is therefore of major importance to determine markers of tolerance to feed restriction of putative use in animal selection. Two indigenous breeds from the Canary Islands, Palmera and Majorera, are commonly used by dairy goat farmers and, interestingly, have different phenotype characteristics albeit with a common ancestry. Indeed, Majorera is well adapted to feed restriction whereas the Palmera is susceptible to feed restriction. In addition, regardless of their importance in dairy production, there are only a limited number of reports relating to these breeds and, to the best of our knowledge, there is no description of their blood metabolite standard values under control conditions or as affected by feed restriction. In this study we analysed the blood metabolite profiles in Majorera and Palmera goats aiming to establish the differential responses to feed restriction between the two breeds and to characterise their metabolite standard values under control conditions. We observed significant differences in creatinine, urea, non-esterified fatty acids (NEFAs), cholesterol, IGF-1 and T3 due to underfeeding. Furthermore, a PCA analysis, revealed that animals submitted to undernutrition could be distinguished from the control groups, with the formation of three separate clusters (Palmera individuals after 22 d of subnutrition (PE22); Majorera individuals after 22 d of subnutrition (ME22) and animals assigned to control conditions (MC0, MC22, PC0 and PC22)), highlighting different responses of the two breeds to undernutrition.

Topics: Animals; Blood Glucose; Blood Proteins; Chlorides; Cholesterol; Creatine Kinase; Creatinine; Fatty Acids, Nonesterified; Female; Food Deprivation; Genetic Variation; Goats; Hydrocortisone; Hydroxybutyrates; Insulin; Insulin-Like Growth Factor I; Leptin; Phosphorus; Principal Component Analysis; Seasons; Sodium; Triglycerides; Triiodothyronine; Urea; Weight Loss

Gastrointestinal hormones are critically involved in the regulation of food intake and body weight. Previous studies support an interplay between gastrointestinal hormones and the serotonergic system. This study explored intestinal neuroendocrine expression patterns in humans with obesity versus nonobese humans.. Jejunum samples were collected from 164 humans with obesity (120 women; BMI (mean ± SD): 43.5 ± 6.6 kg/m(2) ) while they underwent Roux-en-Y gastric bypass surgery and from 18 nonobese humans (7 women; BMI: 23.5 ± 3.0 kg/m(2) ) undergoing distinct intestinal surgeries. mRNA expression of cholecystokinin (CCK), peptide YY3-36 (PYY), nesfatin1, ghrelin, ghrelin O-acyltransferase (GOAT), leptin, leptin receptor (leptinR), glucagon-like-peptide 1 receptor (GLP1R), serotonin transporter (SERT), tryptophan hydroxylase 1 (TPH1), and serotonin receptor 3A (5HT3A R) was determined with qRT-PCR. Ghrelin and GOAT protein expression was quantified using immunohistological stainings. Statistical analyses were performed with SPSS.. Jejunum samples from humans with obesity showed a higher expression of GOAT (mRNA and protein), TPH1, and SERT mRNA compared with the nonobese humans (all P < 0.05). Positive correlations were observed between TPH1, CCK, PYY, and nesfatin1 in nonobese and GOAT, ghrelin, TPH1, SERT, CCK, and PYY in humans with obesity (all P < 0.01).. Our top-down approach substantiates the dysregulation of jejunal neuroendocrine hormones in obesity.

Topics: Acyltransferases; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cholecystokinin; Female; Gastric Bypass; Gastrointestinal Hormones; Gene Expression Regulation; Ghrelin; Humans; Jejunum; Leptin; Middle Aged; Neuroendocrine Cells; Obesity, Morbid; Peptide Fragments; Peptide YY; Weight Loss; Young Adult

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (-4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (-80%), serum leptin (-77%), and serum IGF1 (-34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

Topics: Animals; Body Weight; Bone Density; Female; Genetic Therapy; Hypothalamus; Insulin-Like Growth Factor I; Leptin; Obesity; Rats; Rats, Sprague-Dawley; Weight Loss

The melanin-concentrating hormone (MCH) is a centrally acting peptide implicated in the regulation of energy homeostasis and body weight, although its role in glucose homeostasis is uncertain. Our objective was to determine effects of MCHR1 antagonism on energy budgets and glucose homeostasis in mice.. Effects of chronic oral administration of a specific MCHR1 antagonist (GW803430) on energy budgets and glucose homeostasis in diet-induced obese (DIO) C57BL/6J mice were examined.. Oral administration of GW803430 for 30 days reduced food intake, body weight, and body fat. Circulating leptin and triglycerides were reduced but insulin and nonesterified fatty acids were unaffected. Despite weight loss there was no improvement in glucose homeostasis (insulin levels and intraperitoneal glucose tolerance tests). On day 4-6, mice receiving MCHR1 antagonist exhibited decreased metabolisable energy intake and increased daily energy expenditure. However these effects had disappeared by day 22-24. Physical activity during the dark phase was increased by MCHR1 antagonist treatment throughout the 30-day treatment.. GW803430 produced a persistent anti-obesity effect due to both a decrease in energy intake and an increase in energy expenditure via physical activity but did not improve glucose homeostasis.

Topics: Absorptiometry, Photon; Adipose Tissue; Administration, Oral; Animals; Body Mass Index; Diet, High-Fat; Energy Intake; Energy Metabolism; Glucose; Glucose Tolerance Test; Homeostasis; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Motor Activity; Obesity; Pyrimidinones; Receptors, Somatostatin; Thiophenes; Triglycerides; Weight Loss

High-protein diets favor weight loss and its maintenance. Whether these effects might be recapitulated by certain amino acids is unknown. Therefore, the impact of leucine supplementation on energy balance and associated metabolic changes in diet-induced obese (DIO) mice during and after weight loss was investigated.. DIO C57BL/6J mice were fed a normocaloric diet to induce weight loss while receiving or not the amino acid leucine in drinking water. Body weight, food intake, body composition, energy expenditure, glucose tolerance, insulin, and leptin sensitivity were evaluated. Q-PCR analysis was performed on muscle, brown and white adipose tissues.. DIO mice decreased body weight and fat mass in response to chow, but supplementation with leucine did not affect these parameters. During weight maintenance, mice supplemented with leucine had improved glucose tolerance, increased leptin sensitivity, and lower respiratory quotient. The latter was associated with changes in the expression of several genes modulating fatty acid metabolism and mitochondrial activity in the epididymal white and the brown adipose tissues, but not muscle.. Leucine supplementation might represent an adjuvant beneficial nutritional therapy during weight loss and maintenance, because it improves lipid and glucose metabolism and restores leptin sensitivity in previously obese animals.

Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Blood Glucose; Body Composition; Calorimetry, Indirect; Diet, High-Fat; Dietary Supplements; Energy Metabolism; Gluconeogenesis; Glucose Tolerance Test; Insulin; Intestinal Mucosa; Intestines; Leptin; Leucine; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Weight Loss

The significant weight loss observed with combination naltrexone-sustained release (SR) 32 mg and bupropion SR 360 mg (NB32) therapy is thought to be due, in part, to bupropion stimulation of hypothalamic pro-opiomelanocortin (POMC) neurons, and naltrexone blockade of opioid receptor-mediated POMC autoinhibition, but the neurobiological mechanisms are not fully understood. We assessed changes in brain reactivity to food cues before and after NB32 treatment.. Forty women (31.1±8.1 years; body mass index: 32.5±3.9) received 4 weeks of NB32 or placebo, and were instructed to maintain their dietary and exercise habits. Functional magnetic resonance imaging responses (analyzed using SPM2 and clusters (>100 pixels)) to a 5-min food video (preparation of the subject's favorite food) and a 5-min neutral video (manipulation of neutral objects) under conditions of mild food deprivation (∼14 h) were assessed before and after treatment.. The food cues video induced positive brain activation in visual and prefrontal cortices, insula and subcortical brain regions. The group-by-treatment interaction on regional brain activation was significant and showed that whereas NB32 attenuated the activation in the hypothalamus in response to food cues (P<0.01), it enhanced activation in regions involved in inhibitory control (anterior cingulate), internal awareness (superior frontal, insula, superior parietal) and memory (hippocampal) regions (whole-brain analysis; P<0.05).. Blunting the hypothalamic reactivity to food cues while enhancing the activation of regions involved with self-control and internal awareness by NB32 might underlie its therapeutic benefits in obesity.

Topics: Adolescent; Adult; Appetite; Bupropion; Cues; Diet; Dopamine Uptake Inhibitors; Drug Therapy, Combination; Female; Ghrelin; Humans; Hypothalamus; Leptin; Magnetic Resonance Imaging; Meals; Naltrexone; Obesity; Peptide YY; Treatment Outcome; Weight Loss

Elevated serum leptin levels correlate with inflammation and predict changes in lean body mass in patients with CKD, and activation of the melanocortin system by leptin signaling mediates the pathophysiology of CKD-associated cachexia. We tested whether treatment with a pegylated leptin receptor antagonist (PLA) attenuates cachexia in mice with CKD. CKD and Sham mice received vehicle or PLA (2 or 7 mg/kg per day). At these doses, PLA did not influence serum leptin levels in mice. Treatment with 7 mg/kg per day PLA stimulated appetite and weight gain, improved lean mass and muscle function, reduced energy expenditure, and normalized the levels of hepatic TNF-α and IL-6 mRNA in mice with CKD. Furthermore, treatment with 7 mg/kg per day PLA attenuated the CKD-associated increase in the transcriptional and protein abundance of uncoupling proteins that mediates thermogenesis, and it normalized the molecular signatures of processes associated with muscle wasting in CKD, including proteolysis, myogenesis and muscle regeneration, and expression of proinflammatory muscle cytokines, such as IL-1α, -1β, and -6 and TNF-α. Our results suggest that leptin antagonism may represent a viable therapeutic strategy for cachexia in CKD.

Topics: Animals; Anorexia; Cachexia; Energy Metabolism; Gene Expression; Leptin; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Receptors, Leptin; Renal Insufficiency, Chronic; Signal Transduction; Weight Loss

Enhanced stimulation of the lower gut is hypothesized to play a key role in the weight loss and resolution of diabetes following bariatric surgeries. Ileal transposition (IT) permits study of the effects of direct lower gut stimulation on body weight, glucose homeostasis and other metabolic adaptations without the confounds of gastric restriction or foregut exclusion. However, the underlying mechanisms and the length of the ileum sufficient to produce metabolic benefits following IT surgery remain largely unknown.. To determine the effects of transposing varying lengths of the ileum to upper jejunum on food intake, body weight, glucose tolerance and lower gut hormones, and the expression of key markers of glucose and lipid metabolism in skeletal muscle and adipose tissue in rats.. Adult male Sprague-Dawley rats (n=9/group) were subjected to IT surgery with translocation of 5, 10 or 20 cm of the ileal segment to proximal jejunum or sham manipulations. Daily food intake and body weight were recorded, and an intraperitoneal glucose tolerance test was performed. Blood samples were assayed for hormones and tissue samples for mRNA (RT-qPCR) and/or protein abundance (immunoblotting) of regulatory metabolic markers.. We demonstrate that IT surgery exerts ileal length-dependent effects on multiple parameters including: (1) decreased food intake and weight gain, (2) improved glucose tolerance, (3) increased tissue expression and plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and decreased leptin concentrations and (4) upregulation of key markers of glucose metabolism (glucose transporter-4 (GLUT-4), insulin receptor substrate 1 (IRS-1), adenosine monophosphate-activated protein kinase (AMPK), hexokinase (HK) and phosphofructokinase (PFK)) together with a downregulation of lipogenic markers (fatty acid synthase (FAS)) in muscle and adipose tissue.. Together, our data demonstrate that the reduction in food intake and weight gain, increase in lower gut hormones, glycemic improvements and associated changes in tissue metabolic markers following IT surgery are dependent on the length of the transposed ileum.

Topics: AMP-Activated Protein Kinases; Animals; Biomarkers; Blood Glucose; Eating; Gastrectomy; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Glucose Tolerance Test; Glucose Transporter Type 4; Homeostasis; Ileum; Insulin Receptor Substrate Proteins; Intestinal Mucosa; Leptin; Male; Muscle, Skeletal; Peptide YY; Rats; Rats, Sprague-Dawley; Weight Loss

In the present study, purified sweet cherry anthocyanins (CACN) were evaluated to determine their inhibitory effects on adipocyte differentiation of 3T3-L1 cells and their anti-obesity properties in male C57BL/6 mice fed with high-fat diet (HFD). CACN prevented HFD-induced obesity in C57BL/6 mice. In vivo experiment revealed that 40 and 200 mg/kg of CACN in food reduced the body weight by 5.2% and 11.2%, respectively. CACN supplementation could also reduce the size of adipocytes, leptin secretion, serum glucose, triglyceride, total cholesterol, LDL-cholesterol and liver triglycerides. Furthermore, CACN could effectively reduce the expression levels of IL-6 and TNFα genes, markedly increase the SOD and GPx activity. Our results indicated that CACN slowed down the development of HFD-induced obesity in male C57BL/6 mice.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipose Tissue; Animals; Anthocyanins; Anti-Obesity Agents; Blood Glucose; Diet, High-Fat; Dietary Supplements; Interleukin-6; Leptin; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Phytotherapy; Plant Extracts; Prunus; Tumor Necrosis Factor-alpha; Weight Loss

Remodeling of the extracellular matrix (ECM) of adipose tissue is regarded as part of the pathophysiology of obesity. Secreted protein acidic and rich in cysteine (SPARC) was the first ECM protein described in adipose tissue. Matrix metalloproteinases (MMPs) also play a role in ECM remodeling, and MMP-2 and MMP-9 may be associated with abnormal ECM metabolism. Here, we investigated changes in serum SPARC, MMP-2, and MMP-9 concentrations after bariatric surgery in obese adults.. We recruited 34 obese patients who were scheduled to undergo bariatric surgery for weight loss. We analyzed changes in serum SPARC, MMP-2, and MMP-9 concentrations before and 9 months after bariatric surgery and any associations between changes in SPARC, MMP-2, and MMP-9 concentrations and obesity-related parameters.. Serum leptin levels significantly decreased, and the serum adiponectin level significantly increased after bariatric surgery. The serum SPARC concentration decreased significantly from 165.0 ± 18.2 to 68.7 ± 6.7 ng/mL (p < 0.001), and the MMP-2 concentration also decreased significantly from 262.2 ± 15.2 to 235.9 ± 10.5 ng/mL (p < 0.001). Changes in the serum SPARC concentration were significantly correlated with HOMA-IR changes, and changes in the serum MMP-9 concentration were found to inversely correlate with serum adiponectin changes.. These findings show that significant decreases in serum SPARC and MMP-2 concentrations occur after bariatric surgery. Our results thus suggest that weight loss via bariatric surgery could alter the ECM environment, and that these changes are related to certain metabolic changes.

Topics: Adiponectin; Adipose Tissue; Adult; Bariatric Surgery; Female; Humans; Insulin Resistance; Leptin; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Obesity; Osteonectin; Weight Loss

We recently reported restoration of leptin responsiveness in diet-induced obese (DIO) mice using a pharmacologically optimized, polyethylene-glycolated (PEG)-leptin analog in combination with exendin-4 or FGF21. However, the return of leptin action required discontinuation of high-fat diet (HFD) exposure. Here we assess whether a single peptide possessing balanced coagonism at the glucagon-like peptide 1 (GLP-1) and glucagon receptors can restore leptin responsiveness in DIO mice maintained on a HFD. DIO mice were treated with PEG-GLP-1/glucagon (30 nmol/kg every fourth day) to induce an ∼15% body weight loss, upon which they were randomized to continue PEG-GLP-1/glucagon therapy or reassigned to receive supplemental daily PEG-leptin (185 nmol/kg/day). The addition of PEG-leptin to PEG-GLP-1/glucagon resulted in an ∼18% greater weight loss as compared with PEG-GLP-1/glucagon alone and was accompanied by further decreases in food intake and improved glucose and lipid metabolism. The beneficial effect of PEG-leptin supplementation occurred after an initial body weight loss similar to what we previously reported following reduced dietary fat along with PEG-leptin and exendin-4 or FGF21 cotreatment. In summary, we report that GLP-1/glucagon coagonism restores leptin responsiveness in mice maintained on a HFD, thus emphasizing the translational value of this polypharmacotherapy for the treatment of obesity and diabetes.

Topics: Animals; Diet, High-Fat; Eating; Feeding Behavior; Glucagon; Glucagon-Like Peptide 1; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Polyethylene Glycols; Receptors, Glucagon; Weight Loss

A decline in resting energy expenditure (REE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (EI).. Thirty overweight and obese women (body mass index (BMI)=30.6±3.6 kg/m(2)) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, EI and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured REE was also calculated post intervention (MApost), with REE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI=31.0±3.9 kg/m(2)).. Although mean predicted and measured REE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in REE (-102.9±77.5 kcal per day). MApost was associated with the change in leptin (r=0.47; P=0.04), and the change in resting fat (r=0.52; P=0.01) and carbohydrate oxidation (r=-0.44; P=0.02). Furthermore, MApost was also associated with the change in EI following EX (r=-0.44; P=0.01).. Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in REE also experienced an upregulation in EI, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.

Topics: Adult; Blood Glucose; Body Composition; Body Mass Index; Energy Intake; Energy Metabolism; Exercise; Female; Humans; Leptin; Linear Models; Middle Aged; Nutrition Assessment; Obesity; Overweight; Rest; Surveys and Questionnaires; Weight Loss

Weight regain is associated with the promotion of insulin resistance. The newly discovered myokine irisin, which was proposed to be involved in the management of insulin sensitivity, could play a role in this process. This study aimed to investigate the association between irisin and reduced insulin sensitivity induced by weight regain.. Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) in 136 obese patients who followed an eight-week hypocaloric diet (30% reduced energy expenditure) to lose weight and was re-evaluated four or six months after treatment. Irisin plasma levels, as well as the levels of leptin, adiponectin, ghrelin and TNF-α, were quantified in a sub-cohort (n=73) from the initially studied patients at baseline (T0), at the diet endpoint (T1) and after the follow-up period (T2).. After a successful dietary intervention to lose weight, 50% of the patients who regained the lost weight during the follow-up period were categorized as insulin resistant (HOMA-IR≥2.5) compared with only 25% of patients who maintained the weight loss (p=0.018). Importantly, in addition to the well-studied hormones leptin and adiponectin, irisin plasma levels were statistically associated with several risk factors for insulin resistance. Indeed, the increased risk of insulin resistance during the follow-up period was related to high irisin levels at baseline (odds ratio=4.2; p=0.039).. Circulating irisin predicts the insulin resistance onset in association with weight regain. Therefore, irisin could be secreted as an adaptive response to counteract the deleterious effect of excess adiposity on glucose homeostasis.

Topics: Adiponectin; Adult; Female; Fibronectins; Ghrelin; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Tumor Necrosis Factor-alpha; Weight Loss

Obesity has been linked to a wide spectrum of malignancies, with the strongest association demonstrated for endometrial cancer. Although the mechanisms are not yet entirely clear, a number of risk biomarkers have been proposed, including altered adipokines. Systemic levels of these adipose derived molecules have also been linked in prior research to self-reported quality of life (QOL). The study objective was to examine the hypothesis that adipokine changes during intentional weight loss may be associated with changes in QOL.. Fifty-two female participants were selected from two behavioral weight loss trials (SMART and PREFER) on the basis of achieving successful weight loss at 6month assessment, availability of blood samples and completion of standard SF-36 QOL questionnaires. Levels of adiponectin, leptin, and resistin were measured using xMAP immunoassays. Changes in QOL were examined using linear regression models in relation to pre- and post-intervention changes in biomarker levels and BMI.. Significant changes between pre- and post-intervention were observed for leptin. Controlling for baseline BMI, leptin was the only biomarker that predicted change in QOL (Physical Component Scale, PCS). Linear regression models demonstrated that leptin continued to be a significant predictor of change in PCS when other possible predictor variables were included in the model.. This study is among the first to demonstrate that changes in PCS may be regulated by levels of both metabolic variables and adipokines. An improved understanding of biological mechanisms associated with weight loss and the role of QOL may help guide preventive strategies for obesity-associated cancers.

Topics: Adipokines; Adiponectin; Adult; Body Mass Index; Female; Humans; Leptin; Linear Models; Middle Aged; Obesity; Overweight; Quality of Life; Resistin; Weight Loss; Weight Reduction Programs; Young Adult

Intermittent fasting (IF) is neuroprotective across a range of insults, but the question of whether extending the interval between meals alters neurogenesis after ischemia remains unexplored. We therefore measured cell proliferation, cell death, and neurogenesis after transient middle cerebral artery occlusion (MCAO) or sham surgery (SHAM) in mice fed ad libitum (AL) or maintained on IF for 3 months. IF was associated with twofold reductions in circulating levels of the adipocyte cytokine leptin in intact mice, but also prevented further reductions in leptin after MCAO. IF/MCAO mice also exhibit infarct volumes that were less than half those of AL/MCAO mice. We observed a 30% increase in basal cell proliferation in the hippocampus and subventricular zone (SVZ) in IF/SHAM, relative to AL/SHAM mice. However, cell proliferation after MCAO was limited in IF mice, which showed twofold increases in cell proliferation relative to IF/SHAM, whereas AL/MCAO mice exhibit fivefold increases relative to AL/SHAM. Attenuation of stroke-induced neurogenesis was correlated with reductions in cell death, with AL/MCAO mice exhibiting twice the number of dying cells relative to IF/MCAO mice. These observations indicate that IF protects against neurological damage in ischemic stroke, with circulating leptin as one possible mediator.

Topics: Animals; Cell Death; Cell Proliferation; Fasting; Hippocampus; Infarction, Middle Cerebral Artery; Leptin; Male; Mice; Mice, Inbred C57BL; Neurogenesis; Neurons; Weight Loss

Microarray studies identified Ch12:orf39 (Spexin) as the most down-regulated gene in obese human fat. Therefore, we examined its role in obesity pathogenesis.. Spexin effects on food intake, meal patterns, body weight, respiratory exchange ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with diet-induced obesity (DIO). Its effects on adipocyte [(3)H]-oleate uptake were determined.. In humans, Spexin gene expression was down-regulated 14.9-fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = -0.797) with Leptin. In rats, Spexin (35 µg/kg/day SC) reduced caloric intake ∼32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 µg/kg/day IP) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70 µg/kg/day IP) demonstrated no aversive Spexin effects.. Spexin gene expression is markedly down-regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy.

Topics: Adipocytes; Animals; Body Weight; Down-Regulation; Eating; Energy Intake; Fatty Acids; Feeding Behavior; Humans; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oleic Acid; Peptide Hormones; Protein Array Analysis; Rats; Rats, Wistar; Weight Loss

Different hormones and peptides involved in inflammation have been studied in and related to obesity. The aim of our work is to assess the variations of different molecules related to inflammation in obese patients during the first year following sleeve gastrectomy. This was a prospective study on patients who underwent sleeve gastrectomy. The variations in different clinical, anthropometric, and analytical parameters related to inflammation were determined and analysed in all patients at the preoperative visit and at the first and fifth days, first and sixth months, and 1 year following surgery. We enrolled 20 patients to the study. The median body mass index (BMI) before intervention was 48.5 kg/m2. With respect to comorbidities, 70% of the patients had obstructive sleep apnoea syndrome (OSA), 65% high blood pressure, 45% dyslipidaemia, and 40% diabetes mellitus (DM). The median percentage of BMI lost (%BMIL) 1 year after the intervention was 71%. The dyslipidaemia healing or improvement rate was 100%, whereas it was 87.5% for diabetes, 84.6% for hypertension, and 57.1% for OSA. During the 1-year postintervention period, the average levels of adiponectin increased, although not significantly, whereas those of leptin significantly decreased. In addition, the blood levels of MCP-1, IL-6, CRP, ferritin, and PAI-1 significantly decreased in that period. Sleeve gastrectomy is a surgical technique that is associated with improvements in body weight and comorbid conditions from the first postoperative months, which lead to significant variations in the levels of different inflammation-related parameters and a decrease in the levels of leptin, IL-6, CRP, MCP-1, ferritin, and serpin (PAI-1).

Topics: Adiponectin; Adult; Body Mass Index; C-Reactive Protein; Chemokine CCL2; Female; Ferritins; Follow-Up Studies; Gastrectomy; Humans; Interleukin-6; Laparoscopy; Leptin; Male; Middle Aged; Obesity, Morbid; Plasminogen Activator Inhibitor 1; Prospective Studies; Time Factors; Weight Loss

Obesity represents a rapidly growing threat to the health of populations and diet intervention has been proposed as one of the strategies for weight loss. Ginger and its constituents have been used for their anti-flatulent, expectorant and appetising properties and they are reported to possess gastro-protective and cholesterol-lowering properties. The present study investigated the effects of gingerol on the changes in body weight, serum glucose, insulin, insulin resistance and lipid profile in plasma and liver as well as on the activity of amylase, lipase and leptin in high-fat diet (HFD)-induced obese rats.. HFD-induced obese rats were treated orally with gingerol (25, 50 and 75 mg kg(-1) ) once daily for 30 days. A lorcaserin-treated group (10 mg kg(-1) ) was included for comparison. The levels of body weight, glucose, lipid profile and insulin, insulin resistance, leptin, amylase and lipase were increased significantly (P < 0.05) in HFD rats. Rats treated with gingerol and fed a HFD showed significantly (P < 0.05) decreased glucose level, body weight, leptin, insulin, amylase, lipase plasma and tissue lipids when compared to normal control. The effect at a dose of 75 mg kg(-1) of gingerol was more pronounced than that of the dose 25 mg kg(-1) and 50 mg kg(-1) . The lorcaserin-treated group also manifested similar effects to those of gingerol.. These findings suggested that ginger supplementation suppresses obesity induced by a high fat diet and it might be a promising adjuvant therapy for the treatment of obesity and its complications.

Topics: Amylases; Animals; Anti-Obesity Agents; Blood Glucose; Catechols; Dietary Fats; Fatty Alcohols; Insulin; Leptin; Lipase; Lipids; Male; Molecular Structure; Obesity; Rats; Weight Loss

To compare the regional differences in subcutaneous adipose tissue hormone/cytokine production in abdominally obese women during weight loss.. Forty-two abdominally obese, older women underwent a 20-week weight loss intervention composed of hypocaloric diet with or without aerobic exercise (total energy expenditure: ∼2800 kcal/week). Subcutaneous (gluteal and abdominal) adipose tissue biopsies were conducted before and after the intervention. Adipose tissue gene expression and release of leptin, adiponectin, and interleukin 6 (IL-6) were determined.. The intervention resulted in significant weight loss (-10.1 ± 0.7 kg, P < 0.001). At baseline, gene expression of adiponectin were higher (P < 0.01), and gene expression and release of IL-6 were lower (both P < 0.05) in abdominal than in gluteal adipose tissue. After intervention, leptin gene expression and release were lower in both gluteal and abdominal adipose tissue compared to baseline (P < 0.05-0.01). Abdominal, but not gluteal, adipose tissue adiponectin gene expression and release increased after intervention (both P < 0.05).. A 20-week weight loss program decreased leptin production in both gluteal and abdominal adipose tissue, but only increased adiponectin production from abdominal adipose tissue in obese women. This depot-specific effect may be of importance for the treatment of health complications associated with abdominal adiposity.

Topics: Adiponectin; Adipose Tissue; Adult; Aged; Cytokines; Diet, Reducing; Energy Intake; Exercise; Female; Humans; Interleukin-6; Leptin; Middle Aged; Obesity, Abdominal; Weight Loss

Calorie restriction is a common strategy for weight loss in obese individuals. However, little is known about the impact of moderate hypocaloric diets on obesity-related laboratory parameters in a short-term period. Aim of this study was to evaluate the variation of laboratory biomarkers in obese individuals following a Mediterranean, hypocaloric (1400-1600 Kcal/die) diet. 23 obese, pharmacologically untreated patients were enrolled and subjected to the determination of anthropometric variables and blood collection at baseline, 1 and 4 months after diet initiation. After 4 months of calorie restriction, we observed a significant decrease in body weight and BMI (both P < 0.0001), insulin (P = 0.037), HOMA-IR (P = 0.026), leptin (P = 0.008), and LDH (P = 0.023) and an increase in EGF (P = 0.013). All these parameters, except LDH, varied significantly already at 1 month after diet initiation. Also, lower levels of insulin (P = 0.025), leptin (P = 0.023), and EGF (P = 0.035) were associated with a greater (>5%) weight loss. Collectively, our data support a precocious improvement of insulin and leptin sensitivity after a modest calorie restriction and weight reduction. Moreover, EGF and LDH may represent novel markers of obesity, which deserve further investigations.

Topics: Adipokines; Anthropometry; Biomarkers; Body Mass Index; Caloric Restriction; Diet; Diet, Mediterranean; Epidermal Growth Factor; Female; Humans; Insulin; Insulin Resistance; L-Lactate Dehydrogenase; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Weight Loss

Leptin targets specific receptors (OB-R) expressed in the hypothalamus to regulate energy balance. Leptin decreases food intake in normal weight individuals, but this effect is blunted in obese subjects who are characterized by a state of leptin resistance. The prevention of leptin resistance is one of the major goals of obesity research. Recently, we identified endospanin 1 as a negative regulator of OB-R, which by interacting with OB-R retains the receptor inside the cell. We show here that in obese mice endospanin 1 is upregulated in the hypothalamic arcuate nucleus (ARC), the major brain structure involved in body weight regulation, suggesting that endospanin 1 is implicated in obesity development and/or the installation of leptin resistance. In contrast, silencing of endospanin 1 with lentiviral vectors in the ARC of obese mice fully restores leptin responsiveness when combined with a switch to ad libitum fed chow diet. The recovery of central leptin sensitivity is accompanied by sustained body weight loss and amelioration of blood lipid parameters and steatosis. Collectively, our results define endospanin 1 as a novel therapeutic target against obesity.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Carrier Proteins; Diet, High-Fat; Gene Expression Regulation; Intracellular Signaling Peptides and Proteins; Leptin; Lipids; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; STAT3 Transcription Factor; Weight Loss

Obesity is associated with several diseases including diabetes, nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease, and cancer. Therefore, anti-obesity drugs have the potential to prevent these diseases. In the present study, we demonstrated that flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), exhibited therapeutic potency against obesity. Mice were fed a high-fat diet (HFD) for 6 months, followed by a normal-chow diet (NCD). The flurbiprofen treatment simultaneously administered. Although body weight was significantly decreased in flurbiprofen-treated mice, growth was not affected. Flurbiprofen also reduced the HFD-induced accumulation of visceral fat. Leptin resistance, which is characterized by insensitivity to the anti-obesity hormone leptin, is known to be involved in the development of obesity. We found that one of the possible mechanisms underlying the anti-obesity effects of flurbiprofen may have been mediated through the attenuation of leptin resistance, because the high circulating levels of leptin in HFD-fed mice were decreased in flurbiprofen-treated mice. Therefore, flurbiprofen may exhibit therapeutic potential against obesity by reducing leptin resistance.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Feasibility Studies; Flurbiprofen; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Treatment Outcome; Weight Loss

Weight loss improves insulin sensitivity and exerts sympathomodulatory effects. No data, however, are available on the effects of the weight loss induced by vertical sleeve gastrectomy on sympathetic neural drive, insulin sensitivity, and their reciprocal cross talks. In 10 severe obese hypertensives (age, 54.0±2.3 years [mean±SEM]), we measured sphygmomanometric blood pressure, heart rate, body mass index, homeostatic model assessment index, plasma leptin, muscle sympathetic nerve traffic (microneurography), and baroreflex sensitivity (vasoactive drug technique). Measurements were performed 2 to 3 days before surgery and repeated 6 and 12 months after the procedure. Ten matched hypertensive obeses not undergoing gastrectomy served as controls. Six months after bariatric surgery, a significant (P<0.05) reduction in body mass index (-9.1±1.4 kg/m(2)), sphygmomanometric systolic blood pressure (-10.2±4.5 mm Hg), heart rate (-11.0±2.4 bpm), homeostatic model assessment index (-3-3±1.3 AU), plasma leptin (-53.6±8.8 μg/L), and muscle sympathetic nerve traffic (-15.0±3.4 bursts/100 heart beats) was observed. The weight loss, the plasma leptin reduction, and the sympathetic inhibition were maintained after 12 months, whereas homeostatic model assessment index showed a tendency to return toward presurgery values. A significant improvement in baroreflex control of sympathetic nerve traffic was observed both 6 (+32.1%; P<0.05) and 12 months (+60.7%; P<0.01) after gastrectomy. No significant changes in the above-mentioned variables were detected in the control group. These data provide evidence that massive weight loss induced by sleeve gastrectomy triggers profound sympathoinhibitory effects, associated with a stable and significant reduction in plasma leptin levels, whereas the improvement in insulin sensitivity was attenuated with time and unrelated to the sympathoinhibition.

Topics: Bariatric Surgery; Baroreflex; Blood Pressure; Body Mass Index; Female; Heart Rate; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Sympathetic Nervous System; Treatment Outcome; Weight Loss

The time course of metabolic and cardiovascular changes with weight gain and subsequent weight loss has not been elucidated. The goal of the present study was to determine how weight gain, weight loss and altered body fat distribution affected metabolic and cardiovascular changes in an obese dog model. Testing was performed when the dogs were lean (scores 4-5 on a nine-point scale), after ad libitum feeding for 12 and 32 weeks to promote obesity (>5 score), and after weight loss. Measurements included serum glucose and insulin, plasma leptin, adiponectin and C-reactive protein, echocardiography, flow-mediated dilation and blood pressure. Body fat distribution was assessed by computed tomography. Fasting serum glucose concentrations increased significantly with obesity (P< 0·05). Heart rate increased by 22 (SE 5) bpm after 12 weeks of obesity (P= 0·003). Systolic left ventricular free wall thickness increased after 12 weeks of obesity (P= 0·002), but decreased after weight loss compared with that observed in the lean phase (P= 0·03). Ventricular free wall thickness was more strongly correlated with visceral fat (r 0·6, P= 0·001) than with total body fat (r 0·4, P= 0·03) and was not significantly correlated with subcutaneous body fat (r 0·3, P= 0·1). The present study provides evidence that metabolic and cardiovascular alterations occur within only 12 weeks of obesity in an obese dog model and are strongly predicted by visceral fat. These results emphasise the importance of obesity prevention, as weight loss did not result in the return of all metabolic indicators to their normal levels. Moreover, systolic cardiac muscle thickness was reduced after weight loss compared with the pre-obesity levels, suggesting possible acute adverse cardiovascular effects.

Topics: Adiponectin; Adiposity; Animals; Blood Glucose; C-Reactive Protein; Diet, Reducing; Disease Models, Animal; Disease Progression; Dogs; Female; Heart Rate; Heart Ventricles; Hypertrophy, Left Ventricular; Insulin; Intra-Abdominal Fat; Leptin; Male; Obesity; Ultrasonography; Weight Gain; Weight Loss

The aim of this study was to describe the effect of surgically induced weight loss on vascular function measured by flow-mediated dilatation (FMD) in hypertensive obese patients. This prospective study included 33 patients (78 % females, mean age 53 (9) years) undergoing bariatric surgery (BS). Before and 12 months postoperatively, the BMI, 24-h ambulatory BP, high-sensitivity C-reactive protein (hs-CRP), leptin, homeostasis model assessment (HOMA IR), and abdominal fat were measured. Endothelial function was assessed by FMD. After BS, the excess body weight loss was 71 %; the 24-h [systolic 18(11)//diastolic 7(7) mmHg] BP values, hs-CRP, leptin, HOMA, and abdominal fat significantly decreased, with no changes in endothelial function. Weight loss achieved by BS was associated with a significant improvement in BP and metabolic and inflammation parameters, but FMD did not improve.

Topics: Abdominal Fat; Adult; Bariatric Surgery; Blood Pressure Monitoring, Ambulatory; C-Reactive Protein; Endothelium, Vascular; Female; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Treatment Outcome; Vasodilation; Weight Loss

Weight loss is a prominent early feature of Alzheimer's disease (AD) that often precedes the cognitive decline and clinical diagnosis. While the exact pathogenesis of AD remains unclear, accumulation of amyloid-β (Aβ) derived from the amyloid precursor protein (APP) in the brain is thought to lead to the neuronal dysfunction and death underlying the dementia. In this study, we examined whether transgenic mice overexpressing the Swedish mutation of APP (Tg2576), recapitulating selected features of AD, have hypothalamic leptin signaling dysfunction leading to early body weight deficits. We found that 3-month-old Tg2576 mice, before amyloid plaque formation, exhibit decreased weight with markedly decreased adiposity, low plasma leptin levels, and increased energy expenditure without alterations in feeding behavior. The expression of the orexigenic neuropeptide Y (NPY) in the hypothalamus to the low leptin state was abnormal at basal and fasting conditions. In addition, arcuate NPY neurons exhibited abnormal electrophysiological responses to leptin in Tg2576 hypothalamic slices or wild-type slices treated with Aβ. Finally, the metabolic deficits worsened as Tg2576 mice aged and amyloid burden increased in the brain. These results indicate that excess Aβ can potentially disrupt hypothalamic arcuate NPY neurons leading to weight loss and a pathologically low leptin state early in the disease process that progressively worsens as the amyloid burden increases. Collectively, these findings suggest that weight loss is an intrinsic pathological feature of Aβ accumulation and identify hypothalamic leptin signaling as a previously unrecognized pathogenic site of action for Aβ.

Topics: Adiposity; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Arcuate Nucleus of Hypothalamus; Brain; Brain Chemistry; Disease Models, Animal; Disease Progression; Fasting; Feeding Behavior; Female; Genes, Reporter; Humans; Hypothalamus; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Neurons; Neuropeptide Y; Patch-Clamp Techniques; Plaque, Amyloid; Weight Loss

Food restriction (FR) and refeeding (Re) have been suggested to impair body mass regulation and thereby making it easier to regain the lost weight and develop over-weight when FR ends. However, it is unclear if this is the case in small mammals showing seasonal forging behaviors. In the present study, energy budget, body fat and serum leptin level were measured in striped hamsters that were exposed to FR-Re. The effects of leptin on food intake, body fat and genes expressions of several hypothalamus neuropeptides were determined. Body mass, fat content and serum leptin level decreased during FR and then increased during Re. Leptin supplement significantly attenuated the increase in food intake during Re, decreased genes expressions of neuropepetide Y (NPY) and agouti-related protein (AgRP) of hypothalamus and leptin of white adipose tissue (WAT). Hormone-sensitive lipase (HSL) gene expression of WAT increased in leptin-treated hamsters that were fed ad libitum, but decreased in FR-Re hamsters. This indicates that the adaptive regulation of WAT HSL gene expression may be involved in the mobilization of fat storage during Re, which partly contributes to the resistance to FR-Re-induced overweight. Leptin may be involved in the down regulations of hypothalamus orexigenic peptides gene expression and consequently plays a crucial role in controlling food intake when FR ends.

Topics: Animals; Cricetinae; Eating; Energy Intake; Food Deprivation; Gene Expression Regulation; Hypothalamus; Leptin; Male; Weight Gain; Weight Loss

Anorexia nervosa is a primary psychiatric disorder, with non-negligible rates of mortality and morbidity. Some of the related alterations could participate in a vicious cycle limiting the recovery. Animal models mimicking various physiological alterations related to anorexia nervosa are necessary to provide better strategies of treatment.. To explore physiological alterations and recovery in a long-term mouse model mimicking numerous consequences of severe anorexia nervosa.. C57Bl/6 female mice were submitted to a separation-based anorexia protocol combining separation and time-restricted feeding for 10 weeks. Thereafter, mice were housed in standard conditions for 10 weeks. Body weight, food intake, body composition, plasma levels of leptin, adiponectin, IGF-1, blood levels of GH, reproductive function and glucose tolerance were followed. Gene expression of several markers of lipid and energy metabolism was assayed in adipose tissues.. Mimicking what is observed in anorexia nervosa patients, and despite a food intake close to that of control mice, separation-based anorexia mice displayed marked alterations in body weight, fat mass, lean mass, bone mass acquisition, reproductive function, GH/IGF-1 axis, and leptinemia. mRNA levels of markers of lipogenesis, lipolysis, and the brown-like adipocyte lineage in subcutaneous adipose tissue were also changed. All these alterations were corrected during the recovery phase, except for the hypoleptinemia that persisted despite the full recovery of fat mass.. This study strongly supports the separation-based anorexia protocol as a valuable model of long-term negative energy balance state that closely mimics various symptoms observed in anorexia nervosa, including metabolic adaptations. Interestingly, during a recovery phase, mice showed a high capacity to normalize these parameters with the exception of plasma leptin levels. It will be interesting therefore to explore further the central and peripheral effects of the uncorrected hypoleptinemia during recovery from separation-based anorexia.

Topics: Adipocytes, Brown; Adiponectin; Adipose Tissue; Animals; Anorexia Nervosa; Anxiety, Separation; Body Composition; Disease Models, Animal; Eating; Estrous Cycle; Feeding Behavior; Female; Gene Expression Regulation; Glucose Tolerance Test; Growth Hormone; Insulin-Like Growth Factor I; Leptin; Lipid Metabolism; Mice, Inbred C57BL; Oxidation-Reduction; Phenotype; Reproduction; Time Factors; Weight Loss

The high prevalence of obesity has called attention to the near-intractable problem of sustained weight reduction and its underlying mechanisms. With diet-induced weight loss, achieved body weight is closely related to initial body weight.. The objective was to compare the relation between initial and achieved body mass index (BMI) in patients treated with diet-induced weight loss or bariatric surgery.. We analyzed data from a cohort of 223 healthy individuals who lost a mean (±SD) of 5 ± 3 kg body weight over 3 y by diet (diet group) and data from 182 obese individuals [BMI (in kg/m(2)) ≥35] who had lost an average of 47 ± 17 kg 1 y after Roux-en-Y gastric bypass (a restrictive procedure; n = 71) or biliopancreatic diversion (a malabsorptive procedure; n = 111) (surgery group).. In the diet group, final BMI was strongly related to initial BMI (r = 0.96, P < 0.0001). By multivariate analysis, the decrease in BMI at 3 y was age independent and was predicted only by initial BMI and sex (both P < 0.0001). Strikingly, final BMI was also strongly related to initial BMI (r = 0.67, P < 0.0001) in the surgery group, irrespective of the type of operation. The surgically induced decrease in BMI was predicted by age (P = 0.0002) and initial BMI (P < 0.0001). In 110 surgery patients, serum leptin concentrations decreased from 39 ± 16 to 10 ± 5 ng/mL after surgery (P < 0.0001) and were correlated with BMI both before and after surgery, but the slope of the relation was significantly (P < 0.01) flatter after surgery.. The strong predictivity of initial BMI for achieved BMI observed even when voluntary control of energy intake is interfered with through diverse anatomical rearrangements of the gastrointestinal tract supports the concept of a weight "threshold" paradigm: in the obese, anabolic responses are triggered by adiposity-related signals at a higher threshold, which leads to defense of a higher body weight.

Topics: Adult; Anastomosis, Roux-en-Y; Body Mass Index; Cohort Studies; Diet, Reducing; Energy Intake; Female; Gastric Bypass; Humans; Leptin; Linear Models; Male; Middle Aged; Multivariate Analysis; Obesity; Prevalence; Weight Loss

To measure changes in resting metabolic rate (RMR) and body composition in obese subjects following massive weight loss achieved via bariatric surgery or calorie restriction plus vigorous exercise.. Body composition and RMR were measured in 13 pairs of obese subjects retrospectively matched for sex, body mass index, weight, and age who underwent either Roux-en-Y gastric bypass surgery (RYGB) or participated in "The Biggest Loser" weight loss competition (BLC).. Both groups had similar final weight loss (RYGB: 40.2 ± 12.7 kg, BLC: 48.8 ± 14.9 kg; P = 0.14); however, RYGB lost a larger proportion of their weight as fat-free mass (FFM) (RYGB: 30 ± 12%, BLC: 16 ± 8% [P < 0.01]). In both groups, RMR decreased significantly more than expected based on measured body composition changes. The magnitude of this metabolic adaptation was correlated with the degree of energy imbalance (r = 0.55, P = 0.004) and the decrease in circulating leptin (r = 0.47, P = 0.02).. Calorie restriction along with vigorous exercise in BLC participants resulted in preservation of FFM and greater metabolic adaption compared to RYGB subjects despite comparable weight loss. Metabolic adaptation was related to the degree of energy imbalance and the changes in circulating leptin.

Topics: Adult; Basal Metabolism; Body Composition; Body Mass Index; Body Weight; Energy Metabolism; Female; Gastric Bypass; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Weight Loss

Obesity, defined as a body mass index (BMI) >30 kg/m2, has seen an important increase in prevalence in the last decades, not only in Europe and the United States, but also in developing countries. It is an established risk factor for numerous pathologic conditions like diabetes mellitus, cardiovascular diseases and cancer, but has also been linked to male hypogonadism. Several studies showed a negative impact of excessive BMI on testosterone levels, sexual function and sperm parameters. Possible mechanisms beyond this phenomenon are reduced hypothalamic and pituitary secretory function, excess estrogen production and reduced circulating sex-hormone binding globulin (SHBG). Peptides produced by the adipocyte may also trigger modifications of the reproductive function. Independently of the method used, non-surgical approach or bariatric techniques, weight reduction and a return to a normal BMI have been associated with improvement in the sexual function and levels of sexual hormones in obese males, showing that obesity related hypogonadism is preventable. Sexual and reproductive health might represent additional motivational factors for men in order to maintain a healthy life-style.

Topics: Adipocytes, White; Adiponectin; Body Mass Index; Eunuchism; Humans; Leptin; Male; Obesity; Prevalence; Risk Factors; Testosterone; Weight Loss

In overweight children, high leptin levels are independently associated with higher risk for cardiovascular disease, whereas adiponectin seems to be protective against type 2 diabetes and atherosclerosis. The study examines the predictive value of leptin for weight loss after a 4- to 6-wk inpatient therapy and again after 1 y; as well as the association among weight loss, leptin, and adiponectin levels and changes in cardiometabolic risk factors after therapy.. Body mass index (BMI), blood pressure, Tanner stage, and cardiometabolic risk factors were studied in 402 children (59.2% females, 13.9 ± 2.3 y, BMI 33.8 ± 5.7 kg/m(2)) before and after a 4-to 6-wk inpatient intervention (exercise, diet, and behavioral therapy) and BMI 1 y later (n = 206).. BMI was reduced from 33.8 ± 5.7 to 30.5 ± 5.1 kg/m(2) (P < 0.001) during the lifestyle intervention and remained unchanged after 1 y. Baseline BMI was positively associated with leptin (r = 0.60; P < 0.001) and cardiometabolic risk factors (blood pressure, high-density lipoprotein [HDL] cholesterol, triglycerides). Baseline leptin was associated with BMI and triglycerides (r = 0.39; P < 0.001), baseline adiponectin with HDL-cholesterol (r = 0.40; P < 0.001). Baseline BMI explained 40.7% of the variance in weight loss during therapy. The combination of BMI, sex, and leptin explained 50.4% of the variance. Neither BMI nor leptin predicted weight changes over the long term.. Overweight children maintained a substantial amount of weight loss after participation in a short-term inpatient lifestyle intervention. Baseline BMI was positively associated with weight reduction during the intervention, whereas baseline leptin had only a minor predictive value.

Topics: Adiponectin; Adolescent; Behavior Therapy; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Child; Cholesterol, HDL; Exercise; Feeding Behavior; Female; Humans; Leptin; Life Style; Linear Models; Male; Obesity; Risk Factors; Triglycerides; Weight Loss

Restrictive bariatric surgery procedures currently used include adjustable gastric banding, sleeve gastrectomy (SG), and gastric plication (GP), of which the last two techniques still lack sufficient data and long-term studies on weight loss, surgical complications, resolution of comorbidities, and mechanisms of weight loss. Therefore, gastric plication and sleeve gastrectomy as a standalone procedure are still considered experimental. Our aim was to analyze the effects of SG and GP on body weight, food intake, and endocrine profile.. Forty-four male Wistar rats were randomized into six weight-matched groups and submitted either to SG, GP, or sham-operated. Sham-operated rats were divided into pair-fed and fed ad libitum controls, one for each procedure. Animals were followed up for 21 days after surgery, while body weight and food intake were recorded daily, when fasting ghrelin, leptin, insulin and glucose plasma levels, and ghrelin expression in the stomach were measured.. Rats submitted to SG and GP showed a significant decrease in body weight gain to the same extent as rats pair-fed to the surgical groups when compared to sham-operated fed ad libitum controls. After surgery, SG rats showed no difference in body composition, ghrelin, leptin, insulin, or glucose levels, while GP rats displayed lower body fat content and leptin levels compared to controls. Ghrelin was also lower in GP rats compared to sham-operated pair-fed rats. Ghrelin expression displayed a pattern similar to circulating ghrelin.. SG and GP result in weight loss, although with differences in body composition and metabolic and endocrine profiles.

Topics: Animals; Body Weight; Eating; Feeding Behavior; Gastric Mucosa; Gastroplasty; Ghrelin; Insulin; Leptin; Male; Obesity; Rats; Rats, Wistar; Stomach; Weight Loss

Soluble CD163 (sCD163) is a new macrophage-specific serum marker elevated in inflammatory conditions. sCD163 is elevated in obesity and found to be a strong predictor of the development of type 2 diabetes. We investigated whether dietary intervention and moderate exercise was related to changes in sCD163 and how sCD163 is associated to insulin resistance in obesity.. Ninety-six obese subjects were enrolled: 62 followed a very low energy diet (VLED) program for 8 weeks followed by 3-4 weeks of weight stabilization, 20 followed a moderate exercise program for 12 weeks, and 14 were included without any intervention. Fasting blood samples and anthropometric measures were taken at baseline and after intervention. Thirty-six lean subjects were included in a control group.. sCD163 was significantly higher in obese subjects (2.3 ± 1.0 mg/l) compared with lean (1.6 ± 0.4 mg/l, P < 0.001). Weight loss (11%) induced by VLED resulted in a reduction and partial normalization of sCD163 to 2.0 ± 0.9 mg/l (P < 0.001). Exercise for 12 weeks had no effect on sCD163. At baseline, sCD163 was significantly correlated with BMI (r = 0.46), waist circumference (r = 0.40), insulin resistance measured by the homeostasis model assessment (HOMA-IR; r = 0.41; all P < 0.001), and the leptin-to-adiponectin ratio (r = 0.28, P < 0.05). In a multivariate linear regression analysis with various inflammatory markers, sCD163 (β = 0.25), adiponectin (β = -0.24), and high sensitivity C-reactive protein (hs-CRP; β = 0.20) remained independently and significantly associated to HOMA-IR (all P < 0.05). After further adjustment for waist circumference, only sCD163 was associated with HOMA-IR (P < 0.05).. The macrophage-specific serum marker sCD163 is increased in obesity and partially normalized by dietary-induced weight loss but not by moderate exercise. Furthermore, we confirm that sCD163 is a good marker for obesity-related insulin resistance.

Topics: Adiponectin; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; C-Reactive Protein; Caloric Restriction; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Leptin; Linear Models; Macrophages; Male; Middle Aged; Multivariate Analysis; Obesity; Randomized Controlled Trials as Topic; Receptors, Cell Surface; Waist Circumference; Weight Loss

Treating obesity has proven to be an intractable challenge, in part, due to the difficulty of maintaining reduced weight. In our previous studies of in-patient obese subjects, we have shown that leptin repletion following a 10% or greater weight loss reduces many of the metabolic (decreased energy expenditure, sympathetic nervous system tone, and bioactive thyroid hormones) and behavioral (delayed satiation) changes that favor regain of lost weight. FMRI studies of these same subjects have shown leptin-sensitive increases in activation of the right hypothalamus and reduced activation of the cingulate, medial frontal and parahippocampal gryi, following weight loss, in response to food stimuli. In the present study, we expanded our cohort of in-patient subjects and employed psychophysiological interaction (PPI) analysis to examine changes in the functional connectivity of the right hypothalamus. During reduced-weight maintenance with placebo injections, the functional connectivity of the hypothalamus increased with visual areas and the dorsal anterior cingulate (dorsal ACC) in response to food cues, consistent with higher sensitivity to food. During reduced-weight maintenance with leptin injections, however, the functional connectivity of the right hypothalamus increased with the mid-insula and the central and parietal operculae, suggesting increased coupling with the interoceptive system, and decreased with the orbital frontal cortex, frontal pole and the dorsal ACC, suggesting a down-regulated sensitivity to food. These findings reveal neural mechanisms that may underlie observed changes in sensitivity to food cues in the obese population during reduced-weight maintenance and leptin repletion.

Topics: Adult; Brain Mapping; Diet; Energy Intake; Energy Metabolism; Female; Gyrus Cinguli; Humans; Hypothalamus; Injections, Subcutaneous; Leptin; Magnetic Resonance Imaging; Male; Obesity; Satiation; Weight Loss

This study was designed to determine how gastric bypass affects the sympathetically-mediated component of resting energy expenditure (REE) and muscle sympathetic nerve activity (MSNA).. We measured REE before and after beta-blockade in seventeen female subjects approximately three years post-gastric bypass surgery and in nineteen female obese individuals for comparison. We also measured MSNA in a subset of these subjects.. The gastric bypass subjects had no change in REE after systemic beta-blockade, reflecting a lack of sympathetic support of REE, in contrast to obese subjects where REE was reduced by beta-blockade by approximately 5% (P < 0.05). The gastric bypass subjects, while still overweight (BMI = 29.3 vs 38.0 kg·m(-2) for obese subjects, P < 0.05), also had significantly lower MSNA compared to obese subjects (10.9 ± 2.3 vs. 21.9 ± 4.1 bursts·min(-1) , P < 0.05). The reasons for low MSNA and a lack of sympathetically mediated support of REE after gastric bypass are likely multifactorial and may be related to changes in insulin sensitivity, body composition, and leptin, among other factors.. These findings may have important consequences for the maintenance of weight loss after gastric bypass. Longitudinal studies are needed to further explore the changes in sympathetic support of REE and if changes in MSNA or tissue responsiveness are related to the sympathetic support of REE.

Topics: Adolescent; Adult; Aldosterone; Basal Metabolism; Blood Glucose; Body Composition; Body Mass Index; Cholesterol; Energy Metabolism; Epinephrine; Fasting; Female; Gastric Bypass; Humans; Insulin Resistance; Leptin; Linear Models; Muscle, Skeletal; Norepinephrine; Obesity; Overweight; Sympathetic Nervous System; Triglycerides; Weight Loss; Young Adult

Visceral fat is highly active metabolic and endocrine tissue which secretes many adipokines that act both on local and systemic level. It is believed that adipokines and "low-grade inflammatory state" represent a potential link between obesity, metabolic syndrome, insulin resistance and cardiovascular disease. Leptin and adiponectin are considered to be the most important adipokines with the potential metabolic and cardiovascular effects. Body weight loss improves insulin sensitivity and decreases risk for most complications associated with obesity. The aim of this study was to determine the effects of moderate loss of body weight on the level of leptin and adiponectin, insulin sensitivity and abnormalities of glycoregulation in obese women, to determine whether and to what extent the secretory products of adipose tissue, leptin and adiponectin contribute to insulin sensitivity, as well as to assess their relationship and influence on glycemia and insulinemia during the period of losing body weight using a calorie restricted diet.. The study involved 90 obese female subjects (BMI > or = 30 kg/m2) of different age with weight loss no less than 5% during a six-month period by application of restricted dietary regime. The calorie range was between 1,100-1,350 kcal. Serum levels of leptin and adiponectin, fasting glucose, fasting insulinemia, and Homeostasis Model Assessment of Insulin Resistance (HOMA-R) index were determined in all the subjects initially and after weight reduction. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test--OGTT.. Applying a 6-month restrictive dietary regime the subjects achieved an average weight loss of 8.73 +/- 1.98 kg and 8.64 +/- 1.96%, which led to the reduction of fasting glycemia, fasting insulinemia and HOMA-R index at the maximum level of statistical significance (p < 0.001). The achieved reduction led to a statistically significant decrease of leptin level and increase of adiponectin level (p < 0.001). The correction of the established pre-diabetic disorders of glycoregulation was not statistically significant. There was a statistically significant correlation between the anthropometric parameters, leptin, adiponectin, fasting glycemia, fasting insulinemia and HOMA-R index. There was a positive correlation between leptin, fasting insulinemia and HOMA-R, as well as a statistically significant negative correlation between adiponectin, fasting insulinemia and HOMA-R index (p < 0.01).. Body weight increase and central fat accumulation lead to changes in serum levels of leptin and adiponectin, reduction of insulin sensitivity and development of glycemic dysregulation. Secretory products of adipose tissue, leptin and adiponectin contribute to the genesis of these disorders. The obtained results show that the effect of adiponectin on insulin sensitivity is more significant. The analysis of the effects of weight loss on the investigated parameters shows that moderate weight reduction by restrictive dietary regime lead to changes of investigated parameters at the maximum level of statistical significance. Such results emphasize the importance of weight reduction in obese persons, as well as the need for consistent implementation of restricted dietary regime in the process of treatment of obesity.

Topics: Adipokines; Adolescent; Adult; Blood Glucose; Caloric Restriction; Female; Humans; Insulin Resistance; Leptin; Middle Aged; Obesity; Weight Loss; Young Adult

Diet-induced weight loss is accompanied by compensatory changes, which increase appetite and encourage weight regain. There is some evidence that ketogenic diets suppress appetite. The objective is to examine the effect of ketosis on a number of circulating factors involved in appetite regulation, following diet-induced weight loss.. Of 50 non-diabetic overweight or obese subjects who began the study, 39 completed an 8-week ketogenic very-low-energy diet (VLED), followed by 2 weeks of reintroduction of foods. Following weight loss, circulating concentrations of glucose, insulin, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), leptin, gastrointestinal hormones and subjective ratings of appetite were compared when subjects were ketotic, and after refeeding.. During the ketogenic VLED, subjects lost 13% of initial weight and fasting BHB increased from (mean±s.e.m.) 0.07±0.00 to 0.48±0.07 mmol/l (P<0.001). BHB fell to 0.19±0.03 mmol/l after 2 weeks of refeeding (P<0.001 compared with week 8). When participants were ketotic, the weight loss induced increase in ghrelin was suppressed. Glucose and NEFA were higher, and amylin, leptin and subjective ratings of appetite were lower at week 8 than after refeeding.. The circulating concentrations of several hormones and nutrients which influence appetite were altered after weight loss induced by a ketogenic diet, compared with after refeeding. The increase in circulating ghrelin and subjective appetite which accompany dietary weight reduction were mitigated when weight-reduced participants were ketotic.

Topics: 3-Hydroxybutyric Acid; Adult; Aged; Appetite Regulation; Body Mass Index; Caloric Restriction; Diet, Ketogenic; Fasting; Fatty Acids, Nonesterified; Female; Gastrointestinal Hormones; Ghrelin; Humans; Insulin; Islet Amyloid Polypeptide; Ketosis; Leptin; Male; Middle Aged; Obesity; Overweight; Peptide YY; Postmenopause; Weight Loss

Endogenous sex hormones are risk factors for postmenopausal breast cancer. A potential route for favorable hormonal modification is weight loss.. The objective of the study was to measure change in plasma estradiol and testosterone levels in postmenopausal women in relation to change in body mass index (BMI) and plasma leptin.. The setting was a cohort study of over 100,000 female volunteers from the general population, United Kingdom.. The participants were a sample of 177 postmenopausal women aged over 45 years who provided blood samples during 2004-2005 and again during 2010-2011.. Outcomes were percentage change in plasma estradiol and testosterone levels per 1 kg/m² change in BMI and per 1 ng/mL change in plasma leptin.. Among women with reduction in BMI, estradiol decreased 12.7% (95% confidence interval: [6.4%, 19.5%]; P < .0001) per kg/m² and among women with increased BMI estradiol increased 6.4% [0.2%, 12.9%] (P = .042). The corresponding figures for testosterone were 10.7% [3.0%, 19.0%] (P = .006) and 1.9% [-5.4%, 9.7%] (P = .61) per kg/m². For women with decreases and increases in leptin, estradiol decreased by 3.6% [1.3%, 6.0%] (P = .003) per ng/mL and increased by 1.7% [-0.3%, 3.6%] (P = .094), respectively. The corresponding figures for testosterone were 4.8% [2.0%, 7.8%] (P = .009) and 0.3% [-2.0%, 2.6%] (P = .82) per ng/mL.. In postmenopausal women, changes in BMI and plasma leptin occurring over several years are associated with changes in estradiol and testosterone levels. The results suggest that fat loss by an individual can result in substantial decreases in postmenopausal estradiol and testosterone levels and provides support for weight management to lessen breast cancer risk.

Topics: Adipose Tissue; Aged; Body Mass Index; Breast Neoplasms; Cohort Studies; Down-Regulation; Estradiol; Female; Follow-Up Studies; Humans; Leptin; Middle Aged; Overweight; Postmenopause; Risk Factors; Testosterone; United Kingdom; Up-Regulation; Weight Gain; Weight Loss

Fibroblast growth factor (FGF)-19 and FGF-21 are novel metabolic regulators that improve insulin resistance and obesity in rodents. The aim of the study was to assess the effects of laparoscopic sleeve gastrectomy (LSG) on serum concentrations of FGF-19 and FGF-21 along with circulating bile acids and other relevant hormonal and biochemical parameters.. Seventeen females with obesity undergoing LSG and 15 lean healthy females were included into the study. Anthropometric and biochemical parameters, serum concentrations of FGF-19 and -21, insulin, adiponectin, leptin, C-reactive protein, resistin, amylin (total), ghrelin (active), glucagon-like peptide 1 (GLP-1, active), glucose-dependent insulinotropic peptide (GIP, total), peptide YY (PYY, total), pancreatic polypeptide (PP), and bile acids, and mRNA expression of selected adipokines and inflammatory markers in bioptic samples of subcutaneous fat were assessed at baseline and 6, 12, and 24 months after LSG.. LSG markedly decreased body weight, BMI, waist circumference, and insulin levels and improved systemic inflammation and lipid levels. FGF-19 concentrations increased and FGF-21 concentrations decreased after LSG along with increased adiponectin and decreased leptin, amylin, and ghrelin levels. GLP-1, GIP, PP, and circulating bile acids were not affected by LSG. PYY decreased significantly 24 months after surgery only. mRNA expression analysis in subcutaneous fat showed markedly reduced proinflammatory state.. Our results indicate that increased FGF-19 and decreased ghrelin concentrations could have partially contributed to the improvement of systemic inflammation and some metabolic parameters after LSG, while changes of FGF-21 are rather secondary because of weight loss.

Topics: Adiponectin; Adult; Bile Acids and Salts; Body Mass Index; C-Reactive Protein; Female; Fibroblast Growth Factors; Gastrectomy; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Islet Amyloid Polypeptide; Leptin; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Prospective Studies; Resistin; RNA, Messenger; Subcutaneous Fat; Waist Circumference; Weight Loss

Topics: Animals; Body Mass Index; Circadian Rhythm; CLOCK Proteins; Energy Metabolism; Ghrelin; Humans; Insulin Resistance; Leptin; Male; Mice; Obesity; Satiety Response; Sleep; Suprachiasmatic Nucleus; Time Factors; Weight Gain; Weight Loss

Leptin receptors (ObRs) in the forebrain and hindbrain have been independently recognized as important mediators of leptin responses. It is unclear how leptin activity in these areas is integrated. We tested whether both forebrain and hindbrain ObRs have to be activated simultaneously to change energy balance and to maintain metabolic homeostasis. Previous studies used acute leptin injections in either the third ventricle (1-5 μg) or the fourth ventricle (3-10 μg); here we used 12-day infusions of low doses of leptin in one or both ventricles (0.1 μg/24 h in third, 0.6 μg/24 h in fourth). Male Sprague Dawley rats were fitted with third and fourth ventricle cannulas, and saline or leptin was infused from Alzet pumps for 6 or 12 days. Rats that received leptin into only the third or the fourth ventricle were not different from controls that received saline in both ventricles. By contrast, rats with low-dose leptin infusions into both the third and fourth ventricle showed a dramatic 60% reduction in food intake that was reversed on day 6, a 20% weight loss that stabilized on day 6, and a 50% decrease in body fat at day 12 despite the correction of food intake. They displayed normal activity and maintained energy expenditure despite weight loss, indicating inappropriately high thermogenesis that coincided with increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in the brainstem. Altogether, these findings show that with low doses of leptin, chronic activation of both hypothalamic and brainstem ObRs is required to reduce body fat.

Topics: Animals; Blotting, Western; Dose-Response Relationship, Drug; Eating; Energy Metabolism; Fourth Ventricle; Infusion Pumps; Ion Channels; Leptin; Male; Mitochondrial Proteins; Phosphorylation; Prosencephalon; Rats; Rats, Sprague-Dawley; Receptors, Leptin; Rhombencephalon; STAT3 Transcription Factor; Third Ventricle; Time Factors; Uncoupling Protein 1; Weight Loss

The main cause of obesity is a change in the energy balance in favor of intake. Communication between the hypothalamus and other organs occurs through special peptides, such as ghrelin, leptin, and orexin-A, to provide energy balance. The purpose of this study was to investigate the effects of a laparoscopic gastric band application on insulin resistance and the peptides involved in appetite in morbidly obese patients.. The study group consisted of 20 patients who were operated on for morbid obesity (body mass index [BMI], 48.3±6.7 kg/m2) and the control group contained 20 healthy, normal-weight subjects (BMI, 22.6±2 kg/m2). We obtained blood samples from the study subjects before surgery and one month after surgery, and once from the control group. We measured plasma levels of ghrelin, leptin, orexin-A, and plasma glucose.. Significant weight loss was achieved after surgery (P<0.05). Plasma ghrelin levels were lower in morbidly obese patients (P=0.033), but increased postoperatively (P=0.014), compared with those in the control subjects. Leptin levels were higher in the morbidly obese group (P=0.000), but decreased after the operation (P=0.01). Orexin-A levels were higher in the morbidly obese group (P=0.000), but decreased after the operation (P=0.000). Insulin resistance values also decreased in a manner similar to leptin and orexin-A levels (P=0.000 and P=0.008, respectively).. Laparoscopic gastric band application results in significant weight loss in morbidly obesity patients, even after one month. We found a decrease in patient BMI, increased ghrelin levels, and decreased leptin and orexin-A levels and insulin resistance.

Topics: Adult; Body Mass Index; Case-Control Studies; Energy Metabolism; Female; Gastroplasty; Ghrelin; Humans; Insulin Resistance; Intracellular Signaling Peptides and Proteins; Laparoscopy; Leptin; Male; Neuropeptides; Obesity, Morbid; Orexins; Weight Loss

Different studies have evaluated changes in adipo/cytokine levels after bariatric surgery and have given conflicting results. The adipo/cytokines, leptin and chemerin, and the orexigenic hormone, ghrelin, have been shown to play a role in the regulation of metabolism and appetite. The aims of our study were to test the levels of these molecules after bariatric surgery and to compare the results between Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy.. We analysed circulating levels of chemerin, ghrelin and leptin in 30 morbidly obese women (body mass index of >40 kg/m2). Subjects were studied at three time points: baseline (before the surgery started), and after 6 and 12 months.. After surgery, chemerin (baseline, 95.03 ± 23.79; after 12 months, 76.80 ± 21.51; p = 0.034) and leptin levels (baseline, 248.17 ± 89.16; after 12 months, 63.85 ± 33.48; p < 0.001) were significantly lower than their baseline levels, whereas ghrelin was higher (baseline, 0.87 ± 0.38; after 12 months, 1.08 ± 0.31; p = 0.010). Fasting glucose, insulin and homeostasis model assessment of insulin resistance levels were markedly lower postoperatively. High-density lipoprotein levels moderately increased and triglyceride levels sharply decreased. There were no differences between the types of bariatric surgery in terms of weight reduction, general metabolic state or adipo/cytokine levels after surgery.. Our study demonstrates a marked decrease in fasting leptin and chemerin levels, and an increase in ghrelin levels, after bariatric surgery-induced weight loss, independently of the type of surgery performed. Further studies are needed on the interrelation between the changes in the circulating levels of these molecules and the efficacy of the bariatric surgery procedures to induce the beneficial metabolic changes and to sustain body weight loss.

Topics: Adult; Biomarkers; Blood Glucose; Chemokines; Fasting; Female; Gastrectomy; Gastric Bypass; Ghrelin; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Laparoscopy; Leptin; Male; Obesity, Morbid; Postoperative Period; Spain; Time Factors; Treatment Outcome; Weight Loss

Bariatric surgery has been established as the best option of treatment for morbid obesity. Recently, laparoscopic sleeve gastrectomy (SG) has become very popular because of good postoperative weight loss and low morbidity. The aim of this study was to report our single-center experience with SG regarding feasibility, morbidity, and outcome.. From January 2006 to December 2011, 93 patients (68 female) with a median age of 46 years underwent laparoscopic SG at our department. Thirteen patients had a history of gastric banding with insufficient weight loss or band-related complications. Clinical outcome and laboratory findings were analyzed.. The mean preoperative and postoperative body mass index (BMI) was 44.1 ± 6.9 and 33.4 ± 6.8 kg/m(2), respectively (p < 0.001). The mean excessive body weight loss after a median follow-up of 11.9 months was 55.7 % ± 24.9 %. Three bleedings, two staple line leakages, and a deep wound infection required conversion to laparotomy (n = 1), reoperation (n = 4), or endoscopic stent implantation (n = 2). Resolution of diabetes and dyslipidemia was seen in 85 and 50 % of patients, respectively. Blood test results of HbA1c, cholesterols, triglycerides, and leptin showed significant postoperative improvement.. Laparoscopic SG represents a feasible bariatric procedure with good short-term weight loss, low morbidity rate, and efficient resolution of diabetes and dyslipidemia, especially in patients with lower BMI. The significant decrease of leptin necessitates further studies to understand the ambiguous role of leptin in bariatric surgery.

Topics: Adult; Aged; Body Mass Index; Cholesterol; Diabetes Mellitus, Type 2; Dyslipidemias; Feasibility Studies; Female; Follow-Up Studies; Gastric Bypass; Gastroplasty; Glycated Hemoglobin; Humans; Laparoscopy; Leptin; Male; Middle Aged; Obesity, Morbid; Reoperation; Retrospective Studies; Treatment Outcome; Triglycerides; Weight Loss

This study investigates the effects of a restricted diet (RD) on body composition and musculoskeletal health along with endocrines and molecular mechanism in established mature obese rats. Twenty female rats were fed with a high-fat diet (HFD) ad libitum for 4 months and then assigned to either HFD or RD group for another 4 months. Another 10 rats were on a low-fat diet for 8 months. Outcome measures included body composition, bone mineral density, microarchitecrure, and strength; serum leptin, adiponectin, insulin-like growth factor I, and liver glutathione peroxidase activity; and protein expression and spleen tumor necrosis factor α messenger RNA expression. We hypothesized that mature obese rats on a 35% energy restriction diet for 4 months would improve body composition but degrade microstructural and mechanical properties of long bones, and such changes in musculoskeletal integrity are related to the modulation of obesity-related endocrines and proinflammation. Relative to HFD, RD benefited body composition (decreased body weight and %fat mass and increased %fat-free mass); decreased insulin-like growth factor I and leptin; elevated adiponectin, glutathione peroxidase activity and protein expression and tumor necrosis factor α messenger RNA expression; and suppressed bone formation and increased bone resorption, resulting in decreased trabecular and cortical bone volume, bone mineral density, and bone strength. Relative to low-fat diet, RD had a similar effect on body composition and serum markers but increased bone turnover rate and decreased bone mineral density and strength. Our data suggest that long-term RD has a negative impact on bone remodeling in obese female rats, probably through modification of endocrines and elevation of proinflammation.

Topics: Adiponectin; Animals; Biomarkers; Body Composition; Bone and Bones; Bone Density; Bone Resorption; Caloric Restriction; Diet, Fat-Restricted; Diet, High-Fat; Female; Glutathione Peroxidase; Insulin-Like Growth Factor I; Leptin; Liver; Obesity; Osteogenesis; Proteins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Spleen; Tumor Necrosis Factor-alpha; Weight Loss

Obesity can augment insulin resistance (IR), leading to increased risk of diabetes and heart disease. Leptin, ghrelin, and various fatty acids present in the cell membrane may modulate IR. In this study, we aimed to investigate the impact of weight loss on IR, serum leptin/ghrelin levels, and erythrocyte fatty acids, and studied the associations between changes in these variables. A total of 35 obese (body mass index ≥ 27) adults participated in a weight loss program for 3 months. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR). The obese participants had a mean weight loss of 5.6 ± 3.8 kg followed by a 16.7% and 23.3% reduction in HOMA-IR and leptin (p < 0.001) levels, and an 11.3% increase in ghrelin levels (p = 0.005). The level of erythrocyte saturates decreased by 2.8%, while the level of n-3 polyunsaturates increased by 16.8% (all p < 0.05). The changes in leptin levels (-5.63 vs. -1.57 ng/mL) were significantly different (p = 0.004) in those with improved IR (changes in HOMA-IR < 0) than those without improvement (changes in HOMA-IR ≥ 0), though there were no differences in the changes of ghrelin (p = 0.120) and erythrocyte fatty acids (all p > 0.05) levels. After adjusting for age, gender, changes in ghrelin, and body fat, we found a significant correlation between decreases in leptin and less risk of no improvement in HOMA-IR levels [odds ratio (OR) = 0.69, p = 0.039]. In conclusion, a moderate weight reduction in obese participants over a short period significantly improved IR. This weight reduction concomitantly decreased serum leptin, increased ghrelin, and elevated some erythrocyte unsaturates. Only leptin correlated independently with IR improvement upon multivariable logistic regression analysis, which indicates that leptin may play a role in the modulation of IR following weight loss.

Topics: Adolescent; Adult; Body Mass Index; Female; Ghrelin; Humans; Insulin Resistance; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Obesity; Weight Loss; Young Adult

Previous studies with chronic decerebrate rats and rats infused with leptin into the 4th ventricle suggest that hindbrain leptin receptors attenuate the catabolic effect of forebrain leptin receptor activation. To test this further, rats were fitted with both 3rd and 4th ventricle cannulae. They were infused for 12 days with different combinations of saline, low dose leptin or leptin receptor antagonist (leptin mutein protein). Infusion of 0.1 μg leptin/day into the 3rd ventricle or 0.6 μg leptin/day into the 4th ventricle had no significant effect on food intake, energy expenditure or body composition. Infusion of 2 μg mutein/day into either ventricle caused a small, but significant weight gain. When mutein was infused into one ventricle and leptin into the other, the rats lost weight irrespective of which combination was applied. Surprisingly, rats that received leptin infusions into both ventricles showed an initial hypophagia, no change in energy expenditure, but a 75% loss of carcass fat after 12 days. These data suggest that neuronal pathways activated by leptin receptors in either the forebrain or hindbrain modulate each other's effects. In normal conditions hindbrain leptin may attenuate the catabolic effect of forebrain leptin, but if activity in one area is blocked with mutein, then the catabolic response to leptin in the other ventricle is exaggerated. When receptors in both areas are activated there is an integration of response to produce negative energy balance. This may ensure that leptin causes a loss of fat only when leptin is elevated in both the CSF and periphery.

Topics: Adiposity; Animals; Body Composition; Body Weight; Calorimetry; Eating; Fourth Ventricle; Injections, Intraventricular; Leptin; Male; Prosencephalon; Rats; Rats, Sprague-Dawley; Receptors, Leptin; Rhombencephalon; Third Ventricle; Weight Loss

There is a general assumption that weight loss associated with cocaine use reflects its appetite suppressing properties. We sought to determine whether this was justified by characterizing, in detail, alterations in dietary food intake and body composition in actively using cocaine-dependent individuals. We conducted a cross-sectional case-control comparison of 65 male volunteers from the local community, half of whom satisfied the DSM-IV-TR criteria for cocaine dependence (n=35) while the other half had no personal or family history of a psychiatric disorder, including substance abuse (n=30). Assessments were made of eating behavior and dietary food intake, estimation of body composition, and measurement of plasma leptin. Although cocaine users reported significantly higher levels of dietary fat and carbohydrates as well as patterns of uncontrolled eating, their fat mass was significantly reduced compared with their non-drug using peers. Levels of leptin were associated with fat mass, and with the duration of stimulant use. Tobacco smoking status or concomitant use of medication did not affect the significance of the results. Weight changes in cocaine users reflect fundamental perturbations in fat regulation. These are likely to be overlooked in clinical practice but may produce significant health problems when cocaine use is discontinued during recovery.

Topics: Adolescent; Body Composition; Case-Control Studies; Cocaine-Related Disorders; Cross-Sectional Studies; Diet; Energy Intake; Feeding Behavior; Humans; Leptin; Male; Self Report; Thinness; Weight Loss; Young Adult

Peptide YY (PYY) and ghrelin exhibit a reciprocal association and antagonistic physiological effects in the peripheral circulation. Research has yet to clarify the effect of weight loss on the 24h profile of PYY or its association to 24h ghrelin. We sought to determine if diet- and exercise-induced weight loss affects the 24h profile of PYY and its association with 24h ghrelin in normal weight, premenopausal women. Participants (n = 13) were assessed at baseline (BL) and after a 3-month diet and exercise intervention (post). Blood samples obtained q10 min for 24h were assayed for total PYY and total ghrelin q60 min from 0800 to 1000 h and 2000 to 0800 h and q20 min from 1000 to 2000 h. The ghrelin/PYY ratio was used as an index of hormonal exposure. Statistical analyses included paired t-tests and linear mixed effects modeling. Body weight (-1.85 ± 0.67 kg; p = 0.02), and body fat (-2.53 ± 0.83%; p = 0.01) decreased from BL to post. Ghrelin AUC (5252 ± 2177 pg/ml/24h; p=0.03), 24h mean (216 ± 90 pg/ml; p = 0.03) and peak (300 ± 134 pg/ml; p = 0.047) increased from BL to post. No change occurred in PYY AUC (88.2 ± 163.7 pg/ml; p = 0.60), 24h mean (4.8 ± 6.9 pg/ml; p = 0.50) or peak (3.6 ± 6.4 pg/ml; p = 0.58). The 24h association between PYY and ghrelin at baseline (p = 0.04) was weakened at post (p = 0.14); however, the ghrelin/PYY lunch ratio increased (p = 0.01) indicating the potential for ghrelin predominance over PYY in the circulation. PYY and ghrelin are reciprocally associated during a period of weight stability, but not following weight loss. An "uncoupling" may have occurred, particularly at lunch, due to factors that modulate ghrelin in response to weight loss.

Topics: Adult; Body Composition; Body Weight; Female; Ghrelin; Humans; Leptin; Peptide YY; Premenopause; Weight Loss; Young Adult

The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on metabolic response, weight loss and serum adipokine levels to a high monounsaturated fat hypocaloric diet in obese patients.. A sample of 128 obese patients was analyzed in a prospective way during 3 months.. Eighty eight patients (21 males/67 females) (68.8%) had the genotype 55CC (wild genotype group) and 40 patients (8 males/32 females) (31.3%) 55CT (mutant genotype group). In wild genotype group, BMI (-1.6±1.3 kg/m2), weight (-4.3±3.7 kg), fat mass (-3.5±3.3 kg), waist circumference (-5.1±2.9 cm), total cholesterol (-7.2±10.6 mg/dl), LDL cholesterol (-5.3±12.8 mg/dl) and leptin (-4.7±10.1 ng/ml) decreased. In mutant genotype group, BMI (1.3±2.2 kg/m2), weight (-3.0±1.4 kg), fat mass (-2.5±1.1 kg), waist circumference (-2.8±3.1 cm) and leptin (-5.8±10.7 decreased.. In patients with -55CC UCP3 genotype, a high mono-unsaturated hypocaloric diet reduced BMI, weight, waist circumference, waist to hip ratio, fat mass, LDL-cholesterol, total cholesterol and leptin levels. Carriers of T allele had a different response than -55CC patients, with a significant decrease of the same antropometric parameters, but lower than in the wild genotype group, and without significant changes in cholesterol levels.

Topics: Adult; Body Mass Index; Cholesterol, LDL; Diet, High-Fat; Energy Intake; Female; Humans; Ion Channels; Leptin; Male; Middle Aged; Mitochondrial Proteins; Obesity; Polymorphism, Genetic; Uncoupling Protein 3; Weight Loss

Insulin resistance, dyslipidemia and hypertension are independent mediators of endothelial dysfunction. It is incompletely defined whether dyslipidemia and hypertension in addition to diabetes mellitus type II (DMII), as seen in the metabolic syndrome (MS), worsen diabetes-induced endothelial dysfunction. Furthermore, it is unclear whether treatment influences endothelial dysfunction similarly in MS and DMII. Therefore, we studied vascular reactivity and the effect of in vivo treatment with angiotensin-converting enzyme inhibition (ACE-I) or hypocaloric diet in LDL receptor- and leptin-deficient (ob/ob), double knockout mice (DKO), featuring MS and in ob/ob mice with DMII.. Vascular reactivity was studied in isolated aortic ring segments. Maximum vasorelaxant response to acetylcholine (Ach) was more depressed in DKO than in ob/ob mice, whereas response to bradykinin (BK) was equally attenuated in both genotypes (52 ± 3 and 23 ± 9% reversal of preconstriction induced by 10(-7) M phenylephrine in DKO vs. 76 ± 3 and 23 ± 8% reversal of preconstriction in ob/ob mice, respectively). ACE-I and hypocaloric diet improved ACh-induced vasorelaxation significantly (89 ± 2 and 59 ± 2% reversal of preconstriction in DKO vs. 80 ± 3 and 84 ± 4% in ob/ob mice, respectively), but not the response to BK.. These results indicate a differential impact of DMII and MS on endothelial function. ACE-I and hypocaloric diet improved ACh-, but not BK-induced vasorelaxation in these mouse models of DMII and MS.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Blood Glucose; Caloric Restriction; Captopril; Combined Modality Therapy; Diabetes Mellitus, Type 2; Disease Models, Animal; Dose-Response Relationship, Drug; Dyslipidemias; Endothelium, Vascular; Female; Hypertension; Leptin; Lipids; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Nitric Oxide; Receptors, LDL; Time Factors; Vasodilation; Vasodilator Agents; Weight Loss

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Anorexia; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Humans; Leptin; Male; Weight Loss

Recent studies have shown that xenin can act in the hypothalamus, reducing food intake through a leptin- and melanocortin system-independent mechanism.. To evaluate the impact of body mass reduction on the blood and cerebrospinal fluid (CSF) levels of xenin.. Thirteen obese patients (11 women) selected for roux-in-Y gastric bypass surgery were evaluated before and approximately 8 months after surgery. Xenin was determined in serum and CSF by radioimmunoassay.. As compared with lean subjects, obese patients have increased blood levels of xenin, which reduce after surgery. There are significant correlations between blood xenin and blood leptin and insulin levels. CSF concentration of xenin is ∼10-fold lower than blood levels, and is significantly higher in obese subjects as compared with lean ones, returning to normal levels after body mass reduction. There is a significant linear correlation between CSF and blood levels of xenin.. Xenin is present in the human CSF in a concentration ∼10-fold lower than the blood. Both blood and CSF xenin are correlated with blood levels of important markers of adiposity, leptin and insulin. The levels of CSF xenin are linearly correlated with blood xenin, independently of patient body mass, suggesting that either its transport across the blood-brain barrier is not saturated in the concentration range detected in this study or that there is a coordinated release of xenin from the periphery and the CNS.

Topics: Adolescent; Adult; Biological Transport; Biomarkers; Blood-Brain Barrier; Body Mass Index; Fasting; Female; Gastric Bypass; Humans; Leptin; Male; Middle Aged; Neurotensin; Obesity, Morbid; Radioimmunoassay; Weight Loss

Brain-derived neurotrophic factor (BDNF) is a regulator of energy homeostasis and food intake through hypothalamic signaling. Currently, data regarding BDNF in children with obesity are lacking. We evaluated serum BDNF concentrations in obese children, both before and after lifestyle intervention, in reference to those of lean children.. A total of 90 (24 normal weight; 66 obese) children were studied utilizing a cross-sectional clinical outpatient study design. In addition, longitudinal data analysis was performed in 30 obese children participating in a lifestyle intervention for one year.. Fasting serum BDNF concentrations were higher in obese vs. normal weight children (BDNF 20.3±1.0 vs. 12.5±1.7 ng/mL, respectively, mean±SEM, p<0.001) and correlated significantly to BMI standard deviation score (r=0.426, p<0.001), and leptin (r=0.414, p<0.01). BDNF concentrations were not regulated in response to food, 60 min after ingestion of a liquid test meal. After one year lifestyle intervention, delta BDNF correlated significantly to delta leptin (r=0.475, p<0.01), but not to changes of insulin resistance index HOMA-IR, systolic and diastolic blood pressure, HDL, LDL, and triglycerides. In a multiple stepwise linear regression adjusted for pubertal stage, age, sex, and BMI, delta BDNF correlated significantly (p<0.05) to delta leptin and delta triceps skinfold and in tendency to delta subscapularis skinfold thickness (p=0.050).. Our results in children do not indicate a significant relationship between BDNF and insulin resistance or cardiovascular risk factors. However, the correlation between changes of BDNF and changes of leptin suggests a relationship between BDNF and fat mass.

Topics: Adolescent; Body Mass Index; Brain-Derived Neurotrophic Factor; Child; Cholesterol; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Life Style; Longitudinal Studies; Male; Obesity; Triglycerides; Weight Loss

With the increasing rates of obesity, many people diet in an attempt to lose weight. As weight loss is seldom maintained in a single effort, weight cycling is a common occurrence. Unfortunately, reports from clinical studies that have attempted to determine the effect of weight cycling on mortality are in disagreement, and to date, no controlled animal study has been performed to assess the impact of weight cycling on longevity. Therefore, our objective was to determine whether weight cycling altered lifespan in mice that experienced repeated weight gain and weight loss throughout their lives.. Male C57BL/6J mice were placed on one of three lifelong diets: a low-fat (LF) diet, a high-fat (HF) diet or a cycled diet in which the mice alternated between 4 weeks on the LF diet and 4 weeks on the HF diet. Body weight, body composition, several blood parameters and lifespan were assessed.. Cycling between the HF and LF diet resulted in large fluctuations in body weight and fat mass. These gains and losses corresponded to significant increases and decreases, respectively, in leptin, resistin, GIP, IGF-1, glucose, insulin and glucose tolerance. Surprisingly, weight cycled mice had no significant difference in lifespan (801±45 days) as compared to LF-fed controls (828±74 days), despite being overweight and eating a HF diet for half of their lives. In contrast, the HF-fed group experienced a significant decrease in lifespan (544±73 days) compared with LF-fed controls and cycled mice.. This is the first controlled mouse study to demonstrate the effect of lifelong weight cycling on longevity. The act of repeatedly gaining and losing weight, in itself, did not decrease lifespan and was more beneficial than remaining obese.

Topics: Animals; C-Peptide; Chemokine CCL2; Diet, Fat-Restricted; Diet, High-Fat; Energy Intake; Gastric Inhibitory Polypeptide; Insulin; Interleukin-6; Leptin; Longevity; Male; Mice; Mice, Inbred C57BL; Obesity; Peptide Fragments; Resistin; Time Factors; Weight Gain; Weight Loss

Recent studies have reported a relationship between osteocalcin (OC) levels and factors associated with energy metabolism and insulin resistance. As any detailed understanding of OC mechanisms still remains elusive, this study aimed at revealing a correlation between serum OC levels and obesity in healthy, nonsmoking, Korean obese adults who had undergone weight loss through pharmacological treatment.. 119 healthy, nonsmoking, Korean obese adults were investigated at 3 months following weight loss through pharmacological treatment. Serum OC, leptin, HOMA score, ghrelin, visceral fat mass, total body fat, and BMI were measured.. Increase in serum OC was significantly associated with decreases in: BMI (and weight change %) (r=-0.209, p=0.023), visceral fat mass (r=-0.189, p=0.049), HOMA (r=-0.203 p=0.027), and leptin (r=-0.253 p=0.006), but not with changes in adiponectin (r=+0.029, p=NS), and Ghrelin (r=+0.019, p=NS). Decrease in leptin (β=-0.280, p=0.002) was significantly associated with an increase in serum OC, after pharmacological weight loss treatment was adjusted for age, sex, drug type, and BMI (or visceral fat mass).. Serum OC was significantly increased at 3 months after pharmacological weight loss. We further found that leptin levels were associated with changes in serum OC. These findings suggest a relationship between bone and adipose tissue.

Topics: Adolescent; Adult; Female; Humans; Leptin; Male; Middle Aged; Obesity; Osteocalcin; Republic of Korea; Weight Loss; Young Adult

An intragenic polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism in Caucasian populations (rs1049353). Intervention studies with this polymorphism have yield contradictories results. We decide to investigate the role of polymorphism (G1359A) of (CNR1) gene on metabolic parameters and weight loss secondary to a high monounsaturated fat and high polyunsaturated fat hypocaloric diets in obese subjects. A population of 258 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 3-month period in which subjects received 1 of 2 diets (diet M: high monounsaturated fat diet vs diet P: high polyunsaturated fat diet). One hundred and sixty five patients (63.9%) had the genotype G1359G and 93 (36.1%) patients (A allele carriers) had G1359A (78 patients,30.3%) or A1359A (15 patients,5.8%) genotypes. In subjects with both genotypes, body mass index, weight, fat mass, waist circumference and systolic blood pressures decreased with both diets. With the diet-type M and in both genotype groups, biochemical parameters remained unchanged. After the diet type P and in subjects with both genotypes, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, insulin and homeostasis model assessment for insulin resistance (HOMA-IR) levels decreased. In G1359G genotype subjects after both diets, leptin levels decreased. The finding of this study is the association of the A allele with a lack of improvement on leptin levels. Subjects with both genotypes and after a high polyunsaturated fat hypocaloric diet showed a significant improvement of LDL cholesterol, total cholesterol, HOMA-IR and insulin levels.

Topics: Adult; Alleles; Blood Glucose; Body Mass Index; Cholesterol; Diet, High-Fat; Diet, Reducing; Dietary Fats; Energy Intake; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Feeding Behavior; Female; Genotype; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Receptor, Cannabinoid, CB1; Weight Loss; White People

There is emerging literature demonstrating a relationship between the timing of feeding and weight regulation in animals. However, whether the timing of food intake influences the success of a weight-loss diet in humans is unknown.. To evaluate the role of food timing in weight-loss effectiveness in a sample of 420 individuals who followed a 20-week weight-loss treatment.. Participants (49.5% female subjects; age (mean ± s.d.): 42 ± 11 years; BMI: 31.4 ± 5.4 kg m(-2)) were grouped in early eaters and late eaters, according to the timing of the main meal (lunch in this Mediterranean population). 51% of the subjects were early eaters and 49% were late eaters (lunch time before and after 1500 hours, respectively), energy intake and expenditure, appetite hormones, CLOCK genotype, sleep duration and chronotype were studied.. Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups. Nevertheless, late eaters were more evening types, had less energetic breakfasts and skipped breakfast more frequently that early eaters (all; P<0.05). CLOCK rs4580704 single nucleotide polymorphism (SNP) associated with the timing of the main meal (P=0.015) with a higher frequency of minor allele (C) carriers among the late eaters (P=0.041). Neither sleep duration, nor CLOCK SNPs or morning/evening chronotype was independently associated with weight loss (all; P>0.05).. Eating late may influence the success of weight-loss therapy. Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution - as is classically done - but also the timing of food.

Topics: Adult; Body Mass Index; Circadian Rhythm; CLOCK Proteins; Diet, Mediterranean; Energy Intake; Energy Metabolism; Feeding Behavior; Female; Genotype; Ghrelin; Humans; Leptin; Male; Obesity; Predictive Value of Tests; Sleep; Spain; Surveys and Questionnaires; Time Factors; Treatment Outcome; Weight Loss; Weight Reduction Programs

Food restriction induces a loss of body mass that is often followed by rapid regaining of the lost weight when the restriction ends, consequently increasing a risk of development of obesity. To determine the physiological and behavioral mechanisms underlining the regaining, striped hamsters were restricted to 85% of initial food intake for 4 weeks and refed ad libitum for another 4 weeks. Changes in body mass, energy budget, activity, body composition and serum leptin level were measured. Body mass, body fat mass and serum leptin level significantly decreased in food-restricted hamsters, and increased when the restriction ended, showing a short "compensatory growth" rather than over-weight or obesity compared with ad libitum controls. During restriction, the time spent on activity increased significantly, which was opposite to the changes in serum leptin level. Food intake increased shortly during refeeding, which perhaps contributed to the rapid regaining of body mass. No correlation was observed between serum leptin and energy intake, while negative correlations were found in hamsters that were refed for 7 and 28 days. Exogenous leptin significantly decreased the time spent on activity during food restriction and attenuated the increase in food intake during refeeding. This suggests that low leptin in restricted animals may function as a starvation signal to induce an increase in activity behavior, and high leptin likely serves as a satiety signal to prevent activity during refeeding. Leptin may play a crucial role in controlling food intake when the restriction ends, and consequently preventing overweight.

Topics: Animals; Body Composition; Cricetinae; Eating; Energy Intake; Food Deprivation; Leptin; Male; Motor Activity; Weight Gain; Weight Loss

Obesity is associated with an increased risk for recurrence and all-cause mortality in breast cancer survivors. Excess adiposity is associated with increased estrogen, insulin, and leptin, and with decreased sex hormone binding globulin (SHBG) concentrations, which may promote breast cancer progression and recurrence. This study aimed to assess the effects of weight loss on these factors.. Breast cancer survivors who were overweight or obese (n = 220) and who were enrolled in a weight loss intervention study provided baseline and follow-up blood samples and weight data. Serum estrogens, SHBG, insulin, and leptin were measured at baseline, 6 months, and 18 months.. Weight loss of ≥5% of initial weight decreased leptin and insulin compared with those who did not achieve that amount of weight loss (P < .0001). Weight loss also increased SHBG at 6 and 18 months (P < .01). Postmenopausal women who lost ≥5% of body weight at 6 months had lower estrone (P = .02), estradiol (P = .002), and bioavailable estradiol (P = .001) concentrations than women who did not lose at least 5% of body weight, and weight loss at 18 months was significantly related to a change in serum bioavailable estradiol concentration (P = .02).. Favorable changes in estrogens, SHBG, insulin, and leptin were observed in association with weight loss in these women who were overweight or obese and who had been diagnosed and treated for breast cancer. Weight loss appears to have favorable effects on hormonal and biologic factors associated with increased risk for recurrence and poorer prognosis.

Topics: Aged; Biomarkers; Breast Neoplasms; Estrogens; Female; Humans; Insulin; Leptin; Middle Aged; Overweight; Sex Hormone-Binding Globulin; Weight Loss

Calorie restriction-induced weight loss is accompanied by profound changes in adipose tissue characteristics. To determine the effect of weight loss on differentiation of preadipocytes and secretory capacity of in vitro differentiated adipocytes, we established cultures of these cells from paired subcutaneous adipose tissue biopsies obtained before and at the end of weight-reducing dietary intervention (DI) in 23 obese women. Based on lipid accumulation and the expression of differentiation markers, in vitro adipogenesis increased after weight loss and it was accompanied by enhanced expression of genes involved in de novo lipogenesis. This effect of weight loss was not driven by changes of peroxisome proliferator-activated receptor γ sensitivity to rosiglitazone. Weight loss also enhanced the expression of adiponectin and leptin while reducing that of monocyte chemoattractant protein 1 and interleukin-8 by cultured adipocytes. Thus, the weight-reducing (DI) increased adipogenic capacity of preadipocytes and shifted their secretion toward lower inflammatory profile. Reprogramming of preadipocytes could represent an adaptation to weight loss leading to partial restoration of preobese adipose tissue traits and thus contribute to the improvement of metabolic status. However, enhanced adipogenesis could also contribute to the unwanted weight regain after initial weight loss.

Topics: Adipocytes; Adipogenesis; Adiponectin; Cells, Cultured; Chemokine CCL2; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Leptin; Obesity; PPAR gamma; Rosiglitazone; Thiazolidinediones; Weight Loss

High blood pressure, in relation to blood levels of adipokines such as adiponectin and leptin, is highly associated with an unhealthy lifestyle including sedentary behaviors, poor dietary habits such as excess sodium intake, and heavy drinking. Strategies to reduce blood pressure may benefit the levels of adipokines.. Thus, we aimed to investigate the effects of lifestyle intervention on blood pressure and serum adipokines in middle-aged Korean men with borderline high blood pressure (systolic blood pressure [SBP] ≥ 130 mm Hg or diastolic blood pressure [DBP] ≥ 85 mm Hg).. Fifty-two men (aged 42.5 ± 8.5 years) with normal weight (body mass index [BMI] < 25 kg/m(2)) and high BP (NH group) and 40 men (age 42.0 ± 8.4 years) who were obese (BMI ≥ 25 kg/m(2)) with high BP (OH group) underwent 5 sessions of one-on-one intensive counseling including instruction on a nutritionally balanced diet, a low-sodium diet, how to understand calorie requirements, and strategies to implement regular exercise for blood pressure regulation over 12 weeks. In order to increase the awareness of sodium education, a salt sensory test using an unseasoned soup was performed. Anthropometrics, blood pressure measurements, 24-hour recalls were performed, and blood levels of lipids, fasting plasma glucose, C-reactive protein (CRP), leptin, and adiponectin were analyzed at week 0 and at week 12. Sodium consumption was roughly estimated using the Dish-based Frequency Questionnaire-15.. Weight, BMI, body fat (kg and %), waist circumference, hip circumference, and blood pressure were significantly decreased after 12 weeks (p < 0.05) in all subjects. Similarly, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and CRP were decreased (p < 0.05), but LDL-C/HDL-C was significantly decreased (p < 0.01) only in the obese subjects. At baseline, blood levels of leptin were significantly higher in the obese subjects than in the normal weight subjects. In the obese subjects, a significantly negative correlation was found between leptin levels at baseline and percentage change in DBP (r = -0.338, p < 0.05). After 12 weeks, blood levels of adipokines did not show significant changes.. These results suggest that a short-term (12 weeks) lifestyle intervention had positive effects on blood pressure control and weight reduction in the subjects, but not on their blood levels of adipokines. It is interesting that blood level of baseline leptin was negatively associated with the changes in blood pressure after this short-term intervention.

Topics: Adipokines; Adipose Tissue; Adult; Asian People; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Diet, Sodium-Restricted; Exercise; Fasting; Humans; Hypertension; Leptin; Life Style; Male; Middle Aged; Obesity; Surveys and Questionnaires; Weight Loss

Maintenance of a reduced body weight is accompanied by a decrease in energy expenditure beyond that accounted for by reduced body mass and composition, as well as by an increased drive to eat. These effects appear to be due--in part--to reductions in circulating leptin concentrations due to loss of body fat. Gut microbiota have been implicated in the regulation of body weight. The effects of weight loss on qualitative aspects of gut microbiota have been studied in humans and mice, but these studies have been confounded by concurrent changes in diet composition, which influence microbial community composition. We studied the impact of 20% weight loss on the microbiota of diet-induced obese (DIO: 60% calories fat) mice on a high-fat diet (HFD). Weight-reduced DIO (DIO-WR) mice had the same body weight and composition as control (CON) ad-libitum (AL) fed mice being fed a control diet (10% calories fat), allowing a direct comparison of diet and weight-perturbation effects. Microbial community composition was assessed by pyrosequencing 16S rRNA genes derived from the ceca of sacrificed animals. There was a strong effect of diet composition on the diversity and composition of the microbiota. The relative abundance of specific members of the microbiota was correlated with circulating leptin concentrations and gene expression levels of inflammation markers in subcutaneous white adipose tissue in all mice. Together, these results suggest that both host adiposity and diet composition impact microbiota composition, possibly through leptin-mediated regulation of mucus production and/or inflammatory processes that alter the gut habitat.

Topics: Adipose Tissue, White; Adiposity; Animals; Cecum; Diet, High-Fat; Energy Intake; Energy Metabolism; Intestinal Mucosa; Leptin; Male; Metagenome; Mice; Mice, Inbred C57BL; Weight Loss

Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky (fa(k)/fa(k)) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs.

Topics: Animals; Appetite Depressants; Area Postrema; Combined Modality Therapy; Crosses, Genetic; Dietary Fats; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Leptin; Male; Nerve Tissue Proteins; Neurons; Obesity; Oxytocin; Proto-Oncogene Proteins c-fos; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Receptors, Leptin; Recombinant Proteins; Solitary Nucleus; Weight Loss

Consumption of a high-fat (HF) diet results in insulin resistance and glucose intolerance. Weight loss is often recommended to reverse these metabolic alterations and the use of a high-protein (HP), low-carbohydrate diet is encouraged. In lean rats, consumption of a HP diet improves glycemic control. However, it is unknown whether this diet has a similar effectiveness in rodents with impaired glucose tolerance. Rats were fed a HF or a chow (CH) diet for 6 weeks and then switched to a HP diet or a CH or pair-fed (PF) to the amount of kcals consumed per day by the HP group. Following the diet switch, body weight gain was attenuated as compared to HF rats, and similar between HP, CH, and PF rats. Despite similar weight progression, HP and PF rats had a significant decrease in body fat after 2 weeks, as compared to HF rats. In contrast, CH rats did not show this effect. Glucose tolerance was attenuated more quickly in HP rats than in CH or PF rats. These results indicate that a HP diet may be more effective than a balanced diet for improving glycemic control in overweight individuals.

Topics: Adipose Tissue; Animals; Body Weight; Diet, Carbohydrate-Restricted; Diet, High-Fat; Dietary Proteins; Energy Intake; Energy Metabolism; Enzyme-Linked Immunosorbent Assay; Glucose Intolerance; Glucose Tolerance Test; Insulin; Leptin; Male; Radioimmunoassay; Rats; Rats, Long-Evans; Weight Loss

Glutamate acts in the hypothalamus promoting region-, and cell-dependent effects on feeding. Part of these effects are mediated by NMDA receptors, which are up regulated in conditions known to promote increased food intake and thermogenesis, such as exposure to cold and consumption of highly caloric diets. Here, we hypothesized that at least part of the effect of glutamate on hypothalamic control of energy homeostasis would depend on the control of neurotransmitter expression and JAK2 signaling. The expression of NMDA receptors was co-localized to NPY/AgRP, POMC, CRH, and MCH but not to TRH and orexin neurons of the hypothalamus. The acute intracerebroventricular injection of glutamate promoted a dose-dependent increase in JAK2 tyrosine phosphorylation. In obese rats, 5 days intracerebroventricular treatment with glutamate resulted in the reduction of food intake, accompanied by a reduction of spontaneous motility and reduction of body mass, without affecting oxygen consumption. The reduction of food intake and body mass were partially restrained by the inhibition of JAK2. In addition, glutamate produced an increased hypothalamic expression of NPY, POMC, CART, MCH, orexin, CRH, and TRH, and the reduction of AgRP. All these effects on neurotransmitters were hindered by the inhibition of JAK2. Thus, the intracerebroventricular injection of glutamate results in the reduction of body mass through a mechanism, at least in part, dependent on JAK2, and on the broad regulation of neurotransmitter expression. These effects are not impaired by obesity, which suggest that glutamate actions in the hypothalamus may be pharmacologically explored to treat this disease.

Topics: Animals; Blotting, Western; Feeding Behavior; Fluorescent Antibody Technique; Glutamates; Hypothalamus; Janus Kinase 2; Leptin; Male; Phosphorylation; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Signal Transduction; Tyrosine; Weight Loss

Resistance to brain-mediated effects of leptin is a characteristic feature of obesity, resulting from alterations in leptin receptor signaling in hypothalamic neurons and/or transport across the blood-brain-barrier. We have shown previously, that the latter can be circumvented by intranasal (i.n.) application of leptin in lean rats. This prompted us to test i.n. leptin in animals with diet-induced obesity (DIO) as a basis for future human administration. DIO was induced in male Wistar rats by feeding a cafeteria diet for 25 or 32 wk, respectively. Consecutively, these DIO animals (seven to eight per treatment) and standard diet rats (lean) (14-15 per treatment, matched for age and diet duration) were treated with 0.1, 0.2 mg/kg leptin, or control solution i.n. daily for 4 wk before onset of dark period. Energy intake and body weight were measured daily; blood glucose, serum insulin, and leptin were measured before and after treatment. Expression of hypothalamic neuropeptides was assessed by quantitative real-time PCR. We demonstrate, for the first time, that i.n. leptin reduces appetite and induces weight loss in DIO to the same extent as in lean rats. Our findings are supported accordingly by an altered expression pattern of anorexigenic and orexigenic neuropeptides in the hypothalamus, e.g. proopiomelanocortin, cocaine and amphetamine-related transcript, neuropeptide Y, agouti-related protein. It now appears clear that i.n. leptin is effectively acting in obese animals in the same fashion as in their lean counterparts. These findings now clearly warrant studies in humans and may open new perspectives in the treatment of obesity.

Topics: Adipose Tissue; Administration, Intranasal; Agouti-Related Protein; Animals; Appetite; Blood Glucose; Blood-Brain Barrier; Corticotropin-Releasing Hormone; Diet; Energy Intake; Gene Expression; Humans; Hypothalamus; Leptin; Male; Nerve Tissue Proteins; Neuropeptide Y; Obesity; Pro-Opiomelanocortin; Rats; Rats, Wistar; Receptors, Leptin; RNA, Messenger; Signal Transduction; Weight Loss

The simultaneous rise in the prevalence of asthma and obesity in the world, have demonstrated the importance of the development of treatment strategies. The purpose of this study was to evaluate the short- and long-term results of interdisciplinary therapy on inflammatory biomarkers and lung function in asthmatics obese adolescents.. Seventy-six post-pubertal obese adolescents were recruited, including 50 non-asthmatics [body mass index (BMI), 36 ± 5 kg/m(2) ) and 26 asthmatics (BMI, 39 ± 4 kg/m(2) ). Body composition was measured by plethysmography, and visceral fat was analyzed by ultrasound. Serum levels of adiponectin, leptin, and C-reactive protein (CRP) were analyzed. Asthma and lung function were evaluated according to the American Thoracic Society criteria. Patients were submitted to 1-year weight loss interdisciplinary intervention consisting of medical, nutritional, exercise, and psychological therapy.. After interdisciplinary intervention, the lung function and pro/anti-inflammatory adipokines improved significantly in both groups. Most importantly, there was an increase in adiponectin [4 (1.86-12.9) to 5.1 (2.48-16)], a reduction in CRP [2,073 (385-9,174) to 1,538 (205-7,083)] and leptin concentrations [59 (29-69) to 33 (9-49)] in the asthmatics patients. Furthermore, it was observed a reduction in asthma severity after treatment. In addition, Δ adiponectin was an independent factor to improve lung function after therapy in both groups.. Interdisciplinary therapy resulted in beneficial changes in inflammatory biomarkers profile and lung function in asthmatic and non-asthmatic obese adolescents. Additionally, for the first time we showed that change in adiponectin level was an independent predictor to improve lung function in Brazilian obese adolescents.

Topics: Adipokines; Adiponectin; Adolescent; Asthma; Biomarkers; Body Mass Index; C-Reactive Protein; Combined Modality Therapy; Diet Therapy; Exercise; Female; Humans; Leptin; Lung; Male; Obesity; Psychotherapy, Group; Spirometry; Weight Loss; Young Adult

Long-term dietary intervention frequently induces a rapid weight decline followed by weight stabilization/regain. Here, we sought to identify adipokine biomarkers that may reflect continued beneficial effects of dieting despite partial weight regain.. We analyzed the dynamics of fasting serum levels of 12 traditional metabolic biomarkers and novel adipokines among 322 participants in the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT) of low-fat, Mediterranean, or low-carbohydrate diets for weight loss.. We identified two distinct patterns: Pattern A includes biomarkers (insulin, triglycerides, leptin, chemerin, monocyte chemoattractant protein 1, and retinol-binding protein 4) whose dynamics tightly correspond to changes in body weight, with the trend during the weight loss phase (months 0-6) going in the opposite direction to that in the weight maintenance/regain phase (months 7-24) (P < 0.05 between phases, all biomarkers). Pattern B includes biomarkers (high molecular weight adiponectin, HDL cholesterol [HDL-C], high-sensitivity C-reactive protein [hsCRP], fetuin-A, progranulin, and vaspin) that displayed a continued, cumulative improvement (P < 0.05 compared with baseline, all biomarkers) throughout the intervention. These patterns were consistent across sex, diabetic groups, and diet groups, although the magnitude of change varied. Hierarchical analysis suggested similar clusters, revealing that the dynamic of leptin (pattern A) was most closely linked to weight change and that the dynamic of hsCRP best typified pattern B.. hsCRP, HDL-C, adiponectin, fetuin-A, progranulin, and vaspin levels display a continued long-term improvement despite partial weight regain. This may likely reflect either a delayed effect of the initial weight loss or a continuous beneficial response to switching to healthier dietary patterns.

Topics: Adipokines; Adiponectin; alpha-2-HS-Glycoprotein; Biomarkers; C-Reactive Protein; Cholesterol, HDL; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Diet, Reducing; Fasting; Female; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Progranulins; Retinol-Binding Proteins; Serpins; Weight Loss

The proteasome is a multicatalytic enzyme complex responsible for the degradation of both normal and damaged proteins. An age-related decline in proteasomal activity has been implicated in various age-related pathologies. The relevance of decreased proteasomal activity to aging and age-related diseases remains unclear, however, because suitable animal models are not available. In the present study, we established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity. Tg mice exhibited a shortened life span and developed age-related phenotypes. In Tg mice, polyubiquitinated and oxidized proteins accumulated, and the expression levels of cellular proteins such as Bcl-xL and RNase L were altered. When Tg mice were fed a high-fat diet, they developed more pronounced obesity and hepatic steatosis than did wild-type mice. Consistent with its role in lipid droplet formation, the expression of adipose differentiation-related protein (ADRP) was elevated in the livers of Tg mice. Of note, obesity and hepatic steatosis induced by a high-fat diet were more pronounced in aged than in young wild-type mice, and aged wild-type mice had elevated levels of ADRP, suggesting that the metabolic abnormalities present in Tg mice mimic those in aged mice. Our results provide the first in vivo evidence that decreased proteasomal chymotrypsin-like activity affects longevity and aggravates age-related metabolic disorders, such as obesity and hepatic steatosis.

Topics: Adipose Tissue; Aging; Animals; bcl-X Protein; Cells, Cultured; Diet, High-Fat; Endoribonucleases; Fatty Liver; Insulin; Leptin; Liver; Longevity; Male; Membrane Proteins; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Perilipin-2; Phenotype; Polyubiquitin; Proteasome Endopeptidase Complex; Weight Loss

The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone (P < 0.0001) and follicle-stimulating hormone levels (P < 0.0001), consistent with the estrogenic action of the compound. GSK232802A treatment produced a small but sustained weight loss (4.6 ± 1.0%, P < 0.0001) and reduced adiposity (P < 0.0001), which was due at least in part to a suppression of food intake (3.6 ± 3.7%, P < 0.0001). Physical activity increased during the 3rd mo of treatment (P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment (P = 0.02). Metabolic rate did not change (P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.

Topics: Alkaline Phosphatase; Animals; Body Composition; Body Fat Distribution; Body Weight; Eating; Energy Metabolism; Female; Leptin; Luteinizing Hormone; Macaca mulatta; Motor Activity; Ovariectomy; Selective Estrogen Receptor Modulators; Triiodothyronine; Weight Loss

These preclinical studies aimed to 1) increase our understanding the dietary induction of nonalcoholic steatohepatitis (NASH), and, 2) further explore the utility and mechanisms of glucagon-like peptide-1 receptor (GLP-1R) agonism in NASH. We compared the effects of a high trans-fat (HTF) or high lard fat (HLF) diet on key facets of nonalcoholic fatty liver disease (NAFLD)/NASH in Lep(ob)/Lep(ob) and C57BL6J (B6) mice. Although HLF-fed mice experienced overall greater gains in weight and adiposity, the addition of trans-fat better mirrored pathophysiological features of NASH (e.g., hepatomegaly, hepatic lipid, and fibrosis). Administration of AC3174, an exenatide analog, and GLP-1R agonist to Lep(ob)/Lep(ob) and B6 ameliorated hepatic endpoints in both dietary models. Next, we assessed whether AC3174-mediated improvements in diet-induced NASH were solely due to weight loss in HTF-fed mice. AC3174-treatment significantly reduced body weight (8.3%), liver mass (14.2%), liver lipid (12.9%), plasma alanine aminotransferase, and triglycerides, whereas a calorie-restricted, weight-matched group demonstrated only modest nonsignificant reductions in liver mass (9%) and liver lipid (5.1%) relative to controls. Treatment of GLP-1R-deficient (GLP-1RKO) mice with AC3174 had no effect on body weight, adiposity, liver or plasma indices pointing to the GLP-1R-dependence of AC3174's effects. Interestingly, the role of endogenous GLP-1Rs in NASH merits further exploration as the GLP-1RKO model was protected from the deleterious hepatic effects of HTF. Our pharmacological data further support the clinical evaluation of the utility of GLP-1R agonists for treatment of NASH.

Topics: Animals; Body Composition; Body Weight; Diet; Diet, Fat-Restricted; Diet, High-Fat; Endpoint Determination; Fatty Liver; Gene Expression; Glucagon-Like Peptide-1 Receptor; Hormones; Leptin; Lipids; Liver; Liver Function Tests; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Non-alcoholic Fatty Liver Disease; Peptides; Receptors, Glucagon; Trans Fatty Acids; Weight Loss

Leptin enhances insulin sensitivity in addition to reducing food intake and body weight. Recently, amylin, a pancreatic β-cell-derived hormone, was shown to restore a weight-reducing effect of leptin in leptin-resistant diet-induced obesity. However, whether amylin improves the effect of leptin on insulin sensitivity in diet-induced obesity is unclear. Diet-induced obese (DIO) mice were infused with either saline (S), leptin (L; 500 μg·kg⁻¹·day⁻¹), amylin (A; 100 μg·kg⁻¹·day⁻¹), or leptin plus amylin (L/A) for 14 days using osmotic minipumps. Food intake, body weight, metabolic parameters, tissue triglyceride content, and AMP-activated protein kinase (AMPK) activity were examined. Pair-feeding and weight-matched calorie restriction experiments were performed to assess the influence of food intake and body weight reduction. Continuous L/A coadministration significantly reduced food intake, increased energy expenditure, and reduced body weight, whereas administration of L or A alone had no effects. L/A coadministration did not affect blood glucose levels during ad libitum feeding but decreased plasma insulin levels significantly (by 48%), suggesting the enhancement of insulin sensitivity. Insulin tolerance test actually showed the increased effect of insulin in L/A-treated mice. In addition, L/A coadministration significantly decreased tissue triglyceride content and increased AMPKα2 activity in skeletal muscle (by 67%). L/A coadministration enhanced insulin sensitivity more than pair-feeding and weight-matched calorie restriction. In conclusion, this study demonstrates the beneficial effect of L/A coadministration on glucose and lipid metabolism in DIO mice, indicating the possible clinical usefulness of L/A coadministration as a new antidiabetic treatment in obesity-associated diabetes.

Topics: Animals; Anti-Obesity Agents; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diet, High-Fat; Drug Resistance; Drug Therapy, Combination; Energy Intake; Energy Metabolism; Hypoglycemic Agents; Insulin; Insulin Resistance; Islet Amyloid Polypeptide; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Obesity; Triglycerides; Weight Loss

We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-α, IFN-γ, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-α, IFN-γ, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 ± 19.5 vs 80.9 ± 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.

Topics: Adiponectin; Aged; Antineoplastic Agents; Cachexia; Colorectal Neoplasms; Cytokines; Female; Follow-Up Studies; Ghrelin; Humans; Interferon-gamma; Interleukin-6; Leptin; Lung Neoplasms; Male; Middle Aged; Peptide Hormones; Prognosis; Prospective Studies; Survival Rate; Tumor Necrosis Factor-alpha; Weight Gain; Weight Loss

Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping).. We examined eight obese non-diabetic patients before and within 2 weeks after RYGB. On separate days, oral glucose tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid mixed meal test (200 mL 300 kcal) were performed. We measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance.. Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ before and after the operation or between the tests.. Within 2 weeks after RYGB, we found an increase in insulin secretion and insulin sensitivity. Responses of appetite-regulating intestinal hormones changed dramatically, all in the direction of reducing hunger.

Topics: Adult; Appetite; C-Peptide; Cholecystokinin; Confounding Factors, Epidemiologic; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Leptin; Male; Middle Aged; Obesity, Morbid; Pancreatic Polypeptide; Peptide YY; Postprandial Period; Somatostatin; Time Factors; Weight Loss

The goal was to study lipid profiles (TG, TC, LDL, HDL), effects on serum leptin, and fat tissue adiponectin, and resistin as well as body weight effects of Shan He Jian Fei Granules (SHJFG) in rats on a high fat diet.. Rats were randomly divided into five groups: normal control group fed with normal fat diet, rats on high fat diet receiving low dosage, middle dosage, high dosage of Shan He Jian Fei Granules (SHJFG) as well as a high fat diet group receiving placebo. Rats were treated for 8 weeks. Body weight and naso-anal length of each rat were recorded and Lee's index was calculated. Serum TG, TC, LDL, HDL and leptin concentrations were analyzed. The gene expressions of adiponectin and resistin in adipose tissues were tested by RT-PCR.. Compared to the high-fat diet group, body weights, Lee's indexes, weight of fat tissues and serum TG, TC, LDL and leptin of SHJFG groups significantly decreased (p < 0.05), whereas mRNA expressions of adiponectin and resistin of SHJFG groups significantly increased (p < 0.05).. SHJFG could significantly lower body weight and serum TG, TC, and LDL of obese rats. The effects of SHJFG in lowering leptin synthesis and raising mRNA expression of adiponectin and resistin in fat tissues may act as part of the mechanisms in lowering body weight of obese rats. Further studies are needed to demonstrate whether SHJFG may also reduce overall cardiovascular morbidity and mortality like other lipid lowering drugs.

Topics: Adiponectin; Adipose Tissue; Animals; Dietary Fats; Drugs, Chinese Herbal; Gene Expression; Leptin; Lipid Metabolism; Lipids; Male; Obesity; Rats; Rats, Sprague-Dawley; Resistin; RNA, Messenger; Weight Loss

The effects of leptin on bone are controversial. Although in vitro studies have shown that leptin stimulates osteoblast differentiation and mineralization and inhibits osteoclastogenesis, some rodent studies have shown that leptin administered centrally might result in decreased bone formation. In the present study we have investigated the skeletal effects of supraphysiological concentrations of leptin administered sc to rats. Female Fischer rats were given leptin 100 μg/d, 200 μg/d, or saline by continuous infusion for 9 wk. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry, bone microarchitecture was analyzed by micro-computed tomography, and biomechanical properties were tested by three-point bending experiments. At the end of the study, the body weight was significantly lower in rats receiving leptin compared with controls (-10.8% and -12.0% in low- and high-dose leptin groups, respectively). The high-dose leptin group also significantly lost weight compared with baseline. The plasma leptin concentration was 14- and 33-fold increased in the low- and high-dose groups, respectively. No significant differences in femoral BMD were observed. Whole-body BMD was significantly lower in the low-dose leptin group, whereas there was no difference between the high-dose leptin group and the control. Mechanical strength and microarchitecture were similar in the high-dose and the control group. The low-dose group, however, had decreased cortical volume in the femoral metaphysis, lowered bone strength, and altered moment of inertia. In conclusion, leptin given at very high doses maintains BMD, microarchitecture, and mechanical strength in female rats, despite a significant decrease in body weight.

Topics: Animals; Body Weight; Bone Density; Female; Femur; Leptin; Rats; Rats, Inbred F344; Weight Loss

Because iatrogenic obesity may hinder medication compliance, it would be a reasonable approach to consider antiepileptic drugs (AEDs) that promote weight loss in overweight patients. We performed an open-label, observational study to assess the effects of zonisamide on weight in overweight female epilepsy patients. In particular, we studied how the basal serum leptin level is related to changes in the weight of these patients. We recruited female epilepsy patients with basal body mass index 25 or more. Laboratory findings including serum leptin level were measured and zonisamide was administered as a monotherapy at a dose of 200 to 400mg/day. Six months later, we measured changes in the body weight. Thirty-seven female epilepsy patients enrolled in the study, and 23 of them completed the treatment. Weight loss after zonisamide treatment was correlated with initial body weight (p=0.020), follow-up weight (p=0.010), and basal serum leptin level (p=0.008), but was not correlated with patients' age, results of lipid profile, and dosage of zonisamide. The correlation of the serum leptin level with weight loss was still significant after the effect of the initial weight was adjusted (p=0.042). Our study shows that low serum leptin level is associated with weight loss in overweight female epilepsy patients. This result may be beneficial for selecting AEDs and provide clues for the pathophysiology of zonisamide-induced weight loss.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Epilepsy; Female; Follow-Up Studies; Humans; Isoxazoles; Leptin; Linear Models; Middle Aged; Obesity; Prospective Studies; Weight Loss; Young Adult; Zonisamide

Variable responses of gut hormones have been observed after bariatric procedures. The aim of the present study was to evaluate the ghrelin, glucagon-like peptide 1 (GLP-1), and leptin levels in nonobese canine and obese rat models after weight loss owing to a reversible gastric restriction (RGR) device.. Mongrel dogs and obese Zucker rats were submitted to either surgical implantation or a sham operation and were followed up for 6 wk. The serum fasting ghrelin, GLP-1, and leptin levels in dogs were measured using enzyme-linked immunosorbent assay before and after surgical implantation and after implant removal. The protein expression of mucosa ghrelin, GLP-1, and leptin in the dog and rat stomach were measured using Western blotting.. The RGR implant in dogs and rats resulted in a significant decrease in food intake and body weight. In the nonobese dog, the serum ghrelin level and mucosa ghrelin expression were significantly increased after surgical implantation (P < 0.05) and tended to recover after implant removal. In the obese rat, mucosa ghrelin expression decreased by about 27% (P = 0.06) 6 wk after implantation. A lower serum leptin level in dogs and lower mucosa leptin expression in dogs and rats was observed after surgical implantation compared with the sham procedure (P < 0.05). The RGR implant had no influence on the serum GLP-1 level in dogs or mucosa GLP-1 expression in either animal model.. Our results showed that ghrelin levels are downregulated with short-term RGR implantation in obese rats but upregulated in nonobese dogs, implying that the energy balance could be an important determinant of ghrelin level. The marked suppression of leptin in both animal models might contribute to the weight-reducing effect of the RGR implant.

Topics: Animals; Body Weight; Disease Models, Animal; Dogs; Energy Metabolism; Gastric Mucosa; Gastroplasty; Ghrelin; Glucagon-Like Peptide 1; Leptin; Obesity; Rats; Rats, Zucker; Weight Loss

Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol·kg(-1)·h(-1))] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol·kg(-1)·h(-1)) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats.

Topics: Animals; Body Composition; Body Fat Distribution; Body Weight; Caloric Restriction; Dose-Response Relationship, Drug; Eating; Exenatide; Glucagon-Like Peptide-1 Receptor; Hyperphagia; Leptin; Male; Obesity; Peptides; Rats; Rats, Sprague-Dawley; Receptors, Glucagon; Venoms; Weight Gain; Weight Loss

The biliopancreatic diversion surgery with duodenal switch (BPD-DS) is a surgical procedure that not only induces significant weight loss, but also promotes remission of diabetes. However, the mechanism responsible for this insulin-potentiating effect (both on sensitivity and production) is not yet clearly understood. The insulin-like growth factor (IGF) binding protein 2 (IGFBP-2) is a 36 kDa circulating protein that has been recently suggested to modulate insulin sensitization and fat accumulation. In humans, a low-circulating concentration of IGFBP-2 has been associated with obesity and insulin resistance. We thus tested the hypothesis that BPD-DS would trigger an increase in IGFBP-2 levels. Plasma IGFBP-2 was quantified by enzyme-linked immunosorbent assay in 77 severely obese men and women before and up to 1 year after BPD-DS surgery. Baseline IGFBP-2 levels were 159 ± 17 ng/ml. Plasma IGFBP-2 levels increased significantly as soon as 24 h after BPD-DS surgery and were further augmented at both 6 months and 1 year after the surgery, reaching 748 ± 65 ng/ml. Changes in IGFBP-2 concentrations were significantly and negatively associated with blood glucose, insulin, triglycerides, and total cholesterol levels. The present findings suggest that the rise in IGFBP-2 levels is associated with the improvements in glucose and lipid metabolism in the short- and long-term after BPD-DS. The mechanisms for the augmentation in IGFBP-2 after BPD-DS and its contribution to insulin sensitization remain to be elucidated.

Topics: Adult; Biliopancreatic Diversion; Blood Glucose; Body Composition; Female; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 2; Leptin; Male; Obesity, Morbid; Time Factors; Triglycerides; Up-Regulation; Weight Loss

Weight loss is a characteristic finding of patients with Alzheimer's disease (AD). It seems that precedes cognitive impairment by some years, but the underlying causes are not fully understood. Ghrelin and leptin are involved in energy homeostasis, and may be implicated in weight losing observed in these patients.. To examine the potential relationship between ghrelin and leptin levels and weight loss in patients with AD.. The study included 27 patients (10 men and 17 women) with AD of moderate severity, and 23 controls (10 males and 13 females), matched for age and BMI. Body fat and lean mass content were assessed using a portable apparatus. Cognitive function was assessed with the Mini-Mental State Examination. Basal serum samples for the measurement of leptin, ghrelin, insulin and glucose were obtained, and serum ghrelin, insulin and glucose were measured after a 75-gr glucose load in both groups.. Patients with Alzheimer Disease (AD) have lower lean mass content compared to controls. Basal ghrelin and leptin is similar in patients with AD and controls. The area-under-the-curve for ghrelin (AUC) is lower in male patients with AD compared to control males, while no difference was observed between females AD and controls.. Male patients with AD, in contrast with female patients, fail to maintain a normal energy homeostasis even in the early stages of the disease, as shown by the decreased lean mass content in males AD compared to controls. Disruption of the normal compensatory modulation of ghrelin secretion might contribute to the metabolic changes observed in male patients with AD.

Topics: Aged; Alzheimer Disease; Area Under Curve; Body Composition; Body Fluid Compartments; Body Mass Index; Case-Control Studies; Cognition Disorders; Energy Metabolism; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Severity of Illness Index; Sex Factors; Weight Loss

Osteoprotegerin (OPGN) is a bone-remodeling marker that is associated with various metabolic and vascular complications. Cross-sectional studies in humans have demonstrated an inverse association between leptin, a marker of energy sufficiency, and OPGN. The physiology of OPGN has not been fully elucidated to date. We thus aim to elucidate 1) whether OPGN levels exhibit any gender dimorphism or day/night secretion pattern; and 2) whether there is any effect of acute and/or chronic energy deprivation on its circulating levels and whether such effects are mediated through leptin.. Study A: To evaluate OPGN secretion patterns and OPGN response to acute energy deprivation, we studied 12 healthy subjects under three different conditions for 72 h-in the isocaloric fed state, and during a fasting state with administration of either placebo or metreleptin in replacement doses. Blood samples were obtained every 15 min and pooled hourly during the last 24 h of the study. Study B: To evaluate the effect of chronic energy deprivation on OPGN secretion, we measured its levels in 14 obese subjects before and during weight loss after bariatric surgery.. OPGN levels exhibited a statistically significant (P < 0.01), albeit clinically limited in magnitude, day/night variation pattern in both genders (R(2) = 14.68%; 10.7-14.8% reduction with lower levels around 1600-1800 h; P < 0.01). Males had lower OPGN levels compared to females (1.81 ± 0.04 vs. 3.65 ± 0.07 pmol/liter; P < 0.001). Three days of fasting with either placebo or metreleptin administration did not change OPGN levels. OPGN levels did not change during bariatric surgery-induced weight loss.. OPGN levels are lower in men and exhibit a statistically significant, albeit clinically limited in magnitude, day/night secretion pattern. Neither acute nor chronic energy deprivation leading to significant weight loss has any effects on OPGN levels. Nomenclature Comment: Use of the terms "circadian" and "day/night variation" is meant as follows: Circadian pattern is a functional term that implies a rhythm that has been proven to be regulated by the innate circadian apparatus (anatomical and/or molecular). Conversely, day/night variation pattern is a descriptive term that refers to serum levels that vary during a day, usually in a periodic fashion. It is not known whether this variation is an innate property of the organ that secretes this hormone or whether it is determined by exogenous factors.

Topics: Adult; Bariatric Surgery; Energy Intake; Fasting; Female; Humans; Leptin; Male; Osteoprotegerin; Weight Loss; Young Adult

We showed previously that, at ambient room temperature (22°C), mice maintained at 20% below their initial body weight by calorie restriction expend energy at a rate below that which can be accounted for by the decrease of fat and fat-free mass. Food-restricted rodents may become torpid at subthermoneutral temperatures, a possible confounding factor when using mice as human models in obesity research. We examined the bioenergetic, hormonal, and behavioral responses to maintenance of a 20% body weight reduction in singly housed C57BL/6J +/+ and Lep(ob) mice housed at both 22°C and 30°C. Weight-reduced high-fat-fed diet mice (HFD-WR) showed similar quantitative reductions in energy expenditure-adjusted for body mass and composition-at both 22°C and 30°C: -1.4 kcal/24 h and -1.6 kcal/24 h below predicted, respectively, and neither group entered torpor. In contrast, weight-reduced Lep(ob) mice (OB-WR) housed at 22°C became torpid in the late lights-off period (0200-0500) but did not when housed at 30°C. These studies indicate that mice with an intact leptin axis display similar decreases in "absolute" energy expenditure in response to weight reduction at both 22°C and 30°C ambient temperature. More importantly, the "percent" decrease in total energy expenditure observed in the HFD-WR compared with AL mice is much greater at 30°C (-19%) than at 22°C (-10%). Basal energy expenditure demands are ∼45% lower in mice housed at 30°C vs. 22°C, since the mice housed at thermoneutrality do not allocate extra energy for heat production. The higher total energy expenditure of mice housed at 22°C due to these increased thermogenic demands may mask physiologically relevant changes in energy expenditure showing that ambient temperature must be carefully considered when quantifying energy metabolism in both rodents and humans.

Topics: Adaptation, Physiological; Animals; Body Composition; Body Weight; Caloric Restriction; Diet, High-Fat; Energy Intake; Energy Metabolism; Leptin; Mice; Temperature; Thermogenesis; Weight Loss

To analyze the expression of peroxisome proliferator-activated receptor-γ1 and 2 (PPARγ1 and 2), 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), and leptin in adipose tissue (AT) of obese women during weight loss following Roux-en-Y gastric bypass (RYGB) and to compare these levels with those obtained in AT of nonobese subjects.. Gene expression was determined by real-time RT-PCR prior to surgery and at 3, 6, and 12 months after RYGB.. All obese patients lost weight, reaching a mean BMI of 29.3 ± 1.0 kg/m(2) at 1 year after surgery (-33.9 ± 1.5% of their initial body weight). In obese subjects leptin and 11βHSD1 were over-expressed, whereas PPARγ1 was expressed at lower levels compared to controls. After surgery, leptin and 11βHSD1 gene expression decreased, whereas PPARγ1 expression increased. At 12 months after RYGB, these 3 genes had reached levels similar to the controls. In contrast, PPARγ2 gene expression was not different between groups and types of tissue and remained unchanged during weight loss. We found a positive correlation between BMI and levels of gene expression of leptin and 11βHSD1.. Gene expression of leptin, PPARγ1, and 11βHSD1 in AT is modified in human obesity. This default is completely corrected by RYGB.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adult; Body Mass Index; Female; Gastric Bypass; Humans; Leptin; Middle Aged; Obesity; Obesity, Morbid; PPAR gamma; Subcutaneous Fat; Transcriptome; Weight Loss

Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed tyrosine phosphatase implicated in the negative regulation of leptin and insulin receptor signaling. PTP1B(-/-) mice possess a lean metabolic phenotype attributed at least partially to improved hypothalamic leptin sensitivity. Interestingly, mice lacking both leptin and PTP1B (ob/ob:PTP1B(-/-)) have reduced body weight compared with mice lacking leptin only, suggesting that PTP1B may have important leptin-independent metabolic effects. We generated mice with PTP1B deficiency specifically in leptin receptor (LepRb)-expressing neurons (LepRb-PTP1B(-/-)) and compared them with LepRb-Cre-only wild-type (WT) controls and global PTP1B(-/-) mice. Consistent with PTP1B's role as a negative regulator of leptin signaling, our results show that LepRb-PTP1B(-/-) mice are leptin hypersensitive and have significantly reduced body weight when maintained on chow or high-fat diet (HFD) compared with WT controls. LepRb-PTP1B(-/-) mice have a significant decrease in adiposity on HFD compared with controls. Notably, the extent of attenuated body weight gain on HFD, as well as the extent of leptin hypersensitivity, is similar between LepRb-PTP1B(-/-) mice and global PTP1B(-/-) mice. Overall, these results demonstrate that PTP1B deficiency in LepRb-expressing neurons results in reduced body weight and adiposity compared with WT controls and likely underlies the improved metabolic phenotype of global and brain-specific PTP1B-deficient models. Subtle phenotypic differences between LepRb-PTP1B(-/-) and global PTP1B(-/-) mice, however, suggest that PTP1B independent of leptin signaling may also contribute to energy balance in mice.

Topics: Adiposity; Animals; Body Composition; Diet, High-Fat; Eating; Energy Metabolism; Leptin; Male; Mice; Mice, Knockout; Neurons; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Real-Time Polymerase Chain Reaction; Receptors, Leptin; Weight Loss

To assess the effects of weight loss on serum adipokine levels in polycystic ovary syndrome (PCOS).. We determined serum leptin, adiponectin, resistin, and visfatin levels in 60 overweight/obese women with PCOS and 48 BMI-matched female volunteers. Measurements were repeated after 24 weeks of treatment with orlistat 120 mg 3 times per day along with an energy-restricted diet.. At baseline, serum visfatin concentration was higher in patients with PCOS than in controls (p = 0.036); serum levels of leptin, adiponectin, and resistin did not differ between the two groups. After 24 weeks, a significant reduction in BMI and waist circumference was observed in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). Also serum leptin levels decreased in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). The reduction in serum leptin levels did not differ between groups. Serum adiponectin, resistin, and visfatin levels did not change in either group.. Leptin, adiponectin, and resistin do not appear to play major pathogenetic roles in overweight/obese patients with PCOS. In contrast, visfatin emerges as a potentially important mediator of the endocrine abnormalities of these patients. However, serum visfatin levels are not substantially affected by weight loss.

Topics: Adipokines; Adiponectin; Adult; Anti-Obesity Agents; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hyperandrogenism; Insulin Resistance; Lactones; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Orlistat; Polycystic Ovary Syndrome; Resistin; Waist Circumference; Weight Loss; Young Adult

Leptin is an adipose-derived hormone with established roles in energy balance that can impact the response to refeeding after malnutrition. Although the amount of circulating leptin has traditionally been associated with the amount of adipose tissue, controversy exists as to whether this relationship is constant in both humans and animals and over a wide range of body composition. Our objective was to evaluate whether the leptin - body fat ratio is constant in the range of healthy to low body mass in female Wistar rats. Eight ad libitum fed (C) and eight food-restricted (FR) rats were compared over a period of four weeks. FR rats attained the target 75% of baseline body mass after the first two weeks, which was maintained for the remaining two weeks. Serum leptin and IGF-1 (ELISA) and body composition (DXA) were measured at baseline (t(0)) and once weekly for the remainder of the study (t(1)-t(4)). The leptin - body fat ratio was reduced during the two-week period of weight loss (t(0) = 0.036 ± 0.016 (ng·mL(-1))·g(-1) vs. t(1) = 0.010 ± 0.004 (ng·mL(-1))·g(-1) and t(2) = 0.015 ± 0.007 (ng·mL(-1))·g(-1), p < 0.05). Leptin concentration plateaued at its nadir (~0.24 (ng·mL(-1))·g(-1)) at fat mass < 22 g. IGF-1 was correlated with lean mass (r = 0.45, p < 0.05) and fat mass (r = 0.58, p < 0.05), regardless of body mass. We concluded that the leptin - body fat ratio was reduced early in food restriction and the correlation between these two variables was absent at low body fat.

Topics: Adipose Tissue; Animals; Body Composition; Bone Density; Female; Food Deprivation; Insulin-Like Growth Factor I; Leptin; Rats, Wistar; Weight Loss

Fifteen obese ponies were used in a body weight (BW) reduction programme (BWRP, daily energy intake: 7.0-8.4 MJ/100 kg BW). A frequently sampled intravenous glucose tolerance test was used to assess insulin sensitivity. Subcutaneous adipose tissue biopsies of the tail head were obtained for mRNA gene expression profiles of adiponectin, retinol-binding protein 4 (RBP4), interleukin 6 (IL-6) and macrophage activation marker (CD68) before and after BWRP. Blood samples were analysed for serum leptin, serum RBP4 and plasma adiponectin. Significant BW losses occurred with 7 MJ DE/100 kg BW. Serum leptin and RBP4 were initially similar between insulin-resistant (IR) and insulin-sensitive (IS) ponies, and both significantly decreased during BWRP. Compared with IS ponies, IR ponies initially had significantly lower plasma adiponectin levels. At the beginning of BWRP, mRNA expression of RBP4, adiponectin, IL-6 and CD68 was similar between IR and IS ponies. Plasma adiponectin was strongly related to IR, whereas serum leptin and RBP4 were closely linked to adiposity, independent of insulin sensitivity. Adipose tissue mRNA expression profiles did not clearly reflect these differences. However, the role of subcutaneous adipose tissue in IR remains open.

Topics: Adipokines; Adiponectin; Animals; Blood Glucose; Female; Gene Expression Profiling; Horse Diseases; Horses; Insulin; Insulin Resistance; Interleukin-6; Leptin; Macrophage-Activating Factors; Male; Obesity; Retinol-Binding Proteins; RNA, Messenger; Subcutaneous Fat; Weight Loss

The long-term stability of bodyweight despite wide variation in energy intake and expenditure suggests that at usual weight energy intake and output are 'coupled' to maintain body energy stores. Our model for some of the molecular mechanics of this regulation of energy stores is based on the concept of a neurally encoded 'threshold' for minimum body fat, below which compensatory physiology is invoked to restore body fat. The existence of such a centrally encoded threshold is supported by the similarities in response to maintenance of a reduced weight between lean and obese individuals, and the tendency for weight-reduced individuals to regain weight to levels of fat stores similar to those present prior to initial weight loss. Brain responses to food and the observed changes in energy expenditure that occur during maintenance of a reduced weight are largely reversed by the administration of the adipocyte-derived hormone, leptin. .

Topics: Adipocytes; Autonomic Nervous System; Brain; Energy Intake; Energy Metabolism; Humans; Leptin; Magnetic Resonance Imaging; Muscle, Skeletal; Neurosecretory Systems; Weight Loss

Accumulation of excess body fat increases breast cancer risk after menopause. Whether the localized breast is differently influenced by adipose tissue compared to the rest of the body, has not been well studied. Our purpose was to demonstrate feasibility and preliminarily evaluate serum-based and localized breast biomarker changes resulting from a weight loss intervention among obese postmenopausal women.. We conducted a 12-week pilot controlled dietary and exercise intervention among healthy obese postmenopausal women, collected serum and breast ductal fluid before and after the intervention, and estimated the association with systemic and localized biomarker changes. We recruited 7 obese (mean body mass index = 33.6 kg/m2) postmenopausal women. We collected samples at baseline and the 12th week for: anthropometry; phlebotomy; dual-energy x-ray absorptiometry (lean and fat mass); exercise fitness (maximum oxygen consumption (VO2Max); 1-repetition strength maximum); and breast ductal lavage.. Changes from baseline occurred in body composition and exercise performance including fat mass loss (14% average drop), VO2Max (+36% increase) and strength improvement (+26%). Breast ductal fluid markers declined from baseline with estradiol showing a 24% reduction and IL-6 a 20% reduction. We also observed serum biomarker reductions from baseline including leptin (36% decline), estrone sulfate (-10%), estradiol (-25%), and Il-6 (-33%).. Conduct of the diet and exercise intervention, collection of ductal fluid, and measurement of hormones and cytokines contained in the ductal fluid were all feasible. We preliminarily demonstrated estradiol and IL-6 reductions from baseline in both serum and breast ductal fluid among obese postmenopausal women who participated in the 12-week weight loss diet and exercise intervention.

Topics: Absorptiometry, Photon; Biomarkers; Body Composition; Body Mass Index; Diet; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Estradiol; Estrogens; Estrone; Exercise; Fatty Acids; Feasibility Studies; Female; Fruit; Humans; Interleukin-6; Leptin; Middle Aged; Obesity; Oxygen Consumption; Phlebotomy; Pilot Projects; Postmenopause; Vegetables; Weight Loss

Clusterin, a protein constituent of HDL, was recently shown to bind plasma leptin in vitro and has been proposed to modulate leptin activity. To gain insight into a possible role for plasma clusterin in human obesity, we measured plasma clusterin, leptin, soluble leptin receptor (sObR), and lipoproteins in 70 obese adolescents (12.4 ± 1.6 y; BMI-SD score (SDS-BMI) 2.35 ± 0.47) before and after 3 wk of weight reduction in a dietary camp and in 44 normal weight controls. Binding of plasma leptin to HDL or clusterin was studied using ultracentrifugation and immunoaffinity chromatography. During weight reduction, clusterin decreased from 14.6 ± 4.1 to 10.3 ± 2.9 mg/dL, p < 0.001) in obese adolescents, whereas sObR increased. However, baseline plasma clusterin in obese adolescents did not differ from controls. Clusterin did not correlate with SDS-BMI, weight loss, leptin, or lipoproteins. Only ∼ 1% of plasma leptin was associated with clusterin/apoA-I complexes or with HDL. Our results do not support a role for plasma clusterin as an important leptin-binding protein or modulator of leptin action. The decrease of plasma clusterin during weight reduction may be an effect of the hypocaloric diet rather than being directly linked to weight loss.

Topics: Adolescent; Animals; Child; Clusterin; Diet; Humans; Leptin; Lipoproteins, HDL; Obesity; Receptors, Leptin; Weight Loss

To investigate whether or not reduction of thyroid volume during weight loss is related to adipocytokines and urinary iodine excretion in obese women.. 98 obese and 31 non-obese women consecutively admitted to the endocrinology and metabolism outpatient clinic of the School of Medicine, Akdeniz University were included in the study. Thyroid volume, thyroid function tests, leptin and adiponectin levels, and urinary iodine excretion were measured at baseline and six months after treatment for obesity.. Thyroid volume increased in obese women (p = 0.048). After adjustment for body mass index, there were no significant differences in plasma leptin and serum adiponectin levels between obese and non-obese women (p > 0.05). Thyroid volume correlated positively with body mass index (r = 0.48, p = 0.04), leptin (r = 0.1, p = 0.03), and thyroid-stimulating hormone (r = 0.43, p = 0.001) levels, while there was a negative correlation between thyroid volume and urinary iodine (r = -0.38, p = 0.04) and urinary iodine/creatinine ratio (r = -0.25, p = 0.045) in obese women. Changes in body mass index (p = 0.022) and leptin levels (p = 0.039) were the only factors that significantly affected the change of thyroid volume during weight loss.. Iodine status may play an important role in increased thyroid volume in obese women; however, iodine status did not seem to exert a significant influence on the changes in thyroid volume. On the other hand, changes in both body mass index and plasma leptin levels seemed to be important for changes in thyroid volume.

Topics: Adiponectin; Adult; Analysis of Variance; Body Mass Index; Female; Humans; Iodine; Leptin; Middle Aged; Obesity; Outpatient Clinics, Hospital; Thyroid Function Tests; Thyroid Gland; Turkey; Ultrasonography; Weight Loss; Young Adult

Type 2 diabetes (T2D) resolves rapidly after bariatric surgery, even before substantial weight is lost. However, the molecular pathways underlying this phenomenon remain unclear. Microarray data has shown that numerous genes are differentially expressed in blood after bariatric surgery, including resistin and leptin. Resistin and leptin are circulating hormones derived from adipose tissue, which are associated with obesity and insulin resistance. This study examined expression of these genes before and after bariatric surgery in diabetic and nondiabetic obese patients.. The study included 16 obese patients who underwent bariatric surgery, either Roux-en-Y gastric bypass (RYGB) or adjustable gastric banding. Eight patients had T2D. Preoperative blood samples were collected in PAXgene tubes to stabilize mRNA. Postoperative samples were collected 3 months after surgery. Total RNA was isolated and cDNA was synthesized. Real-time quantitative PCR was used to quantify mRNA. Results were analyzed using Student's t test with a P<0.05 considered significant.. Postoperatively, five diabetic patients had discontinued hypoglycemic medications and one showed improved glycemic control. Both leptin and resistin mRNA levels were elevated in the diabetic group but decreased after surgery to levels near those of the nondiabetic group. Greater downregulation of resistin and leptin expression occurred in patients who lost more excess body weight (EBW), while patients who lost less than 10% EBW had a mean increase in expression of the two genes. Downregulation of both genes was more pronounced after RYGB compared to gastric banding.. Downregulation of resistin and leptin gene expression after bariatric surgery may play a role in normalizing obesity-associated insulin resistance. Interestingly, downregulation is greater after RYGB and in patients who lose a greater proportion of EBW. Targeted therapies for obesity and diabetes may be developed by understanding the pathways by which these adipocytokines contribute to obesity and T2D.

Topics: Diabetes Mellitus, Type 2; Down-Regulation; Gene Expression Regulation; Humans; Insulin Resistance; Leptin; Microarray Analysis; Obesity, Morbid; Polymerase Chain Reaction; Postoperative Period; Resistin; Weight Loss

AT(1)-blockade has been shown to induce weight loss in animals or patients. The aim of this study was to investigate whether weight reduction after AT(1)-blockade is dependent on dose, blood pressure reduction and leptin signalling. Spontaneously hypertensive rats (SHR) and lean and obese Zucker rats were treated for 4 weeks with candesartan (0, 2, 6 or 16 mg/kg/day). Body weight, food intake and hypothalamic mRNA levels of (an)orexigenic peptides were determined. Obese Zucker rats served as a model of primary leptin resistance. In SHR, body mass index and food intake were decreased selectively by 16 mg/kg/day candesartan but not after using normal (2 mg/kg/day) or supranormal (6 mg/kg/day) doses. Correlation analysis between blood pressure and body weight indicated no relationship of hypotensive potency on weight loss. The hypothalamic mRNA levels of the orexigenic peptide MCH (melanin-concentrating hormone) were diminished in parallel. Consistent to the results in SHRs, 16 mg/kg/day candesartan revealed a decrease of body weight, food intake and hypothalamic MCH mRNA levels in lean Zucker rats. In obese Zucker rats, none of these parameters were reduced by candesartan. Loss of body weight and hypophagia are not general features of AT(1)-blockers, since neither was seen after normal or moderately supranormal doses, but they were, after the highest doses. These actions of AT(1)-blockers occur independently of their ability to lower blood pressure. They do depend on an intact leptin signalling, since they were absent in obese Zucker rats that feature a genetic mutation of the leptin receptor.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Dose-Response Relationship, Drug; Eating; Hypothalamus; Leptin; Male; Obesity; Rats; Rats, Inbred SHR; Rats, Zucker; Receptors, Leptin; RNA, Messenger; Signal Transduction; Tetrazoles; Weight Loss

It is unclear whether high plasma leptin in obese individuals represents leptin resistance or whether individuals with marked reductions in leptin concentrations in response to weight loss may be at greater risk of regaining weight. Moreover, whether changes in leptin predict metabolic improvements during weight loss is uncertain.. The objective was to prospectively examine associations between plasma leptin, body fat, and weight and metabolic risk factors in obese children during weight loss.. In obese children and adolescents [n = 203; mean age: 14.1 y, >98th body mass index (BMI) percentile for age and sex] participating in a 2-mo inpatient weight-loss program, we measured changes in body composition (by dual-energy X-ray absorptiometry), plasma leptin, insulin, and lipids. After discharge, anthropometric measures and plasma leptin were remeasured at 6 (n = 139) and 12 (n = 100) mo.. During the 2-mo program, mean (±SD) weight and fat loss were 13.9 ± 4.0 kg and 9.2 ± 2.5 kg, respectively; and mean plasma leptin decreased by 76%. Weight and fat loss were sustained, and no significant differences in BMI-SD score (SDS) or body composition were found between 12 and 2 mo. Baseline leptin was a negative predictor for percentage fat loss at 2, 6, and 12 mo (P < 0.05). The percentage change in leptin during the 2-mo intervention positively correlated with the relative change in fasting insulin, the relative change in LDL cholesterol at 2 mo, percentage fat loss, and change in BMI-SDS at 2 and 6 mo (P < 0.02).. Even in obese children with strongly elevated baseline leptin, large leptin reductions that predict short- and long-term loss of body fat and improvements in lipids and insulin sensitivity can be achieved. Thus, increased plasma leptin in obese children may not necessarily reflect leptin resistance; many children appear to remain leptin sensitive at this age.

Topics: Absorptiometry, Photon; Adipose Tissue; Adolescent; Behavior Therapy; Biomarkers; Body Composition; Body Mass Index; Child; Cholesterol, LDL; Diet, Reducing; Energy Intake; Exercise; Female; Humans; Insulin; Leptin; Male; Obesity; Prospective Studies; Risk Factors; Weight Loss

Bariatric surgery causes durable weight loss. Gut hormones are implicated in obesity pathogenesis, dietary failure, and mediating gastrointestinal bypass (GIBP) surgery weight loss. In mice, we determined the effects of diet-induced obesity (DIO), subsequent dieting, and GIBP surgery on ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). To evaluate PYY's role in mediating weight loss post-GIBP, we undertook GIBP surgery in PyyKO mice.. Male C57BL/6 mice randomized to a high-fat diet or control diet were killed at 4-week intervals. DIO mice underwent switch to ad libitum low-fat diet (DIO-switch) or caloric restriction (CR) for 4 weeks before being killed. PyyKO mice and their DIO wild-type (WT) littermates underwent GIBP or sham surgery and were culled 10 days postoperatively. Fasting acyl-ghrelin, total PYY, active GLP-1 concentrations, stomach ghrelin expression, and colonic Pyy and glucagon expression were determined. Fasting and postprandial PYY and GLP-1 concentrations were assessed 30 days postsurgery in GIBP and sham pair-fed (sham.PF) groups.. DIO progressively reduced circulating fasting acyl-ghrelin, PYY, and GLP-1 levels. CR and DIO-switch caused weight loss but failed to restore circulating PYY to weight-appropriate levels. After GIBP, WT mice lost weight and exhibited increased circulating fasting PYY and colonic Pyy and glucagon expression. In contrast, the acute effects of GIBP on body weight were lost in PyyKO mice. Fasting PYY and postprandial PYY and GLP-1 levels were increased in GIBP mice compared with sham.PF mice.. PYY plays a key role in mediating the early weight loss observed post-GIBP, whereas relative PYY deficiency during dieting may compromise weight-loss attempts.

Topics: Analysis of Variance; Animals; Colon; Diet, Fat-Restricted; Diet, Reducing; Enzyme-Linked Immunosorbent Assay; Gastric Bypass; Gastric Mucosa; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Leptin; Male; Mice; Obesity; Peptide YY; Radioimmunoassay; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; Weight Loss

Suppressor of cytokine signaling-3 (SOCS3) is thought to be involved in the development of central leptin resistance and obesity by inhibiting STAT3 pathway. Because phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in transducing leptin action in the hypothalamus, we examined whether SOCS3 exerted an inhibition on this pathway. We first determined whether leptin sensitivity in the hypothalamic PI3K pathway was increased in brain-specific Socs3-deficient (NesKO) mice. In NesKO mice, hypothalamic insulin receptor substrate-1 (IRS1)-associated PI3K activity was significantly increased at 30 min and remained elevated up to 2 h after leptin intraperitoneal injection, but in wild-type (WT) littermates, the significant increase was only at 30 min. Hypothalamic p-STAT3 levels were increased up to 5 h in NesKO as opposed to 2 h in WT mice. In food-restricted WT mice with reduced body weight, leptin increased hypothalamic PI3K activity only at 30 min, and p-STAT3 levels at 30-120 min postinjection. These results suggest increased leptin sensitivity in both PI3K and STAT3 pathways in the hypothalamus of NesKO mice, which was not due to a lean phenotype. In the next experiment with a clonal hypothalamic neuronal cell line expressing proopiomelanocortin, we observed that whereas leptin significantly increased IRS1-associated PI3K activity and p-JAK2 levels in cells transfected with control vector, it failed to do so in SOCS3-overexpressed cells. Altogether, these results imply a SOCS3 inhibition of the PI3K pathway of leptin signaling in the hypothalamus, which may be one of the mechanisms behind the development of central leptin resistance and obesity.

Topics: Adiposity; Animals; Caloric Restriction; Cell Line; Eating; Genotype; Hypothalamus; Insulin Receptor Substrate Proteins; Janus Kinase 2; Leptin; Mice; Mice, 129 Strain; Mice, Knockout; Neurons; Obesity; Phenotype; Phosphatidylinositol 3-Kinase; Phosphorylation; Pro-Opiomelanocortin; Signal Transduction; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Time Factors; Transfection; Weight Loss

Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be involved in pathways regulating appetite in these structures was therefore assessed in this study. Given that pain, pro-inflammatory cytokines and metabolic hormones can modify food intake, spinal cord cellular activation patterns and plasma concentrations of cytokines and hormones were also studied. Morris hepatoma 7777 cells injected subcutaneously in Buffalo rats provoked a 10% lower body weight and 15% reduction in food intake compared to free-feeding tumor-free animals 4 weeks later when the tumor represented 1-2% of body mass. No differences in spinal cord activation patterns or plasma concentration of pro-inflammatory cytokines were observed between groups. However, the changes in plasma ghrelin and leptin concentrations found in food-restricted weight-matched rats in comparison to ad libitum-fed animals did not occur in anorectic tumor-bearing animals. Real-time PCR showed that tumor-bearing rats did not display the increase in hypothalamic agouti-related peptide mRNA observed in food-restricted weight-matched animals. In addition, microarray analysis and real-time PCR revealed increased ventral striatal prostaglandin D synthase expression in food-restricted animals compared to anorectic tumor-bearing rats. These findings indicate that blunted hypothalamic AgRP mRNA expression, probably as a consequence of relatively high leptin and low ghrelin concentrations, and reduced ventral striatal prostaglandin D synthesis play a role in maintaining cancer-associated anorexia.

Topics: Adaptation, Physiological; Agouti-Related Protein; Analysis of Variance; Animals; Appetite Regulation; Basal Ganglia; Body Weight; Cachexia; Carcinoma, Hepatocellular; Cytokines; Disease Models, Animal; Eating; Gene Expression Regulation; Ghrelin; Hypothalamus; Immunohistochemistry; Intramolecular Oxidoreductases; Leptin; Lipocalins; Liver Neoplasms; Male; Matched-Pair Analysis; Neoplasms, Experimental; Pain Perception; Rats; Rats, Inbred BUF; RNA, Messenger; Spinal Cord; Weight Loss

Sibutramine is an anti-obesity agent that induces weight loss by selective inhibition of neuronal reuptake of serotonin and norepinephrine; however, it is associated with the risk of cardiovascular diseases (CVD), including heart attack and stroke. Here, we analyzed global protein expression patterns in plasma of control and sibutramine-treated rats using proteomic analysis for a better understanding of the two conflicting functions of this drug, appetite regulation, and cardiovascular risk. The control (n=6) and sibutramine-treated groups (n=6) were injected by vehicle and sibutramine, respectively, and 2-DE combined with MALDI-TOF/MS were performed. Compared to control rats, sibutramine-administered rats gained approximately 18% less body weight and consumed about 13% less food. Plasma leptin and insulin levels also showed a significant decrease in sibutramine-treated rats. As a result of proteomic analysis, 23 differentially regulated proteins were discovered and were reconfirmed by immunoblot analysis. Changed proteins were classified into appetite regulation and cardiovascular risk, according to their regulation pattern. Because the differential levels of proteins that have been well recognized as predictors of CVD risk were not well matched with the results of our proteomic analysis, this study does not conclusively prove that sibutramine has an effect on CVD risk.

Topics: Adipose Tissue; Animals; Appetite Depressants; Appetite Regulation; Blood Proteins; Body Weight; Cardiovascular Diseases; Chromatography, Liquid; Cyclobutanes; Electrophoresis, Gel, Two-Dimensional; Insulin; Leptin; Male; Obesity; Proteome; Rats; Rats, Sprague-Dawley; Risk Factors; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Weight Loss

We hypothesized that a combination of low doses of rimonabant and leptin would markedly reduce body weight through the modulation of neuronal activity within the hypothalamus. To this end, high fat diet-induced obese rats were randomized to receive either leptin (0.5mg/kg subcutaneously), rimonabant (3mg/kg), the combination of both, or vehicle, daily for a duration of 2 weeks. A subset of rats was pair-fed to the combination-treated animals and received either vehicle or leptin. At the end of the weight loss phase, leptin treatment was maintained for 7 days while rimonabant was discontinued to assess changes in body weight during the rebound phase. The combination of rimonabant and leptin resulted in a marked inhibition of food intake and a profound reduction in body weight that was greater than achieved with either leptin or rimonabant alone. Treatment with leptin during the rebound phase inhibited compensatory increases in body weight associated with restitution of ad libitum feeding in previously pair-fed rats. Moreover, leptin partially blunted the rebound in food intake and body weight associated with cessation of rimonabant therapy.To investigate the effect of the combination on neuronal firing in the rat hypothalamus, single unit activity was recorded from brain slices containing the ventromedial and arcuate nuclei. The combination of rimonabant and leptin synergistically increased and decreased neuronal firing in the ventromedial and arcuate nuclei, respectively. Overall, these data demonstrate profound anti-obesity effects of combining cannabinoid type 1 receptor antagonists and leptin.

Topics: Animals; Anti-Obesity Agents; Dose-Response Relationship, Drug; Drug Synergism; Leptin; Male; Piperidines; Pyrazoles; Rats; Rats, Sprague-Dawley; Recurrence; Rimonabant; Ventromedial Hypothalamic Nucleus; Weight Loss

Roux-en-Y gastric bypass (RYGB) imparts long-term weight loss, the mechanisms for which are not well understood. Changes in leptin and gastrointestinal (GI) hormones, including glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin, may contribute to the relative success of RYGB compared with conventional weight loss methods. This study evaluated changes in GI hormones and leptin post-RYGB. The study also evaluated whether GI hormones differed after a short-term dose of protein or fat.. GLP-1, PYY, ghrelin, and leptin were assessed in 16 women before RYGB and up to 1 year after RYGB. Plasma was collected before and at several times after a short-term equicaloric dose of protein or fat.. GLP-1 area under the curve (AUC) increased at week 6 and 1 year in the fat beverage (FAT-BEV) group compared with baseline. PYY AUC remained elevated at 1 year in the FAT-BEV group. Ghrelin AUC decreased at week 2, week 6, and 1 year in the protein beverage (PRO-BEV) group compared with baseline. Ghrelin AUC was lower in the PRO-BEV group compared with the FAT-BEV group at week 6. Fasted leptin decreased at all visits in both groups and was lower in the FAT-BEV group compared with the PRO-BEV group at 1 year.. Changes from baseline were evident for all GI hormones and leptin; some differences were evident soon after surgery (ghrelin, leptin), whereas others were maintained long term (GLP-1, PYY, ghrelin, leptin). In response to a short-term stimulus, protein suppressed ghrelin and fat potently stimulated GLP-1 and PYY. Future work in this area is warranted.

Topics: Adult; Area Under Curve; Dietary Fats; Dietary Proteins; Female; Gastric Bypass; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Middle Aged; Obesity, Morbid; Peptide YY; Postoperative Period; Weight Loss

Weight loss and maintenance can be particularly challenging for postmenopausal women given the changes in body composition, metabolism, and lifestyle that can accompany the menopausal transition. Peptides mediating energy homeostasis (ghrelin, leptin, adiponectin, and insulin) may play an important role in the weight and body composition changes of postmenopausal women and may in turn be affected by hormone therapy (HT) use. This study examines how success with weight loss may be related to peptides mediating energy homeostasis and HT use.. The present analysis involves 200 women from a lifestyle intervention trial in overweight, postmenopausal women for whom data on the peptides ghrelin, leptin, adiponectin, and insulin were collected at 0 and 18 months. Peptide levels were compared with changes in weight from 0 to 18 and from 18 to 30 months.. Baseline peptide levels were not significantly related to future weight change. From 0 to 18 months, ghrelin (P = 0.0005) and adiponectin (P ≤ 0.0001) levels increased, whereas leptin (P ≤ 0.0001) and insulin (P = 0.0003) levels decreased with increasing amount of weight loss. However, only leptin change was related to 18-30-month weight change. Women who were on HT at 0 months but discontinued by 18 months had a greater increase in ghrelin level from 0 to 18 months compared with women with continuous HT use or nonuse.. In overweight, postmenopausal women, changes in energy homeostasis peptides relate to both concurrent and future weight change. Future studies should continue to address how ghrelin, leptin, insulin, and adiponectin contribute to body composition changes and weight loss maintenance after menopause.

Topics: Adiponectin; Body Composition; Body Fat Distribution; Energy Metabolism; Estrogen Replacement Therapy; Female; Ghrelin; Homeostasis; Humans; Insulin; Leptin; Middle Aged; Overweight; Postmenopause; Weight Gain; Weight Loss

The cloning of the ob gene and its gene product, leptin, has led to the elucidation of a robust physiologic system that maintains fat stores at a relatively constant level. Leptin is a peptide hormone secreted by adipose tissue in proportion to its mass. Recessive mutations in the leptin gene are associated with massive obesity in mice and humans, establishing a genetic basis for obesity. Leptin circulates in blood and acts on the brain to regulate food intake and energy expenditure. When fat mass falls, plasma leptin levels fall, stimulating appetite and suppressing energy expenditure until fat mass is restored. When fat mass increases, leptin levels increase, suppressing appetite until weight is lost. This system maintains homeostatic control of adipose tissue mass. The discovery of leptin has advanced our understanding of metabolic disease in a number of respects. Its identification has revealed a new endocrine system regulating body weight. This system provides a means by which changes in nutritional state regulate other physiologic systems. A number of leptin deficiency syndromes that are treatable with leptin replacement have been identified. The majority of obese subjects are leptin resistant, which establishes that obesity is the result of hormone resistance. Leptin treatment results in weight loss in a subset of obese patients and can also synergize with other anti-obesity agents to reduce weight in the general population. Leptin provides an entry point for studying a complex human behavior. Finally, this research has established that there is a powerful biological basis for obesity, a fact that is (correctly) changing public perception about the pathogenesis of this medical condition.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Appetite; Body Weight; Energy Metabolism; Feeding Behavior; Female; Homeostasis; Hormone Replacement Therapy; Humans; Leptin; Mice; Mutation; Nutritional Status; Obesity; Rats; Signal Transduction; Weight Loss

Different studies, mostly cross-sectional, have found an association between low levels of thyroid hormones, even within the normal range, and a greater body mass index. The aim of this study was to determine the association between thyroid function and the risk for obesity.. In this population-based prospective study, measurements were made of anthropometric parameters, thyroid hormone function and urinary iodine in a cohort of the Pizarra Study (n = 937), and repeated 6 years later (n = 784). At the second point, measurements were also made of leptin and adiponectin.. Among the persons who were not obese at the start of the study, the odds ratio (OR) of becoming obese for those in the fourth quartile (Q(4)) for free triiodothyronine (FT3) (versus those in Q(1)) was 2·94 (1·46-5·90) (P = 0·005). The OR of becoming obese in persons in Q(4) of FT4 (versus those in Q(1)) was 3·06 (1·23-7·43) (P = 0·01). Those persons in Q(4) of weight gain had a higher FT3 at the 6-year follow-up than those whose weight gain was in Q(1) (P < 0·001). Leptin correlated with thyrotropin (β = 0·58, P = 0·001) and the FT4 (β = -1·12, P = 0·005). Adiponectin correlated with FT3 (r = -0·24, P < 0·001). The urinary iodine correlated negatively with both the BMI (β = -0·08, P = 0·01) and the increase in weight (β = -0·08, P = 0·04).. The changes in the thyroid hormones could be the consequence, rather than the cause, of the increase in weight. The same pathophysiological mechanisms that induce obesity might also be modifying the thyroid hormone pattern.

Topics: Adiponectin; Adult; Body Weight; Cohort Studies; Female; Follow-Up Studies; Humans; Insulin Resistance; Iodine; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Thyroid Hormones; Thyrotropin; Triiodothyronine; Weight Gain; Weight Loss

The association of visfatin, an adipocytokine relevant to the development of inflammation and metabolic disorders, with juvenile obesity needs to be re-established as previously used tests occurred to be nonspecific.. To evaluate visfatin association with a metabolic profile of 88 overweight/obese and 26 lean children/adolescents as well as changes in its levels following weight reduction programme (diet + enhanced physical activity ± metformin).. A case-control and cohort study.. Visfatin was higher in obese than lean and overweight individuals (2·07 vs. 1·53 and 1·47 ng mL(-1) , P = 0·034). Of metabolic syndrome components, central obesity combined with either insulin resistance (IR) or hyperinsulinemia (HI) was associated with increases in circulating visfatin. In girls, visfatin correlated with leptin (r = 0·40, P = 0·009) and thiols (r = -0·36, P = 0·009), which explained 24% in visfatin variability. In boys, visfatin correlated with waist circumference (r = 0·36, P = 0·036), BMI% (r = 0·38, P = 0·025), whole body insulin sensitivity index (r = -0·36, P = 0·036), IL-6 (r = 0·38, P = 0·024) and thiobarbituric acid reactive substances (TBARS) (r = 0·52, P = 0·001), of which IL-6 and TBARS were independent predictors of visfatin elevation, explaining 42% in data variability. Visfatin was significantly lower following weight reduction programme than at baseline (1·43 vs. 1·83 ng mL(-1) , P = 0·033). Visfatin reduction correlated neither with changes in metabolic parameters nor was it affected by metformin. ΔVisfatin correlated exclusively with baseline visfatin (r = 0·612, P < 0·0001), which explained 38% in data variability.. Central obesity combined with HI/IR contributes to visfatin elevation. Visfatin association with metabolic/biochemical variables is gender dependent. Diet + enhanced physical activity are effective in visfatin reduction, the degree of which depends on baseline visfatin.

Topics: Adipokines; Adolescent; Age Factors; Body Mass Index; Case-Control Studies; Cohort Studies; Cytokines; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Obesity; Sex Factors; Statistics as Topic; Weight Loss

The efficacy of exercise as primary prevention of obesity is the subject of intense investigation. Here, we show that voluntary exercise in a mouse strain susceptible to diet-induced obesity (C57B6J) decreases fat mass and increases energy expenditure. In addition, exercise attenuates obesity in mice fed a high-fat diet (HFD). Using FosB immunoreactivity as a marker of chronic neuronal activation, we found that exercise activates leptin receptor-positive neurons in the ventromedial hypothalamic nucleus, involved in homeostatic control of energy balance. FosB immunoreactivity in the ventromedial hypothalamic nucleus is decreased in sedentary mice exposed to HFD but is increased in exercised mice independent of adiposity. To determine whether the antiobesity effects of voluntary exercise improve central nervous system (CNS) leptin action, we measured the anorectic and weight reducing effects of intracerebroventricular (ICV) leptin in sedentary and exercised mice exposed to HFD (EH), as well as in sedentary mice that have been calorie restricted (SR) to match the fat mass of EH mice. ICV leptin was ineffective in lowering food intake and body weight (BW) in sedentary mice exposed to HFD mice. The anorectic potency of leptin was partially restored in EH and SR groups. However, ICV leptin significantly lowered BW in EH but not SR mice. Thus, exercise leads to the maintenance of a lower BW and leaner composition, as well as to improved CNS leptin action, independent of fat mass. These results support the notion that physical exercise directly influences the responsiveness of the CNS circuits involved in energy homeostasis by allowing the defense of a lowered BW.

Topics: Adiposity; Animals; Appetite Regulation; Caloric Restriction; Dietary Fats; Energy Metabolism; Genes, Reporter; Injections, Intraventricular; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Activity; Nerve Tissue Proteins; Neurons; Obesity; Proto-Oncogene Proteins c-fos; Random Allocation; Receptors, Leptin; Ventromedial Hypothalamic Nucleus; Weight Loss

To investigate the effect of hydroxypropyl methylcellulose (HPMC) on weight loss and metabolic disorders associated with obesity using a high-fat diet-induced obese mouse model under a high-fat diet regimen..  Obese male C57BL/6J (B6) mice were fed either a high-fat (60% kcal), low-fat (10% kcal), or high-fat diet plus HPMC (4% and 8%) for 5 weeks. Body, mesenteric adipose, and liver weights were determined at the end of the study. In addition, plasma cholesterol, insulin, glucose, adiponectin, and leptin were analyzed to determine the effects of HPMC. Hepatic and fecal lipids were measured to determine the effect of HPMC on lipid absorption and metabolism.. Supplementation of the high-fat diet with 4% and 8% HPMC resulted in significant weight loss in obese B6 mice. Furthermore, significant decreases were seen in adipose (30%-40%), liver weights (15%-26%), and concentrations of plasma cholesterol (13%-20%) and hepatic lipids (13%-36%). Supplementation with 8% HPMC led to significant improvements in glucose homeostasis and leptin concentrations. Reductions in plasma cholesterol, glucose, and insulin levels were strongly correlated with reduced leptin concentrations. Moreover, increases in fecal secretion of total bile acids, sterols, and fats indicated altered fat absorption when HPMC was incorporated in the diet.. The data indicate that HPMC not only reduces body weight, but also normalizes the metabolic abnormalities associated with obesity and suggest that the effects of HPMC on glucose and lipid homeostasis in B6 mice are mediated by improvements in leptin sensitivity resulting from reduced fat absorption.

Topics: Adiponectin; Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Dietary Fats; Hypromellose Derivatives; Insulin; Leptin; Liver; Male; Methylcellulose; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Random Allocation; Regression Analysis; Weight Loss

Sleeve gastrectomy (SG) is a gaining ground operation amongst the ones applied for treatment of morbid obesity. Though SG is a food limiting operation, the removal of the gastric fundus where ghrelin is mainly produced may indicate a hormonal impact of the procedure. The purpose of this experiment is to study how SG affects the levels of ghrelin and leptin.. Twenty-four male, adult, diet induced obese Wistar rats were divided randomly into groups, one submitted to SG and the other to a sham operation. Fasting blood samples were taken before the operation and 14 weeks after the operation (leptin and acylated and des-acyl ghrelin levels were measured). Tissue samples from the gastric fundus were taken during the operation and at the end of the experiment, and ghrelin expression was measured with RT-PCR.. Statistically significant weight loss was achieved comparing the weight progress of the SG group and the sham operation group. Serum leptin levels were significantly reduced in the SG group (p < 0.05) but not in the sham operation group. Serum acylated ghrelin was not significantly affected in both groups, but a significant decrease was documented in serum des-acyl ghrelin in the SG group (p < 0.05). RT-PCR analysis of the gastric fundus documented a significant decrease (p < 0.0001) in the expression of ghrelin in the SG group.. SG may lead in significant long-term weight loss. SG affects the serum levels of leptin and des-acyl ghrelin but not the levels of acylated ghrelin in this animal model.

Topics: Animals; Gastrectomy; Gastric Fundus; Ghrelin; Leptin; Male; Obesity, Morbid; Random Allocation; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Weight Loss

Currently, there is renewed interest in plant-based medicines and functional foods for the prevention and cure of obesity and its associated risk of cardiovascular disease and metabolic syndrome. In the search for potential anti-obesity compounds from natural sources, the effects of ursolic acid (UA), a pentacyclic triterpenoid widely found in medicinal herbs and fruits, was evaluated for its effects on blood glucose, lipids, and abdominal fat deposition in mice fed a high-fat diet (HFD). Adult male Swiss mice treated or not with UA (0.05%, 50 mg/L, in drinking water) were fed HFD for 15 weeks. A sibutramine (SIB)-treated group (0.05% in drinking water) was included as the positive control. Weekly body weights and food and water consumption were measured, and at the end of the study period, the levels of blood glucose and lipids, the plasma hormones insulin, ghrelin, and leptin, and the abdominal fat accumulation were analyzed. Mice treated with UA and fed HFD showed significantly (P<.05) decreased body weights, visceral adiposity, and levels of blood glucose and plasma lipids relative to their respective controls not fed UA. Also, a significant increase was observed in plasma leptin with a decrease in ghrelin, as well as of amylase and lipase activities. The SIB-treated group also manifested effects similar to those of UA except for the blood glucose level, which was not different from the HFD control. These findings suggest that UA ameliorates abdominal adiposity and decreases the levels of blood glucose and plasma lipids in mice and thus manifests an anti-obesity potential through absorptive and metabolic targets.

Topics: Abdominal Fat; Adiposity; Animals; Anti-Obesity Agents; Blood Glucose; Diet, High-Fat; Fruit; Ghrelin; Herbal Medicine; Insulin; Leptin; Lipids; Male; Mice; Obesity; Pentacyclic Triterpenes; Plant Extracts; Sambucus; Triterpenes; Ursolic Acid; Weight Loss

Leptin has emerged over the past decade as a key hormone not only in energy balance regulation but also in neuroendocrine and inflammatory processes. The aim of the present study was to evaluate whether hyperleptinemia deregulates neuropeptides during weight loss. A total of 86 post-pubertal obese adolescents (with or without hyperleptinemia) participated in one year of interdisciplinary weight loss therapy (clinical, nutritional, psychological and exercise-related). Adipokine and neuropeptide concentrations were measured by ELISA, visceral fat was measured by ultrasound and body composition was measured by pletismography. The hyperleptinemic patients presented a lower alpha-MSH concentration and higher NPY/AgRP ratio while the adiponectin/leptin (A/L) ratio was lower compared with the non-hyperleptinemic group. After therapy, significant improvements in BM, BMI, body fat mass, visceral and subcutaneous fat, HOMA-IR, QUICKI, total cholesterol and triglycerides were observed in both groups. Indeed, we observed significant increases in adiponectin and A/L as well as reductions in leptin and NPY/AgRP ratio in the hyperleptinemic group. In the stepwise multiple linear regression analysis with leptin concentration as the dependent variable, α-MSH and body fat mass (%) were the independent predictors to explain leptin concentration. For the entire group, we found positive correlations between leptinemia and BMI and body fat mass (%) as well as a negative correlation with free fat mass (%) and alpha-MSH. Finally, we verified negative correlations between adiponectin/leptin ratio with total cholesterol and LDL-c, only in hyperleptinemic patients. In conclusion, the hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss.

Topics: Adiponectin; Adolescent; alpha-MSH; Body Composition; Body Fat Distribution; Cholesterol; Diet, Reducing; Down-Regulation; Exercise Therapy; Female; Humans; Intra-Abdominal Fat; Leptin; Male; Neuropeptides; Obesity; Plethysmography; Triglycerides; Ultrasonography; Up-Regulation; Weight Loss; Young Adult

The aim of the present study was to evaluate the effects of surgically induced weight loss on the metabolic profile and adipocytokine levels in premenopausal morbidly obese females.. Twenty premenopausal morbidly obese (MO) women with a median age of 34 years (range: 24-48 years) and a median body mass index (BMI) of 41.47 kg/m(2) (range: 38.0-56.73 kg/m(2)) were studied (13 women underwent gastric banding and 7 women underwent sleeve gastrectomy). In addition, 20 lean premenopausal women with a median age of 32 years (range: 22-44 years) and a median BMI of 20.0 kg/m(2) (range: 18.5-24.7 kg/m(2)) were also studied. Anthropometric measurements and metabolic parameters were analyzed in each patient, along with changes in leptin, adiponectin, resistin, and interleukin-6 (IL-6) before surgery, 6 months after surgery, and 12 months after surgery. Comparisons with the reference normal-weight subjects were also performed.. Both weight and BMI were found to be significantly decreased postoperatively. A 54.5% loss of excess BMI was observed 12 months after surgery, and was associated with significant improvement in all anthropometric and metabolic parameters. Twelve months after surgery we also observed decreased levels of serum leptin, resistin, and IL-6; increased levels of serum adiponectin; and a remarkable improvement in metabolic syndrome markers. Furthermore, postoperative serum resistin and IL-6 levels were found to reach those of normal-weight volunteers.. The results of this study suggest that weight loss through restrictive bariatric surgery results in a significant reduction in leptin, resistin, and IL-6 levels, and an increase in adiponectin levels, in addition to improving insulin sensitivity and glucose and lipid homeostasis in young morbidly obese female patients. These changes were significantly correlated with the magnitude of weight loss.

Topics: Adipokines; Adult; Anthropometry; Bariatric Surgery; Biomarkers; Blood Glucose; Body Mass Index; Case-Control Studies; Female; Follow-Up Studies; Gastroplasty; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Metabolome; Middle Aged; Obesity, Morbid; Premenopause; Resistin; Treatment Outcome; Waist-Hip Ratio; Weight Loss; Young Adult

Wasting is a systemic manifestation of tuberculosis (TB) and is often thought to affect the severity and outcome of the disease. Leptin and several cytokines/proteins are thought to play a role in the relationship between TB, nutritional status and host immune response. The aim of this study was to determine the association of C-reactive protein (CRP), an inflammatory response protein and serum leptin levels with wasting in childhood TB.. A cross-sectional observational analytic study was conducted at two hospitals in West Java from January to March 2010. The subjects were 13 children aged 2-120 months who were infected with TB and 26 healthy children of the same age and gender as the comparison group. History-taking and anthropometric, physical, serum CRP and leptin examinations were conducted for each subject. The association of CRP and serum leptin levels with wasting in childhood TB was studied.. Serum leptin levels were lower (95 percent confidence interval [CI] 314.0-1,228.9 pg/mL, p-value less than 0.001) and serum CRP levels were higher (95 percent CI 16.5-81.1 mg/L) in the subjects than in the comparison group. There were positive correlations between leptin and body mass index (p-value less than 0.001) and between CRP and wasting (p-value less than 0.001), but a negative correlation between leptin and wasting (p-value less than 0.001).. Elevated serum CRP levels and a decrease in serum leptin levels are associated with an increase in wasting in childhood TB.

Topics: Body Mass Index; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Cost-Benefit Analysis; Cross-Sectional Studies; Female; Humans; Immune System; Infant; Leptin; Male; Treatment Outcome; Tuberculosis; Weight Loss

Obesity and stress-related psychiatric disorders are frequently comorbid. However, our understanding of the relationship between diet, everyday life stress and psychiatric disorders is limited. Although the ability of stress to increase the likelihood to develop obesity and its comorbidities in a feed-forward loop has been studied there is a dearth of studies especially at the behavioural level investigating the feedback hypothesis, that is, the consequences of high-fat diet consumption on chronic stress-induced alterations. The effects of unpredictable chronic psychosocial stress on anxiety-like behaviour in the light-dark box, depressive-like behaviour in the forced swim test, hedonic behaviour in the female urine sniffing test and social avoidance in the social interaction test were investigated in a mouse model of diet-induced obesity. Changes in plasma levels of leptin, insulin and corticosterone were also assessed. A clear dissociation in behaviours was observed in mice subjected to diet-induced obesity coupled with chronic stress, with anxiety- and depressive-like behaviour observed in mice on a low- but not on a high-fat diet exposed to chronic social stress. On the other hand, social avoidance and anhedonic behaviour was present following stress independent of diet. Moreover, the effect of chronic stress in lowering leptin levels was most apparent in mice on a high-fat diet. Plasma insulin levels however where only decreased in mice on high- but not low-fat diet. In conclusion, long-term exposure to high-fat diet selectively and robustly protects against some of the behavioural sequelae of chronic unpredictable social stressors. These data show that there is a clear discrimination in the nature of stress-induced behavioural effects sensitive to protection by high-fat diet. Moreover, these results illustrate the strong influence of dietary components on stress-induced psychological factors and thereby emphasize the importance of the brain-gut-axis as a point of future therapeutic intervention.

Topics: Animals; Anxiety; Corticosterone; Depression; Diet, High-Fat; Female; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Stress, Psychological; Weight Loss

Topics: Bone Density; Bone Remodeling; Female; Humans; Leptin; Lumbar Vertebrae; Male; Weight Loss

High energy intake and, specifically, high dietary fat intake challenge the mammalian metabolism and correlate with many metabolic disorders such as obesity and diabetes. However, dietary restriction (DR) is known to prevent the development of metabolic disorders. The current western diets are highly enriched in fat, and it is as yet unclear whether DR on a certain high-fat (HF) diet elicits similar beneficial effects on health. In this research, we report that HF-DR improves metabolic health of mice compared with mice receiving the same diet on an ad libitum basis (HF-AL). Already after five weeks of restriction, the serum levels of cholesterol and leptin were significantly decreased in HF-DR mice, whereas their glucose sensitivity and serum adiponectin levels were increased. The body weight and measured serum parameters remained stable in the following 7 weeks of restriction, implying metabolic adaptation. To understand the molecular events associated with this adaptation, we analyzed gene expression in white adipose tissue (WAT) with whole genome microarrays. HF-DR strongly influenced gene expression in WAT; in total, 8643 genes were differentially expressed between both groups of mice, with a major role for genes involved in lipid metabolism and mitochondrial functioning. This was confirmed by quantitative real-time reverse transcription-PCR and substantiated by increase in mitochondrial density in WAT of HF-DR mice. These results provide new insights in the metabolic flexibility of dietary restricted animals and suggest the development of substrate efficiency.

Topics: Adiponectin; Adipose Tissue, White; Animals; Caloric Restriction; Carbohydrate Metabolism; Cholesterol; Dietary Fats; DNA, Mitochondrial; Epididymis; Gene Expression Profiling; Glucose; Glucose Tolerance Test; Health; Insulin; Leptin; Lipid Metabolism; Male; Metabolic Networks and Pathways; Mice; Mice, Inbred C57BL; Mitochondria; Obesity; Oligonucleotide Array Sequence Analysis; Organ Size; Transcription, Genetic; Weight Gain; Weight Loss

Cross-sectional studies in both humans and animals have demonstrated associations between obesity and altered reward functions at the behavioral and neural level, but it is unclear whether these alterations are cause or consequence of the obese state. Reward behaviors were quantified in male, outbred Sprague-Dawley (SD) and selected line obesity-prone (OP) and obesity-resistant (OR) rats after induction of obesity by high-fat diet feeding and after subsequent loss of excess body weight by chronic calorie restriction. As measured by the brief access lick and taste-reactivity paradigms, both obese SD and OP rats "liked" low concentrations of sucrose and corn oil less, but "liked" the highest concentrations more, compared with lean rats, and this effect was fully reversed by weight loss in SD rats. Acute food deprivation was unable to change decreased responsiveness to low concentrations but eliminated increased responsiveness to high concentrations in obese SD rats, and leptin administration in weight-reduced SD rats shifted concentration-response curves toward that seen in the obese state in the brief access lick test. "Wanting" and reinforcement learning as assessed in the incentive runway and progressive ratio lever-pressing paradigms was paradoxically decreased in both obese (compared with lean SD rats) and OP (compared with OR rats). Thus, reversible, obesity-associated, reduced "liking" and "wanting" of low-calorie foods in SD rats suggest a role for secondary effects of the obese state on reward functions, while similar differences between select lines of OP and OR rats before induction of obesity indicate a genetic component.

Topics: Adiposity; Animals; Caloric Restriction; Corn Oil; Dietary Fats; Disease Models, Animal; Feeding Behavior; Food Preferences; Genetic Predisposition to Disease; Leptin; Male; Motivation; Obesity; Phenotype; Rats; Rats, Sprague-Dawley; Reinforcement, Psychology; Reward; Sucrose; Taste; Weight Loss

Obese, leptin deficient obob mice have profoundly decreased activity and increased food seeking behavior. The decreased activity has been attributed to obesity. In mice, we tested the hypothesis that leptin increases total locomotor activity but inhibits food anticipatory activity. We also sought to determine if leptin induced increases in total locomotor activity are independent of changes in body weight and obesity. We studied obob mice and also created a novel transgenic mouse where leptin is over-expressed in a tetracycline-off system and can be abruptly and non-invasively suppressed by doxycycline within few hours. The studies were performed using two independent behavioral assays: home cage activity (HCA) and running wheel activity (RWA). Systemic administration of leptin (150 ng/hr) to obob mice produced a 122%±30% (mean ± SEM) increase (p≤0.01) in locomotor activity within 2 days In addition, cerebroventricular administration of leptin (5 ng/hr) also produced an early and progressive increase in total locomotor activity beginning on the 1st day (+28±8%; p≤0.05) and increasing to +69±23% on day 3 without a decrease in body weight during this time. The increase in activity was restricted to the dark phase. Conversely, in a tet-off transgenic obob mouse line, acute leptin suppression reduced spontaneous locomotor activity. To further define activities that are leptin regulated, we assayed food anticipatory activity (FAA) and found that it was markedly augmented in obob mice compared to wild type mice (+38±6.7 in obob vs +20±6.3% in wild type at peak; mean ± SEM; p≤0.001) and abolished by leptin. Although melanocortin-3 receptors (MC3R) reportedly mediate FAA, we found augmented FAA and preserved inhibitory effects of leptin on FAA in MC3R-/-obob mice. In summary, this study demonstrates that total activity and FAA are regulated independently by leptin. Leptin, acting in the central nervous system and at physiologic levels, produces early increases in locomotor activity before substantial weight loss. In contrast, leptin suppresses augmented food anticipatory activity in obob mice.

Topics: Animals; Anticipation, Psychological; Feeding Behavior; Injections, Intraventricular; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Mice, Transgenic; Motor Activity; Nervous System; Physical Conditioning, Animal; Receptor, Melanocortin, Type 3; Tetracycline; Time Factors; Weight Loss

Topiramate is newly approved as anticonvulsant that seems to promote body weight loss in humans. The present study was designed to evaluate the weight-controlling properties of topiramate in dietary obese female rats in comparison with sibutramine.. Fifty rats were assigned as normal, high fat diet (HFD), HFD + sibutramine (7.5 mg/kg, p.o.), HFD + topiramate (25 mg/kg, p.o.) and HFD + topiramate (50 mg/kg, p.o.). Body weight was registered, anxiety was tested in Vogel's test and blood pressure (BP) was measured. In addition, liver index, adipose tissue index, fasting blood glucose and serum lipid profile were measured in all groups. Further, serum insulin, leptin and adiponectin were determined.. Feeding with HFD induced a significant increase in body weight of rats as well as insulin resistance and serum lipids as compared to normal group (p<0.05). These measurements were suppressed by sibutramine treatment. However, a significant elevation in BP and anxiety behavior were detected as compared with HFD group (p<0.05). Topiramate (50 mg/kg, p.o.) group showed weight loss, improved insulin resistance, lessened anxiety behavior without influence on BP.. Our data ensures the findings that topiramate has a weight controlling properties with no anxiogenic or hypertensive effects. Further investigations are needed to determine the utility of topiramate in the clinical management of obesity.

Topics: Animals; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Cyclobutanes; Female; Fructose; Insulin; Insulin Resistance; Leptin; Lipids; Obesity; Rats; Topiramate; Weight Loss

To investigate changes in leptin and soluble leptin receptor (SLR) concentrations, and in the free leptin index (FLI) during weight loss and subsequent weight regain; and to ascertain whether these indices remain stable in the rank of the distribution in repeated measures (tracking) during perturbations of weight in obese children.. In a longitudinal study, 115 obese children were examined during a 12- week weight loss programme and 28 months of follow-up. Height, weight, body composition, Tanner stages, testicular size, time of menarche, and concentrations of leptin and SLR were measured at baseline, on days 14, 33, and 82, and from months 10, 16, and 28.. During weight loss, leptin decreased and the SLR increased. During weight regain, leptin increased and the SLR decreased. The partial correlation coefficients expressing the relationship between leptin and SLR were significant in girls during both weight loss and weight regain, whereas in boys they were much weaker and not significant. Leptin, SLR and FLI exhibited individual-specific levels (tracking) during weight loss and regain in boys and girls. The observed tracking seemed stronger during weight loss than during weight regain. The observed tracking was independent of both baseline body mass index (BMI) standard deviation score (SDS) and pubertal development at baseline and of subsequent changes in BMI SDS and puberty stages.. Leptin and the SLR exhibit tracking during weight loss and regain, which indicates individual stability in the leptin system despite challenges of weight.

Topics: Body Mass Index; Child; Female; Follow-Up Studies; Humans; Leptin; Longitudinal Studies; Male; Obesity; Puberty; Receptors, Leptin; Sex Factors; Weight Gain; Weight Loss; Weight Reduction Programs

Gastric bypass is the most popular technique in obesity therapy. We hypothesize that bypass surgery can help to control the body weight in morbid obesity, and this effect can be enhanced by vagus dissection.. Thirty-six Wistar rats were used in this investigation. They were randomly allocated into six groups. Rats in the gastric bypass group (GB1 and GB2) and the bypass with vagus dissection group (VD1 and VD2) received surgery. Rats in the control group (CO1 and CO2) received sham operation. Twenty days later, rats in the CO1, GB1, and VD1 groups were killed and data on body weights, food intakes, fasting glucose, plasma ghrelin and leptin levels, and GHS-R1a and leptin receptor protein expression in the hypothalamus were collected and summarized. One hundred days later, rats in the CO2, GB2, and VD2 groups were also killed and the same experiments were repeated.. Body weights of rats were 258 +/- 4.2 and 232 +/- 2.4 g in the GB1 and VD1 groups, respectively, much lower than the CO1 group (303 +/- 6.9 g). Body weights of rats were 316 +/- 12.3 and 315 +/- 10.3 g in the GB2 and VD2 groups, respectively, much lower than the CO2 group. Food intake in the VD1 group was lower than in the GB1 group, while there were no statistical differences between the VD2 and GB2 groups. Fasting glucose in the GB1 and GB2 groups was much lower than the CO1 and CO2 groups. Plasma ghrelin concentrations were much lower in the GB1 and VD1 groups compared to the CO1 group. One hundred days after surgery, the ghrelin concentrations in the GB2 and VD2 groups were also much lower than the CO2 group. Leptin concentrations decreased significantly with weight loss after bypass surgery. GHS-R1a protein expression in the hypothalamus was much lower in the GB1 and VD1 groups compared to the CO1 group. GHS-R1a protein expressions in the GB2 and VD2 groups were lower than the CO2 group. There were no statistical differences in leptin receptor expression in the hypothalamus (not shown).. Vagus nerve dissection is effective on body weight control in the early stage, but not in the long term. The hypothalamus is important in weight control by modulating ghrelin and leptin expressions. Bypass surgery can modulate the expression of ghrelin and its receptor. Leptin is also modulated by bypass surgery.

Topics: Animals; Dietary Fats; Energy Intake; Gastric Bypass; Ghrelin; Hypothalamus; Leptin; Male; Obesity, Morbid; Random Allocation; Rats; Rats, Wistar; Time Factors; Treatment Outcome; Vagus Nerve; Weight Gain; Weight Loss

Recently, vaspin was identified as a novel adipokine with insulin-sensitizing effects that might be implicated in endogenous glucose regulation. Our objective was to evaluate the impact of acute weight loss and metabolic changes on serum vaspin concentrations in morbidly obese subjects following laparoscopic Roux-en-Y gastric bypass (RYGB) surgery.. Longitudinal, clinical intervention study in 33 morbidly obese subjects before and 12 months after RYGB was conducted. Fasting serum concentrations of vaspin were measured by a commercially available ELISA and correlated with BMI, parameters of insulin sensitivity, and other biochemical measurements. Fasting insulin sensitivity was estimated using the homeostasis model assessment (HOMA) of insulin resistance.. RYGB-induced weight loss resulted in a reduction of circulating vaspin, leptin, insulin, and C-peptide levels as well as of BMI, HbA1c, and HOMA (p < 0.0001, respectively). Changes in serum vaspin concentrations correlated positively with those in HOMA, insulin, C-peptide, HbA1c, and leptin (p < 0.05, respectively) levels. The association between percent change of vaspin and HOMA remained significant even after the adjustment for RYGB-induced changes in BMI.. Following RYGB surgery, changes in serum vaspin concentrations correlate significantly with the reduction of circulating leptin, insulin, and C-peptide levels and with the amelioration of insulin sensitivity. However, further studies have to elucidate whether vaspin is only a biomarker for body-weight-related changes of insulin sensitivity or whether it is implicated in the regulation of human glucose homeostasis.

Topics: Adult; Biomarkers; Blood Glucose; C-Peptide; Female; Gastric Bypass; Homeostasis; Humans; Insulin; Insulin Resistance; Leptin; Male; Menopause; Obesity, Morbid; Serpins; Weight Loss

We have previously shown that combined amylin + leptin agonism elicits synergistic weight loss in diet-induced obese (DIO) rats. Here, we assessed the comparative efficacy of amylin, leptin, or amylin + leptin in the maintenance of amylin + leptin-mediated weight loss. DIO rats pretreated with the combination of rat amylin (50 microg/kg/day) and murine leptin (125 microg/kg/day) for 4 weeks were subsequently infused with either vehicle, amylin, leptin, or amylin + leptin for an additional 4 weeks. Food intake, body weight, body composition, plasma parameters, and the expression of key metabolic genes in liver and white adipose tissue (WAT) were assessed. Amylin + leptin treatment (weeks 0-4) reduced body weight to 87.5% of baseline. Rats subsequently maintained on vehicle or leptin regained all weight (to 104.2 and 101.2% of baseline, respectively), those maintained on amylin had partial weight regain (97.0%). By contrast, weight loss was largely maintained with continued amylin + leptin treatment (91.4%), associated with a 10% decrease in adiposity. Cumulative food intake (weeks 5-8) was reduced by amylin and amylin + leptin, but not by leptin alone. Amylin + leptin, but not amylin or leptin alone, reduced plasma triglycerides (by 55%), total cholesterol (by 19%), and insulin (by 57%) compared to vehicle. Amylin + leptin also reduced hepatic stearoyl-CoA desaturase-1 (Scd1) mRNA, and increased WAT mRNA levels of adiponectin, fatty acid synthase (Fasn), and lipoprotein lipase (Lpl). We conclude that, in DIO rats, maintenance of amylin + leptin-mediated weight loss requires continued treatment with both agonists, and is accompanied by sustained improvements in body composition, and indices of lipid metabolism and insulin sensitivity.

Topics: Adiponectin; Adipose Tissue, White; Amyloid; Analysis of Variance; Animals; Appetite Depressants; Body Composition; Body Weight; Diet; Drug Interactions; Eating; Gene Expression Profiling; Insulin; Islet Amyloid Polypeptide; Leptin; Liver; Male; Obesity; Rats; RNA, Messenger; Weight Loss

The involvement of a systemic inflammatory response, as evidenced by the Glasgow Prognostic Score (GPS), is associated with weight loss and poor outcome in patients with non-small cell lung cancer. There is good evidence that nutritional and functional decline in patients with advanced malignant disease is associated with catabolic changes in metabolism. However, defects in anabolism may also contribute towards nutritional decline in patients with cancer. The aim of the present study was to examine the relationship between IGF-1 and IGFBP-3, performance status, mGPS and survival in patients with inoperable NSCLC.. 56 patients with inoperable NSCLC were studied. The plasma concentrations of IGF-1, IGFBP-3 and leptin were measured using ELISA and RIA.. The patients were predominantly male (61%), over 60 years old (80%), with advanced (stage III or IV) disease (98%), with a BMI> or =20 (84%), an ECOG-ps of 0 or 1 (79%), a haemoglobin (59%) and white cell count (79%) in the reference range. On follow-up 43 patients died of their cancer. On univariate analysis, BMI (p<0.05), Stage (p<0.05), ECOG-ps (p<0.05), haemoglobin (p<0.05), white cell count (p<0.05) and mGPS (p<0.05) were associated with cancer specific survival. There was no association between age, sex, treatment, IGF-1, IGFBP-3, IGF-1:IGFBP-3 ratio, or leptin and cancer specific survival. With an increasing mGPS concentrations of haemoglobin (p<0.005) and IGFBP-3 (p<0.05) decreased. mGPS was not associated with either IGF-1(p>0.20), or leptin (p>0.20).. In summary, the results of this study suggest that anabolism (IGF-1 axis) does not play a significant role in the relationship between nutritional and functional decline, systemic inflammation and poor survival in patients with inoperable NSCLC.

Topics: Aged; Body Mass Index; Carcinoma, Non-Small-Cell Lung; Female; Hemoglobins; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Leukocyte Count; Male; Middle Aged; Neoplasm Staging; Prognosis; Severity of Illness Index; Survival Analysis; Systemic Inflammatory Response Syndrome; Weight Loss

Obesity has become a major public health problem, most commonly treated via dietary restriction to promote weight loss. Although leptin and thyroid hormones are involved in the regulation of energy balance, the role of these hormones after the stabilization of weight loss remains unclear. This study was designed to analyze the effect of thyroid hormone on sustained weight loss and leptin gene expression in obese animals after a loss of 5% to 10% of body weight. Thirty-day-old male Wistar rats were separated into 4 groups: control, obese, calorie restriction (CR), and calorie restriction with triiodothyronine administration (CRT). The obese group had increased weight and adiposity, leptin and insulin levels, and leptin gene expression. Dietary restriction in the CR group resulted in decreased body weight and adiposity, diminished leptin, and increased thyroid hormone receptor beta expression. The CRT group, submitted to dietary restriction with concomitant administration of a physiologic triiodothyronine dose, had thyroid hormone receptor beta expression at levels comparable with those observed in the control group and simultaneously increased leptin expression as compared with that in the CR group, suggesting that thyroid hormone modulates leptin expression under conditions of calorie restriction. Increased leptin expression in the CRT group did not result in increased circulating leptin or a statistically significant reduction in body weight during the treatment period. These data provide impetus for further study, as a longer treatment period may result in increased circulating leptin and, thus, further reduction in body weight during calorie restriction in an obesity model.

Topics: Animals; Body Composition; Body Weight; Caloric Restriction; Energy Intake; Insulin; Leptin; Male; Obesity; Polymerase Chain Reaction; Rats; Rats, Wistar; Triiodothyronine; Weight Loss

The aim of the study was to examine serum markers of bone turnover at 6 and 18 months after Roux-en-Y gastric bypass surgery.. Ten women and 10 men [body mass index (BMI), 50.2 +/- 8.4 kg/m(2)] were studied at 6 months; 10 women and nine men (BMI, 47.2 +/- 6.6 kg/m(2)) were studied at 18 months after surgery.. Serum osteocalcin, bone specific alkaline phosphatase (BAP), N-telopeptide of type 1 collagen (NTX), PTH, 25-hydroxy vitamin D, and leptin were measured.. BMI was reduced 32.7 +/- 6.2% at 6 months after surgery. Serum osteocalcin (6.9 +/- 2.4 to 10.9 +/- 2.6 ng/ml; P < 0.0001), BAP (14.2 +/- 3.7 to 16.4 +/- 4.5 ng/ml; P = 0.04), and NTX (10.9 +/- 1.7 to 19.6 +/- 5.3 nm bone collagen equivalents; P < 0.0001) were increased. Calcium, phosphate, and PTH were unchanged, but 25-hydroxy vitamin D increased (16.0 +/- 8.9 vs. 26.9 +/- 10.6 ng/ml; P <0.0001). The increase in NTX correlated with reduction in serum leptin (r = 0.58; P = 0.007). BMI was reduced 40.9 +/- 7.5% at 18 months after surgery. Serum BAP (17.6 +/- 5.3 to 22.2 +/- 7.8 ng/ml; P = 0.0017) and NTX (10.8 +/- 2.7 to 16.9 +/- 5.5 nm bone collagen equivalents; P < 0.0001) were increased. Calcium, phosphate, and PTH were unchanged, but 25-hydroxy vitamin D increased (17.7 +/- 7.6 to 25.6 +/- 6.8 ng/ml; P < 0.0001). The increase in NTX correlated with reduction in BMI (r = 0.58; P = 0.009) and leptin (r = 0.45; P = 0.04) and the increase in serum 25-hydroxy vitamin D (r = 0.43; P = 0.05). In multiple regression (adjusted model R(2) 0.263; P = 0.013), reduction in leptin was a significant predictor of increase in NTX (P = 0.016), but changes in BMI and 25-hydroxy vitamin D were not.. Weight loss after bariatric surgery is associated with long-term increase in serum markers of bone turnover. The increase in NTX is related to the decrease in leptin, which may signal caloric restriction to the skeleton.

Topics: Adult; Bariatric Surgery; Biomarkers; Body Mass Index; Bone Remodeling; Collagen Type I; Female; Gastric Bypass; Humans; Leptin; Male; Middle Aged; Obesity; Parathyroid Hormone; Peptides; Postoperative Period; Time Factors; Vitamin D; Weight Loss; Young Adult

Maintenance of a body weight 10% above or below that "customary" for lean or obese individuals results in respective increases or decreases in the energy expended in low levels of physical activity (nonresting energy expenditure, NREE). These changes are greater than can be accounted for by the altered body weight or composition and are due mainly to altered skeletal muscle work efficiency at low levels of power generation. We performed biochemical analysis of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle histomorphology. We found that the maintenance of a 10% reduced body weight was associated with significant declines in glycolytic (phosphofructokinase, PFK) enzyme activity and, in particular, in the ratio of glycolytic to oxidative (cytochrome c oxidase, COX) enzyme activity without significant changes in the activities of enzymes relevant to mitochondrial density, respiratory chain activity, or fuel transport; or in skeletal muscle fiber type or glycogen stores. The fractional change in the ratio of PFK/COX activity in subjects following weight loss was significantly correlated with changes in the systemic respiratory exchange ratio (RER) and measures of mechanical efficiency of skeletal muscle at low workloads (pedaling a bicycle to generate 10 or 25 W of power). Thus, predictable changes in systemic skeletal muscle biochemistry accompany the maintenance of an altered body weight and account for a significant portion of the variance in skeletal muscle work efficiency and fuel utilization at reduced body weight.

Topics: Adiponectin; Adult; Biopsy; Blood Glucose; Body Weight; Case-Control Studies; Energy Metabolism; Exercise Test; Female; Glycolysis; Humans; Insulin; Leptin; Male; Middle Aged; Muscle Contraction; Muscle Strength; Muscle, Skeletal; Obesity; Triiodothyronine; Weight Gain; Weight Loss

To investigate the capacity of the adipokine leptin to promote angiogenesis by modulating the function of circulating angiogenic cells (CACs).. In vitro, leptin specifically promoted CAC adhesion to tubular endothelial structures and migration along outgrowing sprouts of endothelial cells. In vivo, stimulation of CACs with leptin increased their capacity to promote new vessel formation in the chorioallantoic membrane of chicken embryos and to improve neovascularization of ischemic murine hind limbs. These effects required the phosphorylation of alphavbeta5 integrins, which depended on the interaction of leptin with its receptor ObR, and on Janus kinase (JAK) 2- and phospholipase C (PLC) gamma-mediated activation of Src kinase. Protein tyrosine phosphatase 1B, a negative regulator of leptin signaling, was overexpressed in CACs from obese, hyperleptinemic individuals, and this was associated with insensitivity of CACs to the angiogenic effects of leptin. Weight loss (by 30+/-15 kg) normalized protein tyrosine phosphatase 1B expression in CACs and restored their responsiveness to leptin. A similar dose-dependent response was found after incubation of CACs from obese subjects with a protein tyrosine phosphatase 1B inhibitor ex vivo.. Our results point to the ObR-Src kinase-alphavbeta5 cross talk as a distinct novel component of the network of specific interactions between integrins and cytokine receptors in angiogenesis.

Topics: Animals; Antigens, CD34; Case-Control Studies; Cell Adhesion; Cell Movement; Chick Embryo; Chorioallantoic Membrane; Disease Models, Animal; Endothelial Cells; Enzyme Activation; Hindlimb; Humans; Ischemia; Janus Kinase 2; Leptin; Leukocyte Common Antigens; Leukocytes, Mononuclear; Male; Mice; Mice, Nude; Muscle, Skeletal; Neovascularization, Physiologic; Obesity; Phospholipase C gamma; Phosphorylation; Platelet Endothelial Cell Adhesion Molecule-1; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Receptors, Leptin; Receptors, Vitronectin; Recombinant Proteins; Signal Transduction; Spheroids, Cellular; src-Family Kinases; Transfection; Up-Regulation; Weight Loss

Hepatic lipidosis is a common pathological finding in the American mink (Neovison vison) and can be caused by nutritional imbalance due to obesity or rapid body weight loss. The objectives of the present study were to investigate the timeline and characterize the development of hepatic lipidosis in mink in response to 0-7 days of food deprivation and liver recovery after 28 days of re-feeding. We report here the effects on hematological and endocrine variables, body fat mobilization, the development of hepatic lipidosis and the alterations in the liver lipid classes and tissue fatty acid (FA) sums. Food deprivation resulted in the rapid mobilization of body fat, most notably visceral, causing elevated hepatosomatic index and increased liver triacylglycerol content. The increased absolute amounts of liver total phospholipids and phosphatidylcholine suggested endoplasmic reticulum stress. The hepatic lipid infiltration and the altered liver lipid profiles were associated with a significantly reduced proportion of n-3 polyunsaturated FA (PUFA) in the livers and the decrease was more evident in the females. Likewise, re-feeding of the female mink resulted in a more pronounced recovery of the liver n-3 PUFA. The rapid decrease in the n-3/n-6 PUFA ratio in response to food deprivation could trigger an inflammatory response in the liver. This could be a key contributor to the pathophysiology of fatty liver disease in mink influencing disease progression.

Topics: Adipose Tissue; Animals; Blood Glucose; Fasting; Fatty Acids, Omega-3; Fatty Liver; Female; Food; Food Deprivation; Hematologic Tests; Leptin; Lipid Metabolism; Liver; Male; Mink; Phosphatidylcholines; Phospholipids; Sex Factors; Triglycerides; Weight Loss

To investigate the role of leptin, ghrelin, GH and IGF-1 in energy balance disturbances in Parkinson's disease (PD).. Thirty-nine patients were included: 11 PD patients with unintentional weight loss, 16 PD patients without weight loss and 12 controls. UPDRS, MMSE, MADRS, appetite scale, BMI, adipose tissue content, plasma leptin and active ghrelin concentrations and serum GH, IGF-1, TSH, T3 and T4, concentrations were evaluated.. A lower plasma leptin concentration and a higher serum IGF-1 concentration were found in PD patients with weight loss. BMI and the content of adipose tissue were positively correlated with leptin concentration in all PD patients. Paradoxically, the lower BMI was, the lower plasma active ghrelin concentration was in PD patients with the weight loss.. These findings confirm that changes of plasma leptin concentration occur in PD patients with loss of weight.

Topics: Adipose Tissue; Aged; Appetite; Body Mass Index; Energy Metabolism; Female; Ghrelin; Growth Hormone; Humans; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Parkinson Disease; Thyroid Hormones; Thyrotropin; Weight Loss

Leptin regulates energy homeostasis by suppressing food intake; however, its role in energy expenditure and fat oxidation remains uncertain in humans.. The aim of the study was to assess 24-h energy metabolism before and after weight loss induced by leptin treatment in congenital leptin-deficient subjects or low-calorie diet in controls.. We measured 24-h energy expenditure, 24-h fat oxidation, and body fat in three null homozygous leptin-deficient obese adults before and after weight loss induced by a 19-wk leptin replacement period (0.02-0.04 mg/kg/d). The same measures were performed in three obese controls pair-matched for sex, age, and weight loss induced by a 10- to 21-wk low-calorie diet. Measurements were preceded for 1 wk of weight stabilization. Energy expenditure was adjusted for fat-free mass, fat mass, sex, and age based on a reference population (n = 842; R(2) = 0.85; P < 0.0001). Similarly, fat oxidation was adjusted for fat-free mass, percentage body fat, energy balance, and diet composition during the 24-h respiratory chamber stay (R(2) = 0.38; P < 0.0001).. Before weight loss, congenital leptin-deficient and control subjects had similar energy expenditure. However, after weight loss ( approximately 15 kg), controls had energy expenditures lower than expected for their new weight and body composition (-265 +/- 76 kcal/d; P = 0.04), whereas leptin-treated subjects had values not different from the reference population (-128 +/- 119 kcal/d; P = 0.67). Before weight loss, fat oxidation was similar between groups. However, after weight loss, leptin-treated subjects had higher fat oxidation than controls (P = 0.005) and higher than the reference population (P = 0.0001).. In congenital leptin-deficient subjects, leptin replacement prevented the decrease in energy expenditure and fat oxidation often observed after weight loss.

Topics: Adaptation, Physiological; Adipose Tissue; Adult; Body Composition; Energy Metabolism; Female; Hormone Replacement Therapy; Humans; Leptin; Male; Oxidation-Reduction; Weight Loss

The skeleton is regarded recently as an endocrine organ that affects energy metabolism. However, there are very limited data available concerning the relationships between the osteoblast-derived hormone osteocalcin, weight status, adiponectin and leptin in obese humans, especially in children.. We analyzed osteocalcin, adiponectin, leptin and insulin resistance (IR) index homeostasis model assessment (HOMA) in 60 obese and 19 age- and gender-matched normal weight children. Furthermore, these parameters were determined in 60 obese children after participating in an outpatient 1-year lifestyle intervention based on exercise, behavior and nutrition therapy.. Sixty obese children had significantly lower osteocalcin levels (26.8+/-0.8 ng ml(-1)) than 19 normal weight controls (32.2+/-2.3 ng ml(-1)). Boys (29.9+/-1.1 ng ml(-1)) showed significantly (P=0.046) higher osteocalcin levels compared with girls (26.4+/-1.2 ng ml(-1)). In stepwise multiple linear regression analysis adjusted for age, gender and pubertal stage, osteocalcin was significantly negatively related to leptin and HOMA, but not to adiponectin. Changes of osteocalcin in the course of 1 year correlated significantly negatively with changes of IR index HOMA (r=-0.25), standard deviation score-body mass index (SDS-BMI) (r=-0.33) and leptin (r=-0.50). Substantial weight loss in 29 obese children led to a significant increase in osteocalcin and a significant decrease in leptin and HOMA. In 31 obese children without substantial weight loss, osteocalcin levels did not change significantly in the course of 1 year.. Osteocalcin levels were lower in obese children and were related to IR and leptin both in cross-sectional and longitudinal analyses. Therefore, osteocalcin might be a new promising link between obesity and IR.

Topics: Biomarkers; Body Mass Index; Body Weight; Bone and Bones; Child; Enzyme-Linked Immunosorbent Assay; Female; Germany; Humans; Insulin Resistance; Leptin; Life Style; Male; Obesity; Osteocalcin; Puberty; Regression Analysis; Sex Factors; Weight Loss

Trodusquemine (MSI-1436) causes rapid and reversible weight loss in genetic models of obesity. To better predict the potential effects of trodusquemine in the clinic, we investigated the effects of trodusquemine treatment in a murine model of diet-induced obesity (DIO). Trodusquemine suppressed appetite, reduced body weight (BW) in a fat-specific manner, and improved plasma insulin and leptin levels in mice. Screening assays revealed that trodusquemine selectively inhibited protein-tyrosine phosphatase 1B (PTP1B), a key enzyme regulating insulin and leptin signaling. Trodusquemine significantly enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) beta and STAT3, direct targets of PTP1B, in HepG2 cells in vitro and/or hypothalamic tissue in vivo. These data establish trodusquemine as an effective central and peripheral PTP1B inhibitor with the potential to elicit noncachectic fat-specific weight loss and improve insulin and leptin levels.

Topics: Animals; Appetite; Body Composition; Cholestanes; Diet; Disease Models, Animal; Hep G2 Cells; Humans; Hypolipidemic Agents; Hypothalamus; Insulin; Leptin; Male; Mice; Mice, Inbred AKR; Mice, Obese; Obesity; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Receptor, Insulin; Spermine; STAT3 Transcription Factor; Weight Loss

We have shown previously that in overweight premenopausal women, changes in macronutrient composition and increasing the number of steps walked per day favorably affect body composition and plasma lipid profiles. As a follow-up, we evaluated the effect of moderate carbohydrate intake and increased physical activity on inflammation and regulation of appetite.. Seventy premenopausal women with a body mass index (BMI) between 25 and 37 kg/m(2) participated in a 10-week weight loss intervention program consisting of the following macronutrient energy distribution: 40% carbohydrate, 30% fat, and 30% protein, in addition to a progressive increase in the number of steps taken per day. Plasma adiponectin, intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), leptin, and ghrelin levels were assessed at baseline and after 10 weeks.. Subjects reduced body weight by 4.5%, waist circumference (WC) by 6.4%, and trunk fat by 4.6%. Plasma insulin and insulin resistance assessed by homeostasis model assessment (HOMA) were reduced after 10 weeks (p < 0.01). Plasma adiponectin was increased by 11% (p < 0.05), and ICAM-1 levels were decreased (p < 0.05) after 10 weeks. A negative correlation was found between changes in insulin and changes in adiponectin between baseline and 10 weeks (r = -0.397, p < 0.01), indicating a role of adiponectin in increasing insulin sensitivity. In addition, plasma ghrelin levels were increased by 17% (p < 0.001), indicating a signal for increased appetite associated with weight loss.. These studies indicate that weight loss interventions involving moderate changes in dietary carbohydrate and increases in physical activity favorably affect insulin sensitivity and decrease inflammation.

Topics: Adipokines; Adult; Appetite Regulation; Body Composition; Body Mass Index; Carnitine; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Double-Blind Method; Exercise; Female; Ghrelin; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leptin; Middle Aged; Premenopause; Vascular Cell Adhesion Molecule-1; Weight Loss

Hypothalamic resistance to the anorexigenic actions of the peripheral adipostat hormone leptin is characteristic of obesity. Here, we use an obese animal model of similar body weight to that of the human to test in vivo whether leptin resistance is due to decreased blood-brain leptin transport or intra-hypothalamic insensitivity, and whether sensitivity to leptin is restored by weight loss. For 40 weeks, adult sheep surgically prepared with intra-cerebroventricular (ICV) cannulae were given a complete natural diet ad libitum ('Obese' group) or in restricted quantities ('Lean' group), and then the dietary amounts were reversed for 16 weeks until mean group body weights converged ('Slimmers' and 'Fatteners', respectively).. ICV leptin injection (0.5 mg) at 8-week intervals acutely decreased voluntary food intake by approximately 35% in the 'Obese' group on each occasion and in 'Slimmers' and 'Fatteners' at the end, providing no evidence of intra-hypothalamic insensitivity. The ratio between endogenous leptin concentrations in ventricular cerebrospinal fluid (CSF) and peripheral blood decreased with increasing leptinaemia in 'Obese' sheep, indicating decreased efficiency of blood-brain leptin transport, whereas leptin concentrations remained low and the CSF:blood ratio remained high in 'Lean' sheep. Compared with 'Fatteners' of similar body weight, 'Slimmers' were hypoleptinaemic, but their CSF:blood leptin concentration ratio remained low. Thus, the obesity-induced impairment of leptin blood-brain transport was sustained despite an approximately 15% weight loss.. These results support the hypothesis that central resistance to leptin in obesity with associated peripheral hyperleptinaemia is attributable to decreased efficiency of leptin transport into the brain and not to intra-hypothalamic leptin insensitivity. However, leptin transport efficiency is not restored after weight loss by caloric restriction despite the prevailing hypoleptinaemia.

Topics: Animals; Biological Transport, Active; Blood-Brain Barrier; Body Weight; Caloric Restriction; Eating; Hypothalamus; Leptin; Male; Obesity; Sheep; Thinness; Weight Loss

Recent studies in humans and mice suggest the implication of the cysteine proteases cathepsins S, L, and K in vascular and metabolic complications of obesity.. Our objective was to identify clinically relevant forms of cathepsin in human obesity.. We conducted a prospective study on two independent cohorts.. The first cohort includes 45 obese women eligible for gastric surgery (age, 39 +/- 1.6 yr; body mass index, 47 +/- 0.99 kg/m(2)) and 17 nonobese women (age, 38 +/- 1.8 yr; body mass index, 21 +/- 0.44 kg/m(2)). The second cohort comprises 29 obese women (age, 57 +/- 0.8 yr; body mass index, 34 +/- 0.69 kg/m(2)) undergoing 6 months of medically supervised caloric restriction.. Cathepsin S, L, and K mRNA levels were determined in surgical adipose tissue biopsies. The proteins were measured in conditioned medium of adipose tissue explants and in circulation.. Obese subjects had a 2-fold increase in cathepsin S mRNA in adipose tissue as compared with normal-weight subjects and an increased rate (1.5-fold) of cathepsin S release in adipose tissue explants. Cathepsin S circulating concentrations were increased with obesity (+30%) and reduced after weight reduction (P < 0.05 for both). By contrast, cathepsin L was unaffected in adipose tissue and serum; cathepsin K was undetectable in circulation and unchanged in adipose tissue.. In humans, cathepsin S is more influenced than cathepsins L and K by changes in energy balance in adipose tissue and circulation. This opens new avenues to explore whether selective inhibition of this protease could reduce cardiovascular risk and ameliorate metabolic status in obese subjects.

Topics: Adipocytes; Adipose Tissue; Adult; Aged; Anastomosis, Roux-en-Y; Animals; Body Mass Index; Caloric Restriction; Cathepsins; Cells, Cultured; Cohort Studies; Cystatin C; Energy Metabolism; Female; Humans; Leptin; Mice; Mice, Obese; Middle Aged; Obesity; Postmenopause; Quebec; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Weight Loss

Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2R binding (measured with autoradiography [(3)H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.

Topics: Analysis of Variance; Animals; Autoradiography; Caudate Nucleus; Corpus Striatum; Eating; Genotype; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Nucleus Accumbens; Phenotype; Putamen; Receptors, Dopamine D2; Spiperone; Tritium; Weight Loss

The effect of stress associated with acute weight reduction on adipocytokine production is incompletely understood. In the present study, we have investigated the changes in circulating adipocytokine concentrations and urinary concentrations of stress markers in male collegiate wrestlers during acute weight reduction for a competition. Twenty healthy Japanese male wrestlers (18-22 years of age) who participated in the national collegiate wrestling tournament were studied. Body weight, body fat amount, serum testosterone, serum leptin, serum adiponectin, urinary 8-hydroxy-2'- deoxyguanosine (8-OHdG) and urinary biopyrrins were analyzed during acute weight reduction for the competition. Body weight, body fat amount and the serum concentrations of testosterone, leptin and adiponectin significantly decreased on the day of weigh-in compared with the levels 12 days before weigh-in. In contrast, urinary concentrations of 8-OHdG and biopyrrins significantly increased on the day of weigh-in compared with the concentrations 12 days before weigh-in. A positive correlation was observed between the serum concentrations of adiponectin and testosterone, and a negative correlation was observed between the concentrations of serum adiponectin and urinary biopyrrins. The present results suggest that rapid weight reduction increases the urinary concentrations of stress markers, which is associated with a decrease in serum concentrations of adiponectin.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adiponectin; Adiposity; Adolescent; Adult; Bilirubin; Biomarkers; Deoxyguanosine; Humans; Leptin; Male; Oxidative Stress; Testosterone; Weight Loss; Wrestling

The relationship between C-reactive protein (CRP), nitric oxide (NO), leptin, adiponectin, and insulin growth factor 1 (IGF-1) is poorly defined in morbidly obese patients before and after gastric bypass and, in some cases, is controversial.. We examined the plasma of 34 morbidly obese patients before and 1, 6, and 12 months after Roux-en-Y gastric bypass surgery.. Obese people had more CRP (21.3 +/- 1.8 microg/ml) and leptin (36.9 +/- 4.0 ng/ml) than those in the control group (nonobese people: CRP = 6.9 +/- 0.9 microg/ml, p < 0.0001; leptin = 7.5 +/- 0.4 ng/ml, p < 0.0001). However, they had less NO (30.4 +/- 2.7 nmol/ml), IGF-1 (77.5 +/- 6.6 ng/ml), and adiponectin (11.1 +/- 1.0 microg/ml) than those in the control group (NO = 45.8 +/- 3.9 nmol/ml, p = 0.0059; IGF-1 = 202.0 +/- 12.0 ng/ml, p < 0.0001; adiponectin = 18.0 +/- 2.0 microg/ml, p < 0.0001). During weight loss, the amount of CRP and leptin decreased until they reached the nonobese values, but the level of NO remained lower than in nonobese people, even 1 year after surgery. The linear regression slopes were negative and very significant for leptin (p = 0.0005) and CRP (p = 0.0018) but were less significant for NO (p = 0.0221). IGF-1 displayed a very good linear regression (both negative and significant) with some anthropometric parameters, including body mass index (p = 0.0025), total fat (p = 0.0177), and the percentage of fat (p < 0.0001).. For the first time, we report the relationship between IGF-1 and CRP, NO, leptin, and adiponectin. For all these parameters, the best and most widely demonstrated improvements in comorbidities before and during weight loss in morbid obesity were associated with CRP and leptin.

Topics: Adiponectin; Adult; Body Mass Index; C-Reactive Protein; Female; Gastric Bypass; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Nitric Oxide; Obesity, Morbid; Weight Loss

Topiramate is an anticonvulsant agent effective in the prophylaxis of migraine, which also induces weight reduction by an unknown mechanism. We investigated the effect of topiramate on metabolic and endocrine parameters in patients with migraine independently of any intention to lose body weight. Six patients (26-61 years old, body mass indices [BMI] 20.9-32.1 kg/m(2)) with migraine were treated with an average dose of 100 mg topiramate/day over a period of 20 weeks. The following parameters were measured every 4-8 weeks: BMI, body fat proportion, waist and hip circumference, HOMA insulin resistance, fasting serum-/plasma concentrations of adiponectin, leptin, ghrelin, vascular endothelial growth factor (VEGF), cortisol, interleukin-6 and tumor necrosis factor (TNF)-alpha. Profound metabolic changes were observed for the whole treatment period. Compared with the baseline value, 20 weeks of treatment reduced the BMI by 7.2+/-1.4%, body fat proportion by 11.6+/-3.6%, waist circumference by 4.2+/-1.2%, leptin by 39.2+/-6.5% and HOMA insulin resistance by 37.3+/-5%, while adiponectin was increased by 69.9+/-17.3% (P<0.05, respectively). VEGF concentrations increased during the week 2-4 by 177.4+/-39.4% (P<0.05) followed by a continuous decrease. There were trends for a reduction in ghrelin concentration, whereas cortisol, interleukin-6 and TNF-alpha values were unchanged. In summary, in this small sample of migraine patients topiramate treatment was associated with increased insulin sensitivity, increased adiponectin concentration and a reduction of body fat in all treated patients. The role of increased VEGF concentrations prior to these metabolic changes is not clear and might, hypothetically, involve a centrally mediated effect of topiramate on body weight regulation.

Topics: Adiponectin; Adipose Tissue; Adult; Anti-Obesity Agents; Anticonvulsants; Body Mass Index; Cytokines; Female; Fructose; Hip; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Migraine Disorders; Prospective Studies; Topiramate; Vascular Endothelial Growth Factors; Waist Circumference; Weight Loss

Cholecystokinin (CCK) acutely synergizes with amylin to suppress food intake in lean mice. To extend on these findings, the present studies sought to identify neural correlates for the interaction of amylin and CCK, as well as further understand the therapeutic potential of CCK-based combinations in obesity. First, c-Fos activation was assessed in various brain nuclei after a single intraperitoneal injection of amylin (5microg/kg) and/or CCK (5microg/kg). Amylin and CCK additively increased c-Fos within the area postrema (AP), predominantly in noradrenergic (e.g., dopamine-beta-hydroxylase-containing) cells. Next, amylin (100 or 300microg/kg/d) and/or CCK (100 or 300microg/kg/d) were subcutaneously infused for 7days in diet-induced obese (DIO) rats. Amylin treatment of DIO rats for 7days induced significant body weight loss. CCK, while ineffective alone, significantly enhanced body weight loss when co-administered with the higher dose of amylin. Finally, the addition of CCK (300microg/kg/d) to leptin (125microg/kg/d), and to the combination of amylin (50microg/kg/d) and leptin (125microg/kg/d), was also explored in DIO rats via sustained subcutaneous infusion for 14days. Infusion of amylin/leptin/CCK for 14days exerted significantly greater body weight loss, inhibition of food intake, and reduction in adiposity compared to amylin/leptin treatment alone in DIO rats. However, co-infusion of CCK and leptin was an ineffective weight loss regimen in this model. Whereas CCK agonism alone is ineffective at eliciting or maintaining weight loss, it durably augmented the food intake and body weight-lowering effects of amylin and amylin/leptin in a relevant disease model, and when combined with amylin, cooperatively activated neurons within the caudal brainstem.

Topics: Amyloid; Analysis of Variance; Animals; Appetite Depressants; Area Postrema; Body Weight; Cholecystokinin; Disease Models, Animal; Dopamine beta-Hydroxylase; Dose-Response Relationship, Drug; Drug Therapy, Combination; Eating; Islet Amyloid Polypeptide; Leptin; Male; Neurons; Obesity; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Weight Loss

Anorexia, cachexia, and insulin resistance are commonly seen in patients with cancer. Adipocyte-derived hormones or adipokines play a role in the regulation of appetite, body weight, and insulin sensitivity. However, their role in cancer-induced cachexia has not been well-established. The objective of this study was to determine the levels of adipokines and their relation to appetite, weight loss, insulin resistance, and other hormones in cancer cachexia.. We measured adiponectin, resistin, and leptin plasma levels in 21 men with cancer cachexia, 24 noncachectic cancer subjects, and 25 noncancer controls matched by age, sex, and pre-illness body weight. Body weight change, appetite scores, insulin resistance assessed by homeostasis model assessment, and other cytokines and hormones were also measured. Differences between groups were measured by analysis of covariance. Relations between variables were examined by linear regression analyses.. Adiponectin levels were similarly elevated in cachectic and noncachectic cancer patients compared with noncancer controls. Leptin levels were significantly decreased in cancer cachexia and were directly associated with appetite and insulin resistance, explaining 37% and 19% of the variance seen in cancer patients, respectively. Resistin levels were not different between groups.. Leptin may play a role in the increased insulin resistance seen in cancer patients. However, these patients are resistant to the orexigenic effects of hypoleptinemia. Other mechanisms besides weight loss are responsible for the increased adiponectin level seen in cancer patients. It is unlikely that resistin plays a major metabolic role in this setting.

Topics: Adipokines; Adiponectin; Adolescent; Adult; Aged; Anorexia; Appetite; Body Weight; Cachexia; Humans; Insulin Resistance; Leptin; Linear Models; Male; Multivariate Analysis; Neoplasms; Resistin; Weight Loss

Microalbuminuria portends an increased risk for renal and cardiovascular diseases in diabetes. In this pilot study, we determined the effect of weight loss induced by different types of bariatric surgery on albuminuria in severely obese type 2 diabetic (T2DM) subjects.. Fifteen consecutive T2DM patients (9M/6F, 51+/-14 years, body mass index (BMI) 49+/-9 kg/m2, HbA1c 7.2+/-1.1 percent) undergoing either Roux-en-Y gastric bypass (RYGB; N=9) or other types of bariatric surgery (N=6) underwent determination of urine albumin/creatinine ratio (UACR) and adipokine and insulin sensitivity during a mixed meal tolerance test performed 2 weeks prior to and 6 months following surgery.. Following RYGB, there was a significant decrease in BMI ((-4.74)+/-(-5.05) kg/m2), fasting glucose, cholesterol, and leptin levels. Insulin sensitivity (Matsuda index [12.05+/-3.81, p=0.003]) and high molecular weight (HMW) adiponectin increased significantly along with a significant reduction in UACR (median, 36 mg/g [7-94] vs. 27 mg/g [5.5-42.5], p=0.01). The reduction in UACR following RYGB was inversely correlated with the Matsuda index (r=-0.74), p=0.02) and HMW adiponectin (r=(-0.67), p=0.04). In contrast, despite reduction in BMI ((-4.11)+/-(-4.10) kg/m2) following other types of bariatric surgery (n=6), there was no significant improvement in insulin sensitivity (0.88+/-2.40, p=0.63), UACR, or HMW adiponectin levels.. RYGB in severely obese DM subjects is associated with a reduction in albuminuria that correlates to the improvement in insulin sensitivity and HMW adiponectin. The data point to a need for larger studies to confirm these findings and evaluate the micro-macrovascular benefits including renal parenchymal benefits of different types of bariatric surgery in T2DM.

Topics: Adiponectin; Albuminuria; Bariatric Surgery; Blood Glucose; Body Mass Index; Cholesterol; Creatinine; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Molecular Weight; Obesity, Morbid; Pilot Projects; Risk Factors; Weight Loss

Surgical intervention produces sustainable weight loss and metabolic improvement in obese individuals. Vertical sleeve gastrectomy (VSG) produces dramatic, sustained weight loss; we investigated whether these changes result from improved sensitivity to leptin.. VSG was performed in Long-Evans rats with diet-induced obesity. Naïve or sham-operated rats, fed either ad libitum or pair-fed with the VSG group, were used as controls. Following surgery, body weights and food intake were monitored. We investigated energy expenditure, meal patterns, leptin sensitivity, and expression of pro-opiomelanocortin/agouti-related peptide/neuropeptide Y in the hypothalamus of the rats.. We observed sustained losses in weight and body fat in male and female rats after VSG. Weight loss persisted after the disappearance of a transient, postsurgical food intake reduction. Resting energy expenditure was similar between control and VSG rats. VSG rats maintained their reduced body weights. However, they responded to a chronic food restriction challenge by overeating, which resulted in prerestriction, rather than pre-VSG, body weights. Consistent with lower adiposity, VSG decreased plasma leptin levels. Although VSG slightly improved leptin's anorectic action, the response was comparable to that observed in controls matched for adiposity by caloric restriction. Changes in hypothalamic neuropeptide expression were consistent with the lower body weight and lower leptin levels but cannot account for the sustained weight loss.. VSG causes sustained reduction in body weight, which results from loss of fat mass. The maintenance of weight loss observed did not result from changes in sensitivity to leptin.

Topics: Agouti-Related Protein; Animals; Eating; Energy Metabolism; Female; Gastrectomy; Leptin; Malabsorption Syndromes; Male; Neuropeptide Y; Obesity; Rats; Rats, Long-Evans; Weight Loss

Leptin may influence sweet taste sensitivity. However, there are no reports on an association between the sweet taste threshold and serum leptin levels during weight loss in humans. We investigated the changes in the sweet taste threshold and the serum leptin levels during a weight-loss program, in connection with a leptin receptor polymorphism (Lys109Arg) that may be related to insulin and glucose metabolism. The study included 20 obese, but otherwise healthy, females (mean age: 55 +/- 7 years, body mass index: 26.1 +/- 1.7 kg/m(2)). Participants completed a 12-week weight-loss program based on energy restriction through diet and exercise, which aimed at achieving their optimal weight. The sweet taste threshold was determined according to the whole-mouth gustatory method. Genetic analyses were performed using the allele-specific DNA assay. Serum leptin levels were decreased from 9.2 +/- 4.5 to 7.9 +/- 4.9 ng/ml (p = 0.014) after body weight loss. The sweet taste threshold also decreased significantly from 0.59 +/- 0.42 to 0.22 +/- 0.20% in a solution of sucrose (p = 0.004). In contrast, there were no differences in changes of the threshold between participants with and without the Lys109 allele. A multiple regression analysis revealed that the changes in serum leptin levels were significantly correlated with those in the sweet taste threshold, independent of the initial threshold levels and the Lys109 allele. In conclusion, the serum leptin levels are decreased significantly during a weight-loss program in obese females, which may be associated with the decrease in the sweet taste threshold.

Topics: Body Mass Index; Body Weight; Female; Humans; Leptin; Middle Aged; Obesity; Taste; Taste Threshold; Weight Loss

The role of 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) in the pathogenesis of obesity has been elucidated in humans and in various rodent models. Obesity is accompanied by disturbances in glucocorticoid metabolism, circulating adipokine levels, and fatty acid (FA) reesterification. This study was undertaken to evaluate glucocorticoid metabolism in sc fat before and after weight loss and to explore putative associations between 11beta-HSD1 and leptin, adiponectin, and FA recycling.. Twenty-seven obese (mean body mass index 44.4 + or - 4.4 kg/m(2)) women underwent gastric bypass surgery. Subcutaneous fat biopsies were collected before and 2 yr after surgery. The expression of 11beta-HSD1, leptin, adiponectin, and phosphoenolpyruvate carboxykinase (PEPCK) mRNA was evaluated with real-time PCR. Serum leptin and adiponectin protein levels were estimated by ELISA.. Two years after gastric bypass surgery, significant reductions were observed in the mean body mass index (from 44.4 to 30.8 kg/m(2)) and mean waist circumference (from 121.9 to 90.6 cm). After weight loss, 11beta-HSD1 mRNA expression decreased 4-fold (P < 0.001). Both leptin and adiponectin mRNA expression decreased, with concomitantly decreased circulating leptin and increased circulating adiponectin levels. PEPCK mRNA expression did not change.. Weight loss after gastric bypass surgery was followed by metabolically favorable changes in insulin sensitivity, circulating leptin and adiponectin, and peripheral glucocorticoid metabolism. A significant reduction in 11beta-HSD1 expression was observed in sc adipose tissue after weight loss. This suggests that up-regulation of 11beta-HSD1 is a consequence, rather than a cause, of obesity.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adipokines; Anthropometry; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Fatty Acids; Female; Gastric Bypass; Humans; Insulin Resistance; Leptin; Obesity; Phosphoenolpyruvate Carboxykinase (ATP); Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Subcutaneous Fat; Weight Loss

To design, manufacture and test a second generation leptin receptor (ObR) agonist glycopeptide derivative. The major drawback to current experimental therapies involving leptin protein is the appearance of treatment resistance. Our novel peptidomimetic was tested for efficacy and lack of resistance induction in rodent models of obesity and appetite reduction.. The glycopeptide containing two additional non-proteinogenic amino acids was synthesized by standard solid-phase methods. Normal mice were fed with peanuts until their blood laboratory data and liver histology showed typical signs of obesity but not diabetes. The mice were treated with the peptidomimetic at 0.02, 0.1 or 0.5 mg/kg/day intraperitoneally side-by-side with 0.1 mg/kg/day leptin for 11 days. After termination of the assay, the blood cholesterol and glucose amounts were measured, the liver fat content was visualized and quantified and the remaining mice returned to normal diet and were allowed to mate. In parallel experiments normal rats were treated intranasally with the glycopeptide at 0.1 mg/kg/day for 10 days.. The 12-residue glycosylated leptin-based peptidomimetic E1/6-amino-hexanoic acid (Aca) was designed to target a principal leptin/ObR-binding interface. E1/Aca induced leptin effects in ObR-positive cell lines at picomolar concentrations and readily crossed the blood-brain barrier (BBB) following intraperitoneal administration. The peptide initiated typical leptin-dependent signal transduction pathways both in the presence and absence of leptin protein. The peptide also reduced weight gain in mice fed with high-fat peanut diet in a dose-dependent manner. Obese mice receiving peptide E1/Aca at a 0.5 mg/kg/day dose lost weight, corresponding to a net 6.5% total body weight loss, while similar mice treated with leptin protein did not. Upon cessation of the weight loss treatment, several obesity-related pathologies (i.e. abnormal metabolic profile and liver histology as well as infertility) normalized in peptide-, but not leptin-treated, mice. Peptide E1/Aca added intranasally to growing normal rats decelerated normal weight gain corresponding to a net 6.8% net total body weight loss with statistical significance.. No resistance induction to peptide E1/Aca or toxicity in either obese or healthy rodents was observed, indicating the potential for widespread utility of the peptidomimetic in the treatment of leptin-deficiency disorders. We provide additional proof for the hypothesis that difficulties in current leptin therapies reside at the BBB penetration stage, and we document that by either glycosylation or intranasal peptide administration we can overcome this limitation.

Topics: Animals; Blood-Brain Barrier; Cell Proliferation; Disease Models, Animal; Fertility; Glycopeptides; Leptin; Mice; Mice, Obese; Obesity; Rats; Receptors, Leptin; Weight Loss

Population-based studies suggest that repetitive cycling of weight loss and regain may be associated with future weight gain. Therefore, to better define the relationship between weight cycling, energy homeostasis, and future weight gain, we examined associations between frequent intentional weight loss and hormonal profiles in postmenopausal women. This cross-sectional study evaluated the relationship between a history of frequent weight loss and biomarkers, including serum glucose, insulin, leptin, and ghrelin, as well as sex steroid hormones. We hypothesized that frequent intentional weight loss would be associated with changes in normal appetite and body weight regulatory hormones, favoring increased appetite and weight gain. One hundred fifty-nine healthy, weight stable, sedentary, overweight, postmenopausal women who had been recruited for an exercise intervention participated in this study. History of intentional weight loss (frequency and magnitude) was assessed by questionnaire. Hormonal assays were performed by radioimmunoassay (insulin, leptin, ghrelin, estrogens, androgens, and dehydroepiandrosterone), chemiluminescence immunoassay (insulin-like growth factor-1), and immunometric assay (sex hormone binding globulin). Analysis of variance and regression analyses were used to investigate the relationship between weight loss history and metabolic hormones. A higher degree of weight cycling, characterized by the frequency of intentionally losing more than 10 lb, was associated with an appetite-stimulating hormonal profile, including higher concentrations of ghrelin (P trend = .04), lower glucose (P trend = .047), and to some extent, lower insulin (P trend = .08). Frequent weight loss was also associated with lower androgen concentrations, including androstenedione (P trend = .02), testosterone (P trend = .04), and free testosterone (P trend = .01). No independent associations between the concentrations of leptin or estrogens and weight cycling were observed. This study suggests that frequent intentional weight loss may affect hormones involved in energy regulation.

Topics: Aged; Androgens; Appetite; Blood Glucose; Body Mass Index; Cross-Sectional Studies; Dehydroepiandrosterone; Energy Metabolism; Estrogens; Female; Ghrelin; Homeostasis; Humans; Insulin; Leptin; Middle Aged; Postmenopause; Testosterone; Weight Gain; Weight Loss

Although weight loss usually decreases very-low-density lipoprotein-triglyceride (VLDL-TG) secretion rate, the change in VLDL-TG kinetics is not directly related to the change in body weight. Circulating leptin also declines with weight loss and can affect hepatic lipid metabolism. The aim of this study was to determine whether circulating leptin is associated with weight loss-induced changes in VLDL-TG secretion.. Ten extremely obese subjects were studied. VLDL-TG secretion rate and the contribution of systemic (derived from lipolysis of subcutaneous adipose tissue TG) and non-systemic fatty acids (derived primarily from lipolysis of intrahepatic and intraperitoneal TG, and de novo lipogenesis) to VLDL-TG production were determined by using stable isotopically labelled tracer methods before and 1 year after gastric bypass surgery.. Subjects lost 33 +/- 12% of body weight, and VLDL-TG secretion rate decreased by 46 +/- 23% (p = 0.001), primarily because of a decrease in the secretion of VLDL-TG from non-systemic fatty acids (p = 0.002). Changes in VLDL-TG secretion rates were not significantly related to reductions in body weight, body mass index, plasma palmitate flux, free fatty acid or insulin concentrations. The change in VLDL-TG secretion was inversely correlated with the change in plasma leptin concentration (r = -0.72, p = 0.013), because of a negative association between changes in leptin and VLDL-TG secretion from non-systemic fatty acids (r = -0.95, p < 0.001).. Weight loss-induced changes in plasma leptin concentration are inversely associated with changes in VLDL-TG secretion rate. Additional studies are needed to determine whether the correlation between circulating leptin and VLDL-TG secretion represents a cause-and-effect relationship.

Topics: Adult; Body Mass Index; Female; Gastric Bypass; Humans; Leptin; Lipid Metabolism; Lipoproteins, VLDL; Male; Obesity, Morbid; Triglycerides; Weight Loss

Cannabinoid-1 (CB(1)) receptor antagonists exhibit pharmacological properties favorable to treatment of obesity, caused by both centrally mediated effects on appetite and peripherally mediated effects on energy metabolism. However, the relative contribution of these effects to the weight loss produced by CB(1) receptor antagonists remains unclear. Here, we compare food intake-related and independent effects of the CB(1)-selective antagonist 1-(7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl)-3-(methylamino) azetidine-3-carboxamide (PF-95453) in obese cynomolgus monkeys. Monkeys were divided into three study groups (n = 10 each) and treated once daily for 8 weeks with either vehicle or PF-95453 as follows: 1, fed ad libitum and dosed orally with vehicle; 2, fed ad libitum and dosed orally with PF-95453 (0.5 mg/kg weeks 1-3, 1.0 mg/kg weeks 4-8); and 3, fed an amount equal to the amount consumed by the drug-treated group and dosed orally with vehicle (pair-fed). PF-95453 treatment significantly reduced food consumption by 23%, body weight by 10%, body fat by 39%, and leptin by 34% while increasing adiponectin by 78% relative to vehicle-treated controls. Pair-fed animals did not exhibit reductions in body weight or leptin but did show significantly reduced body fat (11%) and increased adiponectin (15%) relative to vehicle-treated controls but markedly less than after PF-95453 treatment. Indeed, significant differences were noted between the drug-treated and pair-fed groups with respect to body weight reduction, body fat reduction, increased adiponectin, and leptin reduction. Similar to humans, monkeys treated with the CB(1) receptor antagonist exhibited decreased body weight and body fat, a substantial portion of which seemed to be independent of the effects on food intake.

Topics: Adiponectin; Adiposity; Animals; Anti-Obesity Agents; Azetidines; Blood Glucose; Body Composition; Body Weight; Diet; Dogs; Dose-Response Relationship, Drug; Eating; Endpoint Determination; Feeding Behavior; Glucose Tolerance Test; Leptin; Lipids; Macaca fascicularis; Male; Obesity; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Triazines; Weight Loss

The aim of the present study was to determine the mechanisms underlying Type 2 diabetes remission after gastric bypass (GBP) surgery by characterizing the short- and long-term changes in hormonal determinants of blood glucose.. Eleven morbidly obese women with diabetes were studied before and 1, 6, and 12 months after GBP; eight non-diabetic morbidly obese women were used as controls. The incretin effect was measured as the difference in insulin levels in response to oral glucose and to an isoglycemic intravenous challenge. Outcome measures were glucose, insulin, C-peptide, proinsulin, amylin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) levels and the incretin effect on insulin secretion.. The decrease in fasting glucose (r = 0.724) and insulin (r = 0.576) was associated with weight loss up to 12 months after GBP. In contrast, the blunted incretin effect (calculated at 22%) that improved at 1 month remained unchanged with further weight loss at 6 (52%) and 12 (52%) months. The blunted incretin (GLP-1 and GIP) levels, early phase insulin secretion, and other parameters of β-cell function (amylin, proinsulin/insulin) followed the same pattern, with rapid improvement at 1 month that remained unchanged at 1 year.. The data suggest that weight loss and incretins may contribute independently to improved glucose levels in the first year after GBP surgery.

Topics: Adiponectin; Adult; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Female; Gastric Bypass; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin Secretion; Leptin; Middle Aged; Obesity, Morbid; Postoperative Period; Stomach; Weight Loss

Leptin, a cytokine-like protein, plays an important role in the regulation of body weight through inhibition of food intake and stimulation of energy expenditure. Leptin circulates in blood and acts on the brain, which sends downstream signals to regulate body weight. Leptin therapy has been successful in treating leptin deficient obese patients. However, high levels of leptin have been observed in more common forms of obesity indicating a state of leptin resistance which limits the application of leptin in the treatment of obesity. If the central effect of leptin could be by-passed and genes which respond to leptin treatment could be regulated directly, new therapeutic targets for the treatment of obesity may be possible. The purpose of this study was to identify genes and subsequent pathways correlated with leptin-mediated weight loss.. WE UTILIZED MICROARRAY TECHNOLOGY TO COMPARE HEPATIC GENE EXPRESSION CHANGES AFTER TWO TYPES OF LEPTIN ADMINISTRATION: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We identified 214 genes that correlate with leptin mediated weight loss. Several biological processes such as mitochondrial metabolic pathways, lipid metabolic and catabolic processes, lipid biosynthetic processes, carboxylic acid metabolic processes, iron ion binding and glutathione S-transferases were downregulated after leptin administration. In contrast, genes involved in the immune system inflammatory response and lysosomal activity were found to be upregulated. Among the cellular compartments mitochondrion (32 genes), endoplasmic reticulum (22 genes) and vacuole (8 genes) were significantly over represented.. In this study we have identified key molecular pathways and downstream genes which respond to leptin treatment and are involved in leptin-mediated weight loss. Many of these genes have previously been shown to be associated with obesity; however, we have also identified a number of other novel target genes. Further investigation will be required to assess the possible use of these genes and their associated protein products as therapeutic targets for the treatment of obesity.

Topics: Adipocytes; Animals; Body Weight; Carboxylic Acids; Cell Differentiation; Cell Proliferation; Cluster Analysis; Down-Regulation; Drug Administration Routes; Eating; Female; Gene Expression Profiling; Glutathione Transferase; Hypothalamus; Inflammation; Insulin; Iron; Leptin; Lipid Metabolism; Liver; Lysosomes; Mice; Mitochondria; Obesity; Oligonucleotide Array Sequence Analysis; Weight Loss

Although serum TSH is often elevated in obesity and may be linked to disorders of lipid and glucose metabolism, the clinical relevance of these relationships remains unclear.. Subjects were obese children and adolescents (n=206; mean age 14 yr) undergoing rapid weight and fat loss in a standardized, multidisciplinary, 2-month, in-patient weight loss program.. This was a prospective study that determined thyroid function, glucose and lipid parameters, leptin, anthropometric measures, and body composition measured by dual-energy x-ray absorption at baseline and at the end of the intervention.. At baseline, 52% of children had TSH concentrations in the high normal range (>2.5 mU/liter), but TSH was not correlated with body weight, body mass index sd scores, lean body mass, or body fat percentage. At baseline, independent of adiposity, TSH significantly correlated with total cholesterol (P=0.008), low-density lipoprotein cholesterol (P=0.013), fasting insulin (P=0.010), homeostatic model assessment (HOMA) (P=0.004), and leptin (P=0.006). During the intervention, mean body fat, TSH, HOMA, and fasting insulin decreased by 21, 11, 53, and 54%, respectively. Change (Δ) in TSH did not correlate with Δbody weight or Δbody composition, but ΔTSH significantly correlated with, Δfasting insulin and ΔHOMA, independent of Δbody weight or Δbody composition (P<0.05).. TSH concentrations are elevated in obese children but are not correlated with the amount of excess body weight or fat. During weight loss, independent of changes in body weight or composition, decreases in elevated serum TSH predict decreases in fasting insulin and HOMA. These findings suggest interventions that target high TSH concentrations during weight loss in obese subjects may improve insulin sensitivity.

Topics: Adipose Tissue; Adolescent; Body Composition; Body Mass Index; Body Weight; Fasting; Female; Humans; Insulin; Leptin; Male; Obesity; Patient Selection; Physical Fitness; Reference Values; Regression Analysis; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine; Weight Loss

Some healthy older adults have difficulty regaining weight after acute weight loss, and the reason for this failure to regain weight is unknown. The objective of this study was to determine if elevated leptin or pro-inflammatory cytokine levels are associated with failure to regain weight over two years after an acute weight loss intervention.. Two year prospective study after an acute weight loss intervention.. University of Washington Medical Center from 2001-2006.. Nineteen older (≥ 70 years old) men and women.. Body weights, health status questionnaire, body composition data, serum leptin, glucose, insulin, C- reactive protein and pro-inflammatory cytokine levels were measured every six months for two years.. Five subjects out of 19 failed to regain weight after two years. The subjects who failed to regain weight after 2 years had higher circulating levels of tumor necrosis factor receptor particle 55 (TNFRp55) at baseline and at 6, 12, 18 and 24 months of follow up compared to subjects who regained weight after 2 years (P = 0.02 ).. Five out of 19 older subjects had difficulty regaining weight for up to 2 years following an acute weight loss intervention, and their TNFRp55 levels were persistently higher than in subjects who regained weight. Greater TNF α action, as reflected by higher circulating levels of TNFRp55, could be contributing towards inability of some older persons to regain weight after acute weight loss.

Topics: Aged; Aged, 80 and over; Cytokines; Diet, Reducing; Female; Follow-Up Studies; Humans; Inflammation Mediators; Leptin; Male; Receptors, Tumor Necrosis Factor, Type I; Thinness; Tumor Necrosis Factor Decoy Receptors; Weight Loss

The present study tested the hypothesis that a saturated fatty acid (SFA)-rich diet is more obesogenic than diets with lower SFA content. In 8 female Sprague-Dawley rats fed a low-SFA canola or a moderate-SFA lard-rich diets at 67% of energy for 26 days, body weight gain, final body weight, obesity index, and food and energy intake were comparable. Twenty-nine rats were fed canola or high-SFA butter-rich diets (67% of energy) or chow for 50 days; then high-fat feeding was followed by ad libitum low-fat feeding (27% of energy) for 28 days and by a food-restricted low-fat diet for 32 days. High-fat feeding resulted in a greater body weight gain (P < .04), final body weight (P < .04), and energy intake (P < .008) in butter-fed rats than in canola- and chow-fed controls, after 26 or 50 days. Ad libitum canola and butter low-fat diets or chow feeding resulted in similar weight change, whereas food-restricted low-fat diets led to comparable weight loss and final weight. Canola-fed animals adjusted their intake based on diet energy density, whereas lard and butter-fed animals failed to do so. Abdominal fat (P = .012) and plasma leptin (P = .005) were higher in chow-fed controls than in canola-fed rats, but comparable with those of butter-fed rats. Prone and resistant phenotypes were detected with high-fat feeding. In conclusion, only feeding the high-SFA butter-rich diet led to obesity development and failure to adjust intake based on the energy density and preserving body fat even after weight loss. The high availability of SFA-rich foods in today's obesogenic environment could contribute to develop and maintain obesity.

Topics: Abdominal Fat; Animals; Appetite Regulation; Body Weight; Butter; Diet, Fat-Restricted; Diet, Reducing; Dietary Fats; Energy Intake; Fatty Acids; Fatty Acids, Monounsaturated; Female; Food Deprivation; Leptin; Obesity; Rapeseed Oil; Rats; Rats, Sprague-Dawley; Weight Gain; Weight Loss

In rodents, ovariectomy (OVX) elicits weight gain and diminished responsiveness to homeostatic signals. Here we characterized the response of obese OVX rats to peripheral amylin. Rats received sham surgery (SHAM), OVX, or OVX with hormonal replacement (17β-estradiol, 2 μg per 4 d; OVX+E) and were infused with vehicle or amylin (50 μg/kg · d) for 28 d. Amylin reduced body weight (5.1 ± 1.1%) and food intake (10.9 ± 3.4%) in SHAM rats but was twice as efficacious in OVX rats in reducing weight (11.2 ± 1.9%) and food intake (23.0 ± 2.0%). There were no differences between amylin-treated SHAM and OVX+E rats. OVX decreased metabolic rate (∼24%) and increased respiratory exchange ratio relative to SHAM. Amylin partially normalized metabolic rate (13% increase) in OVX rats and decreased respiratory exchange ratio in OVX and SHAM rats. Regarding central mechanisms, amylin infusion corrected the OVX-induced decrease in hippocampal neurogenesis and increased immobility in the forced swim test. Additionally, amylin increased neurogenesis (∼2-fold) within the area postrema of OVX rats. To assess the contribution of endogenous leptin to amylin-mediated weight loss in OVX rats, amylin was administered to SHAM or OVX Zucker diabetic fatty rats. In SHAM rats, amylin infusion reduced food intake but not body weight, whereas in OVX Zucker diabetic fatty rats, food intake, body weight, and insulin were reduced. Overall, amylin induced greater body weight loss in the absence of estradiol via central and peripheral actions that did not require leptin. These findings support the clinical investigation of amylin in low estradiol (e.g. postmenopausal) states.

Topics: Animals; Diet; Eating; Energy Metabolism; Estradiol; Female; Islet Amyloid Polypeptide; Leptin; Obesity; Ovariectomy; Oxygen Consumption; Rats; Rats, Zucker; Signal Transduction; Swimming; Weight Loss

Topics: Adult; Body Mass Index; Carcinoma; Child, Preschool; Fasting; Humans; Hypothyroidism; Insulin; Leptin; Obesity; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine; Weight Loss

The levels of circulating nonesterified fatty acids increase during obesity and contribute to insulin resistance by inhibiting insulin-stimulated glucose transport and phosphorylation in human muscles. In cells, glucose-6-phosphate is primarily used in glycogenesis and glycolysis; only 1% to 3% is converted to glucosamine-6-phosphate, which enters the hexosamine-biosynthesis pathway. The major end product of this pathway, uridine-5'-diphosphate-N-acetyl-glucosamine, which is increased by exogenous glucosamine (GlcN) administration, mediates insulin resistance. We hypothesized that the administration of GlcN to rats receiving a high-fat (HF) diet may potentiate the effects of an HF diet on glucose tolerance and other metabolic variables. To evaluate this relationship, 2 groups of rats were fed with a control or HF diet; and another 2 groups received glucosamine hydrochloride at a dose of 500 mg/kg dissolved in drinking water for 21 weeks. Metabolic variables related to insulin resistance were then measured. The levels of blood glucose and serum insulin were higher in a glucose tolerance test in the HF group as compared with the control group. Rats receiving GlcN had reduced liver glycogen and only slightly worsened glucose tolerance as compared with control rats, although this did not induce insulin resistance as evaluated by the homeostasis model assessment. Glucosamine administration was able to partially or completely inhibit some effects of the HF diet by reducing fat depot weight and serum leptin levels, thus resulting in a smaller increase in the insulinemic response to a glucose injection and lower postabsorptive glycemia.

Topics: Animals; Blood Glucose; Body Weight; Diet; Dietary Fats; Fatty Acids, Nonesterified; Glucosamine; Glucose Tolerance Test; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Obesity; Rats; Rats, Wistar; Weight Loss

Rapid weight loss with very-low-calorie diet (VLCD) is known to improve insulin sensitivity and decrease adipose tissue masses. The aim was to investigate the effects of VLCD on adipose tissue regional glucose uptake (rGU) and perfusion and their association with adipokines.. Sixteen healthy obese (body mass index 33+/-1.1 kg/m(2)) subjects underwent VLCD for 6 weeks. RGU and perfusion were measured using [(18)F]-fluoro-deoxy-glucose, [(15)O]H(2)O and positron emission tomography.. Blood-flow and rGU expressed per gram of adipose tissue were higher in visceral fat compared to abdominal subcutaneous fat (P<0.01 for both). Dieting decreased weight by 11+/-0.9 kg (P<0.0001). Visceral adipose fat decreased by 25% (P<0.001) and abdominal subcutaneous fat by 16% (P<0.001). Whole body insulin sensitivity increased by 33% (P<0.01). Perfusion of both fat depots decreased (P<0.001), while rGU remained unchanged. Among the adipokines, leptin and interleukin-6 levels seemed to be associated with abdominal subcutaneous and intra-abdominal adipose tissue insulin resistance but not with adipose tissue perfusion.. Abdominal adipose tissue perfusion and rGU are not related in obesity. Rapid weight loss decreases perfusion through adipose tissue depots but has no influence on rGU demonstrating the 'sink' role of adipose tissue.

Topics: Abdominal Fat; Adult; Blood Glucose; Body Mass Index; Caloric Restriction; Female; Humans; Image Processing, Computer-Assisted; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Leptin; Magnetic Resonance Imaging; Male; Middle Aged; Obesity; Positron-Emission Tomography; Regional Blood Flow; Weight Loss

We previously reported that the plasma levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), in a cohort of viscerally obese men are directly correlated with visceral adipose tissue (VAT) accumulation and metabolic risk factors including low HDL-cholesterol and high triacylglycerol. It is not known, however, if such correlations persist after vigorous lifestyle interventions that reduce metabolic risk factors. We analysed the changes in endocannabinoid levels in a subsample from the same cohort following a 1 year lifestyle modification programme, and correlated them with changes in VAT and metabolic risk factors.. Forty-nine viscerally obese men (average age 49 years, BMI 30.9 kg/m(2), waist 107.3 cm) underwent a 1 year lifestyle modification programme including healthy eating and physical activity. Plasma levels of 2-AG and the other most studied endocannabinoid, anandamide, were measured by liquid chromatography-mass spectrometry. Anthropometric and metabolic risk factors, including VAT, insulin resistance and glucose intolerance, HDL-cholesterol and triacylglycerol, were measured.. Most risk factors were improved by the intervention, which led to a significant decrease in body weight (-6.4 kg, p < 0.0001), waist circumference (-8.0 cm, p < 0.0001) and VAT (-30%, p < 0.0001), and in plasma 2-AG (-62.3%, p < 0.0001) and anandamide (-7.1%, p = 0.005) levels. The decrease in levels of 2-AG but not those of anandamide correlated with decreases in VAT and triacylglycerol levels, and with the increase in HDL(3)-cholesterol levels. Multivariate analyses suggested that decreases in 2-AG and VAT were both independently associated with decreases in triacylglycerol.. This study shows that a strong correlation exists between 2-AG levels and high plasma triacylglycerol and low HDL(3)-cholesterol in viscerally obese men.

Topics: Adiponectin; Adipose Tissue; Apolipoproteins; Arachidonic Acids; Body Mass Index; Body Weight; C-Reactive Protein; Endocannabinoids; Glycerides; Humans; Interleukin-6; Leptin; Life Style; Lipids; Male; Obesity; Risk Factors; Triglycerides; Waist Circumference; Weight Loss

Because information on weight changes after lifestyle intervention in children with mutations in the melanocortin 4 receptor (MC4R) gene is scarce, we compared weight changes after lifestyle intervention between children with and without MC4R variations. A group of 514 overweight children (aged 5-16 years), who presented to participate in a 1-year lifestyle intervention based on exercise, behavior, and nutrition therapy were screened for MC4R mutations. For comparison, children with MC4R mutations leading to reduced receptor function (group A) were each of them randomly matched with five children of same age and gender without MC4R mutations (group B). Changes of weight status were analyzed as change of BMI standard deviation scores (BMI-SDSs). Furthermore, 16 children (3.1%) harbored MC4R mutations leading to reduced receptor function, and 17 (3.3%) children carried variations not leading to reduced receptor function. Children with and without MC4R mutations reduced their overweight at the end of intervention to a similar degree (P = 0.318 between groups based on an intention-to-treat analysis). The maintenance of weight loss after intervention among children with MC4R mutations leading to reduced receptor function failed in contrast to children without such mutations (P < 0.001 adjusted for BMI-SDS at baseline, age, and gender in an intention-to-treat analysis). In conclusion, children with MC4R mutations leading to reduced receptor function were able to lose weight in a lifestyle intervention but had much greater difficulties to maintain this weight loss supporting the impact of these mutations on weight status.

Topics: Adolescent; Child; Child, Preschool; Exercise; Female; Humans; Insulin; Leptin; Life Style; Male; Mutation; Nutrition Therapy; Obesity; Receptor, Melanocortin, Type 4; Weight Loss

Leptin may favorably respond to fat mass (FM) losses induced by a low-carbohydrate (LC) diet, although this is unclear. We examined serum leptin concentrations in women in midlife undergoing different dietary approaches to body weight (BW) loss. Women followed either a LC, high-protein (LCHP; n = 13) or high-carbohydrate, low-fat (HCLF; n = 12) diet for 12 weeks. Changes in anthropometric and soft-tissue mass measurements and leptin concentrations were assessed. Women in both diet groups had reductions in BW, BMI, fat-free soft-tissue mass, FM, body fat percentage, and central abdominal fat (CAF) (P < 0.001 for all variables) over the 12-week intervention. These changes were not significantly different between diet groups. Serum leptin concentrations decreased by 41.8% (P < 0.001) in the LCHP group and by 44.3% (P < 0.001) in the HCLF group from baseline to week 12, with no significant difference between groups. The association of CAF (r = 0.73) and FM (r = 0.83) change with leptin change was strong in the HCLF group. Leptin change did not relate to change in any variable in the LCHP group. Both LCHP and HCLF diets favorably lower FM, CAF, and leptin in women, suggesting that beneficial changes in leptin can be similarly achieved through different dietary approaches to BW loss.

Topics: Abdomen; Adipose Tissue; Adult; Body Mass Index; Body Weight; Diet, Reducing; Female; Humans; Leptin; Weight Loss

Leptin is intimately intertwined in the molecular pathophysiology of several cancer types; with regard to lung cancer, however, limited research has been conducted, with overall conflicting results.. The present case-control study comprises 66 non-small-cell lung cancer (NSCLC) cases and 132 healthy controls matched for gender and age. Lifestyle, sociodemographic and medical history information has been obtained in addition to body mass index (BMI) measurements and weight change during the last 2 months. Serum leptin and adiponectin levels were determined following a standard protocol.. In multiple logistic regression analyses, elevated serum leptin emerged as a risk factor for NSCLC independent of central obesity, more pronounced after controlling for BMI and recent weight loss (odds ratio = 4.58, 95% confidence interval: 1.94-10.82). Additionally, smoking and animal foods consumption were strongly associated with the disease, whereas plant foods consumption showed a protective association.. The observed higher serum leptin levels in NSCLC cases might be attributed to direct or indirect effects mediated by cancer- or cachexia-related cytokines. In line with the growth-promoting properties of leptin in the lung tissue documented elsewhere, increased serum leptin concentration may represent a tumor-promoting event during non-small-cell lung carcinogenesis.

Topics: Animals; Body Mass Index; Carcinoma, Non-Small-Cell Lung; Diet; Greece; Humans; Leptin; Life Style; Lung Neoplasms; Meat; Middle Aged; Neoplasm Staging; Overweight; Reference Values; Risk Factors; Smoking; Weight Loss

Methotrexate (MTX) has been frequently used in the treatment of rheumatoid arthritis (RA). However, its action on arthritis associated male hypogonadism, or anorexia related low leptin production has not yet been studied. The well-established model of human RA is rat adjuvant-induced arthritis (AA). In the present series we aimed at the evaluation of the effects of MTX on AA induced inflammatory parameters, testosterone suppression, and anorexia associated lowered leptin release. AA was induced in male Lewis rats by intradermal injection of heat killed Mycobacterium butyricum in incomplete Freund's adjuvant in the base of the tail. Arthritic rats were treated with two doses of MTX: 0.3 and 0.5 mg/kg twice a week orally for the period of 28 days. The evaluated parameters were body mass, hind-paw swelling, arthrogram scores, serum albumin, total testosterone and leptin on days 14, 21 and 28 of AA. MTX treatment ameliorated all parameters studied dose dependently. Higher dose of MTX induced a significant reduction in the hind-paw swelling, arthritic score, and an increase in serum albumin in all examined time intervals of AA. This dose also significantly improved the suppressed testosterone and leptin levels found in arthritic rats. Prophylactic MTX treatment of rats with AA improved all inflammatory and arthritic parameters studied indicating its clear anti-inflammatory effects. The significant improvement of testosterone and leptin shows beneficial effects of MTX on reproduction and anorexia related leptin reduction during chronic AA.

Topics: Animals; Anorexia; Arthritis, Experimental; Dose-Response Relationship, Drug; Drug Administration Schedule; Leptin; Male; Methotrexate; Rats; Rats, Inbred Lew; Serum Albumin; Testis; Testosterone; Weight Loss

We have previously demonstrated the therapeutic usefulness of leptin in lipoatrophic diabetes and insulin-deficient diabetes in mouse models and could also demonstrate its dramatic effects on lipoatrophic diabetes in humans. The aim of the present study was to explore the therapeutic usefulness of leptin in a mouse model of type 2 diabetes with increased adiposity.. To generate a mouse model mimicking human type 2 diabetes with increased adiposity, we used a combination of low-dose streptozotocin (STZ, 120 microg/g body weight) and high-fat diet (HFD, 45% of energy as fat). Recombinant mouse leptin was infused chronically (20 ng [g body weight](-1) h(-1)) for 14 days using a mini-osmotic pump. The effects of leptin on food intake, body weight, metabolic variables, tissue triacylglycerol content and AMP-activated protein kinase (AMPK) activity were examined.. Low-dose STZ injection led to a substantial reduction of plasma insulin levels and hyperglycaemia. Subsequent HFD feeding increased adiposity and induced insulin resistance and further augmentation of hyperglycaemia. In this model mouse mimicking human type 2 diabetes (STZ/HFD), continuous leptin infusion reduced food intake and body weight and improved glucose and lipid metabolism with enhancement of insulin sensitivity. Leptin also decreased liver and skeletal muscle triacylglycerol content accompanied by an increase of alpha2 AMPK activity in skeletal muscle. Pair-feeding experiments demonstrated that leptin improved glucose and lipid metabolism independently of the food intake reduction.. This study demonstrates the beneficial effects of leptin on glycaemic and lipid control in a mouse model of type 2 diabetes with increased adiposity, indicating the possible clinical usefulness of leptin as a new glucose-lowering drug in humans.

Topics: Adipose Tissue; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dietary Fats; Energy Intake; Leptin; Male; Mice; Mice, Inbred C57BL; Streptozocin; Weight Loss

Although bariatric surgery is the most common procedure used to induce weight loss in morbidly obese patients, its effect on plasma satiety factors (leptin, ghrelin, and apolipoprotein (apo)-AIV) is controversial. The aim of this work was to analyze these parameters before and at different times after surgery.. Plasma was obtained from 34 patients before undergoing Roux-en-Y gastric bypass and during weight loss in the 12 months following surgery.. Morbidly obese patients had significantly higher values (147%) of leptin than normal-weight (NW) persons, while their ghrelin levels were 46% less than NW. Apo-AIV levels had approximately the same value in both groups (obese and NW). During weight loss, leptin decreased by 75% and ghrelin increased by 78%. Both parameters reached values less than or near NW, respectively, at 1 year after surgery. During the first month after surgery, apo-AIV plasma levels decreased (47%) but later increased and finally returned to preoperative values. Apo-AIV levels were correlated negatively with leptin and positively with ghrelin. High-density lipoprotein (HDL) levels were positively correlated with those of ghrelin and apo-AIV.. During weight loss, plasma leptin and ghrelin could be good markers of total fat decrease. Ghrelin could also indicate gastric mucous improvement, whereas apo-AIV could indicate the recovery of intestinal function. Changes produced in the HDL levels of morbidly obese patients during weight loss suggest a decreased risk of coronary disease.

Topics: Adipose Tissue; Adult; Apolipoproteins A; Biomarkers; Female; Gastric Bypass; Ghrelin; Humans; Insulin; Leptin; Lipid Metabolism; Male; Middle Aged; Obesity, Morbid; Satiation; Thinness; Time Factors; Weight Loss

Weight loss is a common problem in Parkinson's disease (PD), but the causative mechanisms behind this weight loss are unclear. We compared 26 PD patients with sex and age matched healthy controls. Examinations were repeated at baseline, after one and after two years. Body fat mass was measured by Dual X-ray Absorptiometry (DXA). Seventy three per cent of the PD patients lost body weight. Loss of body fat mass constituted a considerable part of the loss of body weight. In the patients who lost weight, serum leptin levels were lower than in those who did not lose weight. The relationship between low body fat mass and low leptin levels seems to be relevant, at least for female PD patients. It is reasonable to believe that low leptin levels in these patients could be secondary to the decreased body fat mass.

Topics: Absorptiometry, Photon; Adipose Tissue; Aged; Antiparkinson Agents; Female; Follow-Up Studies; Humans; Leptin; Levodopa; Male; Middle Aged; Parkinson Disease; Radioimmunoassay; Sex Factors; Statistics, Nonparametric; Weight Loss

Long-term maintenance of a dietary-induced weight loss continues to be a major health problem and warrants research on innovative approaches to understand weight stability. We investigated the role of the proinflammatory status on weight changes in obese subjects receiving a low-calorie diet (LCD) and during the subsequent 6-month weight maintenance period.. Eighty-four subjects (age: 34.2 +/- 0.53 years; body mass index, BMI: 30.4 +/- 1.8 kg/m(2)) followed an 8-week LCD intervention and were contacted again 6 months later. Body composition, circulating proinflammatory markers [tumor necrosis factor (TNF)alpha, interleukin-6, C-reactive protein and leptin] and mRNA levels of inflammation-related genes [TNFalpha and nuclear factor (NF) kappaB transcription subunits] in peripheral blood mononuclear cells (PBMC) were evaluated.. The 6-month weight regain was predicted by high concentrations of TNFalpha at LCD completion (OR = 4.21, p = 0.036) along with the baseline amount of fat mass (OR = 7.23, p = 0.029). In addition, baseline leptin concentrations (p = 0.028) as well as mRNA levels of TNFalpha and NFkappaB subunits were higher at the end of the dietary intervention (p < 0.05) in PBMC of subjects who regained >or=10% of the dietary-induced weight loss.. These findings demonstrate a role for the proinflammatory state and body adiposity in the prediction of weight-loss regain. This relationship could contribute to the design of more personalized nutritional treatments in obese patients and favor the weight maintenance process.

Topics: Adult; C-Reactive Protein; Female; Gene Expression Profiling; Humans; Inflammation; Interleukin-6; Leptin; Leukocytes, Mononuclear; Male; NF-kappa B; Nutrigenomics; Obesity; Predictive Value of Tests; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Gain; Weight Loss; Young Adult

Adrenomedullin (ADM) is a vasoactive peptide found to be related to obesity and its comorbidities: type 2 diabetes, hypertension, atherosclerosis, and coronary heart disease. ADM is increased both in plasma and in adipose tissue of obese individuals when compared to lean subjects and is considered as a member of the adipokine family. We determined plasma midregional proadrenomedullin (MR-proADM) concentrations in a cohort of 357 subjects with BMI ranging from 17.5 to 42.3 kg/m2 and no additional medical history. In parallel, 28 severely obese patients scheduled to undergo laparoscopic Roux-en-Y gastric bypass (RYGB) surgery were studied at two time points: before and 1 year after surgery. Outcome measurements were: MR-proADM, cortisol, leptin, C-reactive protein (CRP) thyroid-stimulating hormone (TSH), creatinine and metabolic parameters. BMI correlated significantly to plasma MR-proADM levels (r=0.714, P<0.001), also after adjustment for age and gender (r=0.767, P<0.001). In obese subjects, there was a positive relationship between MR-proADM and leptin (r=0.511, P=0.006). Following RYGB, plasma MR-proADM decreased from 0.76+/-0.03 to 0.62+/-0.02 pg/ml (P<0.0001). RYGB-induced changes in MR-proADM correlated significantly to changes in leptin (r=0.533, P=0.004) and in CRP (r=0.429, P=0.023). We conclude that BMI is an independent predictor of circulating MR-proADM levels. Weight loss after RYGB is associated with a significant decrease in plasma MR-proADM, which is related to surgery-induced changes in both circulating leptin and systemic inflammation.

Topics: Adrenomedullin; Biomarkers; Body Mass Index; Cross-Sectional Studies; Down-Regulation; Female; Gastric Bypass; Humans; Inflammation Mediators; Leptin; Male; Obesity; Protein Precursors; Severity of Illness Index; Time Factors; Treatment Outcome; Weight Loss

The effects of 2 diets with different protein contents on weight loss and subsequent maintenance was assessed in obese cats. The control group [Co; n = 8; body condition score (BCS) = 8.6 +/- 0.2] received a diet containing 21.4 g crude protein (CP)/MJ of metabolizable energy and the high-protein group (HP; n = 7; BCS = 8.6 +/- 0.2) received a diet containing 28.4 g CP/MJ until the cats achieved a 20% controlled weight loss (0.92 +/- 0.2%/wk). After the weight loss, the cats were all fed a diet containing 28.0 g CP/MJ at an amount sufficient to maintain a constant body weight (MAIN) for 120 d. During weight loss, there was a reduction of lean mass in Co (P < 0.01) but not in HP cats and a reduction in leptinemia in both groups (P < 0.01). Energy intake per kilogram of metabolic weight (kg(-0.40)) to maintain the same rate of weight loss was lower (P < 0.04) in the Co (344 +/- 15.9 kJ x kg(-0.40) x d(-1)) than in the HP group (377 +/- 12.4 kJ. x kg(-0.40) x d(-1)). During the first 40 d of MAIN, the energy requirement for weight maintenance was 398.7 +/- 9.7 kJ.kg(-0.40) x d(-1) for both groups, corresponding to 73% of the NRC recommendation. The required energy gradually increased in both groups (P < 0.05) but at a faster rate in HP; therefore, the energy consumption during the last 40 d of the MAIN was higher (P < 0.001) for the HP cats (533.8 +/- 7.4 kJ x kg(-0.40) x d(-1)) than for the control cats (462.3 +/- 9.6 kJ x kg(-0.40) x d(-1)). These findings suggest that HP diets allow a higher energy intake to weight loss in cats, reducing the intensity of energy restriction. Protein intake also seemed to have long-term effects so that weight maintenance required more energy after weight loss.

Topics: Animals; Body Composition; Cat Diseases; Cats; Dietary Proteins; Energy Intake; Female; Insulin; Leptin; Male; Nitrogen; Nutritional Requirements; Obesity; Weight Loss

The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) Project uses comprehensive metabolic profiling to probe biochemical mechanisms of weight loss in humans. Measurements at baseline, 2 and 4 weeks, 6 and 12 months included diet, body composition, metabolic rate, hormones, and 80 intermediary metabolites measured by mass spectrometry. In 27 obese adults in a behavioral weight loss intervention, median weight decreased 13.9 lb over the first 6 months, then reverted towards baseline by 12 months. Insulin resistance (HOMA) was partially ameliorated in the first 6 months and showed sustained improvement at 12 months despite weight regain. Ghrelin increased with weight loss and reverted to baseline, whereas leptin and PYY fell at 6 months and remained persistently low. NPY levels did not change. Factors possibly contributing to sustained improvement in insulin sensitivity despite weight regain include adiponectin (increased by 12 months), IGF-1 (increased during weight loss and continued to increase during weight regain), and visceral fat (fell at 6 months but did not change thereafter). We observed a persistent reduction in free fatty acids, branched chain amino acids, and related metabolites that may contribute to improved insulin action. These findings provide evidence for sustained benefits of weight loss in obese humans and insights into mechanisms.

Topics: Adiponectin; Adult; Behavior Therapy; Biomarkers; Body Weight; Diet; Energy Metabolism; Female; Ghrelin; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Middle Aged; Neuropeptide Y; Obesity; Peptide YY; Weight Gain; Weight Loss

Behavioral therapies aimed at reducing excess body fat result in limited fat loss after dieting. To understand the causes for maintenance of adiposity, high-fat (HF) diet-induced obese (DIO) mice were switched to a low-fat chow diet, and the effects of chow on histological and molecular alterations of adipose tissue and metabolic parameters were examined. DIO mice reduced and stabilized their body weights after being switched to chow (HF-chow), but retained a greater amount of adiposity than chow-fed mice. Reduction in adipocyte volume, not number, caused a decrease in fat mass. HF-chow mice showed normalized circulating insulin and leptin levels, improved glucose tolerance, and reduced inflammatory status in white adipose tissue (WAT). Circulating leptin levels corrected for fat mass were lower in HF-chow mice. Leptin administration was used to test whether reduced leptin level of HF-chow mice inhibited further fat loss. Leptin treatment led to an additional reduction in adiposity. Finally, HF-HF mice had lower mRNA levels of beta(3) adrenergic receptor (beta(3)-AR) in epididymal WAT (EWAT) compared to chow-fed mice, and diet change led to an increase in the WAT beta(3)-AR mRNA levels that were similar to the levels of chow-fed mice, suggesting an elevation in sympathetic activation of WAT during diet switch relative to HF-HF mice leading to the reduced leptin level and proinflammatory cytokine content. In summary, HF-chow mice were resistant to further fat loss due to leptin insufficiency. Diet alteration from HF to low fat improved metabolic state of DIO mice, although their adiposity was defended at a higher level.

Topics: Adipose Tissue, Brown; Adipose Tissue, White; Adiposity; Animals; Blood Glucose; Cell Size; Diet, Fat-Restricted; Dietary Fats; Disease Models, Animal; Eating; Fatty Liver; Feeding Behavior; Inflammation; Insulin; Leptin; Macrophages; Male; Mice; Mice, Inbred C57BL; Obesity; Receptors, Adrenergic, beta-3; RNA, Messenger; Time Factors; Weight Loss

Bariatric surgery reverses obesity-related comorbidities, including type 2 diabetes mellitus. Several studies have already described differences in anthropometrics and body composition in patients undergoing Roux-en-Y gastric bypass compared with laparoscopic adjustable gastric banding, but the role of adipokines in the outcomes after the different types of surgery is not known. Differences in weight loss and reversal of insulin resistance exist between the 2 groups and correlate with changes in adipokines.. Fifteen severely obese women (mean body mass index [BMI]: 46.7 kg/m(2)) underwent 2 types of laparoscopic weight loss surgery (Roux-en-Y gastric bypass=10, adjustable gastric banding=5). Weight, waist and hip circumference, body composition, plasma metabolic markers, and lipids were measured at set intervals during a 24-month period after surgery.. At 24 months, patients who underwent Roux-en-Y were overweight (BMI 29.7 kg/m(2)), whereas patients who underwent gastric banding remained obese (BMI 36.3 kg/m(2)). Patients who underwent Roux-en-Y lost significantly more fat mass than patients who underwent gastric banding (mean difference 16.8 kg, P<.05). Likewise, leptin levels were lower in the patients who underwent Roux-en-Y (P=.003), and levels correlated with weight loss, loss of fat mass, insulin levels, and Homeostasis Model of Assessment 2. Adiponectin correlated with insulin levels and Homeostasis Model of Assessment 2 (r=-0.653, P=.04 and r=-0.674, P=.032, respectively) in the patients who underwent Roux-en-Y at 24 months.. After 2 years, weight loss and normalization of metabolic parameters were less pronounced in patients who underwent gastric banding compared with patients who underwent Roux-en-Y gastric bypass. Our findings require confirmation in a prospective randomized trial.

Topics: Adipokines; Adiponectin; Bariatric Surgery; Biomarkers; Body Weight; Female; Follow-Up Studies; Humans; Insulin; Insulin Resistance; Laparoscopy; Leptin; Middle Aged; Obesity, Morbid; Postoperative Period; Recovery of Function; Time Factors; Treatment Outcome; Weight Loss

Adipocytes express all components of the renin-angiotensin system, and the renin-angiotensin system is involved in obesity and insulin resistance. Circulating angiotensin II (Ang II) is detectable in blood, but its significance in human obesity remains unknown. The aim of this study was to investigate plasma Ang II in obese patients with type 2 diabetes mellitus (T2D) and the change during weight loss. Fifty Japanese obese subjects with T2D (body weight, 75.0 +/- 14.1 kg; body mass index, 29.1 +/- 3.7 kg/m(2); visceral fat area [VFA], 169.3 +/- 54.3 cm(2); hemoglobin A(1c), 7.6% +/- 1.5%) were enrolled. The subjects were prescribed a diet of daily caloric intake of 20 kcal/kg for 24 weeks. Plasma Ang II was measured by radioimmunoassay. Leptin, adiponectin, and lipoprotein lipase mass in preheparin serum were also measured as adipocyte-derived factors. After 24 weeks of weight reduction diet, the mean body weight, VFA, and hemoglobin A(1c) decreased significantly by 2.3%, 7.0%, and 8.3%, respectively. The mean plasma Ang II decreased by 24% (P < .0001) and correlated with body weight both at baseline (r = 0.425, P = .0018) and at 24 weeks (r = 0.332, P = .0181). The change in Ang II correlated with changes in body weight (r = 0.335, P = .0167) and VFA (r = 0.329, P = .0191). The change in Ang II also correlated positively with change in leptin (r = 0.348, P = .0127) and tended to correlate negatively with change in lipoprotein lipase mass in preheparin serum (r = -0.260, P = .0683), which is a marker of insulin sensitivity. Plasma Ang II is associated with body weight, decreases during weight loss, and is associated with markers of insulin resistance in obese subjects with T2D.

Topics: Adiponectin; Adipose Tissue; Angiotensin II; Blood Pressure; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Leptin; Lipoprotein Lipase; Male; Middle Aged; Obesity; Tomography, X-Ray Computed; Weight Loss

In this study, we measured ghrelin and leptin in obese Zucker rats after weight loss induced by calorie restriction using either a low-fat (LF) or high-energy palatable (HEPa) diet. After weight loss, the animals were refed lab chow and offered one hour-palatable test meals on the second and fifteenth days of refeeding. Both LF and HEPa rats lost 10% of their initial body weight (P<0.0001). Plasma ghrelin increased with calorie restriction in both groups (P<0.002) with a tendency to a higher increase in the HEPa group while plasma leptin decreased only in the LF group (P<0.01). Both groups ate the same quantity of chow during refeeding and both groups gorged on palatable diet during test meals at a very high constant intensity in HEPa rats. After one week of refeeding, ghrelin levels remained elevated in HEPa rats (+33.2%; P<0.001) while returning to baseline in LF rats. Plasma leptin remained low in LF rats. We conclude that weight loss on a palatable diet is possible if total energy intake is controlled. After stopping restriction, when a palatable diet is available, observed gorging might be dependent on specific ghrelin and leptin changes.

Topics: Adiposity; Animals; Body Weight; Caloric Restriction; Diet; Energy Intake; Feeding Behavior; Ghrelin; Hyperphagia; Leptin; Male; Obesity; Rats; Rats, Zucker; Weight Loss

Genetic variation in the perilipin (PLIN) gene may play a role in the etiology and treatment of obesity.. To examine different polymorphisms in the PLIN gene in relation to body-weight regulation.. 118 subjects followed a 6 wk VLCD, followed by 1 year weight maintenance. Body-weight (BW), body composition, leptin concentration, and polymorphisms of the PLIN gene: PLIN1:rs2289487, PLIN4:rs894160, PLIN6:rs1052700, PLIN5:rs2304795 and PLIN7:rs 2304796 were determined.. BW loss during VLCD was 7.0+/-3.1 kg (p<0.05), and BW regain was 3.7+/-1.4 kg (p<0.05), including changes in body mass index (BMI), waist-circumference, body-composition and leptin concentrations (p<0.05). Linkage disequilibria were observed between PLIN1 and PLIN4: D' >0.9, r2=0.72; PLIN5 and PLIN7: D' >0.9, r2=0.85. In men, body weight, BMI, waist circumference, body fat, leptin concentrations were significantly lower for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles). In women weight loss and loss of fat mass were larger for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles). For PLIN6 genotypes body weight and body fat were lower for homozygotes of the minor allele (T/T) in the men; in the women leptin concentrations were lower. The haplotype of PLIN5 and PLIN7 consisting of A/G and G/G of PLIN5 and A/A of PLIN7 showed a reduction in FM: 5.9+/-0.6 kg vs 3.1+/-0.4 kg, % body fat: 5.5+/-0.6% vs 2.2+/-0.2%, and leptin: 20.5+/-10.8 ng/ml vs 12.9+/-6.7 ng/ml over time in the women (p<0.05).. Since the haplotype of the minor alleles PLIN1-4, PLIN5-7 and PLIN6, was related to body-weight regulation at a lower level of body-weight in the men as well in the women we conclude that the PLIN1-4, 6, and 5-7 locus appears as a genetic influencer of obesity risk in humans.

Topics: Adult; Body Composition; Body Weight; Carrier Proteins; Female; Follow-Up Studies; Genetic Predisposition to Disease; Humans; Leptin; Male; Middle Aged; Obesity; Perilipin-1; Phosphoproteins; Risk Factors; Weight Loss

Adipose tissue physiology plays an important role in mediating disease risk. Weight loss in obese individuals improves indicators of adipocyte physiology. However, the minimum degree of weight loss required to elicit improvements remains unknown. The objective of the present study was to determine the minimum weight loss required to improve adipokine profile and decrease fat cell size in severely obese women. Thirteen severely obese women (body mass index, 50 +/- 3 kg/m(2); age, 35 +/- 1 years) consumed a low-calorie diet for 3 weeks with the goal of losing 5% of their initial weight. Subjects were divided into 2 weight loss groups posttreatment: less than 5% weight loss and 5% to 10% weight loss. Body weight was reduced (P < .05) in both groups (-1.4 +/- 1.0 and -6.8 +/- 0.6 kg, respectively). Adiponectin concentrations increased (P < .05) by 20% in the 5% to 10% weight loss group only. Likewise, leptin and resistin decreased (P < .05) by 37% and 27%, respectively, in the group that lost more weight. Visceral and subcutaneous fat cell size was 41% and 37% smaller (P < .01), respectively, in the 5% to 10% weight loss group. Smaller visceral adipocyte size was related to lower insulin (r = 0.82, P = .01) and glucose (r = 0.58, P = .04) concentrations posttreatment. These findings suggest that a minimum weight loss of 5% is required to improve adipokine profile and decrease fat cell size in severely obese women. These changes in adipocyte physiology may be linked to reductions in metabolic disease risk in this population.

Topics: Adipocytes; Adipokines; Adiponectin; Adult; Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Caloric Restriction; Female; Humans; Inflammation; Insulin; Intra-Abdominal Fat; Leptin; Middle Aged; Obesity; Resistin; Subcutaneous Fat; Weight Loss

We investigate the effects of a 2-month weight-loss programme on plasma levels of adiponectin, leptin and resistin in obese adolescent boys.. Twenty-one obese adolescent boys (BMI = 30.8 +/- 3.2 kg/m(2)) completed the weight-loss programme including: 1/ either energy restriction (R), 2/ or individualized exercise training at the point of maximum lipid oxidation (Lipox(max)) (E), 3/ or energy restriction and training (RE). Body composition, lipid oxidation and plasma levels of adiponectin, leptin and resistin were measured before and after intervention.. Following the weight-loss programme, adolescents of the RE group showed an improvement of their body composition (p < 0.01), an increase in plasma adiponectin (+73.7%, p < 0.01) and a decrease in plasma leptin (-38.8%, p < 0.01) leading to an increase in adiponectine/leptin ratio (ALR, +144.4%, p < 0.01) higher than the R or E groups. E and RE groups only showed a similar significant increase in plasma resistin (p < 0.05) and a significant improvement of lipid oxidation rate at Lipox(max) (p < 0.01 and p < 0.001). In addition, in RE group, ALR is correlated with waist/hip and waist/height ratios, resistin level, homoeostasis mode assessment (HOMA-IR) index and Lipox(max).. In obese adolescents boys, moderate exercise training completed at Lipox(max) and combined with energy restriction improves their ability to oxidize lipids, which is associated with a normalization of their adiponectin, leptin and resistin levels resulting in an improved insulin sensitivity, as attested by a higher ALR and a lower HOMA-IR.

Topics: Adiponectin; Adolescent; Body Composition; Caloric Restriction; Combined Modality Therapy; Diet, Reducing; Exercise; Homeostasis; Humans; Leptin; Lipids; Male; Obesity; Oxidation-Reduction; Regression Analysis; Resistin; Treatment Outcome; Weight Loss

Little longitudinal information is available on changes of growth, insulin-like growth factor-I (IGF-I), its main binding protein (IGFBP-3) and their relationships to leptin and insulin in obese children reducing their overweight. We compared these parameters between baseline and after participating in a one-year lifestyle intervention in 319 obese children. The control group comprised 52 lean children. Obese children demonstrated significantly increased IGFBP-3, leptin, and insulin concentrations and were taller compared to the lean children, while they did not differ in respect to their IGF-I concentrations. Reduction of overweight was associated with a significant decrease of IGFBP-3 SDS, leptin, and insulin concentrations. IGF-I SDS and height SDS did not change after weight loss.. IGFBP-3, leptin and insulin concentrations are increased in obese children and normalized in weight loss demonstrating the reversibility of these alterations. Weight loss due to lifestyle intervention was not associated with growth disturbances.

Topics: Adolescent; Body Constitution; Body Height; Body Weight; Child; Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Life Style; Male; Obesity; Weight Loss

The direct costs of paternal care are relatively well documented in primates, however little research has explored these effects in monogamous rodents. The present study examines the long-term effects that pairing and parenting have on male prairie voles. We hypothesized that there would be a significant weight loss over the course of pairing and parenting, presumably from the energetic demands that accompany these changes in social condition. In a longitudinal study, we followed ten male prairie voles through being housed with their brother; paired with a female; and caring for three consecutive litters. We found a significant drop in bodyweight across time, with maximum weight loss near the weaning of the first litter. At that same time, feeding increased, leading to possible recovery in weight; however, leptin levels dropped precipitously across time and did not recover. Corticosterone did not change significantly across time points, and overall activity levels also did not vary significantly over the course of the study. In addition, newly paired males showed a significant increase in preference for a 2% sucrose solution during a three-hour test, indicating a metabolic need for more calories. A cross-sectional study confirmed leptin and corticosterone findings, and showed significant loss of subcutaneous (inguinal) fat in males that had cared for a litter of pups, when compared to males housed with their brothers or newly paired males. These results suggest that cohabitation with a female, and caring for pups, all have costs for male prairie voles.

Topics: Adrenal Glands; Animals; Arvicolinae; Corticosterone; Cross-Sectional Studies; Dietary Sucrose; Drinking Behavior; Eating; Female; Food Preferences; Leptin; Longitudinal Studies; Male; Motor Activity; Organ Size; Pair Bond; Paternal Behavior; Siblings; Social Behavior; Subcutaneous Fat; Weight Loss

Carrying variants on the leptin receptor gene (LEPR) may have an impact on inflammatory and stress markers. Thus, the aim of the study was to analyze the role of the Lys109Arg LEPR gene polymorphism on inflammatory (leptin and IL-6) and stress (cortisol) markers in obese subjects who followed a hypocaloric diet designed to lose weight.. One hundred and seventy (80 females/90 males) Caucasian subjects (body mass index: 30.8 +/- 2.4 kg/m(2)), were genotyped for the Lys109Arg polymorphism by a PCR/RFLP procedure. Anthropometric measurements were assessed and blood samples were drawn in all the volunteers before and after an 8-week energy-restricted diet (-30% E). Plasma levels of leptin as well as interleukin-6 (IL-6) as proinflammatory markers and circulating cortisol concentrations as a stress hormone were measured.. Weight loss (-6.1 +/- 2.7%; p <0.001) induced significant changes in anthropometric and biochemical determinations. The AA genotype group showed a higher fat mass loss as well as greater total cholesterol decrease compared with the minor allele carriers. Moreover, the G allele carriers were associated with a higher basal risk of inflammation (OR = 2.5; p = 0.042) and stress (OR = 3.3; p = 0.011), which were reduced after weight lowering (p >0.05).. The Arg allele carriers of the Lys109Arg LEPR gene polymorphism were associated with an increased proinflammatory state and stress condition at baseline. These obesity-related markers were importantly decreased after following a hypocaloric diet.

Topics: Adult; Alleles; Body Mass Index; Caloric Restriction; Female; Genotype; Humans; Hydrocortisone; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Obesity; Polymorphism, Genetic; Receptors, Leptin; Stress, Physiological; Weight Loss

Adipocytokines play a key role in the pathophysiology of non-alcoholic fatty liver diseases (NAFLD). Whereas adiponectin has mainly anti-inflammatory functions, leptin, resistin and pre-B cell enhancing factor (PBEF)/Nampt/visfatin are considered as mainly pro-inflammatory mediators regulating metabolic and immune processes.. We prospectively examined the effect of weight loss on systemic levels and/or hepatic expression of adiponectin/adiponectin receptors, leptin/leptin receptors, resistin and PBEF/Nampt/visfatin. Severely obese patients underwent laparoscopic adjustable gastric banding (LABG) and serum samples (n=30) were collected before, and after 6 and 12 months. Paired liver biopsies (before and 6 months after LABG) were obtained from 18 patients.. Bariatric surgery improved insulin resistance, abnormal liver function tests and liver histology. Pronounced weight loss after 6 and 12 months was accompanied by a significant increase in serum adiponectin levels whereas both leptin and PBEF/Nampt/visfatin levels decreased. Resistin serum levels increased after 6 months but fell below baseline values after 12 months. Liver mRNA expression of adiponectin increased slightly after 6 months whereas leptin mRNA expression did not change. Interestingly, weight loss resulted in a significant decrease of hepatic mRNA expression of resistin, PBEF/Nampt/visfatin and both leptin receptor isoforms while expression of type 1 and 2 adiponectin receptor was not affected. Liver immunohistochemistry performed on index and follow-up liver biopsies revealed an increase in adiponectin staining, showed no effect on resistin/leptin positivity, and demonstrated a decrease in PBEF/Nampt/visfatin immunoreactivity.. Weight loss after LABG surgery drives the adipocytokine milieu towards a more anti-inflammatory direction both systemically and in the liver.

Topics: Adipokines; Adiponectin; Adult; Bariatric Surgery; Base Sequence; Cytokines; DNA Primers; Fatty Liver; Female; Gastroplasty; Gene Expression; Humans; Leptin; Liver; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity, Morbid; Prospective Studies; Resistin; RNA, Messenger; Weight Loss

In mice of normal weight and with diet-induced obesity, a high-fat, low-carbohydrate ketogenic diet (KD) causes weight loss, reduced circulating glucose and lipids, and dramatic changes in hepatic gene expression. Many of the effects of KD are mediated by fibroblast growth factor 21 (FGF21). We tested the effects of KD feeding on ob/ob mice to determine if metabolic effects would occur in obesity secondarily to leptin deficiency. We evaluated the effect of prolonged KD feeding on weight, energy homeostasis, circulating metabolites, glucose homeostasis, and gene expression. Subsequently, we evaluated the effects of leptin and fasting on FGF21 expression in ob/ob mice. KD feeding of ob/ob mice normalized fasting glycemia and substantially reduced insulin and lipid levels in the absence of weight loss. KD feeding was associated with significant increases in lipid oxidative genes and reduced expression of lipid synthetic genes, including stearoyl-coenzyme A desaturase 1, but no change in expression of inflammatory markers. In chow-fed ob/ob mice, FGF21 mRNA was elevated 10-fold compared with wild-type animals, and no increase from this elevated baseline was seen with KD feeding. Administration of leptin to chow-fed ob/ob mice led to a 24-fold induction of FGF21. Fasting also induced hepatic FGF21 in ob/ob mice. Thus, KD feeding improved ob/ob mouse glucose homeostasis without weight loss or altered caloric intake. These data demonstrate that manipulation of dietary macronutrient composition can lead to marked improvements in metabolic profile of leptin-deficient obese mice in the absence of weight loss.

Topics: Animals; Calorimetry, Indirect; Diet, Carbohydrate-Restricted; Diet, Ketogenic; Fibroblast Growth Factors; Glucose Intolerance; Glucose Tolerance Test; Homeostasis; Inflammation Mediators; Insulin Resistance; Interleukin-6; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Real-Time Polymerase Chain Reaction; RNA; Triglycerides; Tumor Necrosis Factor-alpha; Weight Loss

In the search for potential antiobese agents from natural sources, this study investigated the effects of betulinic acid (BA), a pentacyclic triterpene from Clusia nemorosa L. (Clusiaceae), in mice on a high-fat diet (HFD). Adult male Swiss mice (n = 8) treated or not with BA (50 mg/L, in drinking water) were fed a HFD during 15 weeks. Mice treated with BA and fed a HFD showed significantly (P < 0.05) decreased body weights, abdominal fat accumulation, blood glucose, plasma triglycerides, and total cholesterol relative to their respective controls fed no BA. Additionally, BA treatment, while significantly elevating the plasma hormone levels of insulin and leptin, decreased the level of ghrelin. However, it caused a greater decrease in plasma amylase activity than the lipase. These findings suggest that BA has an antiobese potential through modulation of fat and carbohydrate metabolism, and it may be a suitable lead compound in the treatment of obesity.

Topics: Abdominal Fat; Adipogenesis; Animals; Anti-Obesity Agents; Betulinic Acid; Blood Glucose; Clusia; Dietary Fats; Ghrelin; Insulin; Leptin; Lipids; Male; Mice; Pentacyclic Triterpenes; Triterpenes; Weight Loss

To investigate the effects of medium chain triglycerides (MCT) on adiposity and the modulation of neuropeptide Y (NPY) and leptin in Wistar rats.. 20 Wistar male rats were fed with diets containing 30% MCT or long chain triglycerides (LCT) for 8 weeks. Serum and hypothalamus leptin were detected by ELISA. RT-PCR was used to quantitatively compare the mRNA levels of recetpor of leptin (Ob-Rb) and NPY. The levels of serum and hypothalamic NPY were assessed by radioimmune assay.. Body weight gains and body fat accumulations of rats fed with the MCT diets were more less than those of rats fed with the LCT diets (P < 0.01). Hypothalamus and serum NPY concentrations in rats fed with the MCT diets were more lower than those in rats fed with LCT diets (P < 0.01). Rats fed with MCT diets had significantly higher ratios of hypothalamus/serum leptin in comparition with rats fed with LCT diets. The Ob-Rb mRNA levels in the hypothalamus in the rats fed with the MCT diets were more higher than in those of rats fed with the LCT diets (P < 0.01). There were no significant differences in NPY expressions between the rats fed with the LCT diets and rats fed with MCT diets.. The MCT diet could decrease rats body weight gain by increasing Ob-Rb expression in hypothalamus and decreasing NPY level.

Topics: Animals; Dietary Fats; Hypothalamus; Leptin; Male; Neuropeptide Y; Random Allocation; Rats; Rats, Wistar; Receptors, Leptin; RNA, Messenger; Triglycerides; Weight Loss

This study assessed if lower than predicted serum leptin concentrations seen during weight loss persisted during weight regain, with possible implications for weight control.. 115 children were investigated during a 12-week weight loss program. 90 children completed the program, and 68 children entered a follow-up program spanning 28 months. Measurements were performed at baseline and day 82 as well as at months 10, 16, and 28. Height, weight, body composition, Tanner stages, testicular size, and serum concentrations of leptin, and insulin were measured at all time points.. Children with the greatest increases in BMI standard deviation score (SDS) exhibited the largest leptin increments. The disproportionate reduction of leptin seen during weight loss recovered after weight loss. Leptin increases mirrored increases in BMI SDS during weight regain, and the leptin-BMI SDS relationship seen during follow-up resembled the baseline leptin-BMI SDS relationship.. Proportional increases of leptin and BMI SDS during weight regain suggests an intact leptin response during re-accumulation of fat. Following the pronounced reduction of leptin during weight loss, leptin levels were restored during weight regain to an extent where leptin levels were comparable with those at baseline, which is indicative of an inefficient lipostatic control exerted by leptin during weight regain.

Topics: Adolescent; Body Height; Body Mass Index; Child; Female; Follow-Up Studies; Humans; Insulin; Leptin; Longitudinal Studies; Male; Menarche; Obesity; Puberty; Testis; Weight Gain; Weight Loss

Maintenance of weight loss is often unsuccessful because of metabolic adaptations that conserve energy. Studies in rodents suggest that a reduction in leptin level during weight loss signals to the brain to increase feeding and decrease energy expenditure. In this issue of the JCI, Rosenbaum et al. examined this concept in obese patients who lost weight and were maintained at 10% below their initial weight (see the related article beginning on page 2583). Brain activity responses to visual food stimuli were visualized using functional MRI. Leptin levels fell during weight loss and increased brain activity in areas involved in emotional, cognitive, and sensory control of food intake. Restoration of leptin levels maintained weight loss and reversed the changes in brain activity. Thus, leptin is a critical factor linking reduced energy stores to eating behavior. Potentially, leptin therapy could sustain weight loss by overriding the tendency toward energy conservation.

Topics: Animals; Appetite Regulation; Brain; Echo-Planar Imaging; Energy Metabolism; Food; Humans; Leptin; Mice; Models, Biological; Obesity; Photic Stimulation; Weight Loss

Leptin is a member of the IL-6 cytokine family and is primarily produced by adipose tissue. At high enough concentration, leptin engages leptin receptors expressed in the hypothalamus that regulate a variety of functions, including induction of weight loss. Mice deficient in leptin (ob/ob) or leptin receptor (db/db) function exhibit thymic atrophy associated with a reduction in double-positive (DP) thymocytes. However, the mediator of such thymic atrophy remains to be identified, and the extent to which leptin acts in the periphery vs. the hypothalamus to promote thymocyte cellularity is unknown. In the present study, we first demonstrate that thymic cellularity and composition is fully restored in ob/ob mice subjected to adrenalectomy. Second, we observe that ob/ob mice treated with low-dose leptin peripherally but not centrally exhibit increased thymocyte cellularity in the absence of any weight loss or significant reduction in systemic corticosterone levels. Third, we demonstrate that reconstitution of db/db mice with wild-type bone marrow augments thymocyte cellularity and restores DP cell frequency despite elevated corticosterone levels. These and additional data support a mode of action whereby leptin acts in the periphery to reduce the sensitivity of DP thymocytes to glucocorticoid-mediated apoptosis in vivo. Strikingly, our data reveal that leptin's actions on thymic cellularity in the periphery can be uncoupled from its anorectic actions in the hypothalamus.

Topics: Adrenalectomy; Age Factors; Animals; Apoptosis; Atrophy; Chimera; Corticosterone; Flow Cytometry; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Obesity; Receptors, Leptin; Thymus Gland; Weight Loss

The metabolic effects of leptin may involve both centrally and peripherally mediated actions with a component of the central actions potentially independent of alterations in food intake. Ob/ob mice have significant abnormalities in lipid metabolism, correctable by leptin administration. We used ob/ob mice to study the relative importance of the subtypes of actions of leptin (central vs. peripheral; food intake dependent vs. independent) on lipid metabolism. Mice were treated for 3 d with leptin, either centrally [intracerebroventricular (icv)] or peripherally (ip), and compared with mice pair-fed to the leptin-treated mice (PF) and with ad libitum-fed controls (C). All treatment groups (icv, ip, PF) showed indistinguishable changes in liver weight; hepatic steatosis; hepatic lipidemic profile; and circulating free fatty acids, triglycerides, and cholesterol lipoprotein profile. Changes in the expression of genes involved in lipogenesis and fatty acid oxidation in liver, muscle, and white fat were broadly similar in ip, icv, and PF groups. Leptin (both icv and ip) stimulated expression of both mitochondrial and peroxisomal acyl-coenzyme A oxidase (liver) and peroxisomal proliferator-activated receptor-alpha (skeletal muscle) to an extent not replicated by pair feeding. Leptin had profound effects on peripheral lipid metabolism, but the majority were explained by its effects on food intake. Leptin had additional centrally mediated effects to increase the expression of a limited number of genes concerned with fatty acid oxidation. Whereas we cannot exclude direct peripheral effects of leptin on certain aspects of lipid metabolism, we were unable to detect any such effects on the parameters measured in this study.

Topics: Adipocytes; Animals; Brain; Eating; Fatty Acids; Gene Expression Regulation; Injections, Intraperitoneal; Injections, Intraventricular; Leptin; Lipid Metabolism; Liver; Mice; Mice, Obese; Muscle Proteins; Muscle, Skeletal; Triglycerides; Weight Loss

Aldoketoreductase 1C3 (AKR1C3) is a functional prostaglandin F synthase and a negative modulator of the availability of ligands for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma). AKR1C3 expression is known to be associated with adiposity, one of the components of the metabolic syndrome. The aim of this study was to characterize the expression of AKR1C3 in the adipose tissue and adipocytes and to investigate its potential role in the metabolic syndrome. Using microarray analysis and realtime PCR, we studied the expression of AKR1C3 in adipose tissue samples from obese subjects with or without metabolic complications, during very low calorie diet-induced weight loss, and its expression in isolated human adipocytes of different sizes. The adipose tissue AKR1C3 expression levels were marginally lower in obese subjects with the metabolic syndrome compared with the levels in healthy obese subjects when analyzed using microarray (p = 0.078) and realtime PCR (p < 0.05), suggesting a secondary or compensatory effect. The adipose tissue mRNA levels of AKR1C3 were reduced during and after dietinduced weight-loss compared to the levels before the start of the diet (p < 0.001 at all time-points). The gene expression of AKR1C3 correlated with both adipose tissue mRNA levels and serum levels of leptin before the start of the diet (p < 0.05 and p < 0.01, respectively). Furthermore, large adipocytes displayed a higher expression of AKR1C3 than small adipocytes (1.5-fold, p < 0.01). In conclusion, adipose tissue AKR1C3 expression may be affected by metabolic disease, and its levels are significantly reduced in response to dietinduced weight loss and correlate with leptin levels.

Topics: 3-Hydroxysteroid Dehydrogenases; Adipose Tissue; Adult; Aldo-Keto Reductase Family 1 Member C3; Diet, Reducing; Female; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Humans; Hydroxyprostaglandin Dehydrogenases; Leptin; Male; Metabolic Syndrome; Middle Aged; Molecular Sequence Data; Obesity; Oligonucleotide Array Sequence Analysis; Tissue Distribution; Weight Loss

The high-fat diet (HFD)-fed mouse is a model of obesity, impaired glucose tolerance, and insulin resistance. The main objective of this study was to elucidate the molecular mechanisms underlying the antidiabetogenic and weight-lowering effects of 17beta-estradiol (E(2)) in this mouse model. C57BL/6 female mice (8 wk old) were fed on a HFD for 10 mo. E(2), given daily (50 microg/kg s.c.) during the last month of feeding, decreased body weight and markedly improved glucose tolerance and insulin sensitivity. Plasma levels of insulin, leptin, resistin, and adiponectin were decreased. We demonstrated that E(2) treatment decreased the expression of genes encoding resistin and leptin in white adipose tissue (WAT), whereas adiponectin expression was unchanged. Furthermore, in WAT we demonstrated decreased expression levels of sterol regulatory element-binding protein 1c (SREBP1c) and its lipogenic target genes, such as fatty acid synthase and stearoyl-CoA desaturase 1 (SCD1). In the liver, the expression levels of transcription factors such as liver X receptor alpha and SREBP1c were not changed by E(2) treatment, but the expression of the key lipogenic gene SCD1 was reduced. This was accompanied by decreased hepatic triglyceride content. Importantly, E(2) decreased the hepatic expression of glucose-6-phosphatase (G-6-Pase). We conclude that E(2) treatment exerts antidiabetic and antiobesity effects in HFD mice and suggest that this is related to decreased expression of lipogenic genes in WAT and liver and suppression of hepatic expression of G-6-Pase. Decreased plasma levels of resistin probably also play an important role in this context.

Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Animals; Dietary Fats; Estradiol; Fatty Acids; Female; Gene Expression; Glucose Intolerance; Glucose Tolerance Test; Hypoglycemic Agents; Insulin; Leptin; Liver; Mice; Mice, Inbred C57BL; Obesity; Resistin; Reverse Transcriptase Polymerase Chain Reaction; Transfection; Triglycerides; Weight Loss

Adipocytes regulate blood vessel formation, and in turn endothelial cells promote preadipocyte differentiation through the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF)-A. Some adipocytokines and hormones also have an effect on vascular development.. Our objectives were to analyze the relationship between weight and circulating VEGF-A in morbidly obese subjects before and after bariatric surgery, and investigate the relationship between circulating VEGF-A and certain adipocytokines and hormones regulating adipocytes.. A total of 45 morbidly obese women and nine lean females were included in the study. Patients underwent bariatric surgery: vertical banded gastroplasty (n=17), gastric bypass (n=17), and biliopancreatic diversion (n=11). Serum samples for VEGF-A, adiponectin, leptin, ghrelin, and insulin were obtained preoperatively and 9-12 months after surgery.. Obese patients showed significantly higher VEGF-A levels than controls (306.3+/-170.3 vs. 187.6+/-91.9 pg/ml; P=0.04), decreasing to 246.1+/-160.4 after surgery (P<0.001), with no differences among surgical procedures. In controls there was an inverse correlation between VEGF-A and ghrelin (r=-0.85; P<.01), but not in obese patients. Leptin and insulin concentrations were increased in obese patients, with a significant decrease shown after weight loss with surgery. Conversely, adiponectin concentrations were lower in obese patients, with a significant increase shown after weight loss with surgery. Ghrelin was higher in controls than obese patients, decreasing after gastric bypass and biliopancreatic diversion, but not after vertical banded gastroplasty.. Serum VEGF-A levels are significantly higher in obese patients than in lean controls, decreasing after weight loss with bariatric surgery, behaving similarly to other hormones related to adipose mass like leptin and insulin.

Topics: Adipokines; Adult; Aged; Bariatric Surgery; Diabetes Mellitus, Type 2; Female; Ghrelin; Humans; Hypertension; Insulin; Leptin; Middle Aged; Obesity, Morbid; Sleep Apnea, Obstructive; Vascular Endothelial Growth Factor A; Weight Loss; Young Adult

A significant association between hypertension and obesity has been noted in several epidemiological studies. In particular, a progressive increase has been demonstrated, both in men and women, in the prevalence of hypertension in relation to the different measures of obesity. Such association is independent of age, gender, and also probably the ethnic group. It has also been shown that obesity may antedate and predict the development of hypertension. Even among subjects with normal or optimal blood pressure, the obese subjects are more likely to develop high blood pressure levels in the following years. The opposite can also be true. Hypertensive subjects are more likely to develop obesity than normotensive ones. It has been suggested that initial sympathetic hyperactivity may lead to high blood pressure and progressive hyperstimulation, followed by down-regulation, of beta-adrenergic receptors, with subsequent development of obesity because of the lesser beta-adrenoceptor that induces dissipation of calories. Visceral obesity seems to be more important than subcutaneous obesity with respect to high blood pressure. Finally, in addition to the well established relation between low weight at birth and adult hypertension, it has also been shown that any transient increases in body weight may be paralleled by increases in blood pressure at any time in life. Obesity may be associated with hypertension through an increased sympathetic tone, increased fluid retention and insulin resistance. Animal models of hypertension associated with obesity may be suitable to investigate in detail the pathophysiological mechanisms of such association. In this setting decreased nitric oxide production and resistance to leptin have been identified as important determinants of obesity in hypertension. From a therapeutic standpoint, it is well known that weight reduction is associated with a drop in blood pressure. Unfortunately, however, obese hypertensive subjects who loose weight in the short term often do not succeed to maintain the weight loss, with consequent new gain in body weight and blood pressure. Thus, weight reduction should be maintained in the long term to elicit a sustained and effective antihypertensive efficacy.

Topics: Adult; Animals; Body Mass Index; Clinical Trials as Topic; Disease Models, Animal; Female; Follow-Up Studies; Humans; Hypertension; Leptin; Male; Meta-Analysis as Topic; Nitric Oxide; Obesity; Practice Guidelines as Topic; Prevalence; Risk Factors; Sex Factors; Time Factors; Weight Gain; Weight Loss

This study systematically assessed the weight management effects of a novel experimental DNA-customized nutraceutical, LG839 (LifeGen, Inc., La Jolla, CA, USA).. A total of 1058 subjects who participated in the overall D.I.E.T. study were genotyped and administered an LG839 variant based on polymorphic outcomes. A subset of 27 self-identified obese subjects of Dutch descent, having the same DNA pattern of four out of the five candidate genes tested (chi-square analysis) as the entire data set, was subsequently evaluated. Simple t tests comparing a number of weight management parameters before and after 80 days of treatment with LG839 were performed.. Significant results were observed for weight loss, sugar craving reduction, appetite suppression, snack reduction, reduction of late night eating (all P<0.01), increased perception of overeating, enhanced quality of sleep, increased happiness (all P<0.05), and increased energy (P<0.001). Polymorphic correlates were obtained for a number of genes (LEP, PPAR-gamma2, MTHFR, 5-HT2A, and DRD2 genes) with positive clinical parameters tested in this study. Of all the outcomes and gene polymorphisms, only the DRD2 gene polymorphism (A1 allele) had a significant Pearson correlation with days on treatment (r=0.42, P=0.045).. If these results are confirmed in additional rigorous, controlled studies, we carefully suggest that DNA-directed targeting of certain regulator genes, along with customized nutraceutical intervention, provides a unique framework and strategic modality to combat obesity.

Topics: Anti-Obesity Agents; Appetite; Cross-Sectional Studies; Dietary Supplements; Feeding Behavior; Genotype; Humans; Hyperphagia; Leptin; Methylenetetrahydrofolate Reductase (NADPH2); Obesity; Polymorphism, Genetic; PPAR gamma; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Retrospective Studies; Reward; Syndrome; Weight Loss

To observe the effect of high-frequency electroacupuncture (EA) on lipid metabolism in obesity rats.. Fifty-one SD rats were randomized into control group (n=13), model group (n=19) and EA group (n=19). Obesity model was duplicated by feeding the rats with high fat forage and subcutaneous injection of 15% glutamate sodium solution. EA (100 Hz, 3-5 mA) was applied to "Housanli" (ST 36), "Sanyinjiao" (SP 6), "Guanyuan" (CV 4) and "Zhongwan" (CV 12) for 10 min everyday and for 28 days. Lee's index, body weight, area and the number of the adipose cells around the left kidney were detected. Blood samples were collected for assaying serum triglyceride (TG), total cholesterol (TC) with cholesterol oxidase phenol 4-aminoantipyrine peroxidase (CHOD-PAP) method, glycerol phosphate oxidase-p-aminophenazone (GPO-PAP) methods, high density lipid-cholesterol (HDL-C) with phosphotungstic acid- Mg2+ method, low density lipid-cholesterol (LDL-C) with polyvingel sulfate (PVS) sedimentation method and plasma lipoprotein lipase (LPL) with immunoturbidmetry endpoint method, and serum insulin and leptin contents with radioimmunoassay respectively.. After modeling, in comparison with control group, Lee's index, serum TG, TC, LDL-C, fat weight, adipose cell area, serum leptin and insulin contents in model group increased considerably (P<0.05, 0.01), while serum HDL-C, plasma LPL, adipose cell number decreased significantly (P<0.05, 0.01). Following EA, compared with model group, Lee's index, serum TG, TC, LDL-C, fat weight, adipose cell area, serum leptin and insulin levels decreased significantly in EA group (P<0.05, 0.01), whereas serum HDL-C, plasma LPL, and adipose cell number increased apparently (P<0.01).. High frequency EA can effectively improve abnormal lipid metabolism, and reduce fat accumulation in obesity rats, which may be closely associated with its effect in regulating the balance between leptin and insulin levels.

Topics: Acupuncture Points; Animals; Body Mass Index; Body Size; Cholesterol, HDL; Electroacupuncture; Insulin; Leptin; Lipid Metabolism; Obesity; Random Allocation; Rats; Rats, Sprague-Dawley; Triglycerides; Weight Loss

Involuntary weight loss affects 20% of community dwelling older adults. The underlying mechanism for this disorder is unknown. Objective is to determine if failure of older persons to regain weight is associated with elevated pro-inflammatory cytokine and leptin levels.. Prospective diet intervention study.. University of Washington Medical Center from 2001-2005.. Twenty-one younger (18-35 years old) and nineteen older (>or= 70 years old) men and women.. Each subject was placed for two weeks on a weight-maintaining diet, followed in sequence by 2 weeks of 30% caloric restriction, then 4 weeks of ad libitum food intake.. Plasma leptin levels, fasting serum pro-inflammatory cytokine levels, and peripheral blood mononuclear cell cytokine levels were measured.. Leptin levels in the two cohorts decreased after caloric restriction and increased after ad-libitum food consumption resumed. Plasma TNF alpha levels were higher in older subjects compared to younger adults. However, there was no association between changes in TNF alpha levels and changes in AUC leptin.. Leptin levels in healthy older individuals responded appropriately in a compensatory manner to changes in body weight. These data do not support a cytokine dependent elevation in leptin levels as being responsible for the failure of older adults to regain weight.

Topics: Adolescent; Adult; Age Factors; Aged; Aging; Area Under Curve; Cytokines; Diet, Reducing; Female; Humans; Leptin; Male; Obesity; Weight Loss; Young Adult

The aims of the present study were to examine 1) whether changes in circulating leptin levels occur in response to six months of aerobic exercise training (ET) without concomitant weight loss; 2) whether there is a different response with respect to gender; and 3) the relationship between age and leptin and whether this relationship has any impact on the response to ET without weight-loss.. Thirty-eight healthy, sedentary men and women (age 38.43+/-2.24, range 18-59 years) participated in 6 months of supervised, moderate intensity (ET) performed 4 days per week. Maintenance of usual dietary practices were encouraged to minimize weight-loss. Participants were evaluated for circulating fasting leptin, body mass, body fat percentage and maximal aerobic power (VO2max) prior to and after ET.. There was no decrease in body weight or leptin concentration (17.69+/-2.67 vs 16.85+/-3.12 ng dL(-1)). Gender did not affect the response to exercise training. The bivariate correlation between leptin and age was not significant, but the relationship reached significance after controlling for body fat percentage and VO2max (r = -0.358, P < 0.05). Age did not affect the response of leptin concentration to ET.. It is probable that changes in leptin concentration reported previously with ET may be attributable to concomitant weight loss, but age does not play a role in how leptin responds to ET.

Topics: Adipose Tissue; Adolescent; Adult; Age Factors; Anthropometry; Body Mass Index; Body Weight; Cardiovascular Physiological Phenomena; Exercise; Exercise Tolerance; Female; Humans; Leptin; Male; Middle Aged; Prospective Studies; Respiration; Respiratory System; Time Factors; Weight Loss; Young Adult

Obesity has been associated with an increased prevalence of asthma and poorer control of this disease. However, the mechanisms by which obesity can influence airway function and make asthma more difficult to control remain uncertain. The physiological changes associated with obesity can contribute to respiratory symptoms and these should be differentiated from those caused by asthma. Obesity can possibly influence the development of asthma through genetic, developmental, hormonal, neurogenic or mechanical influences. Breathing at low lung volumes and changes in the pattern of breathing in obese subjects may alter airway smooth muscle plasticity and airway function. The release by adipocytes of various cytokines and mediators such as Interleukin-6, TNF-alpha, eotaxin, and leptin, and the reduction of anti-inflammatory adipokines in obese subjects may possibly contribute to the development or increased clinical expression of asthma in promoting airway inflammation. Reduced asthma control and impaired response to asthma therapy have been reported in obese patients. Obesity-related co-morbidities such as Sleep Apnea and Gastro-esophageal reflux may also contribute to this poor control. Weight loss improves asthma control and reduces medication needs. Research is needed to better define the optimal management of obese asthmatic patients.

Topics: Asthma; Body Mass Index; Canada; Cytokines; Humans; Leptin; Obesity; Prevalence; Risk Factors; Treatment Outcome; Weight Loss

The ghrelin and leptin levels have been reported to be correlated with weight loss after bariatric surgery. However, the serial changes of ghrelin and leptin levels after laparoscopic minigastric bypass surgery (LMGBP) have not been reported yet. Therefore, we aimed to evaluate their serial changes and to analyze their relations to weight reduction after LMGBP.. Serial fasting serum leptin and ghrelin concentrations were measured in 68 morbidly obese patients before (M0) and 1 (M1), 3 (M3), 6 (M6), and 12 (M12) months after LMGBP surgery. The correlations between ghrelin, insulin, and leptin concentrations and weight reduction were analyzed.. Leptin levels were significantly reduced at 1, 3, 6, and 12 months after surgery, respectively (vs M0, p < 0.001), whereas the ghrelin concentrations were not significantly changed after surgery. The percent of excess BMI lost (%EBL) 12 months after surgery was negatively correlated with higher preoperative ghrelin concentrations (p = 0.004) and larger preoperative BMI (p = 0.002) in the multivariate analysis.. Higher preoperative ghrelin concentrations and larger BMI are predictive of less %EBL at 12 months after LMGBP surgery.

Topics: Adult; Female; Gastric Bypass; Ghrelin; Humans; Insulin; Laparoscopy; Leptin; Male; Obesity, Morbid; Predictive Value of Tests; Time Factors; Weight Loss

In subjects with obesity, diabetes and coronary artery disease, circulating levels of leptin increased while that of adiponectin is decreased. In this study we have investigated effects of physiological and pharmacological weight reduction on leptin and adiponectin mRNA expression. Wistar rats were fed either standard laboratory chow for 16 weeks (chow-fed) or given a fat-enriched, glucose-enriched diet (diet-fed) for 8 weeks. After 8 weeks, diet-fed group was subdivided into three subgroups, namely, an untreated obese, or were returned to chow diet, or treated with fenofibrate for further 8 week. After 16 weeks, compared with chow-fed group, diet-fed rats had significantly higher body weight, epididymal fat pad mass, and plasma levels of insulin, leptin, adiponectin, non-esterified fatty acids and triglycerides (P<0.001, for all). Moreover, untreated obese rats had significantly (P<0.01, for both) raised levels of Ob mRNA but reduced adiponectin mRNA levels in epididymal fat pads compared with chow-fed group. These changes were corrected by chronic removal of the high-energy diet and fenofibrate treatment. These findings indicate that physiological or pharmacological lowering of body weight together with circulating plasma lipids play a significant role in leptin and adiponectin synthesis and metabolism.

Topics: Adiponectin; Adipose Tissue; Animals; Epididymis; Fatty Acids, Nonesterified; Fenofibrate; Gene Expression Regulation; Hypolipidemic Agents; Leptin; Male; Obesity; Random Allocation; Rats; Rats, Wistar; RNA, Messenger; Triglycerides; Weight Loss

Some studies suggest that increased consumption of soy protein hydrolysates may cause body weight loss but the mechanism of action is unknown. The objective of this investigation was to determine whether intracerebroventricular (i.c.v.) infusion of soy protein hydrolysates decrease food intake and body weight. Adult male Sprague Dawley rats (n = 24) received i.c.v. injections of soy hydrolysate I (SH I) or soy hydrolysate II (SH II) three times weekly for 2 weeks. Krebs solution and leptin were used as negative and positive controls respectively. SH I (6.5-20 kDa with a strong band at 14 kDa) was produced by hydrolysis with alcalase, and SH II (approximately 2 kDa) was obtained by hydrolysis and ultrafiltration. Leptin successfully reduced body weight (-1.60 g) 24 h (p = 0.0093) after the third injection. SH I caused significant (p = 0.0009) decreases in body weight (-1.70 g) 24 h after the third injection but not after 48 h. SH II showed a tendency to prevent body weight gain but this effect was short of statistical significance (p < 0.40). Food intake was not affected by any of the soy hydrolysate treatments but leptin injection did cause significant decreases in food intake (p < 0.05). Data suggest that soy alcalase hydrolysate can decrease, in the short term, the rate of body weight gain independently of food consumption. This preliminary data show that soy peptides may play a role on body weight regulation, possibly by increasing energy utilization.

Topics: Animals; Body Weight; Brain; Cross-Over Studies; Energy Intake; Energy Metabolism; Injections, Intraventricular; Leptin; Male; Obesity; Protein Hydrolysates; Random Allocation; Rats; Rats, Sprague-Dawley; Soybean Proteins; Time Factors; Weight Loss

Hypocaloric diet-induced weight loss produces a coordinated decrease in plasma leptin levels and an increase in plasma ghrelin levels. The aim of the present study was to determine whether subjects who lose significant weight experience changes in circulating ghrelin and leptin levels.. A population of 66 obese patients was analyzed. Leptin, active ghrelin blood levels, and other cardiovascular risk factors were measured before and after 3 mo of a hypocaloric diet.. Sixty-six patients (17 male, 49 female) gave informed consent and were enrolled in the study. Forty-six patients did not lose 5% of initial weight (group I, weight loss 1.4 +/- 2.5 kg) and 20 patients lost weight (>5% of initial weight; group II, weight loss 7.1 +/- 2.6 kg). In group I, active ghrelin levels increased (7.40 +/- 8 versus 19.40 +/- 32 pg/mL, P < 0.05) and leptin levels decreased (102.6 +/- 86 versus 89.30 +/- 76 ng/mL, P < 0.05). In group II, leptin levels also decreased significantly (69.80 +/- 67 versus 53.50 +/- 59 ng/mL, P < 0.05). Active ghrelin in this group did not show differences (24.20 +/- 41 versus 10.30 +/- 12 pg/mL, NS). In the multivariate analysis with a dependent variable (change in active ghrelin levels, pg/ml) in group II adjusted by age and sex, only basal fat mass and basal intake of protein remained in the model. In the multivariate analysis with a dependent variable (change in leptin levels, pg/ml) in group II adjusted by age and sex, only basal fat mass and BMI remained in the model.. Patients with weight loss secondary to a hypocaloric diet did not change active ghrelin levels and decreased leptin levels after treatment.

Topics: Anthropometry; Calorimetry, Indirect; Cardiovascular Diseases; Diet, Reducing; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Risk Factors; Weight Loss

To determine the mechanism of weight loss caused by high doses of N-butyldeoxynojirimycin (NB-DNJ) in healthy lean and leptin-deficient obese (ob/ob) mice.. Healthy lean and obese mice were treated with NB-DNJ by the following methods: admixed with their diet, delivered by subcutaneously implanted mini-pumps or by intraperitoneal or intracerebroventricular (ICV) injection. Daily changes in body weight and food intake were recorded during the experimental period. The effect of NB-DNJ treatment on subcutaneous adipose tissue and on epididymal fat pads was measured.. Lean mice treated with NB-DNJ, admixed with their diet, lost weight in the form of adipose tissue. This resulted in a 40% reduction in skin thickness (control, 358 +/- 11 microm; NB-DNJ treated 203 +/- 6 microm) and a reduction in epididymal fat pad weights after 5 weeks of treatment at 2400 mg/kg/day (control, 0.0154 +/- 0.001; NB-DNJ treated, 0.0026 +/- 0.0005 as ratios of fat pad weight to total body weight). Following the depletion of adipose tissue mass, the mice grew normally and did not have any reduction in lean mass. Obese mice treated with NB-DNJ also lost weight or gained weight at a greatly reduced rate compared with non-treated controls. Body weights at 6 months of age were: lean control, 29.10 +/- 1.15 g; lean NB-DNJ treated, 22.73 +/- 0.29 g; obese control, 63.25 +/- 1.5 g; obese NB-DNJ treated from 5 weeks of age, 35.30 +/- 1.68 g; obese NB-DNJ treated from 12 weeks of age, 38.84 +/- 1.26 g. Both the lean and obese groups of mice treated with NB-DNJ ate up to 30% less than untreated controls. Daily food intake (powder diet) were: lean control, 4.15 +/- 0.54 g; obese control, 4.14 +/- 0.2 g; lean NB-DNJ treated 2.9 +/- 0.37 g; obese NB-DNJ treated, 2.88 +/- 0.47 g. Mice treated with the N-substituted galactose imino sugar analogue, N-butyldeoxygalactonojirimycin (NB-DGJ) did not lose weight. Mice experienced similar weight loss or lack of weight gain when fed a restricted diet that mimics the drug-induced level of food consumption. Delivery of 2 nmol NB-DNJ by ICV injection into lean mice also caused similar reductions in food intake. Food intake: saline vehicle, 4.30 +/- 0.12 g; NB-DNJ, 3.37 +/- 0.19 g; NB-DGJ, 4.03 +/- 0.16 g; 2-deoxyglucose, 4.7 +/- 0.15 g.. NB-DNJ causes weight loss as a result of reduced food consumption due to central appetite suppression.

Topics: 1-Deoxynojirimycin; Adipose Tissue; Animals; Appetite Regulation; Enzyme Inhibitors; Leptin; Mice; Mice, Obese; Obesity; Weight Loss

The aim of this study was to investigate responses of ghrelin, leptin, and adiponectin to a weight reduction period of 10 weeks in male subjects with high lean body mass and low body fat values. Fourteen male bodybuilders (7 competitors: 28.3 +/- 10.3 years, 175.3 +/- 5.4 cm, 82.2 +/- 9.3 kg; 7 controls: 22.4 +/- 3.0 years, 182.4 +/- 6.9 cm, 85.3 +/- 10.5 kg) participated in this study. The subjects were tested 3 times: 11 weeks (TEST1), 5 weeks (TEST2), and 3 days (TEST3) before the national championships. Testing procedure included dual-energy x-ray absorptiometry scan; calculation of daily energy intake and expenditure; and venous blood sampling for fasting ghrelin, leptin, and adiponectin. In the competitors' group, a significant (P < .05) 4.1-kg loss of body fat was observed that resulted in 6.5% +/- 1.5% of the body fat at the end of the study. Ghrelin increased significantly by 20.4% by TEST2. By TEST3, ghrelin was further increased by 6% (P > .05). The pattern of leptin was opposite, with a significant 27.7% decrease at TEST2 and no further decrease at TEST3 (P > .05). No significant change was observed in adiponectin concentration during the study. In the control group, no significant changes in biochemical parameters were observed. In conclusion, ghrelin concentration significantly increases, but is suppressed in conditions of limited energy availability that is accompanied by significant body mass loss in male subjects with initial low body fat values.

Topics: Absorptiometry, Photon; Adiponectin; Adult; Body Composition; Diet, Reducing; Energy Intake; Energy Metabolism; Ghrelin; Humans; Leptin; Male; Sports; Statistics, Nonparametric; Weight Loss

The objective of the present study was to analyze the effects of chronic melatonin (10 microg/g body weight) on body weight and the main energetic reserves, particularly hepatic and muscle content of proteins, lipids and glycogen in goldfish. In addition, we studied plasma leptin and ghrelin, and hypothalamic content of neuropeptide Y (NPY) and monoamines after chronic melatonin treatment in order to elucidate a possible interplay between melatonin and these feeding regulators on the body weight regulation in this species. Body weight gain and specific growth rate were reduced (74% and 76%, respectively) after chronic (10 days) intraperitoneal (i.p.) treatment with melatonin. The carbohydrate and lipid metabolism was regulated by melatonin in goldfish, because this indoleamine reduced muscle glycogen stores and increased lipid mobilization. A suppressive trend, but not statistically significant, in circulating ghrelin was observed after chronic treatment with melatonin. Chronic melatonin administration significantly reduced noradrenergic metabolism and increased dihydroxiphenylacetic acid content in the hypothalamus, without significant modifications in the serotoninergic system. Thus, it could be suggested that melatonin may mediate its action on energy balance in fish, at least in part, via interactions with hypothalamic catecholaminergic system. Plasma leptin and hypothalamic NPY remained unaltered after melatonin treatment, suggesting that these feeding regulators may not be involved in the effects of melatonin on energy homeostasis in fish.

Topics: Animals; Biogenic Monoamines; Feeding Behavior; Ghrelin; Goldfish; Leptin; Melatonin; Nutritional Status; Weight Loss

Serum amyloid A (SAA) is a novel link between increased adipose tissue mass and low-grade inflammation in obesity. Little is known about the factors regulating its serum concentration and mRNA levels. We investigated the association between SAA and leptin in obese and normal weight subjects and analyzed the effect of weight reduction on serum SAA concentration and gene expression in adipose tissue of the obese subjects.. Seventy-five obese subjects (60+/-7 years, body mass index (BMI) 32.9+/-2.8 kg/m(2), mean+/-s.d.) with impaired fasting plasma glucose or impaired glucose tolerance and other features of metabolic syndrome, and 11 normal weight control subjects (48+/-9 years, BMI 23.7+/-1.9 kg/m(2)) were studied at the baseline. Twenty-eight obese subjects underwent a 12-week intensive weight reduction program followed by 5 months of weight maintenance. Blood samples and abdominal s.c. adipose tissue biopsies were taken at the baseline and after the follow-up. Gene expression was studied using real-time quantitative PCR.. The gene expressions in women and serum concentrations of leptin and SAA were interrelated independently of body fat mass in the obese subjects (r=0.54, P=0.001; r=0.24, P=0.039 respectively). In multiple linear regression analyses, leptin mRNA explained 38% of the variance in SAA mRNA (P=0.002) in the obese women. Weight loss of at least 5% increased SAA mRNA expression by 48 and 36% in men and women, but serum SAA concentrations did not change.. The association between SAA and leptin suggests an interaction between these two adipokines, which may have implications in inflammatory processes related to obesity and the metabolic syndrome.

Topics: Adipocytes; Adipose Tissue; Aged; Body Weight; Female; Gene Expression; Glucose Intolerance; Humans; Inflammation; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; RNA, Messenger; Serum Amyloid A Protein; Weight Loss

Topics: Animals; Diet; Energy Metabolism; Exercise; Humans; Leptin; Obesity; Rats; Weight Loss

Little is known about the genetic factors that cause alterations in gallbladder motility, cholesterol crystal nucleation, biliary lipids, and, ultimately, cholesterol gallstones. Obese, leptin-deficient (Lep(ob)) mice have large gallbladder volumes with decreased contraction in vitro and are predisposed to cholesterol crystal formation. Leptin administration to these mice causes weight loss and restores gallbladder function. We hypothesize that administration of leptin to Lep(ob) mice would cause weight loss, decrease gallbladder volume, and change gallbladder genes related to gallbladder motility, nucleating factors, and lipid metabolism.. Twenty-four 8-week-old Lep(ob) mice were fed a nonlithogenic diet for 4 weeks. Twelve mice received daily IP saline injections, and 12 received 5 mug/g recombinant leptin. Gallbladder mRNA was pooled and analyzed on murine genome microarray chips. Selected genes were confirmed by real-time polymerase chain reaction (PCR) in a second group of mice treated by the same protocol.. Leptin-deficient mice given leptin had significant weight loss and reductions in gallbladder volume. These mice had upregulation of the leptin receptor (p = 0.007; PCR = 1.1-fold increase) but downregulation of leptin (p = 0.003; PCR = 13.5-fold decrease). Leptin upregulated the cholecystokinin A receptor (p < 0.001; PCR = 3.1-fold increase), acetylcholine beta2 receptor (p = 0.005), and the Ca+-calmodulin-dependent protein kinase (p = 0.002) genes. Leptin also altered immunoglobulin heavy chain 4 (p = 0.005; PCR = 17.7-fold increase), mucin 3 (p = 0.006), and carboxylesterase (p = 0.016; PCR = 2.5-fold decrease) genes. Leptin downregulated 3-hydroxy 3-methylglutaryl coenzyme A reductase (p = 0.006; PCR = 2.5-fold decrease) and LDL receptor (p = 0.003).. Leptin modulates obesity and regulates gallbladder genes related to cholesterol gallstone pathogenesis.

Topics: Animals; Female; Gallbladder; Gallstones; Leptin; Mice; Mice, Obese; Obesity; Oligonucleotide Array Sequence Analysis; Organ Size; RNA, Messenger; Weight Loss

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high-risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in 23 older, obese men and women (aged 66 +/- 1 yr, body mass index 33.2 +/- 1.4 kg/m(2)) with impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise training [5 days/wk for 60 min at 75% maximal oxygen consumption (Vo(2max))] with either normal caloric intake (eucaloric group, 1,901 +/- 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 +/- 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (Vo(2max)), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P < 0.05). Improvements in body composition, leptin, and basal fat oxidation were greater in the hypocaloric group. Following the intervention, there was a correlation between the increase in basal fat oxidation and the decrease in IMCL (r = -0.53, P = 0.04). In addition, basal fat oxidation was associated with circulating leptin after (r = 0.65, P = 0.0007) but not before the intervention (r = 0.05, P = 0.84). In conclusion, these data show that exercise training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved but that such a trend may rely on reducing caloric intake in addition to exercise training.

Topics: Adiponectin; Adiposity; Aged; Body Composition; Caloric Restriction; Diet, Reducing; Dietary Fats; Exercise; Female; Glucose Intolerance; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Muscle, Skeletal; Obesity; Oxidation-Reduction; Oxygen Consumption; Physical Fitness; Weight Loss

Decreased expression or function of UCP3 (uncoupling protein 3) could reduce energy expenditure and increase the storage of energy as fat. Some studies have pointed to a role of UCP3 in the regulation of whole body energy homeostasis, diet induced obesity, and regulation of lipids as metabolic substrates. The C/C genotype of a polymorphism in the UCP3 promoter (-55C-->T) is associated with an increased expression of UCP3 mRNA in muscle. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on adipocytokines response and weight loss secondary to a hypocaloric diet in obese patients. A population of 107 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after three months of a hypocaloric diet, an indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure, a serial assessment of nutritional intake with 3-day written food records, and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1520 kcal, 52% of carbohydrates, 25% of lipids and 23% of proteins). The exercise program consisted of aerobic exercise for at least 3 times per week (60 minutes each). The mean age was 49.5+/-34.5 years and the mean BMI 34.5+/-4.8, with 27 males (25.3%) and 80 females (74.7%). Ninety patients (25 males/65 females) (83.6%) had the genotype 55CC (wild group) and 17 patients (2 male/15 females) (16.4%) 55CT (mutant group). The percentage of responders (weight loss) was similar in both groups (wild group: 84.7% vs. mutant group: 81.8%). BMI, weight, fat mass, systolic blood pressure, LDL cholesterol, waist circumference, and waist-to-hip ratio decreased in the wild group and RMR and VO (2) were increased. In the mutant group, BMI and weight decreased. Leptin and IL-6 levels have a significant decrease in the wild group (9.6%: p<0.05) and (30.5%: p<0.05), respectively. Patients with -55CC genotype have a significant decrease in leptin, interleukin 6, BMI, weight, fat mass, systolic blood pressure, LDL cholesterol, waist circumference, waist-to-hip ratio weight, fat mass, and systolic blood pressure.

Topics: Adipokines; Blood Pressure; Body Mass Index; Caloric Restriction; Calorimetry, Indirect; Cholesterol, LDL; Diet, Reducing; DNA Primers; Female; Genotype; Humans; Interleukin-6; Ion Channels; Leptin; Male; Middle Aged; Mitochondrial Proteins; Obesity; Polymorphism, Genetic; Uncoupling Protein 3; Weight Loss

Weight loss in cystic fibrosis (CF) may be associated with altered levels of appetite stimulating peptide ghrelin and the appetite decreasing peptide leptin. However, prior data on leptin in CF are conflicting, while the data on ghrelin are scarce. We hypothesized that weight loss in CF is associated with low levels ghrelin and elevated levels of leptin.. Plasma ghrelin, leptin, TNF-alpha, IL-1 and IL-6, BMI, fat free mass (FFM), fat mass (FM) were measured in 74 CF adults and 20 controls. CF subjects were divided into 3 groups based on lung disease: mild (n=19), moderate (n=30) and severe (n=25).. Severe CF patients (% predicted FEV1 27+/-7; median BMI 21 kg/m2) had significantly elevated ghrelin and decreased leptin compared to controls and other CF subjects. Ghrelin correlated (r value, p value) with BMI (-0.35,<0.001), FFM (-0.22,<0.05), FM (-0.41,<0.0001), FEV1 (-0.62,<0.001), TNF-alpha (0.51,<0.0001), IL-1 (0.56,<0.0001), and IL-6 (0.33,<0.01). Leptin correlated (r value, p value) with BMI (0.40,<0.0001), FM (0.56,<0.0001), FEV1 (0.34,<0.05), IL-1 (-0.51,<0.05) and TNF-alpha (-0.43,<0.0001). BMI and FEV1 were independent predictors of ghrelin (-0.35,<0.05;-0.59,<0.001). FM was a predictor of leptin (0.56,<0.0001). Cytokines were elevated only in severe CF (severe CF vs. controls, pg/ml): TNF-alpha (3.4+/-0.6 vs. 1.2+/-0.4), IL-1 (3.5+/-1 vs. 0.2+/-0.1), IL-6 (17.4+/-4 vs. 2.4+/-2).. Elevated ghrelin and decreased leptin levels are a consequence rather than a cause of weight loss in advanced CF.

Topics: Adult; Biomarkers; Body Mass Index; Case-Control Studies; Cystic Fibrosis; Female; Flow Cytometry; Ghrelin; Humans; Interleukin-1; Interleukin-6; Leptin; Male; Middle Aged; Regression Analysis; Respiratory Function Tests; Tumor Necrosis Factor-alpha; Weight Loss

In order to investigate whether weight loss can lead to improvement of the mononuclear cell (MNC) proinflammatory state, 21 nondiabetic obese women with mean age 34+/-2 years (mean+/-s.e.m.) and BMI 32.5+/-1.2 kg/m2 were enrolled in a 12-week caloric restriction and light exercise-based weight loss program. Ten lean women served as controls. Reverse transcription-PCR of proinflammatory cytokines and adipocytokines as well as homeostasis model assessment of insulin resistance (HOMA-IR) were determined before and after weight reduction. Nuclear factor kappaB (NF-kappaB) binding to DNA and inhibitors of NF-kappaB (IkappaB-alpha and IkappaB-beta) obtained from peripheral MNCs were measured. Overall, subjects lost a mean of 4.0+/-0.4 kg (5.0+/-0.3% of their initial body weight) (P<0.01). In addition to significant reductions in BMI, fasting glucose and insulin concentrations, mean serum high-sensitivity C-reactive protein (hs-CRP), migration inhibitor factor (MIF), leptin and visfatin levels decreased by 49.0, 66.6, 17.2, and 50.2%, respectively (all P<0.05), while adiponectin concentrations rose by 33.9% (P<0.05). The DNA binding of the transcriptionally active NF-kappaB from (p65/p50) decreased by 38.1% (P<0.05). Elevated levels of mRNA of NF-kappaB related proinflammatory genes, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), MIF, and matrix metalloproteinase-9 (MMP-9), decreased significantly after weight loss. Although mRNA expression of Rel-A, p105, IkappaB-alpha, IkappaB-beta decreased significantly, their protein levels did not change after weight loss. As a group, NF-kappaB binding activity correlated with HOMA-IR (r=0.332, P=0.049) and marginally with values of BMI (r=0.308, P=0.059). In conclusion, weight loss by 5% of initial weight in nondiabetic obese women led to significant improvement in activated intranuclear NF-kappaB binding as well as several transcriptions of proinflammatory genes regulated by NF-kappaB.

Topics: Adult; Blood Glucose; C-Reactive Protein; Case-Control Studies; Female; Humans; I-kappa B Proteins; Inflammation; Insulin; Interleukin-6; Intramolecular Oxidoreductases; Leptin; Leukocytes, Mononuclear; Macrophage Migration-Inhibitory Factors; Matrix Metalloproteinase 9; NF-kappa B; NF-KappaB Inhibitor alpha; Nicotinamide Phosphoribosyltransferase; Obesity; Tumor Necrosis Factor-alpha; Weight Loss

CRH, the hypothalamic component of the hypothalamic-pituitary adrenal axis, attenuates inflammation through stimulation of glucocorticoid release, whereas peripherally expressed CRH acts as a proinflammatory mediator. CRH is expressed in the intestine and up-regulated in patients with ulcerative colitis. However, its pathophysiological significance in intestinal inflammatory diseases has just started to emerge. In a mouse model of acute, trinitrobenzene sulfonic acid-induced experimental colitis, we demonstrate that, despite low glucocorticoid levels, CRH-deficient mice develop substantially reduced local inflammatory responses. These effects were shown by histological scoring of tissue damage and neutrophil infiltration. At the same time, CRH deficiency was found to be associated with higher serum leptin and IL-6 levels along with sustained anorexia and weight loss, although central CRH has been reported to be a strong appetite suppressor. Taken together, our results support an important proinflammatory role for CRH during mouse experimental colitis and possibly in inflammatory bowel disease in humans. Moreover, the results suggest that CRH is involved in homeostatic pathways that link inflammation and metabolism.

Topics: Animals; Anorexia; Colitis, Ulcerative; Corticotropin-Releasing Hormone; Disease Models, Animal; Female; Gene Expression; Inflammation; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Reverse Transcriptase Polymerase Chain Reaction; Trinitrobenzenesulfonic Acid; Weight Loss

Evidence suggests that when animals are chronically deprived of calories, the reward of a food stimulus becomes more salient. Recently leptin has been implicated in food reward. The objective of this study was to examine the effect of weight-loss on food hedonics and on the reinforcing value of palatable snack food, and to determine whether plasma leptin concentrations were related to these variables. Fifteen apparently healthy obese adults (n=9 women and 6 men; age=33.5+/-7.8; BMI=35.7+/-1.1 kg/m(2)) were subjected to 8 weeks of caloric deprivation (-700 kcal/day). Plasma leptin (ELISA), body weight and composition (Dual X-ray Absorptiometry), food reinforcement (concurrent schedules task) and food hedonics (visual analogue scale) were measured pre- and post-intervention. Body weight decreased by 5.2+/-2.7% (p=0.001) while leptin decreased by 30.1+/-32.6% (p=0.001). Relative to baseline, after weight-loss food hedonics or "liking" was rated significantly higher for the food reinforcers (p=0.001) offered at sessions end, and this change was not significantly correlated with changes in plasma leptin. No significant effect of weight-loss was noted for the reinforcing value of palatable snack food. In conclusion, after 8 weeks of caloric deprivation there was no change in the reinforcing value of palatable snack foods, but the rating of food "liking" increased ~10%, and this increase was independent of weight-loss.

Topics: Adult; Analysis of Variance; Caloric Restriction; Energy Metabolism; Food Preferences; Humans; Leptin; Male; Pain Measurement; Reinforcement Schedule; Reinforcement, Psychology; Weight Loss

Our objective was to compare the effects of a low-carbohydrate diet to a high-carbohydrate/calorie-restricted diet on weight loss, hormones, and transplanted colon tumor growth. Eighty male C57BL/6 mice consumed a diet-induced obesity regimen (DIO) ad libitum for 7 weeks. From Weeks 8 to 14, the mice consumed a 1) DIO diet ad libitum (HF); 2) low-carbohydrate diet ad libitum (LC); 3) high-carbohydrate diet ad libitum (HC); or 4) HC calorie restricted diet (HC-CR). MC38 cells were injected at Week 15. At the time of injection, the HC-CR group displayed the lowest body weight (25.5 +/- 0.57 g), serum insulin-like growth factor I (IGF-I; 135 +/- 56.0 ng/ml), and leptin (1.0 +/- 0.3 ng/ml) levels. This group also exhibited the longest time to palpable tumor (20.1 +/- 0.9 days). Compared to the HF group, the HC group exhibited lower body weight (39.4 +/- 1.4 vs. 32.9 +/- 0.7 g, respectively), IGF-I (604 +/- 44.2 vs. 243.4 +/- 88.9 ng/ml, respectively), and leptin (15.6 +/- 2.2 vs. 7.0 +/- 0.7 ng/ml, respectively) levels but similar tumor growth. IGF-I levels were lower in the LC group (320.0 +/- 39.9 ng/ml) than the HF group, but tumor growth did not differ. These data suggest LC diets do not slow colon tumor growth in obese mice.

Topics: Animals; Caloric Restriction; Colonic Neoplasms; Diet, Carbohydrate-Restricted; Energy Intake; Insulin-Like Growth Factor I; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Random Allocation; Weight Loss; Xenograft Model Antitumor Assays

Weight regain after weight loss may not be due primarily to voluntary return to social habits but may be explained by changes in peripheral hormonal signals activating hunger and encouraging feeding behavior.. The objective of this study was to investigate physiologic adaptations to weight loss that may encourage weight regain.. The study had a within-subject repeated-measure design [12 healthy, obese men, 33-64 y, body mass index (in kg/m(2)) 30-46] and was a clinical intervention investigation of circulating metabolites and hunger-satiety responses before and after weight loss. Measures included anthropometry (bioelectrical impedance, body weight, and waist circumference), concentrations of circulating hormones and metabolites [ketone bodies, free fatty acids (FFAs), insulin, leptin, glucose, and cholecystokinin (CCK)], and measures of hunger and satiety at baseline, 8 wk after weight loss with a very-low-energy diet, and 1 wk after weight maintenance.. Weight loss led to a reduction in postprandial CCK secretion (P = 0.016). However, when subjects were ketotic (elevated circulating beta-hydroxybutyrate concentrations), CCK secretion was sustained at concentrations before weight loss. After weight loss, there were reduced postprandial FFA concentrations (P = 0.0005). The presence of ketosis sustained FFA to concentrations before weight loss (P = 0.60).. Rapid weight loss of approximately 10% of initial body weight results in a reduction in postprandial CCK and FFA concentrations.

Topics: Adaptation, Physiological; Adult; Anthropometry; Body Mass Index; Cholecystokinin; Eating; Fatty Acids, Nonesterified; Gastrointestinal Tract; Humans; Hunger; Insulin; Ketone Bodies; Ketosis; Leptin; Male; Middle Aged; Nutritional Physiological Phenomena; Obesity; Peptide Hormones; Postprandial Period; Satiation; Signal Transduction; Weight Loss

In this study, we describe changes of plasma levels of the hypothalamic neuropeptide orexin A in obese children during the reduction of body weight and its relationship to other biochemical and anthropometrical parameters. We measured orexin A fasting plasma levels by the RIA method in 58 obese children--33 girls and 25 boys; mean age 13.1+/-0.38 years (range 7-18.5) before and after 5 weeks of weight-reduction therapy. Leptin, IGF-1, and IGFBP-3 levels were measured in all the subjects and were compared to orexin A levels and anthropometrical data. Average weight in subjects before weight-reduction was 74.2+/-2.79 kg and after weight-loss 67.4+/-2.60 kg (p<0.0001). Orexin A levels before the therapy were 33.3+/-1.97 pg/ml and after the therapy 51.7+/-3.07 pg/ml (p<0.0001). Levels of orexin A were not significantly different between girls and boys (p=0.7842). We found negative correlation between orexin A and age (r = -0.5395; p<0.0001), body height (r = -0.4751; p=0.0002), body weight (r = -0.4030; p=0.0017) and BMI (r = -0.2607; p=0.0481). No correlation was found between orexin A and IGF-1, IGFBP-3 or leptin. Orexin A plasma levels increased during body weight loss, whereas the reverse was true for leptin levels. These findings support the hypothesis that orexin A may be involved in regulation of nutritional status in children.

Topics: Adolescent; Aging; Body Height; Body Mass Index; Body Weight; Child; Female; Humans; Insulin-Like Growth Factor I; Intracellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptides; Nutritional Status; Obesity; Orexins; Radioimmunoassay; Weight Loss

Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.

Topics: Adiponectin; Adipose Tissue; Algorithms; Animals; Body Composition; Calorimetry, Indirect; Cats; Cytokines; Diet; Dietary Carbohydrates; Dietary Proteins; Energy Intake; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Insulin Resistance; Leptin; Male; Models, Statistical; Obesity; Oxidation-Reduction; Weight Loss

Obesity may be regarded as a low-grade inflammatory state.. The aim of this study was to evaluate changes in pro-inflammatory adipocytokines and the innate immune system, cardiovascular risk, and insulin sensitivity after massive weight loss.. This was a longitudinal study.. The study was conducted at Catholic University, Rome.. There were 10 normoglucose-tolerant obese women evaluated before and 36 months after bilio-pancreatic diversion (BPD). Glucose sensitivity (M value) was estimated using the euglycemic-hyperinsulinemic clamp. Mannan-binding lectin (MBL), bactericidal/permeability increasing protein (BPI), alpha-defensins, soluble CD14 receptor (sCD14), C-reactive protein, adiponectin, leptin, visfatin, IL-6, and TNF-alpha were assayed.. After massive weight loss (53% of excess body weight), leptin (P

Topics: Acute-Phase Reaction; Adipocytes; Adiponectin; Adult; alpha-Defensins; Antimicrobial Cationic Peptides; Blood Glucose; Blood Proteins; Body Composition; C-Reactive Protein; Cytokines; Female; Humans; Immune System; Insulin Resistance; Interleukin-6; Leptin; Lipopolysaccharide Receptors; Longitudinal Studies; Mannose-Binding Lectin; Membrane Proteins; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity, Morbid; Solubility; Tumor Necrosis Factor-alpha; Weight Loss

Recent findings suggest that low plasma peptide YY (PYY) levels may contribute to diet-induced human obesity and justify PYY replacement therapy. Although the pharmacological value of PYY is controversial, further study of the secretion of the precursor PYY(1-36) and the pharmacologically active PYY(3-36) is indicated to determine the potential role in energy balance regulation.. Our objective was to determine the effects of acute and chronic changes in human body weight on circulating levels of the putative satiety hormone peptide YY.. Total plasma PYY levels (PYY(1-36) + PYY(3-36)) were measured in 66 lean, 18 anorectic, 63 obese, and 16 morbidly obese humans. In addition, total PYY was measured in 17 of the obese patients after weight loss and in the 18 anorectic patients after weight gain. Fasting PYY(3-36) levels were measured in 17 lean and 15 obese individuals.. Fasting total plasma PYY levels were highest in patients with anorexia nervosa (80.9 +/- 12.9 pg/ml, P < 0.05) compared with lean (52.4 +/- 4.6 pg/ml), obese (43.9 +/- 3.8 pg/ml), or morbidly obese (45.6 +/- 11.2 pg/ml) subjects. In obese patients, weight loss of 5.4% was associated with a 30% decrease in fasting total PYY plasma levels. In anorectic patients, weight gain had no effect on fasting PYY. PYY(3-36) levels did not differ between lean (96.2 +/- 8.6 pg/ml) and obese (91.5 +/- 6.9 pg/ml) subjects.. Our findings do not support a role for abnormal circulating PYY in human obesity. We conclude that circulating PYY levels in humans are significantly elevated in anorexia nervosa and, given the controversially discussed anorectic effect of PYY, could theoretically contribute to that syndrome.

Topics: Adult; Anorexia; Body Weight; Energy Intake; Fasting; Female; Humans; Leptin; Obesity, Morbid; Peptide Fragments; Peptide YY; Receptors, Cell Surface; Receptors, Leptin; Satiety Response; Weight Gain; Weight Loss

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Humans; Hypoventilation; Leptin; Obesity; Respiration, Artificial; Respiratory System; Sleep Apnea, Obstructive; Syndrome; Weight Loss

Our goal was to assess the awakening cortisol response (ACR) in obese and reduced obese men and women.. Fifty-one men (16 lean, 19 abdominally obese, and 16 reduced obese) and 31 women (12 lean, 10 subcutaneously obese, and 9 reduced obese) were selected to participate to this study. Strict ranges of BMI and waist circumference were used to select the participants. Medical examination, psychological assessment, anthropometric measurements, and blood sampling were undergone at the laboratory. Cortisol response to awakening was determined with saliva cortisol sampling being taken immediately at the time of awakening and 30 minutes thereafter over 3 days within a period of 2 months.. Men with visceral obesity exhibited an enhanced ACR, whereas this response tends to return to normal in a reduced obese state. In women, peripheral fat accumulation does not modify ACR, but weight loss increased the response.. These results highlight gender effects on ACR of obese and reduced obese subjects, which could be accounted for by the different fat distribution profiles that characterize men and women. They also provide further support for the usefulness of ACR in assessing the hypothalamic-pituitary-adrenal axis activity status.

Topics: Adult; Arousal; Body Fat Distribution; Female; Humans; Hydrocortisone; Leptin; Male; Middle Aged; Obesity; Saliva; Sex Characteristics; Thinness; Weight Loss

Leptin, an adipokine, a major regulator of food intake, was recently suggested to play a role in immune response. We previously showed that weight reduction following IFNalpha therapy is due, at least in part, to direct induction of adipose tissue apoptosis. We now studied the effect of leptin on IFNalpha treated adipocytes in vitro and in vivo. Diet induced obese C57/B6 mice were treated continually with recombinant (r) IFNalphaA/D + leptin (100 U/g body weight + 10 microg/day, respectably) or leptin (10 microg/day) alone for 8 days. Co-administration of IFNalphaA/D + leptin significantly reduced plasma cholesterol (P<0.001), glucose (P<0.007) and pro-apoptotic protein levels (P<0.05). Additionally, co-administration prevented loss of body weight due to adipocyte apoptosis. Thus, leptin co-administration with IFNalphaA/D decreases some of the side effects of IFNalpha administration such as weight loss, cholesterol and glucose levels.

Topics: 3T3 Cells; Animals; Apoptosis Regulatory Proteins; Blood Glucose; Cholesterol; Humans; Interferon-alpha; Leptin; Mice; Mice, Inbred C57BL; Recombinant Proteins; Weight Loss

Despite high leptin levels, most obese humans and rodents lack responsiveness to its appetite-suppressing effects. We demonstrate that leptin modulates NPY/AgRP and alpha-MSH secretion from the ARH of lean mice. High-fat diet-induced obese (DIO) mice have normal ObRb levels and increased SOCS-3 levels, but leptin fails to modulate peptide secretion and any element of the leptin signaling cascade. Despite this leptin resistance, the melanocortin system downstream of the ARH in DIO mice is over-responsive to melanocortin agonists, probably due to upregulation of MC4R. Lastly, we show that by decreasing the fat content of the mouse's diet, leptin responsiveness of NPY/AgRP and POMC neurons recovered simultaneously, with mice regaining normal leptin sensitivity and glycemic control. These results highlight the physiological importance of leptin sensing in the melanocortin circuits and show that their loss of leptin sensing likely contributes to the pathology of leptin resistance.

Topics: Agouti-Related Protein; alpha-MSH; Animals; Arcuate Nucleus of Hypothalamus; Body Composition; Diet; Dietary Fats; Dose-Response Relationship, Drug; Gene Expression Regulation; Hypothalamus; In Vitro Techniques; Intercellular Signaling Peptides and Proteins; Leptin; Male; Melanocortins; Mice; Mice, Inbred C57BL; Neurons; Neuropeptide Y; Obesity; Pro-Opiomelanocortin; RNA, Messenger; Signal Transduction; Weight Loss

Apolipoprotein E (apoE) is a multifunctional protein that is highly expressed in human and murine adipose tissue. Endogenous adipocyte apoE expression influences adipocyte triglyceride turnover and modulates the expression of genes involved in lipid synthesis and oxidation. We now demonstrate the regulation of adipose tissue apoE expression by nutritional status in lean and obese mice. Obesity induced by high-fat diet, or by hyperphagia in ob/ob mice, produces significant reduction of adipose tissue apoE expression at the protein and messenger RNA level. Fasting in C57BL/6J mice for 24 h significantly increased apoE protein and messenger RNA levels. In ob/ob mice, transplantation of adipose tissue from lean littermate controls to restore circulating leptin levels produced significant weight loss over 12 wk and also produced an increase in adipose tissue apoE expression. The increase in adipose tissue apoE expression in this model, however, did not require leptin. Adipose tissue apoE was also significantly increased in ob/ob mice after a 48-h fast or after 7 days of caloric restriction. In summary, obesity suppresses adipose tissue apoE expression, whereas fasting or weight loss increases it. From our previous observations, these changes in adipose tissue apoE expression will have significant impact on adipose tissue lipid flux and lipoprotein metabolism. Furthermore, these results suggest adipose tissue apoE participates in defending adipose tissue and organismal energy homeostasis in response to nutritional perturbation.

Topics: Adipose Tissue; Animals; Apolipoproteins E; Caloric Restriction; Diet, Atherogenic; Fasting; Food; Gene Expression Regulation; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Weight Loss

To examine the role of the brain stem melanocortin system in long-term energy regulation, we assessed the effects of overproduction of proopiomelanocortin (POMC) in the caudal brain stem of F344xBN rats with adult-onset obesity. Recombinant adeno-associated viral vector encoding POMC gene was delivered to the nucleus of solitary tract (NTS) in the hindbrain, and food intake, body weight, glucose and fat metabolism, brown adipose tissue thermogenesis, and mRNA levels of neuropeptides and melanocortin receptors were assessed. POMC delivery resulted in sustained reduction in food intake and body weight over 42 days and improved insulin sensitivity. At death, in recombinant adeno-associated viral vector-POMC-treated rats vs. control rats, alpha-melanocyte-stimulating hormone in NTS increased nearly 21-fold, whereas hypothalamic alpha-melanocyte-stimulating hormone remained unchanged. Visceral adiposity decreased by 37%; tissue triglyceride content diminished by 26% and 47% in liver and muscle, respectively; serum triglyceride and nonesterified fatty acids were reduced by 35% and 34%, respectively; phosphorylation of acetyl-CoA carboxylase was elevated by 63% in soleus muscle; brown adipose tissue uncoupling protein 1 increased by 30%; and melanocortin 3 receptor expression declined by 60%, whereas neuropeptide Y, agouti-related protein, and MC4 receptor mRNA levels were unchanged in the NTS. In conclusion, POMC overexpression in the NTS produces a characteristic unabated hypophagia that is uniquely different from the anorexic tachyphylaxis following POMC overexpression in the hypothalamus. The sustained anorectic response may result from absence of compensatory elements in the NTS, such as increased agouti-related protein expression, suggesting melanocortin activation of the brain stem may be a viable strategy to alleviate obesity.

Topics: Adiposity; alpha-MSH; Animals; Animals, Genetically Modified; Anorexia; Appetite Regulation; Body Weight; Energy Metabolism; Gene Expression Regulation; Gene Transfer Techniques; Genetic Therapy; Leptin; Male; Melanocortins; Obesity; Pro-Opiomelanocortin; Rats; Rats, Inbred F344; Solitary Nucleus; Tachyphylaxis; Time Factors; Weight Loss

White adipose tissue is the principal site for lipid accumulation. Males and females maintain distinctive white adipose tissue distribution patterns. Specifically, males tend to accumulate relatively more visceral fat, whereas females accumulate relatively more subcutaneous fat. The phenomenon of maintaining typical sex-specific fat distributions suggests sex-specific mechanisms that regulate energy balance and adiposity. We used two distinct approaches to reduce fat mass, caloric restriction (CR), and surgical fat removal (termed lipectomy) and assessed parameters involved in the regulation of energy balance. We found that male and female mice responded differentially to CR- and to lipectomy-induced fat loss. Females decreased energy expenditure during CR or after lipectomy. In contrast, males responded by eating more food during food return after CR or after lipectomy. Female CR mice conserved subcutaneous fat, whereas male CR mice lost adiposity equally in the subcutaneous and visceral depots. In addition, female mice had a reduced capability to restore visceral fat after fat loss. After CR, plasma leptin levels decreased in male but not in female mice. The failure to increase food intake after returning to ad libitum intake in females could be due to the relatively stable levels of leptin. In summary, we have found sexual dimorphisms in the response to fat loss that point to important underlying differences in the strategies by which male and female mice regulate body weight.

Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Body Fat Distribution; Caloric Restriction; Corticosterone; Energy Intake; Energy Metabolism; Estrous Cycle; Female; Ion Channels; Leptin; Lipectomy; Male; Mice; Mice, Inbred Strains; Mitochondrial Proteins; Sex Characteristics; Uncoupling Protein 1; Weight Loss

Weight loss after bariatric surgery varies between patients, and predicting the extent thereof is often inaccurate. The aim of this study was to assess the potential of preoperative plasma leptin and body weight in predicting the maximum weight loss within 2 years after Roux-en-Y gastric bypass (RYGBP).. The study comprised 68 subjects (39 women, 29 men; mean age 36.4 +/- 10.2 years, body weight 130.3 +/- 24.8 kg, BMI 44.4 +/-6.8 kg/m2) undergoing RYGBP who were followed for 2 years. Baseline and maximum follow-up plasma leptin and weight were assessed.. Mean maximum weight reduction of 50.5 +/- 19.1 kg (38.0 +/- 9.0%, range 24-100 kg) was noted at 15 +/- 4 months after RYGBP. Baseline plasma leptin was 37.9 +/- 14.5 ng/ml, and decreased to 17.4 +/- 8.1 ng/ml (P < 0.001) at maximum weight reduction. No significant correlation between baseline plasma leptin and absolute or relative weight reduction or minimum body weight achieved was noted. No significant plasma leptin threshold which would be predictive for any consistent extent of weight loss was found. However, baseline body weight was a strong determinant of minimum body weight attained (r = 0.67; P < 0.01) and of maximum absolute weight reduction (r = 0.81; P < 0.01).. Preoperative plasma leptin concentration cannot be used as a predictor of weight reduction following RYGBP. Preoperative body weight is a reliable predictor of post-RYGBP weight loss.

Topics: Adult; Body Weight; Female; Follow-Up Studies; Gastric Bypass; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Predictive Value of Tests; Time Factors; Treatment Outcome; Weight Loss

To find factors associated with successful weight maintenance (WM) in overweight and obese subjects after a very low-calorie diet (VLCD).. Subjects (133) followed a VLCD (2.1 MJ/d) for 6 weeks in a free-living situation. Of these, 103 subjects (age, 49.6 +/- 9.7 years; BMI, 30.9 +/- 3.8 kg/m(2)) completed the following 2-year WM period. Body weight (BW), body composition, leptin concentration, attitude toward eating, and physical activity were determined right before (t0) and after (t1) the VLCD, after 3 months (t2), after 1 year (t3), after 1.5 years (t4), and after 2 years (t5).. BW loss during VLCD was 7.2 +/- 3.1 kg. After 2 years, follow-up BW regain was 69.0 +/- 98.4%. After 2 years of WM, 13 subjects were successful (<10% BW regain), and 90 were unsuccessful (>10% BW regain). At baseline, these groups were significantly different in BMI (33.7 +/- 4.7 vs. 30.5 +/- 3.5 kg/m(2), respectively; p < 0.05) and fat mass (38.3 +/- 9.8 vs. 32.1 +/- 8.3 kg, p < 0.05). Successful subjects increased their dietary restraint significantly more during the whole study period (dietary restraint score, -4.9 +/- 4.4 vs. -2.1 +/- 3.8). Furthermore, %BW regain was associated with the amount of percentage body fat lost during VLCD, which indicates that the more fat lost, the better the WM, suggesting a fat free mass-sparing effect.. Characteristics such as the ability to increase dietary restraint and maintain this high level of restraint, fat free mass sparing, and a relatively high baseline BMI and fat mass were associated with successful long-term WM (<10% regain after 2 years).

Topics: Adult; Attitude; Body Composition; Body Weight; Diet; Eating; Exercise; Follow-Up Studies; Humans; Leptin; Middle Aged; Netherlands; Surveys and Questionnaires; Time Factors; Weight Loss

Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women.. Ten glucose-normotolerant, fertile, obese women (BMI >40 kg/m2, aged 38.66 +/- 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method.. No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P = 0.05) and postobese women (P < or = 0.01) as was the decrease in dehydroepiandrosterone (P < or = 0.05 and P < or = 0.01, respectively). CBG decreased from 51.50 +/- 12.76 to 34.33 +/- 7.24 mg/l (P < or = 0.01) following BPD. FCI increased from 11.15 +/- 2.85 to 18.16 +/- 6.82 (P < or = 0.05). Insulin secretion decreased (52.04 +/- 16.71 vs. 30.62 +/- 16.32 nmol/m(-2); P < or = 0.05), and insulin sensitivity increased by 163% (P < or = 0.0001). Serum CBG was related to BMI (r(0) = 0.708; P = 0.0001), body weight (r(0) = 0.643; P = 0.0001), body fat percent (r(0) = 0.462; P = 0.001), C-reactive protein (r(0) = 0.619; P = 0.004), and leptin (r(0) = 0.579; P = 0.007) and negatively to M value (r(0) = -0.603; P = 0.005).. After massive weight loss in morbidly obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity.

Topics: Adipose Tissue; Adult; Bariatric Surgery; Blood Glucose; Blood Pressure; Body Size; Cholesterol; Dexamethasone; Human Growth Hormone; Humans; Hydrocortisone; Leptin; Middle Aged; Obesity; Reference Values; Transcortin; Weight Loss

Obesity and high blood pressure (BP) commonly coexist in patients, and both conditions are associated with elevated sympathetic nervous activity. We tested whether the sympathetic nervous system was differently affected in men and women by the body mass index (BMI), BP, leptin and weight loss.. We measured muscle sympathetic nerve activity (MSNA, microneurography), BP and plasma leptin concentrations in 167 age-matched normotensive and hypertensive men and women divided into three subgroups: lean, BMI < 25 kg/m; overweight, BMI > or = 25 and < 30 kg/m; and obese, BMI > or = 30 kg/m. These measurements were repeated in a subgroup of 19 obese subjects who underwent a 12-week diet.. Women with hypertension had increased MSNA compared with their normotensive counterparts (37 +/- 2 versus 25 +/- 2 bursts/min, analysis of variance, P < 0.001) and MSNA was significantly related to BP (P < 0.05, r = 0.236) but not to BMI. MSNA in men with hypertension was no different from that in normotensive subjects (33 +/- 2 versus 30 +/- 2 bursts/min), but MSNA was significantly related to BMI (P < 0.05, r = 0.249). Diet resulted in the same degree of weight loss in men and women, but induced a decrease in MSNA only in men (43 +/- 3 to 34 +/- 3 bursts/min, P < 0.01). The plasma leptin concentration was higher in women than in men, and for both groups it was related to BMI not BP (r = 0.497, P < 0.001 in women and r = 0.483, P < 0.001 in men).. These data demonstrate a gender difference in the regulation of the sympathetic nervous system, in which MSNA mainly relates to BP in women and to BMI in men.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Muscle, Skeletal; Neural Conduction; Neurology; Obesity; Sex Factors; Sympathetic Nervous System; Weight Loss

To compare weight loss, body composition, and metabolic changes in response to carbohydrate versus dietary energy restriction (DER) in obese mice.. One hundred C57BL/6 mice were randomized into five groups of 20. The group of high-carbohydrate (HC) mice consumed an HC diet ad libitum and the group of high-fat (HF) mice consumed an HF diet ad libitum for 14 weeks. Additional groups consumed the HF diet for 7 weeks ad libitum and during weeks 8-14 were switched to either a low-carbohydrate diet (LC) consumed ad libitum, the HC diet pair-fed (PF) to the energy intake of the LC group, or an HC DER regimen providing 70% of the energy intake of the HF group.. At 14 weeks, the LC and HF groups weighed more and exhibited higher percent fat mass and lower bone mineral density than the HC, PF, and DER groups. Relative to the DER group, the LC group displayed comparable serum ketone bodies but higher serum glucose, triglycerides, cholesterol, leptin, insulin, and insulin-like growth factor-1.. In contrast to DER, the LC diet did not cause weight loss or reduce serum markers associated with obesity-related diseases other than diabetes in obese mice, suggesting that carbohydraterestriction without reduced energy intake does not induce weight loss.

Topics: Animals; Blood Glucose; Body Composition; Caloric Restriction; Cholesterol; Dietary Carbohydrates; Dietary Fats; Energy Intake; Insulin; Insulin-Like Growth Factor I; Ketone Bodies; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Random Allocation; Triglycerides; Weight Loss

Topics: Amenorrhea; Estradiol; Female; Humans; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Leptin; Malnutrition; Physical Exertion; Pituitary-Adrenal System; Weight Loss

Previously, 40% food restriction of male Siberian hamsters over 21 days in short-day (SD) photoperiod induced characteristic changes in expression of hypothalamic arcuate nucleus energy balance genes; mRNAs for neuropeptide Y, agouti-related peptide, and leptin receptor were upregulated, and those of proopiomelanocortin and cocaine- and amphetamine-regulated transcript were depressed. The present study examined the effect of refeeding hamsters for 6 days (approximately 50% recovery of weight differential) or 19 days (resumption of appropriate weight trajectory). Hyperphagia continued throughout refeeding, but differences in fat pad weights and leptin levels had disappeared after 19 days. Cocaine- and amphetamine-regulated transcript gene expression was depressed by prior restriction in both refed groups. The depressive effect of prior restriction on proopiomelanocortin gene expression had disappeared after 19 days of refeeding. There was no effect of prior food restriction on neuropeptide Y or agouti-related peptide gene expression. Expression of the anorexigenic brain-derived neurotrophic factor was downregulated in the ventromedial nucleus after SD exposure for 12 wk. In the SD food restriction study, there were effects of photoperiod on brain-derived neurotrophic factor gene expression but not of prior food restriction. Hypothalamic energy balance genes in the hamster respond asynchronously to return to a seasonally appropriate body weight. The achievement of this weight rather than the weight at which caloric restriction was imposed is the critical factor. The differential responses of hypothalamic energy balance genes to food restriction and refeeding are poorly characterized in any species, a critical issue given their potential relevance to human weight loss strategies that involve caloric restriction.

Topics: Animals; Body Weight; Brain-Derived Neurotrophic Factor; Caloric Restriction; Cricetinae; Eating; Gene Expression; Hypothalamus; Leptin; Male; Neuropeptides; Organ Size; Phodopus; Photoperiod; Radioimmunoassay; Weight Loss

The study aimed to examine if dysmetabolic subjects (MetS+) have lower adiponectin gene expression and lower circulating adiponectin levels than non-dysmetabolic obese subjects (MetS-) at baseline, if adiponectin expression and adiponectin concentration rise more in the dysmetabolic group during weight loss, and if v-SNARE Vti1a (vesicle transport soluble NSF attachment protein receptor vps10p tail interacting 1a) expression increases during the weight loss, as a mechanism for increased adiponectin secretion. Twenty-one obese MetS+ and 19 obese MetS- subjects underwent a very low-energy diet for 16 weeks followed by 2 weeks of refeeding. Abdominal subcutaneous adipose tissue biopsies and blood samples were taken before, during, and after dieting for DNA microarray, reverse transcriptase-polymerase chain reaction, and biochemical analyses. Serum adiponectin was also assessed in a sex- and age-matched healthy, nonobese reference group. Weight decreased by 26.3+/-9.8 kg in the MetS+ group and 28.2+/-8.4 kg in the MetS- group with concomitant reductions in insulin, hemoglobin A1c, and triglycerides that were more pronounced in the MetS+ group. Initially, the MetS+ subjects had lower serum adiponectin, but the differences disappeared at week 8, with a continuous increase in serum adiponectin throughout the study in both groups to a level that was higher than in the reference group. The expression of adiponectin and v-SNARE Vti1a did not differ between the groups or over time. In conclusion, obese subjects with the metabolic syndrome had lower circulating adiponectin than subjects without the syndrome. Weight loss increased serum levels of adiponectin without a parallel increase in adiponectin gene expression. The mechanisms involved in the regulation of adiponectin levels merits further investigation.

Topics: Adiponectin; Adipose Tissue; Adult; Body Weight; Diet, Reducing; Energy Intake; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Glycated Hemoglobin; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA; SNARE Proteins; Triglycerides; Weight Loss

The objectives of this study were to determine 1) whether the extent of weight loss is predictive of the degree of changes in hormone and lipid levels; 2) the interactions between energy regulating hormones after weight loss through an energy deficit/exercise protocol diet and exercise; 3) whether initial metabolic parameters are indicative of the extent of weight loss.. Thirty-five hyperlipidemic females (BMI 28-39 kg/m2) 35-60 years old participated in a six month weight loss trial. Weight loss resulted from a diet and exercise program that when combined produced a 30% energy deficit. Fasting plasma taken during 2 wk stabilization periods at the beginning and end of the study was analysed for lipids, hormone and glucose levels.. Average weight loss was 11.7 +/- 2.5 kg (p < 0.0001). TC, LDL-C, and triacylglycerols decreased 9.3 +/- 9.5% (p < 0.0001), 7.4 +/- 12.2% (p < 0.001), and 26.8 +/- 19.6% (p < 0.05), respectively, while HDL-C increased (p < 0.05) by 8.2 +/- 16.3%. Leptin levels declined (p < 0.001) 48.9 +/- 16.0% and ghrelin levels rose (p < 0.001) 21.2 +/- 26.7%. While overall levels of adiponectin did not differ, individual values changed such that weight loss predicted increases in adiponectin levels. Though initial weight did not predict weight loss, baseline lipid and insulin levels positively predicted weight loss.. Initial metabolic parameters may be predictors of weight loss. Beneficial effects of weight loss as achieved through diet and exercise on measured parameters indicate moderate weight loss reduces key risk factors of cardiovascular disease in overweight individuals.

Topics: Adiponectin; Adult; Blood Glucose; Cardiovascular Diseases; Combined Modality Therapy; Diet, Reducing; Energy Metabolism; Exercise; Female; Ghrelin; Humans; Hyperlipidemias; Leptin; Lipids; Middle Aged; Obesity; Peptide Hormones; Predictive Value of Tests; Risk Factors; Weight Loss

The adipocyte influences eating behavior and metabolism via cytokine secretion. We report our findings of adipokine secretion in a cohort of diabetic and nondiabetic morbidly obese patients before and after Roux-en-Y gastric bypass (RYGB).. Ten morbidly obese subjects who underwent uncomplicated RYGB were studied: five were diabetic and nine were female. Nonfasting plasma levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha were determined preoperatively and 6 mo postoperatively. C-reactive protein (CRP) was followed as a marker of the metabolic syndrome.. The patient age was 42 +/- 11 y, and the preoperative BMI was 50 +/- 6 kg/m(2). The 6 mo BMI fell to 33 +/- 5 kg/m(2) (P < 0.0001), and there were no differences between diabetics and nondiabetics with respect to amount of weight loss. In nondiabetic patients, there were significant increases compared with preoperative levels for adiponectin, resistin, and tumor necrosis factor-alpha; leptin was significantly decreased while CRP was unchanged. CRP and leptin levels were both significantly lower (P < 0.05), while all other protein levels were unchanged in diabetic patients.. At 6 mo postoperation, RYGB significantly altered most adipokine levels for nondiabetic patients. Only CRP and leptin were changed in diabetic patients. All patients lost a significant amount of weight over 6 mo, suggesting a different metabolic effect between nondiabetic and diabetic patients after RYGB.

Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Hormones; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity, Morbid; Pilot Projects; Resistin; Tumor Necrosis Factor-alpha; Weight Loss

The effect of acupuncture induced weight reduction on menstrual activity is definitely not a negligible issue. By analyzing the existing materials about the mutual influence of neuroendocrine system and clinical trails, it is known that there exists a close interrelation between acupuncture-induced weight reduction and menstruation. Acupuncture treatment can achieve the effects of weight reduction and menstrual improvement via regulating activities of leptin, thyroid gland system and hypothalamus-pituitary-adrenal cortex axis. Clinical practice has demonstrated that acupuncture stimulation of some commonly-used acupoints for weight reduction also has a favorable regulation on menstrual activity in obesity women.

Topics: Acupuncture Points; Acupuncture Therapy; Female; Humans; Leptin; Menstruation; Obesity; Weight Loss

The objective was to evaluate ghrelin and growth hormone (GH) interactions and responses to a growth hormone-releasing hormone (GHRH)/arginine test in severe obesity before and after surgically-induced weight loss.. Our study population included 11 severely obese women 39 +/- 12 years of age, with a mean BMI of 48.6 +/- 2.4 kg/m2, re-studied in a phase of stabilized body weight, with a BMI of 33.4 +/- 1.2 kg/m2, 18 months after having successfully undergone biliopancreatic diversion (BPD). A GHRH/arginine test was performed before and 18 months after BPD to evaluate ghrelin and GH interactions. Active ghrelin, measured by radioimmunoassay (RIA), and GH, measured by chemiluminescence assay, were assayed before and after the GHRH/arginine test.. Fasting serum GH levels and GH area under the curve (AUC) significantly increased from 0.2 +/- 0.05 ng/mL to 1 +/- 0.3 ng/mL (p < 0.05) and from 514.76 +/- 98.7 ng/mL for 120 minutes to 1957.3 +/- 665.1 ng/mL for 120 minutes after bariatric surgery (p < 0.05), respectively. Although no significant change in fasting ghrelin levels was observed (573 +/- 77.9 before BPD vs. 574.1 +/- 32.7 after BPD), ghrelin AUC significantly increased from -3253.9 +/- 2180.9 pg/mL for 120 minutes to 1142.3 +/- 916.4 pg/mL for 120 minutes after BPD (p < 0.05). Fasting serum insulin-like growth factor (IGF)-1 concentration did not change significantly (133.6 +/- 9.9 ng/mL before vs. 153.3 +/- 25.2 ng/mL after BPD).. Our study demonstrates that the mechanisms involved in ghrelin and GH secretion after the secretagogue stimulus (GHRH/arginine) are consistent with patterns observed in other populations.

Topics: Adult; Arginine; Biliopancreatic Diversion; Blood Glucose; Female; Ghrelin; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Middle Aged; Obesity, Morbid; Peptide Hormones; Weight Loss

The U.S. Environmental Protection Agency is currently validating assays that will be used in a Tier I Screening Battery to detect endocrine disrupting chemicals. A primary concern with the Protocols for the Assessment of Pubertal Development and Thyroid Function in Juvenile Male and Female Rats is that a nonspecific reduction in body weight (BWT) during the exposure period may potentially confound the interpretation of effects on the endocrine endpoints. Wistar rats were underfed 10, 20, 30, or 40% less than the ad libitum food consumed by controls from postnatal days (PNDs) 22 to 42 (females) or PNDs 23 to 53 (males). Terminal BWT of females and males were 2, 4, 12, and 19% and 2, 6, 9, and 19% lower than controls, respectively. In the females, neither the age of pubertal onset nor any of the thyroid hormone endpoints were affected by food restriction (FR) that led to a 12% decrease in BWT. Similarly, none of the male reproductive endpoints examined were altered by FR that led to a 9% BWT decrease. However, decreased triiodothyronine and thyroxin was observed in FR males with a 9% reduced BWT. While these data support the use of the maximum tolerated dose for BWT (10%) for the female protocol, effects on the male thyroid endpoints indicate that a slightly lower limit (

Topics: Adrenal Glands; Animals; Blood Glucose; Body Weight; Endocrine Disruptors; Female; Food Deprivation; Genitalia, Female; Genitalia, Male; Kidney; Leptin; Liver; Male; Organ Size; Pituitary Gland; Rats; Rats, Wistar; Reproducibility of Results; Sexual Maturation; Thyroid Gland; Thyroid Hormones; Toxicity Tests; Vagina; Weight Loss

To investigate whether changes in leptin concentrations during weight loss can be explained by gender, puberty, baseline adiposity and changes in adiposity, body composition, rate of weight loss, physical activity and insulin concentrations.. A longitudinal study with 9 repeated measures during a 12-week weight loss programme.. Fifty-three boys and 62 girls (7.9-15.2 years) with body mass index (BMI) standard deviation scores (SDS) of median 2.78 and 2.70, respectively.. Height, weight, fat mass percentage assessed by bioimpedance, Tanner stages, testicular size, physical activity scores, blood leptin (ng/ml) and insulin concentrations (pmol/l) were measured at baseline, and except for Tanner stage and testicular size, repeated regularly during the programme.. The weight loss was accompanied by a steep decline in leptin concentrations during the first 10-11 days, followed by a less steep decline until day 82. Leptin declined to 39% in boys and 51% in girls of the level that was expected given the relationship at baseline between leptin and BMI SDS, and the BMI SDS changes during weight loss. The biphasic leptin decline was independent of gender, puberty, baseline adiposity or concomitant changes in BMI SDS, fat mass percentage, rate of weight loss, physical activity scores or insulin concentrations.. The biphasic leptin decline, which exceeded the level expected, was independent of puberty, baseline adiposity and changes in adiposity, body composition, rate of weight loss, physical activity scores and insulin concentrations. The dissociation of the leptin-weight relationship during weight loss may contribute to the general leptin variability in obese subjects.

Topics: Adiposity; Adolescent; Body Composition; Child; Female; Humans; Insulin; Leptin; Longitudinal Studies; Male; Motor Activity; Obesity; Osmolar Concentration; Puberty; Sex Factors; Time Factors; Weight Loss

Adipocyte fatty acid-binding protein (A-FABP) has been reported to be increased in obese adults and to be related to metabolic syndrome. Because studies concerning A-FABP in weight loss are limited and studies in obese children are missing, we analyzed A-FABP in obese children before and after weight loss. Fasting serum A-FABP, leptin, insulin, glucose, triglycerides, low-and high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and tumor necrosis factor alpha concentrations as markers of the metabolic syndrome, and weight status (body mass index and percentage body fat based on skinfold measurements) were determined in 30 obese children (median age, 11.9 years) before and after participating in a 1-year obesity intervention. Furthermore, A-FABP levels were measured in 10 nonobese children of similar age, sex, and pubertal stage. Obese children had significantly (P < .001) higher A-FABP concentrations compared with nonobese children. In backward multivariate linear regression analysis, A-FABP correlated significantly (P < .05) with percentage body fat and leptin, but not with any of the markers of the metabolic syndrome. Changes of A-FABP concentrations correlated significantly with changes of percentage body fat (r = 0.53, P = .001) and leptin (r = 0.55, P < .001), but not with any changes of parameters of the metabolic syndrome. Substantial weight loss in 10 children led to a significant (P < .05) decrease in A-FABP levels in contrast to the 20 children without change of weight status. In cross-sectional as well as longitudinal analyses, A-FABP levels were related to weight status and leptin levels. Further longitudinal studies are necessary to study the relationship between A-FABP concentrations and parameters of the metabolic syndrome.

Topics: Adipose Tissue; Adolescent; Blood Pressure; Body Mass Index; C-Reactive Protein; Child; Cross-Sectional Studies; Fatty Acid-Binding Proteins; Female; Humans; Leptin; Longitudinal Studies; Male; Metabolic Syndrome; Multivariate Analysis; Obesity; Regression Analysis; Tumor Necrosis Factor-alpha; Weight Loss

Topics: Adipose Tissue; Animals; Leptin; Liver; Models, Biological; Weight Loss

Weight loss is common in patients with chronic obstructive pulmonary disease (COPD). However, the mechanisms of this weight loss are still unclear.. Sixty male patients with stable COPD and 45 healthy male controls participated in this study. The COPD patients were divided into two groups, that is, the emphysema and chronic bronchitis groups, by the transfer coefficient of carbon monoxide. The body composition, resting energy expenditure (REE), plasma leptin levels and serum tumor necrosis factor-alpha (TNF-alpha) were measured in all the study participants. The difference and correlation of these parameters were investigated between the two groups.. Emphysematous patients were characterized by a lower body mass index (BMI) and fat-mass (FM) compared with the chronic bronchitis patients (p < 0.001). The plasma leptin levels, as corrected for the FM, were not different between the COPD patients and healthy controls (78.3 +/- 30.9 pg/mL/kg vs. 70.9 +/- 17.3 pg/mL/kg, respectively), and the plasma leptin levels, as adjusted for the FM, were also not different between the two groups of COPD patients. In the chronic bronchitis patients, the plasma leptin concentration was correlated with the BMI (r = 0.866, p < 0.001) but it was not correlated with the BMI in the emphysema patients. The serum TNF-alpha levels were higher in the stable COPD patients than those in the controls, but there was no statistical difference (10.7 +/- 18.6 pg/mL vs. 7.2 x 3.5 pg/mL, respectively, p0.05). The leptin concentration was well correlated with the BMI and %FM in the patients with chronic bronchitis and the leptin concentration was only correlated with the %FM (r = 0.450, p = 0.027) in emphysema patients. There was no correlation between the plasma leptin concentration, as adjusted for the fat mass, and the activity of the TNF-alpha system.. The interaction of leptin and the activity of the TNF-alpha system in the pathogenesis of tissue depletion may not play an important role in chronic stable COPD patients.

Topics: Aged; Body Composition; Bronchitis, Chronic; Case-Control Studies; Emphysema; Energy Metabolism; Humans; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Tumor Necrosis Factor-alpha; Weight Loss

Body weight loss is a common but one of the most serious sequelae after gastrectomy. Ghrelin, a novel gastric hormone that up-regulates body weight through appetite control and metabolic reaction, seems to be affected by gastric surgery.. Early postoperative alteration of serum ghrelin was evaluated at days 3 and 7 after gastrectomy for 13 hospital patients. In 64 outpatients who had previously undergone total gastrectomy (TG: 26 patients) or distal gastrectomy (DG: 38 patients) 4.6 months to 136 months (average, 41 months) earlier, the association between their serum ghrelin and leptin levels and postoperative body weight was investigated.. Serum ghrelin declined immediately and greatly after TG to 12% of the preoperative level (day 3 and day 7), whereas the decline was less significant after DG at 39% (day 3) and 56% (day 7). In outpatients, serum ghrelin after TG was very low compared with the control (18.6 fmol/mL versus 92.1 fmol/mL, P<0.0001), irrespective of the period after surgery, whereas the level after DG recovered and was equivalent to the control (73.4 fmol/mL, P=0.355). Body weight loss was more apparent in TG patients than in DG patients, showing postoperative reduction of body mass index (DeltaBMI) -3.940 versus -1.949 (P<0.0001). Serum leptin concentration, reflecting the systemic fat volume, significantly correlated with BMI in both TG and DG patients, and tended to be lower in TG patients than in DG patients (800 pg/mL versus 1158 pg/mL, P=0.236).. Persistent decline of serum ghrelin and body weight was observed commonly after total gastrectomy. Further study is needed as to whether or not ghrelin administration can improve the body weight level for these patients.

Topics: Aged; Anastomosis, Roux-en-Y; Female; Gastrectomy; Gastroenterostomy; Ghrelin; Humans; Leptin; Male; Middle Aged; Outpatients; Peptide Hormones; Postoperative Complications; Stomach Neoplasms; Weight Loss

Exercise improves glucose metabolism and delays the onset and/or reverses insulin resistance in the elderly by an unknown mechanism. In the present study, we examined the effects of exercise training on glucose metabolism, abdominal adiposity, and adipocytokines in obese elderly. Sixteen obese men and women (age = 63 +/- 1 yr, body mass index = 33.2 +/- 1.4 kg/m2) participated in a 12-wk supervised exercise program (5 days/wk, 60 min/day, treadmill/cycle ergometry at 85% of heart rate maximum). Visceral fat (VF), subcutaneous fat, and total abdominal fat were measured by computed tomography. Fat mass and fat-free mass were assessed by hydrostatic weighing. An oral glucose tolerance test was used to determine changes in insulin resistance. Exercise training increased maximal oxygen consumption (21.3 +/- 0.8 vs. 24.3 +/- 1.0 ml.kg(-1).min(-1), P < 0.0001), decreased body weight (P < 0.0001) and fat mass (P < 0.001), while fat-free mass was not altered (P > 0.05). VF (176 +/- 20 vs. 136 +/- 17 cm2, P < 0.0001), subcutaneous fat (351 +/- 34 vs. 305 +/- 28 cm2, P < 0.03), and total abdominal fat (525 +/- 40 vs. 443 +/- 34 cm2, P < 0.003) were reduced through training. Circulating leptin was lower (P < 0.003) after training, but total adiponectin and tumor necrosis factor-alpha remained unchanged. Insulin resistance was reversed by exercise (40.1 +/- 7.7 vs. 27.6 +/- 5.6 units, P < 0.01) and correlated with changes in VF (r = 0.66, P < 0.01) and maximal oxygen consumption (r = -0.48, P < 0.05) but not adipocytokines. VF loss after aerobic exercise training improves glucose metabolism and is associated with the reversal of insulin resistance in older obese men and women.

Topics: Adiposity; Age Factors; Blood Glucose; Exercise; Exercise Test; Exercise Therapy; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Obesity; Oxygen Consumption; Triglycerides; Weight Loss

Bariatric surgery is the most effective treatment for achieving long-term weight loss in morbidly obese patients. This study investigated prospective changes in gut hormones and metabolic indices after Roux-en-Y gastric bypass (RYGB).. Six patients were seen before, and at 1, 3 and 6 months after operation. Blood was collected after a 12-h fast and at regular intervals after a mixed 420-kcal meal. Hormonal responses were determined, and comparisons between basal levels and areas under the curve were made. Visual analogue scores were used to assess satiety, hunger and nausea.. Mean body mass index decreased from 48.3 kg/m(2) before surgery to 36.4 kg/m(2) 6 months after RYGB. This was accompanied by a decrease in fasting leptin (P < 0.001) and insulin (P = 0.021) levels. At 1, 3 and 6 months after operation, progressively increasing peptide YY (P < 0.001), enteroglucagon (P = 0.045) and glucagon-like peptide 1 (P = 0.042) responses were observed. There was no change in fasting ghrelin levels (P = 0.144). Postprandial satiety was significantly increased by 1 month after surgery and this was maintained until the end of the study (P < 0.001).. RYGB resulted in substantial weight loss with enhanced postprandial satiety, a sustained weight plateau, and proportionate reduction in fasting insulin and leptin levels. Lack of the expected increase in appetite and food intake as components of a counter-regulatory response may be explained by gut adaptation and the consequent graded rise in the levels of gut hormones that promote satiety.

Topics: Adaptation, Physiological; Anastomosis, Roux-en-Y; Area Under Curve; Body Mass Index; Gastric Bypass; Gastrointestinal Hormones; Humans; Insulin; Leptin; Obesity, Morbid; Postprandial Period; Prospective Studies; Satiation; Weight Loss

The observation that loss of orexin (hypocretin) neurons causes human narcolepsy raises the possibility that other acquired disorders might also result from loss of hypothalamic neurons. To test this possibility for body weight, mice with selective loss of melanin concentrating hormone (MCH) neurons were generated. MCH was chosen to test because induced mutations of the MCH gene in mice cause hypophagia and leanness. Mice with ablation of MCH neurons were generated using toxin (ataxin-3)-mediated ablation strategy. The mice appeared normal but, after 7 weeks, developed reduced body weight, body length, fat mass, lean mass, and leptin levels. Leanness was characterized by hypophagia and increased energy expenditure. To study the role of MCH neurons on obesity secondary to leptin deficiency, we generated mice deficient in both ob gene product (leptin) and MCH neurons. Absence of MCH neurons in ob/ob mice improved obesity, diabetes, and hepatic steatosis, suggesting that MCH neurons are important mediators of the response to leptin deficiency. These data show that loss of MCH neurons can lead to an acquired leanness. This has implications for the pathogenesis of acquired changes of body weight and might be considered in clinical settings characterized by substantial weight changes later in life.

Topics: Adipose Tissue; Animals; Ataxin-3; Blood Glucose; Cell Death; Crosses, Genetic; Diabetes Mellitus, Experimental; Energy Intake; Energy Metabolism; Fasting; Fatty Liver; Female; Gene Expression; Hypothalamic Hormones; Hypothalamus; Insulin; Leptin; Machado-Joseph Disease; Male; Melanins; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Transgenic; Nerve Tissue Proteins; Neurons; Neuropeptides; Nuclear Proteins; Obesity; Pituitary Hormones; Recombinant Fusion Proteins; Repressor Proteins; Thinness; Transcription Factors; Weight Loss

The hormone ghrelin and the adipocytokines leptin and adiponectin participate in body weight regulation. In response to weight loss, ghrelin and adiponectin levels increase and leptin decreases. Cancer cachexia is a complex metabolic state, characterized by loss of muscle mass and adipose tissue together with anorexia. The authors hypothesized that responses of these hormones may be attenuated in cancer cachexia.. Fasting plasma ghrelin, adiponectin, and leptin levels, as well as weight loss, were determined in 40 cancer patients: 18 of them suffered from cancer-induced cachexia, and 22 served as a comparison group. Hormone levels were measured before administration of cancer therapy.. A similar distribution of age, gender, and diagnosis was observed in both study groups, but the cachectic patients had higher rates of metastatic disease and lower albumin levels. No significant correlation was observed between plasma adiponectin levels and weight loss. Mean plasma ghrelin levels were higher among cachectic compared with noncachectic patients. Notably, the association between ghrelin levels and weight loss was only modest, and in a third of the cachectic patients, ghrelin levels were equal to or lower than those in the noncachectic group. Plasma leptin levels showed gender-dependent associations, and significantly lower levels were found among cachectic women but not among cachectic men.. Results suggested a gender-dependent attenuation of expected physiologic responses to weight loss among cancer cachexia patients. Thus, impaired response of adiponectin, ghrelin, and leptin may play a role in the pathogenesis of cancer cachexia syndrome.

Topics: Adiponectin; Aged; Breast Neoplasms; Cachexia; Colonic Neoplasms; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Peptide Hormones; Sex Factors; Weight Loss

Conjugated linoleic acid (CLA), which contains a conjugated double-bond system, and n-3 highly unsaturated fatty acids such as docosahexaenoic acid (DHA) are widely known to improve lipid metabolism. To examine the possibility that a fatty acid with a combination of these structural features might have stronger physiological effects, we prepared conjugated DHA (CDHA) by alkaline isomerization of DHA and examined its effects on lipid and sugar metabolism in rats. Rats were force fed with 200 mg of test oils [linoleic acid (LA), DHA, CLA or CDHA] everyday for 4 weeks. Compared with the animals from the other groups, those in the CDHA group showed a significant weight loss in white adipose tissue (57% of adipose tissue weight in the LA group) and significant decreases in the levels of liver triacylglycerol (TG; 65% of TG level in the LA group) as well as total cholesterol (TC; 88% of TC level in the LA group), indicating suppression of lipid accumulation in the liver and adipose tissue. In addition, plasma TG and TC levels significantly decreased (69% of TG level and 82% of TC level in the LA group), indicating improved lipid metabolism. In the liver, the fatty acid synthesis system was inhibited and the fatty acid beta-oxidation system was activated, whereas the free fatty acid, glucose and tumor necrosis factor alpha levels in the plasma were lowered following CDHA administration. Hence, intake of CDHA appears to suppress the accumulation of fat in the liver and epididymal adipose tissue and improves lipid and sugar metabolism in rats.

Topics: Adipose Tissue; Animals; Blood Glucose; Cholesterol; Diet; Docosahexaenoic Acids; Fatty Acids; Fatty Acids, Nonesterified; Hydrogen-Ion Concentration; Insulin; Isomerism; Leptin; Linoleic Acid; Linoleic Acids, Conjugated; Lipid Metabolism; Liver; Male; Organ Size; Phospholipids; Rats; Rats, Sprague-Dawley; Safflower Oil; Triglycerides; Tumor Necrosis Factor-alpha; Weight Loss

The insulin-mimetic adipocytokine visfatin has been linked to obesity. The influence of weight loss on plasma visfatin concentrations in obese subjects is unknown yet.. In this study we investigated whether plasma visfatin concentrations are altered by weight loss in patients with obesity.. In a prospective study, fasting plasma visfatin, leptin, and adiponectin concentrations were measured before and 6 months after gastric banding in 31 morbidly obese patients aged 40 +/- 11 yr with a body mass index (BMI) of 46 +/- 5 kg/m(2). Fourteen healthy subjects aged 29 +/- 5 yr with a BMI less than 25 kg/m(2) served as controls.. Visfatin plasma concentrations were markedly elevated in obese subjects (0.037 +/- 0.008 microg/ml), compared with controls (0.001 +/- 0.000 microg/ml, P < 0.001). Gastric banding reduced BMI to 40 +/- 5 kg/m(2), visfatin to 19.2 +/- 10.9 ng/ml, and leptin from 39.0 +/- 12.4 to 29.7 +/- 10.0 ng/ml and increased adiponectin from 0.015 +/- 0.007 to 0.017 +/- 0.007 microg/ml (all P < 0.05) after 6 months. Insulin sensitivity as estimated by the homeostasis model assessment insulin resistance index was unchanged from 5.8 +/- 3.1 to 4.6 +/- 1.9 (P = 0.13), but individual changes of insulin resistance and visfatin were significantly associated (P < 0.05, r = -0.43).. Elevated plasma visfatin concentrations in morbidly obese subjects are reduced after weight loss. This may be related to changes in insulin resistance over time.

Topics: Adiponectin; Adult; Body Mass Index; Cohort Studies; Cytokines; Female; Gastroplasty; Humans; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity, Morbid; Prospective Studies; Treatment Outcome; Weight Loss

Weight regain after weight loss is the most significant impediment to long-term weight reduction. We have developed a rodent paradigm that models the process of regain after weight loss, and we have employed both prospective and cross-sectional analyses to characterize the compensatory adaptations to weight reduction that may contribute to the propensity to regain lost weight. Obese rats were fed an energy-restricted (50-60% kcal) low-fat diet that reduced body weight by 14%. This reduced weight was maintained for up to 16 wk with limited provisions of the low-fat diet. Intake restriction was then removed, and the rats were followed for 56 days as they relapsed to the obese state. Prolonged weight reduction was accompanied by 1) a persistent energy gap resulting from an increased drive to eat and a reduced expenditure of energy, 2) a higher caloric efficiency of regain that may be linked with suppressed lipid utilization early in the relapse process, 3) preferential lipid accumulation in adipose tissue accompanied by adipocyte hyperplasia, and 4) humoral adiposity signals that underestimate the level of peripheral adiposity and likely influence the neural pathways controlling energy balance. Taken together, long-term weight reduction in this rodent paradigm is accompanied by a number of interrelated compensatory adjustments in the periphery that work together to promote rapid and efficient weight regain. These metabolic adjustments to weight reduction are discussed in the context of a homeostatic feedback system that controls body weight.

Topics: Adipose Tissue; Animals; Body Weight; Carbohydrate Metabolism; Circadian Rhythm; Diet, Fat-Restricted; Energy Intake; Energy Metabolism; Insulin; Leptin; Lipid Metabolism; Male; Models, Biological; Obesity; Proteins; Rats; Rats, Wistar; Weight Gain; Weight Loss

Despite a preliminary understanding of leptin-skeletal interactions, data in humans are inconsistent and the exact roles of leptin on bone metabolism have not yet been defined. The aim of this study was to examine the possible role of leptin in the regulation of bone metabolism in healthy, physically trained adults.. Body composition and bone mass (dual-energy X-ray absorptiometry), anthropometry, serum leptin, insulin, cortisol, osteocalcin, C-terminal telopeptide of type I collagen (CTx) and total plasma proteins were measured in judoists at normal body weight, after weight reduction and after weight regain. Physical training, weight cycling history, menstrual status and nutritional intake using a 7-day food record were assessed.. Precompetitive weight loss averaged 4 +/- 0.3% of bodyweight and resulted in a significant decrease in leptin levels of 64% (P < 0.001) and of 31% for insulin (P < 0.0001). CTx and cortisol concentrations rose by 33% (P < 0.0001) and 81% (P < 0.05) respectively. Osteocalcin and total plasma protein remained unaffected by weight loss. A 4 +/- 0.5% weight regain induced a 276% increase in leptin levels (P < 0.001) and an 18% increase in insulin (P < 0.001). CTx and cortisol decreased by 23% (P < 0.0001) and 27% (P < 0.05) respectively. Changes in leptin were significantly correlated with changes in bone resorption marker in response to both weight loss (r = 0.56, P < 0.01) and regain (r = 0.44, P < 0.05).. These findings suggest that leptin is involved in the regulation of bone metabolism in healthy adults and might play a potential role in the prevention of osteoporosis.

Topics: Adult; Biomarkers; Body Weight; Bone and Bones; Cohort Studies; Diet; Female; Hormones; Humans; Leptin; Life Style; Male; Martial Arts; Menstrual Cycle; Motor Activity; Weight Loss

Despite irrefutable epidemiologic evidence, cigarette smoking remains the major preventable cause of lung disease morbidity worldwide. The appetite-suppressing effect of tobacco is a major behavioral determinant of smoking, but the underlying molecular and neuronal mechanisms are not understood. Neuropeptide Y (NPY) is an orexigenic neuropeptide, whose activity in the hypothalamic paraventricular nucleus governs appetite.. To compare the effects of smoke exposure and equivalent food restriction on body weight, organ mass, cytokines, and brain NPY in Balb/c mice.. A pair-feeding study design compared smoke exposure (4 wk; 1 cigarette, 3 x /d, 5 d/wk) to equivalent food restriction (pair-fed) and sham-exposed control mice.. Smoke exposure rapidly induced mild anorexia. After 4 wk, smoke-exposed and pair-fed groups were lighter than control mice (22.0 +/- 0.2, 23.2 +/- 0.5, 24.9 +/- 0.4 g, respectively; p < 0.05). Brown and white fat masses were only reduced by smoke exposure, relative to control mice. NPY concentration in the paraventricular nucleus was significantly and paradoxically reduced by smoke exposure, despite lower plasma leptin concentrations; this was not observed in the pair-fed group experiencing 19% food restriction. Adipose mRNA expression of uncoupling proteins, inflammatory cytokines interleukin 6 and tumor necrosis factor alpha, and adipose triglyceride lipase was decreased by smoke exposure, and even lower in pair-fed mice.. In contrast to food restriction, smoke exposure caused a reduction in hypothalamic NPY and fat mass, and regulated adipose cytokines. These findings may contribute to understanding weight loss in smoking-related lung disease and in the design of more effective smoking cessation strategies.

Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Anorexia; Appetite Regulation; Body Weight; Carrier Proteins; Hypothalamus; Interleukin-6; Ion Channels; Leptin; Male; Membrane Proteins; Mice; Mice, Inbred BALB C; Mitochondrial Proteins; Neuropeptide Y; RNA, Messenger; Smoking; Tumor Necrosis Factor-alpha; Uncoupling Protein 1; Uncoupling Protein 3; Weight Loss

Partitioning of body energy content in the aleptinemic ob/ob mouse differs from that in wild-type mice, but it is not known whether parallel differences exist between humans with leptin (Lep) gene mutations and healthy adults. The objective of this study was to evaluate body composition in three leptin-treated Turkish adults homozygous for a missense mutation (C-->T substitution at codon 105 resulting in Arg-->Trp) of Lep.. Subjects, one male and two female Turkish family members, were evaluated at baseline and treated for 18 months with r-MetHuLeptin. Patient data (fat mass, energy content) were compared with adult sex-specific predicted values (adjusted for weight, height, and age) derived in healthy control subjects.. Weight loss with leptin treatment was substantial, ranging from 43.9% to 52.1%. At baseline and with leptin treatment, the two women had a fat mass and energy content similar (+/-12%) to predicted values. Baseline fat and energy content in the male patient was high compared with predicted values (e.g., fat +33%) but approached and reached normal values (e.g., fat, +2%) after 18 months of leptin therapy.. Adult women with Lep mutations had body composition similar to normal women at baseline and with leptin treatment. In contrast, the man with a Lep mutation had high body fat in the untreated state but a normal male phenotype with leptin administration, possibly secondary to androgenic fat partitioning effects. Fat and energy partitioning can, thus, be quantitatively assessed and linked with potential hormonal mechanisms in humans with inherited disturbances in energy regulation.

Topics: Adult; Anti-Obesity Agents; Body Composition; Energy Intake; Female; Homozygote; Humans; Leptin; Male; Mutation, Missense; Obesity; Predictive Value of Tests; Treatment Outcome; Weight Loss

Acute administration of leucine has been shown to stimulate certain protein synthesis related anabolic processes. However, the effect of chronic leucine administration in a catabolic situation caused by food restriction (FR) has not been established. We therefore evaluated the effect of chronic leucine supplementation on the body composition and some indicators of protein nutritional status of rats submitted to FR.. Adult male Wistar rats were submitted to 50% FR for 6 weeks. The control group received the AIN-93M diet and the leucine group received the same diet supplemented with 5.91 g L-leucine/kg ration. We then determined carcass chemical composition, serum leptin, albumin and total protein concentrations, and protein, DNA and RNA concentrations in gastrocnemius muscle and liver.. No difference in final body weight was observed between groups. However, the leucine group presented a lower amount of body fat (P < 0.05). Leptin concentration showed a directly proportional correlation with the amount of body fat (r = 0.88, P < 0.05), but no significant difference in serum leptin concentration was observed between groups (P = 0.08). Regarding protein nutritional status, liver protein concentration was higher in the leucine group (P < 0.05). In the gastrocnemius muscle, a higher RNA concentration (P < 0.05) and a tendency towards higher DNA concentration (P = 0.06) were observed in the leucine group.. The results indicate that low-dose leucine supplementation increases body fat loss and improves liver protein status and the capacity of muscle protein synthesis in rats submitted to FR.

Topics: Adipose Tissue; Animals; Body Composition; Caloric Restriction; Dietary Supplements; Leptin; Leucine; Liver; Male; Muscle Proteins; Muscle, Skeletal; Nutritional Status; Proteins; Random Allocation; Rats; Rats, Wistar; Serum Albumin; Weight Loss

Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-alpha.. Seventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups: group COPD IA (patients without malnutrition during acute exacerbation, n = 25), group COPD IB (patients without malnutrition during stable disease, n = 29), group COPD II (patients with malnutrition during stable disease, n = 18). To eliminate the effect of sex differences, all patients and controls were male. Body mass index (BMI), percent ideal body weight (IBW%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference (MAMC), serum leptin and TNF-alpha levels, serum prealbumin (PA), serum transferrin (TF), serum albumin (Alb), total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure (MIP) and maximal expiration pressure (MEP) were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed.. Serum leptin levels were significantly lower in group COPD II [(4.07 +/- 3.42) ng/ml] than in group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml] (P < 0.05). There was no statistically significant difference in serum leptin levels between group COPD IA [(10.82 +/- 6.40) ng/ml], group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml]. There was no statistically significant difference in serum TNF-alpha levels between group COPD II [(8.03 +/- 3.37) pg/ml], group COPD IA [(8.90 +/- 1.60) pg/ml], and group COPD IB [(7.25 +/- 2.08) pg/ml]. There was no significant correlation between leptin and TNF-alpha in any group.. Leptin was not involved in anorexia and weight loss of COPD patients. There was no statistically significant difference in serum leptin levels between COPD patients during stable stage and acute exacerbation, and there was no significant correlation between TNF-alpha and leptin during the regulation of the energy balance in COPD patients.

Topics: Adult; Aged; Anorexia; Humans; Leptin; Male; Malnutrition; Middle Aged; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha; Weight Loss

Serotonin (5-HT) plays an important role in controlling food intake and regulating body weight. In addition, clinical studies suggest a possible role for 5-HT in the etiology of anorexia nervosa. Recently, we have examined the effects of pharmacological manipulation of the 5-HT system in female rats exposed to conditions that promote activity-based anorexia (ABA). In this animal model of anorexia nervosa, rats are food restricted (2 h access/day) while given the opportunity to exercise in running wheels. These conditions promote symptoms of anorexia nervosa including hypophagia, hyperactivity, progressive weight loss, and disruptions of the ovarian reproductive cycle. Previously, we demonstrated that increased 5-HT activity increased the weight loss associated with ABA in female rats. Here, we investigated whether decreased 5-HT activity would attenuate symptoms of ABA. Food-restricted female rats received injections of 8-OH-DPAT, a drug that reduces serotonergic neurotransmission, or saline vehicle 40 min prior to food access. During this restricted-feeding phase, food intake was similar between groups; however, 8-OH-DPAT prevented the hyperactivity observed in saline-treated rats. This resulted in less weight loss in 8-OH-DPAT-treated rats, suggesting that decreased activation of the 5-HT system attenuates the development of ABA.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Anorexia Nervosa; Body Temperature; Eating; Estrus; Female; Leptin; Motor Activity; Rats; Rats, Long-Evans; Serotonin; Serotonin Receptor Agonists; Weight Loss

Obesity and type 2 diabetes are world wide health issues and their incidence is rapidly increasing. Currently the biological factors responsible for the development of obesity are only partially understood. Recent research has shown that maternal nutrition during pregnancy may have long-term metabolic consequences in offspring. In the present study we investigated interactions between prenatal and postnatal nutrition on leptin sensitivity and obesity development. Wistar rats were time-mated and randomly assigned to either ad-libitum (AD) or to 30% of ad-libitum (UN) food intake throughout pregnancy. After weaning, female offspring were fed standard chow, a high-fat diet or a calorie restricted diet. Female offspring of UN dams were growth retarded at birth and showed increased susceptibility to diet-induced obesity on a high-fat diet. At 142 +/- 5 days of age, leptin sensitivity was measured as a response to 14 days of leptin treatment (2.5 microg/g/day, s.c.). In UN offspring fed chow, leptin treatment failed to reduce food intake and weight loss was diminished. This leptin resistance observed in UN offspring was independent of diet-induced obesity and was associated with fasting hyperinsulinemia and hypertriglyceridemia. Our study suggests that prenatal nutrition can shape future susceptibility to obesity through alterations in leptin sensitivity and changes in energy metabolism during adult life.

Topics: Animals; Animals, Newborn; Diet; Dietary Fats; Disease Susceptibility; Eating; Energy Intake; Female; Fetal Growth Retardation; Hyperinsulinism; Hypertriglyceridemia; Injections; Leptin; Nutrition Disorders; Obesity; Pregnancy; Prenatal Nutritional Physiological Phenomena; Rats; Rats, Wistar; Weight Loss

Ghrelin is a peptide hormone with orexigenic properties, primarily produced by the stomach. Different changes in fasting ghrelin levels have been reported following bariatric surgery. In this study, we investigate the hypothesis that because ghrelin is mainly produced by the fundus of the stomach, biliopancreatic diversion with sleeve gastrectomy with total resection of the gastric fundus and duodenal switch (BPD-DS) will cause substantial decrease in circulating ghrelin levels.. Serum fasting ghrelin, leptin and adiponectin concentrations were measured by ELISA in 13 patients with morbid obesity who achieved weight loss by BPD-DS, before the operation and 18 months after.. After BPD-DS, BMI decreased significantly, from 59.15+/-15.82 kg/m(2) to 32.91+/-6.46 kg/m(2) (P=0.001). Serum fasting ghrelin level decreased from 1.44+/-0.77 ng/ml to 0.99+/-0.35 ng/ml (P=0.019). Serum leptin level decreased from 1.81+/-0.38 ng/ml to 1.65+/-0.32 ng/ml, (P=0.196), and adiponectin level increased from 37.85+/-11.24 microg/ml to 39.84+/-16.27 microg/ml (P=0.422).. BPD-DS is associated with markedly suppressed ghrelin levels, possibly contributing to the longlasting weight-reducing effect of the procedure. Leptin levels decreased and adiponectin increased, as expected, after weight loss. Sleeve gastrectomy with resection of the gastric fundus seems to be the main cause of the postoperative reduction in ghrelin levels.

Topics: Adiponectin; Adult; Biliopancreatic Diversion; Duodenum; Fasting; Female; Gastrectomy; Ghrelin; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Peptide Hormones; Weight Loss

The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Eating; Energy Intake; Energy Metabolism; Fasting; Hypothalamus; Injections, Intraventricular; Leptin; Leucine; Neurons; Neuropeptide Y; Phosphorylation; Protein Kinases; Rats; Rats, Long-Evans; Ribosomal Protein S6; Ribosomal Protein S6 Kinases; Signal Transduction; Sirolimus; STAT3 Transcription Factor; TOR Serine-Threonine Kinases; Valine; Weight Loss

Little is known concerning pancreatic polypeptide (PP) in weight loss and in childhood obesity.. Fasting PP, leptin and insulin concentrations were determined in 38 obese children and compared with 35 lean children of the same age, gender and pubertal stage. Furthermore, changes of PP concentrations over a 1-year period were analyzed in the obese children participating in a weight loss intervention program.. Obese children had significantly (P<0.01) lower PP, and higher leptin and insulin levels compared to lean children. In multiple linear regression analysis, PP was significantly negatively correlated to body mass index (P<0.01), but not to leptin, insulin, age, gender and pubertal stage. Changes of PP did not significantly correlate to changes of insulin (r=0.07, P=0.343) and leptin (r=-0.02, P=0.459). The substantial weight loss in 17 children led to a significant (P<0.05) increase in PP and decrease in insulin and leptin. In the 21 children without substantial weight loss, there were no significant changes in PP, insulin and leptin.. PP concentrations are decreased in obese children and independent of age, gender, pubertal stage, leptin and insulin. The decrease of PP in obese children normalized after weight loss. Therefore, low PP concentrations reflect the overweight status, rather than cause it.

Topics: Anthropometry; Biomarkers; Body Mass Index; Child; Fasting; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Obesity; Pancreatic Polypeptide; Puberty; Weight Loss

To evaluate the effect of weight loss after bariatric surgery (BS) on peripheral adipocytokines, renal parameters and other cardiovascular risk factors (CVRFs).. A total of 70 (41 women) extremely obese adults were prospectively studied before and 12 months after surgery.. 24 (15 women) normal-weight adults. Anthropometric, biochemical and renal parameters were recorded.. Presurgery, adiponectin (ADPN) was lower, whereas leptin, insulin resistance, C-reactive protein, creatinine clearance and albuminuria were higher in patients than controls (P<0.001). All parameters improved postsurgery. Changes in ADPN correlated negatively with leptin, insulin resistance, albumin, C-reactive protein, and creatinine clearance. Multiple regression analysis: using changes in ADPN as the dependent variable, only changes in insulin resistance (P=0.005) and albumin (P=0.019) were significant independent determinants for changes in ADPN. No statistical differences were found in relation to the degree of obesity.. Patients changed to obesity type I after surgery. This implies a substantial improvement of CVRFs including ADPN, creatinine clearance and albuminuria. Changes in plasma ADPN correlated negatively with insulin resistance and with albuminemia but not with renal parameters. The lack of differences between different degrees of obesity suggests that the relationship between weight and CVRFs no longer exists when obesity becomes very extreme.

Topics: Adiponectin; Adult; Albuminuria; Bariatric Surgery; C-Reactive Protein; Cardiovascular Diseases; Creatinine; Female; Humans; Insulin Resistance; Kidney; Leptin; Male; Metabolic Clearance Rate; Middle Aged; Obesity; Prospective Studies; Serum Albumin; Weight Loss

Serum HGF is elevated in obese individuals. This study examined the contribution of excess adipose tissue to increased circulating HGF levels in obesity. Serum HGF was measured by ELISA before and after weight loss due to bariatric surgery or a 24-h fast. At 6.1 +/- 0.1 mo following surgery, BMI (50.6 +/- 1.6 vs. 35.1 +/- 1.3 kg/m(2); P < 0.0001) and serum HGF were significantly decreased (1,164 +/- 116 vs. 529 +/- 39 pg/ml, P < 0.001). A 24-h fast did not change serum HGF, but serum leptin was significantly reduced (67.7 +/- 7.1 vs. 50.3 +/- 8.3 ng/ml, P = 0.02). HGF secretion in vitro from adipocytes of obese (BMI 40.3 +/- 2.8 kg/m(2)) subjects was significantly greater (80.9 +/- 10.4 vs. 21.5 +/- 4.0 pg/10(5) cells, P = 0.008) than release from adipocytes of lean (BMI 23.3 +/- 1.4 kg/m(2)) subjects. HGF mRNA levels determined by real-time RT-PCR were not different in adipocytes from lean (BMI 24.0 +/- 0.8 kg/m(2)) and obese (45.7 +/- 3.0 kg/m(2)) subjects, but serum HGF was significantly elevated in the obese individuals studied (787 +/- 61 vs. 489 +/- 49 pg/ml, P = 0.001). TNF-alpha (24 h treatment) significantly increased HGF release from subcutaneous adipocytes 23.6 +/- 8.3% over control (P = 0.02). These data suggest that elevated serum HGF in obesity is in part attributable to excess adipose tissue and that this effect can be reversed by reducing adipose tissue mass through weight loss. Increased HGF secretion from adipocytes of obese subjects may be due to posttranscriptional events possibly related to adipocyte size and stimulation by elevated TNF-alpha in the adipose tissue of obese individuals.

Topics: Adipocytes; Adult; Bariatric Surgery; Biopsy; Female; Hepatocyte Growth Factor; Humans; Leptin; Male; Middle Aged; Obesity; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Subcutaneous Fat; Tumor Necrosis Factor-alpha; Weight Loss

Body weight loss is observed commonly after esophagectomy with gastric tube reconstruction in thoracic esophageal cancer patients. The functional and anatomical alteration of the stomach by this surgery should affect ghrelin secretion, a novel gastric hormone that upregulates body weight through appetite control and metabolic reaction.. Early-phase postoperative alteration of serum ghrelin was measured before and at day 3 and day 7 after surgery in 9 patients. With 26 other patients, who had previously undergone surgery from 3 months to 67 months (mean, 25 months) before the present study period, the late-phase postoperative alteration of serum ghrelin was investigated along with postoperative body weight loss and serum leptin.. Serum ghrelin concentration, which was equivalent to the control group before surgery (88.6 fmol/mL vs 97.5 fmol/mL) significantly decreased by half at 3 and 7 days after surgery. Thereafter, the serum ghrelin decline continued in the outpatients within 1 year after surgery (58.8 fmol/mL), while it was marginal in those from 1 to 3 years after surgery (77.2 fmol/mL). Serum ghrelin was significantly higher than the control after 3 years (185.1 fmol/mL). Thus, a significant positive correlation was observed between ghrelin and time after surgery (P < .0001). Postoperative body weight loss was significant, averaged as DeltaBMI - 2.7 in the outpatients (P < .0001). Until 3 years after surgery, a significant correlation between ghrelin and postoperative body weight loss was observed (P = .0152), with those having higher serum ghrelin showing less body weight loss. Serum leptin correlated well with body weight (P = .0144), but not with postoperative time, the degree of body weight loss, or serum ghrelin concentration.. Gastric tube replacement for esophagectomy resulted in temporary reduction of ghrelin production, which is associated with body weight loss after surgery. The decline of ghrelin may play some role in the serious body weight loss after esophagectomy, thus encouraging clinical application of exogenous recombinant ghrelin for these patients.

Topics: Aged; Aged, 80 and over; Body Mass Index; Esophageal Neoplasms; Esophagectomy; Esophagoplasty; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Peptide Hormones; Quality of Life; Weight Loss

Neurotensin is produced mainly in the N cells of the ileum and has a role in appetite regulation; levels are decreased in obese subjects and increase after bariatric surgery. Mature neurotensin is very unstable, with a short half-life.. The objective of this study was to compare baseline and postoperative levels of the more stable neurotensin precursor, proneurotensin/neuromedin (pro-NT/NMN), in patients after gastric banding, gastric bypass, and nonoperated controls, respectively, during long-term follow-up.. This was a prospective observational study in a university hospital.. Overnight fasting plasma pro-NT/NMN concentrations were measured with a new sandwich immunoassay in morbidly obese subjects at baseline and 6, 12, and 24 months after gastric banding (n = 8), Roux-en-Y gastric bypass (n = 5), and in nonoperated controls (n = 7).. After gastric bypass and banding, body weight decreased by (mean +/- sd) 29.5 +/- 5.5 and 22.8 +/- 5.9 kg, respectively. The decrease after 3 and 6 months was more pronounced after gastric bypass compared with gastric banding (P < 0.05). Plasma pro-NT/NMN levels in patients after gastric bypass increased from 246.3 +/- 174.3 pmol/liter on admission to 748.3 +/- 429.6 pmol/liter after 24 months (P < 0.01). In contrast, in patients with gastric banding, pro-NT/NMN concentrations remained stable (207.3 +/- 60.5 pmol/liter at admission, 226.6 +/- 116.8 pmol/liter after 24 months). Neither body weight nor plasma pro-NT/NMN levels changed in nonoperated controls.. Plasma pro-NT/NMN levels show a more pronounced increase after gastric bypass compared with gastric banding, suggesting that specific bariatric surgical procedures result in distinct alterations of gastrointestinal hormone metabolism. The more stable precursor pro-NT/NMN provides a new tool to quantify neurotensin levels in clinical practice.

Topics: Adult; Female; Follow-Up Studies; Gastric Bypass; Ghrelin; Humans; Leptin; Male; Middle Aged; Neurotensin; Obesity, Morbid; Peptide Hormones; Prospective Studies; Protein Precursors; Weight Loss

It has been found that the expression of fatty acid binding protein 2 (FABP2) mRNA is under dietary control. A G-to-A transition at codon 54 of FABP2 results in an amino acid substitution (from Ala 54 to Thr 54). This polymorphism was associated with high insulin resistance and high fasting insulin concentrations. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 protein on the response to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients.. A population of 69 obese (body mass index > 30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of the lifestyle modification program, indirect calorimetry, tetrapolar electrical bioimpedance measurement, blood pressure recording, serial assessment of the nutritional intake (3 days of written food records), and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1,520 kcal; 52% carbohydrates, 25% lipids, and 23% proteins). The exercise program consisted of aerobic exercise for at least three times/week (60 min each). Statistical analysis was performed for combined Ala54/Thr54 and Thr54/Thr54 as a mutant group and wild-type Ala54/Ala54 as second group.. The mean age was 45.5 +/- 16.7 years, the mean body mass index was 34.1 +/- 5.1, and there were 14 males (20.3%) and 55 females (79.7%) with a weight loss of 3.17 +/- 3.5 kg (3.5%). Thirty-seven patients (53.6%) had the genotype Ala54/Ala54 (wild-type group) and 32 (46.4%) patients either the genotype Ala54/Thr54 (26 patients, 30.2%) or the genotype Thr54/Thr54 (6 patients, 16.2%). The percentage of responders (weight loss) was similar in both groups (89.2 vs. 90.6%). In the wild-type group, body mass index, weight, fat mass, low-density lipoprotein cholesterol level, and waist circumference decreased, whereas the VO2 (oxygen consumption) increased. In the mutant group, glucose, body mass index, weight, waist circumference, and systolic blood pressure decreased, and VO2 increased. No differences were detected between basal values in both groups. Only the leptin levels showed a significant decrease in the wild-type group (23.85%; p < 0.05), with no statistically significant difference in the mutant group (2.59%; NS). Resistin, tumor necrosis factor alpha, interleukin 6, insulin, and C-reactive protein remained without changes in both groups.. Weight loss is associated with different changes, depending on the FABP2 genotype. Carriers of the Thr54 allele have a different response than wild-type obese subjects, with a significant decrease of systolic blood pressure and glucose levels in Thr54 carriers and a significant decrease in fat mass, low-density lipoprotein cholesterol, and leptin in wild-type patients.

Topics: Adipose Tissue; Blood Glucose; Blood Pressure; Cholesterol, LDL; Diet, Reducing; Exercise; Fatty Acid-Binding Proteins; Female; Genotype; Humans; Leptin; Life Style; Male; Middle Aged; Obesity; Oxygen Consumption; Polymorphism, Genetic; Prospective Studies; RNA, Messenger; Treatment Outcome; Weight Loss

Aging is associated with appetite decline, weight loss, reduced fat-free mass (FFM), and increased fat mass (FM). Ghrelin and leptin are short- and long-term determinants of energy balance respectively, whose dysregulation could alter food intake. We evaluate the relationship of circulating ghrelin and leptin responses to standardized oral mixed nutrient load (SOMNL) with body composition, daily food intake, and insulin sensitivity in healthy elderly subjects (ES).. Twenty-six ES (12/14 M/F, 69+/-4 years) and ten young healthy controls (LY) (5/5 M/F, 27+/-3 years) were studied at the International Center for the Assessment of Nutritional Status (Milan, Italy) with air plethysmography, dual energy X-ray absorptiometry, indirect calorimetry, and dietary intake assessment. Basal and postprandial ghrelin, leptin, testosterone, glucose, insulin and C-peptide concentrations, and insulin resistance (homeostasis model assessment (HOMA-R)) and sensitivity (quantitative insulin-sensitivity check index (QUICKI)) were evaluated.. Basal ghrelin levels were similar in ES and LY, whereas leptin was higher in ES than LY, in agreement with the higher amount of FM. Basal and percentage change in ghrelin were inversely related to FFM, appendicular skeletal muscle mass (SMM), and QUICKI, but not to FM. Basal and percentage change in leptin were directly related to FM and not to FFM indexes. Ghrelin basal concentration was negatively correlated with energy and protein intake and with QUICKI. Percentage change in Ghrelin after SOMNL correlated negatively with protein intake, but positively with resting energy expenditure and energy intake, and glucose, insulin, C-peptide basal concentrations, and HOMA-R.. In ES, basal and postprandial ghrelin increases with FFM, specifically SMM, reduction, whereas leptin increases with relative FM increases.

Topics: Adipose Tissue; Adult; Aged; Aging; Body Composition; Eating; Energy Metabolism; Female; Ghrelin; Humans; Leptin; Male; Muscle, Skeletal; Peptide Hormones; Postprandial Period; Weight Loss

Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

Topics: Animals; Cells, Cultured; Dietary Fats; Fatty Liver; Glucose; Homeostasis; Leptin; Mice; Mice, Knockout; Pro-Opiomelanocortin; Signal Transduction; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Weight Loss

Human obesity is characterized by high levels of leptin, and it has been suggested that obese patients may be leptin resistant. The aim of our study was to investigate the influence of Lys656Asn polymorphism in the leptin receptor gene on leptin response and weight loss secondary to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients.. A population of 67 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of lifestyle modification program, bipolar electrical bioimpedance, blood pressure, and a serial assessment of nutritional intake with 3 days written food records and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1520 kcal, 52% carbohydrates, 25% lipids and 23% proteins). The exercise program consisted of aerobic exercise for at least three times per week (60 min each). Statistical analysis was performed for the combined Lys656/Asn656 and Asn656/Asn656 as mutant group and type Lys656/Lys 656 as wild-type second group.. Sixty seven patients gave informed consent and were enrolled in the study. The mean age was 45.7 +/- 16.6 years and the mean BMI 34.1 +/- 5.1, with 18 males (26.9%) and 49 females (73.1%). Thirty six patients (10 males/26 females) (46.8%) had the genotype Lys656/Lys 656 (wild-type group) and 31 patients (8 males/23 females) (46.3%) Lys656/Asn656 (n = 28, 41.8%) or Asn656/Asn656 (n = 3, 4.5%) (mutant group). The percentage of responders (weight loss) was similar in both groups (91.7 vs. 87.1%). In wild-type group (responders and nonresponders), BMI, weight, fat mass, systolic blood pressure and waist circumference decreased. In mutant group, BMI, weight and waist circumference decreased. No differences were detected between basal values in both groups. Only leptin levels decreased significantly in wild-type group (11.5%; p <0.05) (57.3 +/- 31.5 ng/mL vs. 45.8 +/- 29.3 ng/mL; p <0.05). In mutant group, leptin increased without statistical differences (0.44%; ns).. Patients with Asn656 allele of LEPR gene have a different response than wild-type patients, and Lys656Lys patients have a significant decrease in weight, BMI, fat mass, waist circumference, systolic blood pressure and leptin levels.

Topics: Adult; Asparagine; Body Mass Index; Exercise; Female; Humans; Leptin; Life Style; Lysine; Male; Middle Aged; Obesity; Polymorphism, Genetic; Receptors, Cell Surface; Receptors, Leptin; Weight Loss

To quantify plasma concentrations of hormones that regulate energy homeostasis in order to establish possible mechanisms for greater weight loss after Roux-en-Y gastric bypass (RYGBP) compared with gastric banding (BND).. Four groups of women were studied: lean (n = 8; mean BMI, 21.6 kg/m2); BND (n = 9; BMI, 35.8; 25% weight loss), RYGBP (n = 9; BMI, 34.2; 36% weight loss), and controls matched for BMI to the surgical groups (n = 11; BMI, 34.4).. Fasting total peptide YY (PYY) and PYY(3-36) immunoreactivity were similar among all groups, but the postprandial response in the RYGBP group was exaggerated, such that 30 minutes after the meal, total and PYY(3-36) levels were 2- to 4-fold greater compared with all other groups. Maximal postprandial suppression of total ghrelin was blunted in the BND group (13%) compared with RYGBP (27%). Postprandial suppression of octanoylated ghrelin was also less in BND (29%) compared with RYGBP (56%). Fasting insulin was lower in RYGBP (6.6 microU/mL) compared with BND (10.0 microU/mL). Compared with lean controls, leptin concentrations were significantly higher in BND but not in RYGBP. There was a greater increase in post-meal satiety in the RYGBP group compared with BND and overweight controls.. The differences between RYGBP and BND subjects in postprandial concentrations of PYY and ghrelin would be expected to promote increased satiety and earlier meal termination in RYGBP and may aid in greater weight loss. The differences in insulin and leptin concentrations associated with these procedures may also reflect differences in insulin sensitivity and energy partitioning.

Topics: Adult; Analysis of Variance; Area Under Curve; Female; Gastric Bypass; Gastroplasty; Ghrelin; Glucose Tolerance Test; Humans; Insulin; Leptin; Middle Aged; Obesity, Morbid; Peptide Hormones; Peptide YY; Postprandial Period; Satiety Response; Weight Loss

Weight-loss maintenance after following an energy-restricted diet is a major problem that a number of studies are trying to characterise. The aim of the present study was to investigate the role of IL-6 -174G>C and PPAR-gamma2 Pro12Ala variants on weight regulation in obese subjects receiving a low-energy diet and at 1 year after the acute slimming period. Sixty-seven volunteers (age 34.7 (SD 7.0) years; BMI 35.8 (SD 4.8) kg/m(2)) were enrolled in a 10-week dietary intervention and were contacted again 1 year after the end of this period. Body composition was measured at three times during the study. Also, PPAR-gamma2 Pro12Ala and IL-6 -174G>C polymorphisms were analysed in the participants. No statistical differences were observed depending on the genetic variants at baseline for anthropometric variables, or after the intervention. However, the C allele of the -174G>C IL-6 gene polymorphism was more frequently observed (P=0.032) in subjects with successful weight maintenance (<10 % weight regain). In fact, the C allele partially protected against weight regain (odds ratio 0.24; P=0.049), while the conjoint presence of both gene variants (C+ and Ala+) further improved the ability for weight maintenance (odds ratio 0.19; P=0.043). The present study demonstrates that the C allele of the -174G>C polymorphism gives protection against regain of weight lost. Moreover, the presence of the Ala allele of the PPARgamma-2 together with the C allele strengthens this protection. These findings support a role for these polymorphisms on weight regulation and suggest a synergetic effect of both variants on weight maintenance after following a diet to lose weight.

Topics: Adult; Alleles; Biomarkers; Body Composition; C-Reactive Protein; Caloric Restriction; Female; Gene Frequency; Genotype; Humans; Interleukin-6; Leptin; Male; Obesity; Polymorphism, Genetic; PPAR gamma; Weight Gain; Weight Loss

Interrelations between fat distribution, muscle lipid infiltration, adipocytokines, insulin resistance, and moderate weight loss have not been investigated in obese older subjects.. The objective was to evaluate relations between fat distribution, muscle lipid content, adipocytokines, and insulin resistance in older women and the effects of moderate weight loss.. In 35 healthy women aged 58-83 y, body mass index, waist circumference, sagittal abdominal diameter (SAD), and body composition measured by dual-energy X-ray absorptiometry were evaluated. A midthigh single computed tomography scan was performed to determine subcutaneous adipose tissue (AT), intermuscular AT (IAT), muscular tissue, and muscle lipid infiltration, evaluated as low-density lean tissue. Metabolic variables, insulin resistance measured by homeostasis model assessment, adiponectin, leptin, and high-sensitivity C-reactive protein were measured in all subjects and after weight loss in a subgroup of 15 obese women.. Waist circumference and SAD were positively correlated with leptin and insulin resistance and negatively correlated with adiponectin. Adiponectin was associated negatively with insulin resistance and positively with HDL cholesterol, whereas leptin was positively associated with insulin resistance and triacylglycerols. Midthigh subcutaneous AT was associated with insulin resistance and leptin, whereas IAT was associated with triacylglycerols. Stepwise regression with insulin resistance as the dependent variable and body mass index, SAD, triacylglycerols, HDL cholesterol, adiponectin, leptin, high-sensitivity C-reactive protein, and midthigh subcutaneous AT as independent variables showed that SAD entered the regression first (R(2) = 0.492) followed by adiponectin (R(2) = 0.63). After moderate weight loss, midthigh subcutaneous AT, IAT, low-density lean tissue, leptin, and insulin resistance decreased significantly; no significant changes in adiponectin were observed.. Fat distribution indexes and adiponectin are independently associated with insulin resistance. Even in older women, moderate weight loss improves body fat distribution, muscle lipid infiltration, and insulin resistance. Moderate weight loss results in a significant decrease in leptin but no changes in adiponectin.

Topics: Abdominal Fat; Absorptiometry, Photon; Adiponectin; Adipose Tissue; Aged; Aged, 80 and over; Body Composition; C-Reactive Protein; Female; Humans; Insulin Resistance; Leptin; Lipids; Middle Aged; Muscle, Skeletal; Obesity; Waist-Hip Ratio; Weight Loss

Topics: Body Mass Index; Endothelium, Vascular; Gastroplasty; Humans; Inflammation; Laparoscopy; Leptin; Obesity; Regression Analysis; Sympathetic Nervous System; Weight Loss; World Health Organization

Ghrelin is a peptide hormone with orexigenic properties, primarily produced by the stomach. Leptin and adiponectin are the two adiposity products that participate in body weight control. Leptin always decreases and adiponectin increases after weight loss. Different changes in fasting ghrelin levels have been reported following bariatric surgery. In this study, we compare the changes in fasting ghrelin, leptin and adiponectin levels in 3 groups of patients who achieved weight loss by either diet, MacLean vertical banded gastroplasty (VBG) or biliopancreatic diversion with duodenal switch (BPD-DS).. Serum fasting ghrelin, leptin and adiponectin concentration was measured in 40 obese patients who achieved weight loss by either diet (n=14), VBG (n=13) or BPD-DS (n=13), before and after weight loss. The follow-up period was 18 months for BPD-DS and VBG and 6 months for diet. Serum ghrelin level was measured by ELISA.. BMI was significantly decreased in all 3 groups: 9.2+/-2.4% (P<0.01) following diet, 38.47+/-7.26% (P<0.01) after VBG, and 42.88+/-9.09% after BPD-DS (P<0.01). Serum fasting ghrelin level increased after diet (110.45+/-117.84%, P=0.002) and VBG (65.48+/-92.93%, P=0.001),but decreased after BPD-DS (-21.63+/-28.63%, P=0.019). Leptin concentration decreased and adiponectin increased in all groups.. Unlike after diet or gastric restrictive surgery, BPD-DS is associated with markedly suppressed ghrelin levels, possibly contributing to the weight-reducing effect of this operation. Sleeve gastrectomy seems to be the main cause of this reduction.

Topics: Adiponectin; Adult; Biliopancreatic Diversion; Caloric Restriction; Female; Follow-Up Studies; Gastroplasty; Ghrelin; Humans; Leptin; Male; Middle Aged; Obesity; Peptide Hormones; Prospective Studies; Weight Loss

This study aimed to investigate the regulation of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) gene expression in primary skeletal muscle myotubes, derived from human donors, after exposure to globular adiponectin (gAd) and leptin.. Four distinct primary cell culture groups were established [Lean, Obese, Diabetic, Weight Loss (Wt Loss); n = 7 in each] from rectus abdominus muscle biopsies obtained from surgical patients. Differentiated myotube cultures were exposed to gAd (0.1 microg/mL) or leptin (2.5 microg/mL) for 6 hours. AdipoR1 and AdipoR2 gene expression was measured by real-time polymerase chain reaction analysis.. AdipoR1 mRNA expression in skeletal muscle myotubes derived from Lean subjects (p < 0.05) was stimulated 1.8-fold and 2.5-fold with gAd and leptin, respectively. No increase in AdipoR1 gene expression was measured in myotubes derived from Obese, Diabetic, or Wt Loss subjects. AdipoR2 mRNA expression was unaltered after gAd and leptin exposure in all myotube groups.. Adiponectin and leptin are rapid and potent stimulators of AdipoR1 in myotubes derived from lean healthy individuals. This effect was abolished in myotubes derived from obese, obese diabetic subjects, and obese-prone individuals who had lost significant weight after bariatric surgery. The incapacity of skeletal muscle of obese and diabetic individuals to respond to exogenous adiponectin and leptin may be further suppressed as a result of impaired regulation of the AdipoR1 gene.

Topics: Adiponectin; Adult; Cells, Cultured; Diabetes Mellitus; Female; Gene Expression Regulation; Humans; Leptin; Male; Middle Aged; Muscle Fibers, Skeletal; Muscle, Skeletal; Obesity; Receptors, Adiponectin; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger; Weight Loss

We investigated the impact of weight-bearing, aerobic exercise- and diet-induced weight loss on markers of bone turnover during a larger study of changes in metabolic fitness during short-term weight reduction using a repeated-measures, within-subject experimental design. Subjects (N = 19) underwent 6 weeks of energy restriction (reduced by approximately 3140 kJ/d) and aerobic exercise ( approximately 1675 kJ/d, walking or jogging at 60% maximum oxygen consumption) to induce a 5% reduction in body weight. Bone turnover markers and hormones were measured in serum collected at baseline and after 6 weeks of weight loss. Despite a 5% reduction in body weight at week 6, markers of bone formation, osteocalcin, and bone alkaline phosphatase, were significantly increased, and resorption markers, C-terminal cross-links of type I collagen and soluble receptor activator of nuclear factor kappaB ligand, were unchanged after 6 weeks of energy restriction and exercise. The concentration of leptin was significantly reduced after weight loss, but insulin-like growth factor I (IGF-I) and cortisol levels were unaffected. In conclusion, weight-bearing, aerobic exercise training may favorably affect the balance between bone resorption and formation during weight loss.

Topics: Adolescent; Adult; Alkaline Phosphatase; Bone Resorption; Exercise; Female; Humans; Leptin; Male; Obesity; Osteocalcin; Osteogenesis; Overweight; Weight Loss; Weight-Bearing

Our goal was to study how plasma leptin concentration, superoxide dismutase (SOD) activity, and weight loss are related in obese adults.. Serum leptin concentration, SOD activities, general biochemical data, and body composition measurements were obtained for 62 overweight and obese subjects before and after an 8-week body weight reduction (BWR) regimen. The subjects were on dietary control, performed moderate aerobic and strength training exercises, and attended educational lectures.. The measurement results indicated that the following criteria were significantly reduced: body weight [84.4 +/- 17.0 vs. 79.3 +/- 16.1 (standard error) kg, p < 0.001]; BMI (31.5 +/- 4.3 vs. 29.4 +/- 4.2 kg/m(2), p < 0.001), and fat mass (33.3 +/- 10.0 vs. 29.8 +/- 10.4 kg, p < 0.001). Plasma leptin levels also significantly decreased from 31.5 +/- 17.6 to 26.5 +/- 17.2 ng/mL (p < 0.001). Additionally, SOD activity was significantly increased from 261.4 +/- 66.0 to 302.7 +/- 30.9 U/mL (p < 0.001). Based on linear regression analysis results, a 3.78- to 8.13-kg reduction in weight can be expected after the 8-week BWR regimen when initial leptin concentration was 5 to 30 ng/mL.. We found that an 8-week exercise and diet program was effective in reducing weight and fat mass and, notably, had further beneficial effects on leptin resistance and SOD activity. Additionally, this study demonstrated that initial plasma leptin concentration may be used as a predictor for weight loss outcome.

Topics: Adolescent; Adult; Body Composition; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Exercise Therapy; Female; Humans; Leptin; Male; Middle Aged; Obesity; Physical Education and Training; Predictive Value of Tests; Sex Factors; Superoxide Dismutase; Treatment Outcome; Weight Loss

Weight cycling is one of the widely used weight reduction strategies; however, the adverse effects of this method include regaining significant amounts of weight. The molecular mechanisms underlying weight gain following cycles of dietary deprivation and refeeding are still poorly understood. One of the possibilities is that repeated loss and gain of weight may promote fat deposition in adipose tissue. To test this hypothesis we investigated serum leptin levels and lipogenic enzyme activities in white adipose tissue (WAT) of male Wistar rats during 12 days of ad libitum feeding following multiple cycles of alternating food deprivation and refeeding. Rats subjected to eight cycles of food deprivation and refeeding (MFR group) showed significantly decreased circulating leptin levels when compared with control rats (nearly 50% decrease in leptin levels, P < 0.01). Throughout 12 days of ad libitum feeding, serum leptin levels increased modestly but remained significantly (24%, P < 0.05) lower than control levels. Fatty acid synthase (FAS) and malic enzyme (ME) activities (chosen as representatives of enzymes directly involved in fatty acid synthesis) were found to be considerably higher in WAT of MFR rats refed for 3 days in comparison to control rats, and remained elevated even after 12 days of refeeding. These observations suggest that the elevation of lipogenic enzyme activities induced by multiple cycles of dietary deprivation followed by refeeding persists for several days, markedly increasing the lipogenic capacity of adipose tissue, which, accompanied by a decrease in circulating leptin levels, may promote weight gain.

Topics: Adipose Tissue, White; Animals; Blood Glucose; Diet, Reducing; Epididymis; Fatty Acid Synthases; Food Deprivation; Insulin; Leptin; Lipids; Malate Dehydrogenase; Male; Organ Size; Rats; Rats, Wistar; Weight Gain; Weight Loss

To help understand the mechanisms by which weight loss is maintained after Roux-en-Y gastric bypass (RYGBP), we measured circulating concentrations of total and bioactive octanoylated ghrelin, peptide YY (PYY), glucose, and insulin in the fasted state and in response to a liquid test meal in three groups of adult women: lean (n = 8); weight-stable 35 +/- 5 months after RYGBP (n = 12; mean body mass index, 33 kg/m(2)); and matched to the surgical group for body mass index and age (n = 12). Fasting plasma total ghrelin levels were nearly identical between RYGBP (425 +/- 54 pg/ml) and the matched controls (424 +/- 28 pg/ml) and highest in lean controls (564 +/- 103 pg/ml). The response to the test meal was comparable between lean and RYGBP groups, with 27% and 20% maximal suppression, respectively, whereas the magnitude of suppression was significantly diminished in the matched controls (17%) compared with the lean group. Fasting levels of octanoylated ghrelin were highest in the lean controls, 220 +/- 36 pg/ml vs. 143 +/- 27 in the RYGBP group (P = 0.05) and 127 +/- 12 pg/ml in the matched controls (P < 0.05). The magnitude of maximal postmeal suppression of octanoylated ghrelin was more marked than with total ghrelin, but similar among groups, ranging from 44-47%. In response to the test meal, there was an early exaggerated rise in PYY in the RYGBP group, such that the peak PYY concentration was 163 +/- 24 pg/ml compared with 58 +/- 17 (P < 0.01) and 77 +/- 23 (P < 0.05) in the matched and lean controls, respectively; area under the curve at 90 min was significantly greater compared with both control groups. Leptin and fasting insulin concentrations and homeostasis model of assessment insulin resistance indices were nearly identical between lean and RYGBP subjects and significantly higher in the body mass index-matched controls. In summary, the absence of a compensatory increase in ghrelin concentrations that usually occurs with diet-induced weight loss, and the exaggerated postprandial PYY response after RYGBP, may contribute to weight loss and to the ability of an individual to maintain weight loss after this surgical procedure.

Topics: Adult; Anastomosis, Roux-en-Y; Appetite; Blood Glucose; Fasting; Female; Gastric Bypass; Ghrelin; Humans; Insulin; Leptin; Pain Measurement; Peptide Hormones; Peptide YY; Weight Loss

Obesity is associated with insulin resistance and premature atherosclerosis. The human adipose tissue produce several adipokines including monocyte chemoattractant protein (MCP)-1, associated with cardiovascular disease and found to be involved in the pathogenesis of atherosclerosis in vitro.. (1) To compare mRNA levels of MCP-1, leptin and a macrophage-specific marker (CD68) in isolated adipocytes vs stromal-vascular (SV) cells, (2) to compare mRNA levels of MCP-1 in human adipose tissue to circulating MCP-1 and adiposity (eg BMI: kg/m2) and (3) investigate the effect of weight loss in obese subjects on circulating MCP-1 and leptin.. (1) MCP-1 and CD68 mRNA levels in isolated adipocytes vs SV cells were 17% (P<0.01) and approximately 2% (P<0.001), respectively. Leptin mRNA levels in SV cells were approximately 1% of that in isolated adipocytes (P<0.01). (2) MCP-1 mRNA levels correlated with circulating MCP-1 (P<0.05) and BMI (P<0.05). (3) A 12% weight loss (P<0.001) was associated with a 25% decrease in insulin levels (P<0.01). Circulating MCP-1 and leptin decreased by 20% (P<0.001) and by 24% (P<0.001), respectively.. The findings demonstrate that MCP-1 is produced in isolated human adipocytes. In addition, the findings suggest that MCP-1 may be involved in obesity-related health complications and support the hypothesis that weight loss is beneficial by improving the low-grade inflammation observed in obesity.

Topics: Adipocytes; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Body Constitution; Cells, Cultured; Chemokine CCL2; Female; Humans; Leptin; Male; Obesity, Morbid; RNA, Messenger; Weight Loss

AMP-activated protein kinase (AMPK) acts as a cellular energy sensor, being activated during states of low energy charge. Hypothalamic AMPK activity is altered by hormonal and metabolic signals and mediates the feeding response. To determine the effect of diabetes on hypothalamic AMPK activity, we assayed this activity in streptozotocin (STZ)-induced diabetic rats. Compared with control rats, STZ-induced diabetic rats had significant hyperphagia and weight loss. Hypothalamic AMPK phosphorylation and alpha2-AMPK activity were higher and acetyl-CoA carboxylase activity was lower in diabetic rats than in control rats. Chronic insulin treatment or suppression of hypothalamic AMPK activity completely prevented diabetes-induced changes in food intake as well as in hypothalamic AMPK activity and mRNA expression of neuropeptide Y and proopiomelanocortin. Plasma leptin and insulin levels were profoundly decreased in diabetic rats. Intracerebroventricular administration of leptin and insulin reduced hyperphagia and the enhanced hypothalamic AMPK activity in diabetic rats. These data suggest that leptin and insulin deficiencies in diabetes lead to increased hypothalamic AMPK activity, which contributes to the development of diabetic hyperphagia.

Topics: Adipose Tissue; AMP-Activated Protein Kinases; Animals; Diabetes Mellitus, Experimental; Energy Intake; Gene Transfer Techniques; Genes, myc; Hyperphagia; Hypothalamus; Insulin; Leptin; Male; Multienzyme Complexes; Organ Size; Phosphorylation; Protein Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; Weight Loss

Disruption of the RIIbeta regulatory subunit of protein kinase A (PKA) results in mice with a lean phenotype, nocturnal hyperactivity, and increased resting metabolic rate. In this report, we have examined whether deletion of RIIbeta would lead to increased metabolism and rescue the obese phenotype of the leptin-deficient ob/ob (ob) mouse. Body weight gain and food consumption were decreased, whereas basal oxygen consumption and nocturnal locomotor activity were increased in the double mutant animals compared with ob mice. The ob mice are unable to maintain body temperature when placed in a cold environment due to a loss of brown adipose tissue activation, and this cold sensitivity was partially rescued by concomitant disruption of RIIbeta. These findings indicate that PKA modifies the phenotype of the leptin-deficient mouse, leading to increases in both thermogenesis and energy expenditure.

Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Carrier Proteins; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; Cyclic AMP-Dependent Protein Kinases; Energy Metabolism; Gene Deletion; Gene Expression; Ion Channels; Leptin; Membrane Proteins; Mice; Mice, Obese; Mitochondrial Proteins; Motor Activity; Obesity; Oxygen Consumption; RNA; Uncoupling Protein 1; Up-Regulation; Weight Loss

Certain adipose-produced signals are secreted in proportion to body fat mass and are involved in regulation of the energy metabolism of the whole body. Leptin, IL6 and adiponectin can be considered as adiposity signals. Several Single Nucleotide Polymorphisms (SNPs) in genes encoding for these molecules are known to influence their concentration in situations of stable weight. We hypothesized that polymorphism effects could be better detected in a situation of negative energy balance and that modified concentrations of adiposity signal genes could change the dynamics of weight gain in obese subjects.. 65 obese patients undergoing gastric banding surgery were genotyped for LEP+19A-->G, LEP-2548G-->C, IL6-174G-->C, APM1-11377C-->G and PM1-11391G-->A common SNPs. BMI and concentrations of leptin, IL6 and adiponectin were measured before surgery and after 1 year.. All SNPs except IL6-174G-->C SNP were associated with modifications of the circulating concentrations of signals produced by adipose tissue at baseline. During weight loss, variant genotype carriers of LEP -2548 and +19 SNPs were characterized by a trend towards less decrease in circulating leptin. Weight loss was associated with an increase in IL6 concentration (16.9%+/-12.2) in the IL6-174 C/C genotype carriers, whereas the C/G or G/G genotypes carriers showed a decrease in IL6 (19.9%+/-5.2, P=0.001).. We observed that the SNPs studied could modulate the concentration of adiposity signals not only at baseline but also during weight loss. Such variations may be sensed by the homeostatic feedback system that controls energy balance and may in turn contribute to some disturbances in weight regulation.

Topics: Adiponectin; Adult; Body Mass Index; Case-Control Studies; Chi-Square Distribution; Energy Metabolism; Female; Gastroplasty; Genetic Markers; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Male; Middle Aged; Obesity, Morbid; Polymorphism, Single Nucleotide; Postoperative Period; Preoperative Care; Probability; Prognosis; Prospective Studies; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome; Weight Loss

The role of ghrelin in weight control after surgery is not clear. We examined plasma ghrelin and leptin levels in patients with morbid obesity undergoing biliopancreatic diversion (BPD) of Scopinaro.. 30 adult patients (27 females, 3 males), undergoing elective BPD were recruited from the Hospital Surgery Service. Fasting blood samples for biochemical determinations were drawn before surgery and 1, 3 and 12 months after BPD. Human plasma ghrelin was measured by RIA.. During the study period, weight, BMI and serum leptin levels decreased significantly at all sample points compared to preoperative values. Ghrelin plasma levels increased during the study, with statistical significance at 3 months and 1 year after surgery compared with preoperative levels. While leptin changes correlated with changes in BMI, no correlation was found between ghrelin and leptin or BMI changes.. Plasma ghrelin levels could be decreased in obese patients as a compensatory mechanism to their nutritional state, but our results do not support the postulated beneficial role of ghrelin in the 1-year weight loss after BPD. They rather suggest that weight loss somehow stimulates ghrelin secretion, even in the absence of part of the stomach.

Topics: Adult; Analysis of Variance; Biliopancreatic Diversion; Biomarkers; Body Mass Index; Cohort Studies; Fasting; Female; Follow-Up Studies; Ghrelin; Humans; Leptin; Male; Middle Aged; Monitoring, Physiologic; Obesity, Morbid; Peptide Hormones; Postoperative Care; Probability; Radioimmunoassay; Sensitivity and Specificity; Time Factors; Weight Loss

The aim of the present study was to evaluate differences in the metabolic risk profile in formerly obese women, in whom a significant weight loss was obtained by Swedish adjustable gastric band (SAGB) operation or by diet alone.. A total of 40 patients (24 after SAGB and 16 after diet) participated in the study. Clinical data, including body mass index (BMI), waist-to-hip ratio, body fat content and blood pressure values, as well as laboratory results [fasting glucose, insulin, homeostasis model assessment (HOMA) index, leptin, lipid values and markers of subclinical inflammation] were evaluated before a planned abdominoplastic operation.. Patients in the SABG group had lost a significantly greater amount of weight (52.7 +/- 10.0 kg) compared with the diet group (20.0 +/- 11.5 kg; p < 0.001), and the percent excess weight loss was 69.1 +/- 11.4 in the SAGB group and 54.5 +/- 17.7 (p < 0.040) in the diet group. Before the abdominoplastic operation neither the mean BMI nor the percentage of fat mass revealed a significant difference between the groups. Fasting insulin (6.1 +/- 3.0 microU/ml) and the HOMA index (1.4 +/- 0.7) as a measure of insulin resistance were significantly lower in the SAGB than in the diet group (fasting insulin: 8.2 +/- 3.8 microU/ml; p < 0.048; HOMA index: 2.0 +/- 1.0; p < 0.031). Swedish adjustable gastric band patients showed significantly lower plasma leptin levels (9.4 +/- 10.8 ng/ml) than the dietary-treated patients (13.9 +/- 9.6 ng/ml; p < 0.014), while tumour necrosis factor-alpha serum levels were increased in the SAGB group (17.6 +/- 7.3 pg/ml) compared with the diet group (11.9 +/- 0.49 pg/l; p < 0.048).. The extensive weight loss in formerly obese women after SAGB operation was paralleled by a favourable metabolic profile indicating a higher degree of insulin sensitivity than in women after a successful, but less pronounced weight loss by diet alone.

Topics: Adult; Biomarkers; Blood Glucose; Body Composition; Body Mass Index; Diet, Reducing; Female; Follow-Up Studies; Gastroplasty; Humans; Insulin; Insulin Resistance; Leptin; Middle Aged; Obesity; Tumor Necrosis Factor-alpha; Weight Loss

Several investigations that yielded different results in terms of net changes in body composition of weight-losing cancer patients have been reported that employed a variety of methods based on fundamentally different technology. Most of those reports were cross-sectional, whereas to the authors' knowledge there is sparse information available on longitudinal follow-up measurements in relation to other independent methods for the assessment of metabolism and performance.. For the current report, the authors evaluated time course changes in body composition (dual-energy X-ray absorptiometry) with measurements of whole body and regional distribution of fat and lean tissue in relation to food and dietary intake, host metabolism (indirect calorimetry), maximum exercise capacity (walking test), and circulating hormones in cancer patients who were receiving palliative care during 4-62 months of follow-up. The entire cohort comprised 311 patients, ages 68 years +/- 3 years who were diagnosed with solid gastrointestinal tumors (84 colorectal tumors, 74 pancreatic tumors, 73 upper gastrointestinal tumors, 51 liver-biliary tumors, 3 breast tumors, 5 melanomas, and 21 other tumor types).. Decreased body weight was explained by loss of body fat, preferentially from the trunk, followed by leg tissue and arm tissue, respectively. Lean tissue (fat-free mass) was lost from arm tissue, whereas trunk and leg tissue compartments increased, all concomitant with declines in serum albumin, increased systemic inflammation (C-reactive protein, erythrocyte sedimentation rate), increased serum insulin, and elevated daily caloric intake; whereas serum insulin-like growth factor 1 (IGF-1), resting energy expenditure, and maximum exercise capacity remained unchanged in the same patients. Serum albumin levels (P < 0.001), whole body fat (P < 0.02), and caloric intake (P < 0.001) predicted survival, whereas lean tissue mass did not. Daily intake of fat and carbohydrate was more important for predicting survival than protein intake. Survival also was predicted by serum IGF-1, insulin, leptin, and ghrelin levels (P < 0.02 - P < 0.001). Serum insulin, leptin, and ghrelin (total) levels predicted body fat (P < 0.001), whereas IGF-1 and thyroid hormone levels (T3, free T3) predicted lean tissue mass (P < 0.01). Systemic inflammation primarily explained variation in lean tissue and secondarily explained loss in body fat. Depletion of lean arm tissue was related most to short survival compared with the depletion of lean leg and trunk tissue.. The current results demonstrated that body fat was lost more rapidly than lean tissue in progressive cancer cachexia, a phenomenon that was related highly to alterations in the levels of circulating classic hormones and food intake, including both caloric amount and diet composition. The results showed importance in the planning of efficient palliative treatment for cancer patients.

Topics: Adipose Tissue; Aged; Blood Sedimentation; Body Composition; C-Reactive Protein; Cohort Studies; Dietary Carbohydrates; Dietary Fats; Eating; Energy Intake; Energy Metabolism; Exercise Tolerance; Follow-Up Studies; Ghrelin; Hormones; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Longitudinal Studies; Muscle, Skeletal; Neoplasms; Palliative Care; Peptide Hormones; Serum Albumin; Survival Rate; Weight Loss

Obesity is frequently associated with left ventricular hypertrophy, even when uncomplicated by hypertension or diabetes mellitus. Left ventricular hypertrophy is an important risk factor for congestive heart failure.. The objective of this study was to evaluate the relationship between leptin and left ventricular mass in uncomplicated, morbid (grade 3) obesity and the existence of leptin receptors and intracellular signaling proteins in the human heart.. Left ventricular mass (LVM) was calculated through electrocardiogram reading in normotensive grade III obese patients (World Health Organization classification) undergoing bariatric surgery [laparoscopic adjustable gastric banding (LAGB)] at baseline and 1 yr later. The control group was composed of healthy lean normotensive subjects. Leptin receptors were detected by PCR and immunocytochemistry in human heart biopsies.. This study was performed at university hospitals.. Thirty-one grade 3 obese patients and 30 healthy nonobese normotensive, age- and sex-matched control subjects were studied.. Obese subjects underwent LAGB to induce weight loss and were evaluated at baseline and after 1 yr.. LVM, plasma leptin, glucose, insulin levels, and homeostasis model assessment index were higher in obese than in lean controls (P < 0.01); at univariate regression analysis, LVM correlated with body mass index, leptin, and homeostasis model assessment index; at multiple regression analysis, LVM only correlated with leptin levels (P = 0.001). Obese subjects were reevaluated 1 yr after LAGB, when their body mass index changed from 46.2 +/- 1.24 to 36.6 +/- 1.05 kg/m(2) (P < 0.01); the decrease in LVM correlated only with the decrease in leptin levels (P < 0.01). We demonstrated that long and short isoforms of the leptin receptor and intracellular proteins mediating leptin signaling were expressed in human heart by RT-PCR, immunocytochemistry, or both methods.. These data suggest that leptin could contribute to the left ventricular hypertrophy in humans.

Topics: Adult; Body Mass Index; Female; Humans; Hypertrophy, Left Ventricular; Leptin; Male; Obesity, Morbid; Receptors, Cell Surface; Receptors, Leptin; Regression Analysis; Weight Loss

This study investigated leptin and neuropeptide Y levels in children with cancer, the relationship of those levels to cachexia, and their usefulness as prognostic indicators. Twenty-three newly diagnosed children with cancer were included in the study. The median age at diagnosis was 8 years (range 1.5-14), and the male to female ratio was 13:10. Body mass index, serum leptin and neuropeptide Y levels were measured at diagnosis and at each cycle of chemotherapy. The mean neuropeptide Y level was 211.1 pmol/l at diagnosis and decreased to 92.8 pmol/l at the fifth cycle of chemotherapy. In contrast, the mean leptin level was 3.9 ng/ml at diagnosis and increased to 13.0 ng/ml at the fifth cycle of chemotherapy. Thus, levels of these factors are influenced by treatment status and disease progression. The mean neuropeptide Y level at diagnosis was 82.32 pmol/l in children with complete remission and 430.16 pmol/l in those who died with disease during the follow-up period. The mean leptin level at diagnosis was 6.60 ng/ml in children with complete remission and 0.192 ng/ml in patients who died with disease during the follow-up period. The neuropeptide Y and leptin levels seem to be related to prognosis and could be used as prognostic indicators in the follow-up of children with cancer.

Topics: Adolescent; Anorexia; Biomarkers; Cachexia; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Leptin; Male; Neoplasms; Neuropeptide Y; Prognosis; Weight Loss

The objective of this study was to evaluate, in dogs, the effects of obesity and weight loss on plasma total ghrelin and leptin concentrations. Twenty-four Beagle dogs, 12 control lean and 12 obese dogs of both genders and aged between 1 and 9 years, were used for the experiments. Mean body weight was 12.7+/-0.7 kg for the lean group and 21.9+/-0.8 kg for the obese group. The trial was divided into three phases. During phase 1, all 24 Beagle dogs were fed a maintenance diet. During phase 2, the obese dogs were submitted to a weight loss protocol with a high protein-low energy diet. The weight loss protocol ended once dogs reached optimal body weight. During phase 3, the dogs that were submitted to the weight loss protocol were maintained at their optimal body weight for 6 months. Plasma total ghrelin, leptin, insulin and glucose concentrations were measured to evaluate the effects of obesity and weight loss on these parameters in dogs. Body weight, body condition score, thoracic and pelvic perimeters, and ingested food amounts were also recorded during the study. Obese dogs demonstrated a significant decrease in plasma ghrelin and a significant increase in plasma leptin and insulin concentrations when compared with control dogs. During weight loss, significant increases in plasma total ghrelin and glucose and significant decreases in plasma leptin and insulin were observed. The increase in plasma ghrelin concentrations seemed to be transient. Body weight and the morphometric parameters correlated positively with leptin concentrations and negatively with total ghrelin concentrations. These results suggest that ghrelin and leptin could play a role in dogs in the adaptation to a positive or negative energy balance, as observed in humans.

Topics: Animals; Blood Glucose; Dog Diseases; Dogs; Female; Ghrelin; Insulin; Leptin; Male; Obesity; Peptide Hormones; Weight Loss

Leptin deficiency has been associated with extreme obesity and hyperphagia in rodents and humans. A rare genetic disorder in humans yields the absence of the hormone leptin, extreme obesity, and a ravenous appetite. Reports on these rare cases have indicated that therapy using leptin injections can yield significant weight loss and changes in appetite. The aim of this report on acute leptin therapy in three leptin deficient adults was to provide a microanalysis of changes in eating behavior and ratings of hunger and satiety. In addition to substantial weight loss, 15 weeks of leptin therapy was associated with approximately 50% reduction in food intake and substantial changes in ratings of hunger and satiety before most meals. After short-term leptin therapy, the three participants ate until ratings indicated they were satiated, which was comparable to the ratings before leptin therapy. These findings suggest that one of the primary effects of acute leptin therapy may be to reduce the ravenous hunger associated with leptin deficiency, resulting in reduced food intake and significant weight loss. These results are discussed in the context of the scientific literature pertaining to leptin and its effects on appetite and obesity.

Topics: Adult; Appetite; Dose-Response Relationship, Drug; Eating; Female; Humans; Hunger; Leptin; Male; Obesity; Satiety Response; Weight Loss

Maintenance of human energy homeostasis is regulated by a complex network. Peptides secreted from the gastrointestinal tract (GI) are signaling to the brain and other organs initiating or terminating food intake and energy expenditure. In the present study we investigated basal plasma levels of apelin, orexin-A, and leptin in morbid obese patients. In addition, we measured in a subgroup of these patients in the same individual orexin-A and leptin plasma levels one year after gastric banding surgery.. Basal plasma values were determined in obese patients (BMI=48+/-1 kg/m2n=32) after an overnight fast and compared to healthy, normal weighted (BMI=22+/-2 kg/m2n=12) controls. In addition, blood samples were collected in a subgroup of patients (BMI=48+/-1 kg/m2n=8) the day before surgery and 1 year after the operation. Apelin, orexin-A, and leptin levels were analysed using ELISAs.. One year after the operation obese patients significantly lost weight (from 48+/-2 kg/m2 to 39+/-2 kg/m2; p<0,001). Apelin, orexin-A and leptin levels in obese patients were significantly higher compared to control individuals (736+/-50 pg/ml vs. 174+/-14 pg/ml, p<0.0001; 75.3+/-24.1 pg/ml vs. 0.8+/-0.4 pg/ml, p<0.0001; 79.0+/-2.4 ng/ml vs. 5.8+/-0.8 ng/ml, p<0.0001, respectively). Apelin and leptin plasma concentrations also correlated significantly with BMI (r=0.769, p<0.0001; r=0.778; p<0.0001, respectively), while orexin-A correlation was rather weak (r=0.335, p<0.03). No difference between pre- and post-operative orexin-A levels was observed, while leptin plasma levels significantly decreased from 45.1+/-5.4 ng/ml to 27.3+/-6.0 ng/ml (p=0.015).. Apelin, orexin-A, and leptin plasma levels correlated positively with the BMI. One year after gastric banding with significant loss in BMI basal plasma levels of leptin decreased, while orexin-A remained unchanged.

Topics: Adult; Apelin; Body Mass Index; Carrier Proteins; Enzyme-Linked Immunosorbent Assay; Female; Gastric Mucosa; Gastrointestinal Tract; Gastroplasty; Humans; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Neuropeptides; Obesity, Morbid; Orexins; Time Factors; Weight Loss

The complex pathology of disease has sparked the development of novel protein expression profiling techniques that require validation in clinical settings. This study focuses on multiplexed analyses of adipocytokines and biomarkers linked to the metabolic syndrome, diabetes, and cardiovascular disease.. Multiplexed immunoassays using fluorescent microspheres and the Luminex-100 system were performed on plasma from 80 obese patients (40 with the metabolic syndrome) before and after 6-8 weeks of diet-induced weight loss. Leptin, insulin, C-peptide, monocyte chemoattractant protein-1 (MCP-1), eotaxin, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and IL-6 concentrations measured with multiplex panels from 3 different manufacturers were compared with results from commercial ELISAs. Detection limits and between- and within-run imprecision were determined for each analyte. Bland-Altman analysis was used to determine agreement between multiplexed immunoassays and ELISAs.. Correlation between the Luminex multiplexed assays and ELISAs was good for leptin (Linco), insulin (Linco), MCP-1 (Biosource and Upstate), and eotaxin (Biosource) with correlation coefficients of 0.711-0.895; fair for eotaxin (Upstate) and C-peptide (Linco) with correlation coefficients of 0.496-0.582; and poor for TNF-alpha, IL-8, and IL-6 (Linco, Biosource, Upstate, and R&D) with correlation coefficients of -0.107 to 0.318. Within- and between-run imprecision values for the multiplex method were generally <15%. Relative changes in plasma leptin and insulin concentrations after diet-induced weight loss were similar whether assessed by multiplex assay or ELISA.. Although this technology appears useful in clinical research studies, low assay sensitivity and poor correlations with conventional ELISA methods for some analytes with very low plasma concentrations should be considered when using the Luminex platform in clinical studies.

Topics: Adipose Tissue; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Cytokines; Female; Fluorescent Dyes; Humans; Immunoassay; Insulin; Interleukin-6; Interleukin-8; Leptin; Male; Metabolic Syndrome; Microspheres; Middle Aged; Obesity; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss

Melanocortin-4 receptors (MC4Rs) are involved in the regulation of food intake, sympathetic nervous activity, and adrenal and thyroid function by leptin. The role of MC4Rs in regulating energy balance by leptin was investigated using double heterozygote or homozygous leptin (Lep(ob)) and Mc4r gene mutant mice. Double heterozygous or homozygous mutants were generated by crossing MC4R knockout (Mc4r-/-) mice, backcrossed onto C57BL/6J, with B6.V-Lep(ob) mice. Energy expenditure was measured using indirect calorimetry. The effect of leptin on food intake, weight loss, insulin, and corticosterone was compared for Lep(ob)/Lep(ob)Mc4r-/- mice and Lep(ob)/Lep(ob) mice. Double heterozygous and homozygous mutants exhibited an additive effect on fat mass. The 2-fold increase in body weight associated with severe obesity of Lep(ob)/Lep(ob) mice was associated with a significantly higher 24 h total and resting energy expenditure. The effect of obesity on energy expenditure was attenuated by 50% in Lep(ob)/Lep(ob) Mc4r+/- and Lep(ob)/Lep(ob) Mc4r-/- mice. Loss of MC4Rs did not affect basal food intake of Lep(ob)/Lep(ob) mice but was associated with partial leptin resistance in terms of food intake and weight loss. Leptin suppression of insulin and corticosterone in Lep(ob)/Lep(ob) mice were not significantly affected by Mc4r genotype. These results suggest a complex interaction between the Lep and Mc4r genes in energy homeostasis and suggest that MC4Rs retain significant anti-obesity function in the obese leptin-deficient state. Increased adiposity with double mutations may involve a reduction in energy expenditure. MC4Rs might have a modest role in the regulation of energy balance by exogenously administered leptin, primarily effecting food intake.

Topics: Adipose Tissue; Animals; Energy Intake; Homozygote; Leptin; Mice; Mutation; Receptor, Melanocortin, Type 4; Receptors, Leptin; Weight Loss

To study the relationships between leptin, soluble leptin receptor (sOB-R), and insulin resistance in obese children before and after weight reduction.. We determined fasting serum leptin, sOB-R, and insulin resistance index (Homeostasis model assessment (HOMA)) in 36 obese children at baseline and 1 y later and compared them to 72 lean children matched for age, gender, and pubertal stage. The changes of leptin (Deltaleptin) and sOB-R (DeltasOB-R) over the 1 y period were correlated to the changes of HOMA (DeltaHOMA), the changes of weight status, and the changes of percentage body fat (Delta%BF) based on skinfold measurements. Multiple linear regression analyses were conducted for the dependent variables Deltaleptin and DeltasOB-R, including DeltaBMI and DeltaHOMA as independent variables adjusted for age, gender, and pubertal stage. Changes of leptin and sOB-R levels were analyzed in 11 obese children after they had lost weight substantially (decrease SDS-BMI>0.5) and compared to 11 obese children without substantial weight loss matched for age, gender, and pubertal stage.. Obese children showed significantly (P<0.001) higher leptin and lower sOB-R levels. Deltaleptin correlated significantly to DeltaSDS-BMI (r=0.28, P<0.05), Delta%BF (r=0.44, P<0.05), and DeltaHOMA (r=0.42, P<0.01), while DeltasOB-R correlated significantly to DeltaSDS-BMI (r=-0.42, P<0.01) and Delta%BF (r=-0.47, P<0.01), but not to DeltaHOMA. In contrast to DeltasOB-R, Deltaleptin correlated significantly to DeltaHOMA (P=0.02) in multiple linear regression analysis. Substantial weight loss led to a significant increase in sOB-R (P=0.02) and to a decrease in HOMA (P=0.02). In children without substantial weight loss, there were no changes in sOB-R, while HOMA (P=0.04) and leptin (P=0.02) increased significantly.. The decrease of sOB-R and the increase of leptin levels in obese children normalized after weight loss. Therefore, these changes are consequences rather than the cause of overweight. In contrast to sOB-R, leptin levels are associated with insulin resistance.

Topics: Adolescent; Age Factors; Child; Female; Homeostasis; Humans; Insulin Resistance; Leptin; Male; Obesity; Receptors, Cell Surface; Receptors, Leptin; Weight Loss

Adipose tissue affects metabolism by secreting various adipokines. Lipodystropic mice benefit both from leptin replacement therapy and from transplantation of normal fat. Leptin-deficient Lep(ob)/Lep(ob) (ob/ob) mice can also be treated with leptin. Surprisingly, there have been no reports of successful treatment of obese ob/ob mice by transplantation of normal white adipose tissue (WAT). If WAT transplantation is ineffective in treating insulin resistance and diabetes in obese individuals, its applicability may be limited in humans as such abnormalities are usually associated with obesity. In the current study, we tested whether WAT transplantation might prevent, and even reverse, abnormalities characteristic of ob/ob mice. To assess the preventive potential, 6-week-old ob/ob mice were transplanted, subcutaneously, with gonadal fat pads from normal mice. Profound effects on multiple physiological phenotypes were achieved despite leptin levels below 25% of those in control mice. WAT from one donor reduced body weight gain, and WAT from 4 or 8 donors prevented obesity in ob/ob mice. Nonfasting insulin levels and insulin tolerance test were normalized. Corticosterone elevation was also prevented. Finally, WAT from 4 donors restored fertility in ob/ob females. The effects of WAT transplantation were long-lasting, with body weight gain suppressed for at least 40 weeks. To assess the therapeutic potential, obese 13-month-old ob/ob mice with a long history of leptin deficiency were used. Their body weight decreased by approximately 50% when transplanted with WAT from 8 donors. As in young recipients, transplantation greatly reduced nonfasting insulin, suggesting normalized insulin sensitivity. Thus, WAT transplantation was effective for both prevention and therapy. In the future, WAT transplantation may become a useful alternative to hormone replacement in treating not only lipodystropy, but also certain types of obesity.

Topics: Adipose Tissue; Animals; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Infertility, Female; Insulin; Insulin Resistance; Leptin; Mice; Mice, Obese; Obesity; Time Factors; Weight Loss

The adipose tissue derived cytokine leptin, modifies energy balance via effects on both food intake and energy expenditure. It is not clear, however, whether the component of energy expenditure accounted for by voluntary (nonexercise) physical activity is increased in response to leptin. The aim of this study was to investigate the effect of exogenously administered leptin on physical activity in the marsupial Sminthopsis crassicaudata. Body weight, tail width and food intake, were measured daily and physical activity was measured hourly in normal lean S. crassicaudata (n=8) with ad libitum access to standard laboratory diet. After 5 days baseline the animals were divided into two equal groups (n=4), and either human recombinant leptin (2.5 mg/kg) or placebo was administered twice daily intraperitoneally. Approximately 81% of the total daily activity during the baseline period occurred during the nocturnal phase. After 9 days of leptin administration, there were significant decreases in body weight (P<0.001) and fat content (P<0.01), which were not accompanied by a decrease in total energy intake. Overall daily physical activity increased (P=0.028); this effect was confined to the dark phase (P=0.033). We conclude that in lean S. crassicaudata the exogenous administration of human recombinant leptin results in a decrease in adiposity which occurs in the absence of a measurable effect on food intake and is associated with an increase in non-exercise physical activity at least over the duration of this study.

Topics: Adipose Tissue; Animals; Body Weight; Circadian Rhythm; Eating; Humans; Leptin; Male; Marsupialia; Motor Activity; Recombinant Proteins; Tail; Weight Loss

Leptin augments glucose and lipid metabolism independent of its effect on satiety. Administration of leptin in rodents increases skeletal muscle beta-oxidation by activating AMP-activated protein kinase (AMPK). We previously reported that, as hyperleptinemic as obese human subjects, transgenic skinny mice overexpressing leptin in liver (LepTg) exhibit enhanced insulin sensitivity and lipid clearance. To assess skeletal muscle AMPK activity in leptin-sensitive and -insensitive states, we examined phosphorylation of AMPK and its target, acetyl CoA carboxylase (ACC), in muscles from LepTg under dietary modification. Here we show that phosphorylation of AMPK and ACC are chronically augmented in LepTg soleus muscle, with a concomitant increase in the AMP-to-ATP ratio and a significant decrease in tissue triglyceride content. Despite preexisting hyperleptinemia, high-fat diet (HFD)-fed LepTg develop obesity, insulin-resistance, and hyperlipidemia. In parallel, elevated soleus AMPK and ACC phosphorylation in regular diet-fed LepTg is attenuated, and tissue triglyceride content is increased in those given HFD. Of note, substitution of HFD with regular diet causes a robust recovery of soleus AMPK and ACC phosphorylation in LepTg, with a higher rate of body weight reduction and a regain of insulin sensitivity. In conclusion, soleus AMPK and ACC phosphorylation in LepTg changes in parallel with its insulin sensitivity under dietary modification, suggesting a close association between skeletal muscle AMPK activity and sensitivity to leptin.

Topics: Acetyl-CoA Carboxylase; Adenosine Monophosphate; Adenosine Triphosphate; AMP-Activated Protein Kinases; Animals; Carrier Proteins; Diet; Dietary Fats; Glucose Intolerance; Hyperlipidemias; Insulin Resistance; Ion Channels; Leptin; Liver; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitochondrial Proteins; Multienzyme Complexes; Muscle, Skeletal; Obesity; Phosphorylation; Protein Serine-Threonine Kinases; RNA, Messenger; Stearoyl-CoA Desaturase; Triglycerides; Uncoupling Protein 1; Weight Loss

We tried to unravel why leptin's fat store depleting action levels off in the course of long-term applications. Supplying leptin by minipump infusion for 2 months to ob/ob mice at rates between 115 pmol day(-1) and 460 pmol day(-1) resulted in stable plasma leptin levels between 0.2 ng ml(-1) and 8 ng ml(-1). Initial treatment effects were leptin dose-dependent reductions in food intake and body mass, especially in fat content, followed by re-increases of food intake to levels only 4-18% below pre-treatment levels. Decreased body mass subsequently stabilized dose-dependently with body fat contents between 4% and 33% showing that total fat depletion was not a precondition for the progressive reduction of leptin-induced anorexia. Oxygen consumption measurements excluded contributions of enhanced energy dissipation to fat depletion. Plasma insulin concentrations declined from excessively high pre-treatment levels to steady, leptin dose-dependent levels within the normal range. Temporary anorexia in response to repeated additional 1-day leptin injections (100 pmol g(-1) day(-1)) remained unchanged throughout long-term leptin infusion. Among various alternatives considered to explain the adipostatic equilibrium attained at new, dose-dependent levels under long-term leptin treatment, interaction between the leptin signal and at least one counteracting signal increasing with fat depletion is proposed as the most plausible working hypothesis.

Topics: Adipose Tissue; Animals; Body Composition; Dose-Response Relationship, Drug; Drug Resistance; Eating; Energy Metabolism; Feedback; Insulin; Leptin; Male; Mice; Mice, Obese; Obesity; Signal Transduction; Weight Loss

The circulatory levels of two appetite regulatory hormones i.e. leptin and ghrelin were estimated in sojourners and acclimatized subjects to investigate their possible role in high altitude (HA) induced anorexia. A group of 30 lowlanders who had never visited HA were inducted to a height of 3600 m by air and after 48 h they were further taken to an altitude of 4300 m by road. Blood samples were collected after 48 h stay at 3600 m and again after 48 h and 7 days of stay at 4300 m during 0700-0730 h. There was a decrease in energy intake (850 kcal/day) of sojourners, which resulted in loss of body weight by 2.12 kg at HA. At an altitude of 4300 m there was a significant increase in leptin over basal levels (54.9%, p < 0.001) at 48 h that persisted even after 7 days of stay at this altitude. Ghrelin levels of sojourners decreased by more than 30% in comparison to basal values at 48 h of ascent to HA. Leptin levels of acclimatized lowlanders were also higher in comparison with control group (acclimatized group 7.6 + 0.6 ng/ml vs. control 5.6 + 0.5 ng/ml, p < 0.01, n = 50).

Topics: Acclimatization; Adult; Altitude; Anorexia; Cross-Sectional Studies; Energy Intake; Ghrelin; Humans; India; Leptin; Longitudinal Studies; Military Personnel; Peptide Hormones; Weight Loss

Enlarged fat cells and leptin hypersecretion are hallmarks of common obesity.. The objective of this study was to investigate fat cell size and leptin production in the basal state after long-term steady-state weight reduction to the nonobese state.. This prospective case-control study had a duration of 3 +/- 1 (mean +/- sd) yr.. Twenty-five obese women (cases) were studied. Each case was compared with a control subject matched for age, sex, and body mass index (BMI) at nadir of weight for the cases.. This study was conducted at Karolinska University Hospital (Stockholm, Sweden).. The subjects were followed until they reached a steady-state weight reduction after lifestyle modification or bariatric surgery (cases). Treatment target was the nonobese state (BMI < 30 kg/m2). Subcutaneous adipose tissue secretion of leptin, serum leptin levels, and fat cell volume were determined after an overnight fast.. Ten obese women (40%) reached the nonobese state. This was accompanied by marked decreases in fat cell volume, leptin secretion, and serum leptin concentrations (P < 0.0001). The postobese cases had 43% smaller fat cell volume (P = 0.0008), 68% lower adipocyte leptin production (P = 0.001), and 54% lower serum leptin levels (P = 0.0007) than control subjects, despite almost identical percent body fat in the two groups. Fat cell volume, but not percent body fat or BMI, was directly proportional to leptin secretion and serum leptin concentrations.. Adipose tissue hyperplasia (too many small fat cells) and low leptin production resulting in relative hypoleptinemia in the fasting (basal) state are common features of the postobese state in women.

Topics: Adipocytes; Adipose Tissue; Adult; Body Mass Index; Case-Control Studies; Female; Humans; Hyperplasia; Leptin; Middle Aged; Obesity; Prospective Studies; Weight Loss

To investigate changes in adipocyte hormones and lipid oxidation during and after a weight-reduction programme in severely obese adolescents.. Longitudinal-clinical investigation including a 9-month multidisciplinary weight-reduction programme in a specialised institution with lifestyle education, moderate energy restriction and regular physical activity, followed by a 4-month period at home.. A total of 26 (12 boys and 14 girls) severely obese adolescents (mean BMI: 33.9 kg/m2; 41.5% fat mass (FM)).. Before starting (M0), at the end (M9), and 4 months after the end (M13) of the intervention blood samples were collected at fast, body composition was assessed by dual X-ray absorptiometry, and energy expenditure (EE) and substrate oxidation were assessed by whole-body indirect calorimetry over 24 h.. At M9, adolescents had lost 19.0% body weight (BW), 41.3% FM (P<0.001), with a minor fat free mass (FFM) loss in girls (6.4%, P<0.001) but no significant FFM changes in boys. Plasma leptin concentration at M9 was 70% lower (P<0.001), whereas plasma adiponectin concentration was 26.6% higher (P<0.001). The results also suggest that after adjustment for FFM and energy balance, sleeping and sedentary activity lipid oxidation rates were higher at M9 than at M0. At M13, plasma adiponectin, insulin, glucose and LDL concentrations returned to the initial levels, and leptin to an intermediate level in the 10 adolescents who had regained BW. Adjusted lipid oxidation rate decreased in both groups of subjects but it was not correlated to any change in plasma adipocyte hormones, which rather changed in relation to FM modifications.. Moderate energy restriction and regular moderate and high intensity physical activities in obese adolescents induced beneficial changes in BW and composition, lipid oxidation and blood parameters, especially adipocyte hormones.

Topics: Adipocytes; Adiponectin; Adolescent; Blood Glucose; Child; Female; Humans; Insulin; Leptin; Lipid Peroxidation; Longitudinal Studies; Male; Obesity; Oxidation-Reduction; Weight Loss

The gut hormone peptide YY(3-36) (PYY) reduces food intake via hypothalamic Y2 receptors in the brain. There is not much known about PYY in obese children.. The objective of this study was to investigate the role of PYY in the metabolic changes in obese children and its change during weight loss.. The study was performed at a university medical center.. We studied 73 obese children and 45 age-matched normal-weight children.. We determined fasting serum total PYY and leptin by RIA in obese and normal-weight children. Fasting PYY was also measured in 28 obese children before and after completion of a 1-yr outpatient weight reduction program.. PYY, insulin, and body mass index were the main outcome measures.. Obese children demonstrated significantly lower PYY levels than lean children (median, 67 vs. 124 pg/ml; P < 0.001). Fasting PYY correlated negatively to the degree of overweight. PYY levels did not differ significantly between boys and girls, nor between prepubertal and pubertal children. The group of patients participating in the outpatient weight reduction program was divided into four quartiles according to their changes in body mass index SD score over a 1-yr period. PYY increased significantly in patients with the most effective weight loss, but decreased in the subgroup of children with weight gain.. PYY is negatively correlated to the degree of overweight, with reduced values in obese compared with normal-weight children. Decreased PYY levels could predispose subjects to develop obesity. Our results indicate that low pretreatment PYY levels that increase during weight loss may be a predictor of maintained weight loss.

Topics: Case-Control Studies; Child; Energy Metabolism; Fasting; Female; Homeostasis; Humans; Leptin; Male; Obesity; Peptide YY; Radioimmunoassay; Weight Loss

Genetic variation in the peroxisome proliferator-activated receptor gamma2 (PPARgamma2), glucocorticoid receptor (GRL), and ciliary neurotrophic factor (CNTF) genes may play a role in the etiology of obesity.. We examined biological, psychological, and genetic determinants associated with weight maintenance (WM) after weight loss.. Subjects (n = 120) followed a 6-wk diet and then a 1-y period of WM. Body weight (BW), body composition, leptin concentration, attitude toward eating (measured with the Three-Factor Eating Questionnaire), physical activity, and the polymorphisms of the PPARgamma2, GRL, and CNTF genes were measured.. BW loss was 7.0 +/- 3.1 kg. After 1 y, 21 subjects showed successful WM (<10% regain); 99 were unsuccessful (> or =10% regain). Compared with unsuccessful subjects, successful subjects had a higher increase in dietary restraint over time (4.8 +/- 5.0 and 1.8 +/- 3.9, respectively; P < 0.01) but significantly less sensation of general hunger (-4.0 +/- 4.9 and -1.2 +/- 2.7, respectively; P < 0.05). Successful subjects had a significantly different frequency distribution for the PPARgamma2 (P = 0.05) and GRL (P < 0.05) genes than did unsuccessful subjects. The more successful genotypes showed a higher baseline body mass index and waist circumference (PPARgamma2), a greater decrease in disinhibition of dietary restraint (GRL), and less sensation of hunger (GRL). The G/G genotype (GRL) was an independent predictor of successful WM.. The different genotypes of the PPARgamma2 and GRL genes contribute to WM, either directly (GRL) or indirectly (PPARgamma2 and GRL) via baseline body mass index and waist circumference, and to changes in Three-Factor Eating Questionnaire scores.

Topics: Adult; Aged; Attitude to Health; Body Composition; Caloric Restriction; Ciliary Neurotrophic Factor; Diet, Reducing; Eating; Exercise; Female; Genotype; Humans; Hunger; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity; Patient Compliance; Polymorphism, Genetic; PPAR gamma; Receptors, Glucocorticoid; Surveys and Questionnaires; Weight Loss

To determine whether or not the weight (and fat) loss induced by oleoyl-oestrone treatment results only as a consequence of decreased food intake, we compared treated animals with a pair-fed model. To this end, Wistar female rats received daily oral gavages of 10 mumol/kg per d oleoyl-oestrone in sunflower oil, or vehicle alone for 10 or 20 d. A second group of rats received the gavage of sunflower oil and the same amount of food ingested as the oleoyl-oestrone-treated animals (pair-fed group). Rats treated with oleoyl-oestrone maintained glucidic metabolism homeostasis despite a marked decrease in adipose tissue weight (P<0.001). Pair-fed rats exhibited a different pattern, comparable to short-term starvation, with greatly decreased glycogen stores (P<0.0001). The most significant effects were detected in the 10 d period groups. Oleoyl-oestrone affected the activity of the ponderostat system not only by decreasing appetite but also by modifying energy partition: treated animals maintained their glucose and energy homeostasis despite decreased food intake and the massive depletion of lipid stores.

Topics: 3-Hydroxybutyric Acid; Adiponectin; Administration, Oral; Animals; Anti-Obesity Agents; Blood Glucose; Cholesterol; Dietary Fats, Unsaturated; Eating; Estrone; Female; Homeostasis; Insulin; Leptin; Oleic Acids; Organ Size; Plant Oils; Rats; Rats, Wistar; Sunflower Oil; Triglycerides; Weight Loss

A successful weight loss program is essential treatment for obesity-related diseases, but it is well known that the majority of individuals do not succeed in weight loss maintenance. The present study evaluates hormonal mechanisms and the relationship of beta2-adrenoceptor polymorphisms involved in individuals who regain weight after initially successful weight loss.. Overweight Japanese men (n = 154) were enrolled in a 24-month weight loss program. Body mass index (BMI), total body fat mass, plasma norepinephrine (NE) and leptin levels, and beta2-adrenoceptor polymorphisms (Arg16Gly, Gln27Glu) were measured every 6 months for the 24-month period. Maintenance of weight loss was defined as significant weight loss (>or=10% reduction) from entry weight at 6 months and maintenance of the weight loss for an additional 18 months. Rebound weight gain was defined as significant weight loss at 6 months but subsequent regain of body weight during the next 18 months.. The results showed that 37 subjects maintained weight loss during 24 months, whereas 36 subjects had rebound weight gain. The BMI at entry and calorie intake and physical activity at each period were similar between the two groups. Subjects who maintained weight loss had at entry a significantly lower fat mass and plasma NE levels compared to those with rebound weight gain. Body fat mass, NE, and leptin levels at entry predicted the degree of change in body weight during the 24-month study period. Subjects with rebound weight gain had a significantly higher frequency of the Gly16 allele for the beta2-adrenoceptor polymorphism compared to subjects who had a 24-month maintenance of weight loss. Subjects carrying the Gly16 allele also had significantly higher plasma NE, leptin, and body fat mass levels and a greater waist-to-hip ratio both at entry and throughout the study.. A high initial degree of body fat mass and high plasma NE levels as determined by the Gly16 allele for the beta2-adrenoceptor polymorphisms predict those individuals who will have rebound weight gain after their initial successful weight loss.

Topics: Adult; Alleles; Blood Pressure; Body Mass Index; Eating; Exercise; Gene Frequency; Genotype; Heart Rate; Humans; Hypertension; Leptin; Linear Models; Male; Multivariate Analysis; Norepinephrine; Overweight; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Receptors, Adrenergic, beta-3; Time Factors; Weight Gain; Weight Loss

Topics: Blood Pressure; Heart Rate; Humans; Leptin; Norepinephrine; Overweight; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Weight Gain; Weight Loss

Maintenance of a reduced body weight is accompanied by decreased energy expenditure that is due largely to increased skeletal muscle work efficiency. In addition, decreased sympathetic nervous system tone and circulating concentrations of leptin, thyroxine, and triiodothyronine act coordinately to favor weight regain. These "weight-reduced" phenotypes are similar to those of leptin-deficient humans and rodents. We examined metabolic, autonomic, and neuroendocrine phenotypes in 10 inpatient subjects (5 males, 5 females [3 never-obese, 7 obese]) under 3 sets of experimental conditions: (a) maintaining usual weight by ingesting a liquid formula diet; (b) maintaining a 10% reduced weight by ingesting a liquid formula diet; and (c) receiving twice-daily subcutaneous doses of leptin sufficient to restore 8 am circulating leptin concentrations to pre-weight-loss levels and remaining on the same liquid formula diet required to maintain a 10% reduced weight. During leptin administration, energy expenditure, skeletal muscle work efficiency, sympathetic nervous system tone, and circulating concentrations of thyroxine and triiodothyronine returned to pre-weight-loss levels. These responses suggest that the weight-reduced state may be regarded as a condition of relative leptin insufficiency. Prevention of weight regain might be achievable by strategies relevant to reversing this leptin-insufficient state.

Topics: Adult; Body Composition; Body Mass Index; Body Weight; Calorimetry; Diet, Reducing; Energy Intake; Energy Metabolism; Female; Humans; Leptin; Male; Muscle, Skeletal; Neurosecretory Systems; Obesity; Phenotype; Thyroxine; Time Factors; Triiodothyronine; Weight Loss

Topics: Animals; Anti-Obesity Agents; Ciliary Neurotrophic Factor; Humans; Hypothalamus; Leptin; Mice; Models, Biological; Neurons; Obesity; Weight Loss

Oesophageal cancer patients with substantial weight loss have worse prognosis. Weight loss is often refractory to the nutritional support. Causes of the weight loss are multiple: oesophageal stricture, frequent alcohol abuse, cancer related cachexia. It may be a consequence of metabolic changes mediated by cytokines, hormones and tumour derived products. Leptin, a protein produced by adipocytes, is an important signalling molecule in energy regulation, metabolism of fatty acids and it can also augment tumour growth of various cancer cell lines. Enhanced intake of poly-unsaturated fatty acids may play an important role in the reversal of cancer related weight loss.. In this study we examined the nutritional status (pre-treatment weight-loss, actual weight, body mass index), serum levels of leptin, soluble leptin receptor, TNF-alpha, IGF-1 and plasma phosphatidyl-cholin fatty acids before the beginning of treatment, after the onset of treatment and shortly before its completion. In the group of 38 pts (33 men, 5 women), mean age 58 years, statistically significant mean pre-treatment weight-loss 8 kg and significant mean weight loss 2 kg after chemoradiotherapy was observed. Concomitant chemoradiation led to transient elevation of serum leptin level despite the weight loss during chemoradiotherapy. Significant changes in the distribution of fatty acids in plasmatic phosphatidyl-cholin were observed.. Our results show the possibility for direct influence of chemoradiotherapy on body weight regulation in advanced oesophageal cancer patients.

Topics: Adult; Aged; Combined Modality Therapy; Esophageal Neoplasms; Fatty Acids; Female; Humans; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Phosphatidylcholines; Receptors, Cell Surface; Receptors, Leptin; Tumor Necrosis Factor-alpha; Weight Loss

To determine the concentrations of leptin and ghrelin, which have opposite effects on appetite, energy expenditure, and weight control, in the plasma of patients with Crohn's disease (CD), which is often associated with weight loss and malnutrition.. Plasma leptin and ghrelin 'concentrations were determined in 28 outpatients with CD by radioimmunoassay. Age- and sex-matched controls with and without Helicobacter pylori (H pylori) infection (28 for each) were enrolled in the study. Circulating levels of these hormones were assessed with respect to CD activity, disease localization and medical treatment.. There were no significant differences in ghrelin levels between CD patients and H pylori-negative controls. However, circulating ghrelin levels were significantly lower in H pylori-infected subjects than in CD patients and uninfected controls. Plasma leptin levels were comparable among the groups. Localization and medication profile had no significant impact on circulating ghrelin and leptin levels.. Apart from H pylori infection, CD itself has no significant influence on circulating ghrelin and leptin levels in the outpatients who were mostly in inactive state.

Topics: Adolescent; Adult; Case-Control Studies; Crohn Disease; Female; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Malnutrition; Middle Aged; Peptide Hormones; Weight Loss

We compared cardiovascular risk factors in younger and older patients with Type 2 diabetes mellitus and higher than normal body mass index (BMI) and percentage of body fat (% BF) after a 1-yr weight-reduction program in order to clarify the benefits of weight loss in the overweight elderly. Groups of 52 younger and 50 older patients consumed low-calorie diets and participated in a simple moderate-intensity aerobic exercise program for 1 yr. At three times during the program (start, 6 months, 12 months), 10 measures were taken for each participant: BMI, total cholesterol (TC), triglyceride (TG), % BF, waist circumference (WC), fasting plasma glucose, hemoglobulin A1c (HbA1c), leptin, high-sensitivity C-reactive protein (hs-CRP), and adiponectin levels. While changes in BMI, TC and TG were evidently the same in both age groups (p-value: 0.11, 0.33, 0.70, respectively), raw figures for change in % BF, WC, fasting plasma glucose, HbA1c, leptin, hs-CRP, and adiponectin values were significantly greater in the older group (p-value: 0.02, 0.01, 0.03, 0.04, 0.02, 0.01, 0.03 respectively). However, after adjusting for % BF and WC, these changes were no longer significant (p-values: 0.08, 0.07, 0.08, 0.06, 0.10, respectively), indicating that weight loss is equally beneficial for overweight patients with Type 2 diabetes in both age groups. Benefits were gained mainly through reduced body fat. Simple life-style modification of adding 20-min daily aerobic exercise and an adequate but restricted calorie diet is more effective in elderly diabetic patients.

Topics: Adiponectin; Adipose Tissue; Adult; Aged; Blood Glucose; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Diet, Fat-Restricted; Exercise Therapy; Fasting; Female; Humans; Leptin; Male; Obesity; Risk Factors; Taiwan; Triglycerides; Waist-Hip Ratio; Weight Loss

The use of low-calorie diets is a common strategy for body-weight reduction purposes, but the time-course of the metabolic changes induced by moderately energy-restricted, otherwise balanced, diets is still poorly known. The aim of this nutritional intervention design was to study in obese women the effect of a balanced low-calorie diet on the metabolic rate, and metabolic fuel utilization changes during the weight loss process through the application of breath tests with stable isotope-labeled tracers. Seven obese (body mass index >30 kg/m(2)) women were assigned to a 10-week dietary hypoenergetic intervention regime supplying 55% of energy as carbohydrate, 30% as fat and 15% as protein. Metabolic rate and substrate utilization were evaluated for 6 h in separate occasions during the weight loss program by indirect calorimetry and after 13C-labeled glucose, triolein and leucine administration. Body weight loss after 10 weeks was 4.2+/-1.1 kg, while the percent body fat decrease was about 5%. Slimming was accompanied by a marked decrease in fasting leptin (about 25%). Postprandial carbohydrate utilization after the administration of a test meal with the same macronutrient distribution as the experimental low-energy diet was decreased (24.1%, P<0.05) as a consequence of the dietary restriction, which was associated with lower insulin plasma levels (P<0.05). Although protein and lipid oxidation were not significantly different after weight reduction (day 1 versus day 70), the metabolic utilization of these substrates tended to increase. Moreover, marginally significant indications obtained on days 15 and 45 suggest that the weight and body composition changes are attributable to a shift in endogenous and exogenous glucose utilization in favor of lipid burning. The breath tests determinations, which were performed on different occasions along the experimental trial, confirmed that the cumulative 13C output decreased for labeled tracers with time, being only statistically significant for the glucose utilization between days 15 and 45. In summary, the weight and fat mass losses were associated with a lower carbohydrate oxidation, which were probably compensated by an increase in lipid oxidation without major changes in protein mobilization.

Topics: Adipose Tissue; Adult; Calorimetry, Indirect; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Energy Metabolism; Female; Glucose; Humans; Insulin; Leptin; Lipid Metabolism; Obesity; Time Factors; Triglycerides; Weight Loss

The primary aim of this study was to find whether any association exists between serum levels of proinflammatory cytokines, mainly IL-6, and the most important comprehensive geriatric assessment (CGA) variables such as functional status, cognitive functions and nutrition in a population of elderly cancer patients. The secondary aims were to find whether any difference existed between: i) age groups, ii) performance status scores, iii) patients who had lost weight versus those who had not. Eighty-four elderly patients with advanced cancer were included in the study (stage III 15.4%, and stage IV 72.6%). Serum levels of IL-6 and CRP were significantly higher in elderly than in the other adult cancer patients. Among the CGA variables investigated, the most affected were functional status assessed by IADL, cognitive functions by MMSE and nutrition. The ECOG PS was shown to be significantly associated with all the dimensions of CGA investigated: poor PS (>/=2) corresponded to severe disabilities. As for the relationship of serum IL-6 with CGA variables, the strongest correlations were between IL-6 and functional status assessed by both Katz ADL (p=0.0003), IADL (p=0.0070) and nutrition (p=0.0013). Moreover, we observed an association, although not statistically significant, between functional disability (ADL and IADL) and high IL-6 levels in individuals with weight loss. IL-6 levels seem to be independently associated with all CGA variables investigated in the present study in a population of elderly cancer patients. Because the most important CGA variables, in particular functional status, have been observed to be strongly associated with survival, the present study, confirming our previously reported ones, suggests that IL-6 may be a reliable marker of disease outcome and supports the feasibility of using IL-6 as a sensitive outcome marker in studies based on novel approaches aiming at modifying age- and cancer-related biologic mechanisms.

Topics: Age Factors; Aged; Aged, 80 and over; C-Reactive Protein; Female; Geriatric Assessment; Humans; Interleukin-6; Leptin; Male; Neoplasm Staging; Neoplasms; Tumor Necrosis Factor-alpha; Weight Loss

Topics: Animals; Carotid Artery, External; Corticosterone; Dehydration; Disease Models, Animal; Disease Progression; Hypothalamus; Infarction, Middle Cerebral Artery; Ischemia; Leptin; Osmolar Concentration; Pharyngeal Muscles; Postoperative Complications; Rats; Reproducibility of Results; Thyrotropin; Tongue; Weight Loss

Ghrelin is a gastrointestinal peptide that stimulates food intake and growth hormone (GH) secretion. We studied the biosynthesis and secretion of ghrelin in a cancer cachexia mouse model. G361, a human melanoma cell line, was inoculated into nude mice. The body weight was reduced and the plasma concentration of interleukin-1beta (IL-1beta) was markedly higher in tumor-inoculated mice compared with vehicle-treated mice. Furthermore, white adipose tissue (WAT) weight, blood sugar level, and plasma concentrations of leptin and nonesterified fatty acids (NEFA) were significantly lower in tumor-inoculated mice. The plasma concentration of ghrelin increased with the progression of cachexia. The levels of both ghrelin peptide and mRNA in the stomach were also upregulated in tumor-inoculated mice. This study demonstrates that both ghrelin biosynthesis and secretion are stimulated in the long-term negative energy balance of tumor-inoculated cachectic mice. These findings suggest the involvement of ghrelin in the regulation of energy homeostasis in cancer cachexia.

Topics: Adipose Tissue; Animals; Blood Glucose; Cachexia; Energy Metabolism; Fatty Acids, Nonesterified; Female; Gene Expression Regulation, Neoplastic; Ghrelin; Humans; Interleukin-1; Leptin; Melanoma; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Organ Size; Peptide Hormones; RNA, Messenger; Stomach; Tumor Cells, Cultured; Weight Loss

Recent studies have suggested that leptin, a plasma protein secreted by adipocytes, may play a role in artherothrombosis. In this study, we tested the hypothesis that leptin contributes to in vivo endothelial dysfunction in obese subjects. A cross-sectional comparison of plasma leptin, soluble thrombomodulin (sTM) and soluble vascular adhesion molecule-1 (VCAM-1) was carried out in 35 obese women (age 48+/-13) selected with a body mass index (BMI) > or =30kg/m(2) and 25 normal weight women (age 50+/-11, BMI < 25). An additional study was conducted to determine the short-term effects of weight loss induced by caloric restriction. Plasma levels of leptin, sTM and sVCAM-1 were measured before and after weight loss. Obese women had higher levels of leptin (35+/-22 versus 22+/-19, P<0.01), sTM (4.8+/-1.8 versus 1.9+/-1.5, P<0.001) and sVCAM-1 (726+/-109 versus 583+/-50, P<0.001) than non-obese women. sTM and sVCAM-1 concentrations had a positive correlation with BMI (sTM, r=0.70, P<0.001; sVCAM-1, r=0.60, P<0.001), waist circumference (sTM, r=0.66, P<0.001; sVCAM-1, r=0.37, P<0.01) and leptin levels (sTM, r=0.53, P<0.001; sVCAM-1, r=0.42, P<0.005). At multiple regression analysis leptin predicted sTM and sVCAM-1 independently of obesity measures and other covariates. Twenty-nine obese patients who completed the program of weight reduction showed a significant decrease in leptin, sTM, and sVCAM-1 levels. The magnitude of decrease of sTM and sVCAM-1 was related to the magnitude of reduction in leptin levels. Therefore, our results show that obesity is associated with enhanced levels of atherosclerosis markers. These abnormalities are related to abdominal obesity possibly mediated by leptin levels, and are reversible with weight loss.

Topics: Arteriosclerosis; Biomarkers; Body Mass Index; Cross-Sectional Studies; Female; Humans; Leptin; Middle Aged; Obesity; Receptors, Leptin; Thrombomodulin; Vascular Cell Adhesion Molecule-1; Weight Loss

To study the influence of dietary intervention on plasma ghrelin levels in obese children and adolescents with anorexia nervosa (AN). Study design Prepubertal obese children (n=16) and 16 anorexic adolescents were studied at three different points: clinical diagnosis and after a reduction or recuperation of 25% and 50% of the initial BMI SD score. Controls included 21 Tanner growth stage 1 and 36 Tanner growth stage 5 subjects. We analyzed plasma ghrelin levels and their correlation with plasma levels of leptin, insulin, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 1 (IGFBP-1), insulin-like growth factor binding protein 2 (IGFBP-2), insulin-like growth factor binding protein 3 (IGFBP-3), and integrated concentration of growth hormone (ICGH) before and after dietary intervention.. At diagnosis, ghrelin levels were significantly decreased in obese children (52% of control levels) and significantly increased in adolescents with AN (164% of control levels). After dietary intervention, ghrelin increased in obese patients but without reaching control levels even after a 50% reduction in body mass index (BMI). In adolescents with AN, ghrelin levels normalized after a 25% increase in BMI. Ghrelin correlated negatively with the BMI and positively with IGFBP-1 levels in controls but not in obese patients or in patients with AN at diagnosis. The positive correlation between ghrelin and IGFBP-1 was recovered after dietary intervention.. Plasma ghrelin levels present opposite changes in obesity and AN after dietary intervention, suggesting that ghrelin is a good marker of nutritional status.

Topics: Adolescent; Anorexia Nervosa; Body Mass Index; Female; Ghrelin; Growth Hormone; Humans; Leptin; Linear Models; Male; Nutritional Status; Obesity; Peptide Hormones; Weight Loss

To examine the hypothesis of an influence of leptin on growth factors and on biochemical markers of bone turnover of prepubertal overweight children.. 395 prepubertal children, 6-13 years of age, were selected and the relationships between circulating serum levels of leptin and insulin-like growth factor I (IGF-I), insulin growth factor binding protein-3 (IGFBP-3) and some biochemical markers of bone turnover (osteocalcin, OC; carboxyterminal propeptide of type I procollagen, PICP, and carboxyterminal propeptide of type I collagen, ICTP) were analyzed. The subjects were subdivided into normal weight (NW, n = 163) and weight excess (WE, n = 232) subjects.. Significant differences between the two groups were found for leptin (p < 0.01), IGF-I (p < 0.01) and IGFBP-3 (p < 0.01), with higher values in WEs, and for OC (p < 0.01) with higher values in NWs. A significant reduction of leptin (p < 0.01) and IGFBP-3 (p < 0.01) serum values and an increase of those of OC (p < 0.01) and PICP (p < 0.05), but not of ICTP, were registered in 103 WEs who showed a drop in weight excess during a weight-excess reduction program. No variations were observed in 26 non-responsive subjects. In a multivariate analysis in which leptin, corrected by BMI and sex, was the independent variable, a significant negative correlation was found with PICP (beta = -0.235, p < 0.01), IGF-I (beta = -0.180, p < 0.01) and height velocity (beta = -0.155, p < 0.01). There was no correlation with OC, ICTP and IGFBP-3. The results demonstrate that nutritional status and leptin levels are involved in the regulation of growth factors and biochemical markers of bone formation.

Topics: Anthropometry; Biomarkers; Bone Remodeling; Case-Control Studies; Child; Collagen Type I; Female; Growth Substances; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Multivariate Analysis; Obesity; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Weight Loss

The aim of this study was to determine whether photoperiod-induced changes in body and fat mass are accompanied by changes in leptin and corticosterone concentrations in collared lemmings. At weaning, eighty male lemmings were maintained in either long photoperiod (LD, n = 40 ) or short photoperiod (SD, n = 40 ). Ten weeks post-weaning lemmings were weighed and assigned to a secondary photoperiod that consisted of either remaining in the same photoperiod or being transferred to the alternate photoperiod (LD-LD, LD-SD, SD-SD, and SD-LD; n = 20 per group). Ten days post-switch, half the animals from each group were sacrificed. The remaining animals were sacrificed on day 21 post-switch. Blood was collected for determination of serum leptin and corticosterone, and carcasses were analyzed for body composition. LD-SD lemmings gained the most weight, whilst SD-LD lemmings lost weight. SD-LD lemmings had significantly lower leptin levels relative to fat mass than SD-SD lemmings. Corticosterone levels were higher in the SD-LD than SD-SD lemmings on both days 10 and 21. Levels were not significantly different between LD-LD and LD-SD lemmings; however by day 21 the levels were slightly lower in the LD-SD lemmings. Discussion. Lemmings showed seasonally appropriate body weight changes in response to the changing photoperiod. Weight loss was associated with higher corticosterone, and lower leptin levels adjusted for fat mass. Neither relative leptin levels, nor corticosterone levels changed significantly with weight gain. Our results indicate that corticosterone and leptin are associated more with seasonal weight loss than weight gain in lemmings.

Topics: Animals; Arvicolinae; Binding, Competitive; Body Composition; Body Weight; Corticosterone; Enzyme-Linked Immunosorbent Assay; Leptin; Male; Photoperiod; Seasons; Weight Gain; Weight Loss

To evaluate the effect of massive weight loss on insulin sensitivity, soluble adhesion molecules, and markers of the insulin resistance syndrome (IRS).. Eighteen morbidly obese patients underwent gastric banding and were evaluated before and 6 and 12 months after surgery. Total insulin secretion, hepatic insulin extraction, and insulin sensitivity were analyzed by oral glucose-tolerance test model analysis. In addition, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, leptin, high-sensitivity C-reactive protein, plasminogen activating factor-1 (PAI-1), and tissue plasminogen activator were measured.. BMI dropped from 45.22 +/- 5.62 to 36.99 +/- 4.34 kg/m(2) after 6 months and 33.72 +/- 5.55 kg/m(2) after 12 months (both p < 0.0001). This intervention resulted in a significant reduction of blood pressure (p < 0.00001), triglycerides (p < 0.01), fasting blood glucose (p = 0.03), basal insulin (p < 0.001), and basal C-peptide (p = 0.008) levels. Total insulin secretion decreased (p < 0.05), whereas hepatic insulin extraction (p < 0.05) and oral glucose insulin sensitivity index (p < 0.0001) increased compared with baseline. Leptin (p < 0.0001) and E-selectin levels decreased significantly after 6 and 12 months (p = 0.05), whereas significantly lower levels of intercellular adhesion molecule-1 and PAI-1 were only seen after 6 months. Subclinical inflammation, measured by high-sensitivity C-reactive protein, was lowered to normal ranges. No changes were observed in vascular cell adhesion molecule-1 and tissue plasminogen activator levels.. Although gastric banding ameliorates several features of the IRS, including 29.05% improvement in insulin sensitivity and blood pressure and reduction of soluble adhesion molecules and PAI-1, considerable weight loss did not normalize all components of the IRS in morbidly obese patients.

Topics: Adult; Arteriosclerosis; C-Peptide; Cell Adhesion Molecules; E-Selectin; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin; Insulin Resistance; Intercellular Adhesion Molecule-1; Leptin; Male; Obesity, Morbid; Plasminogen Activators; Stomach; Vascular Cell Adhesion Molecule-1; Weight Loss

The aims of this study were to determine in the marsupial Sminthopsis crassicaudata, the effects of leptin on food intake, body weight, tail width (a reflection of fat stores), and leptin mRNA, after caloric restriction followed by refeeding ad libitum with either a standard or high-fat preferred diet. S. crassicaudata (n = 32), were fed standard laboratory diet (LabD; 1.01 kcal/g, 20% fat) ad libitum fo 3 days. On days 4-10, animals received LabD at 75% of basal intake and then (days 11-25) were fed either LabD or a choice of LabD and mealworms (MW; 2.99 kcal/g, 30% fat); during this time, half the animals (n = 8) in each group received either leptin (2.5 mg/kg) or PBS intraperitoneally two times daily. On day 26, animals were killed and fat was removed for assay of leptin mRNA. At baseline, body weight, tail width, and food intake were similar in each group. After caloric restriction, body weight (P < 0.001) and tail width (P < 0.001) decreased. On return to ad libitum feeding in the PBS-treated animals, body weight and tail width returned to baseline in the LabD-fed animals (P < 0.001) and increased above baseline in the MW-fed animals (P < 0.001). In the LabD groups, tail width (P < 0.001) and body weight (P < 0.001) decreased after leptin compared with PBS. In the MW groups, the increase in tail width (P < 0.001) and body weight (P = 0.001) were attenuated after leptin compared with PBS. The expression of leptin mRNA in groups fed MW were greater in PBS than in leptin-treated animals (P < 0.05). Therefore, after diet-induced weight loss, leptin prevents a gain in fat mass in S. crassicaudata; this has potential implications for the therapeutic use of leptin.

Topics: Animals; Blood Glucose; Blotting, Northern; Body Weight; Diet, Reducing; Dietary Fats; DNA, Complementary; Eating; Electrophoresis, Agar Gel; Fatty Acids, Nonesterified; Leptin; Male; Marsupialia; Obesity; RNA, Messenger; Tail; Weight Loss

Assess insulin sensitivity and metabolic status of obese patients with stable weight loss at long term following biliopancreatic diversion (BPD).. The study was carried out in 36 nondiabetic severely obese patients undergoing BPD. Serum concentration of glucose, insulin and leptin were determined prior to and at 2 y following the operation. Insulin sensitivity was calculated according to the homeostatic model assessment (HOMA IR).. At 2 y following BPD, weight loss in all subjects corresponded to a marked drop in serum leptin concentration and improvement of insulin sensitivity within physiological range. Following the operation, HOMA IR values were positively correlated with serum leptin concentration independently of body mass index values.. The stable weight loss following BPD at long term is accompanied by a complete reversal of the preoperative insulin resistance. Serum leptin concentration and HOMA IR data were positively related only postoperatively, suggesting that the action of factors that could influence the relation between leptin and insulin action in the obese status can be reverted.

Topics: Adolescent; Adult; Biliopancreatic Diversion; Blood Glucose; Body Mass Index; Female; Follow-Up Studies; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Postoperative Period; Weight Loss

At baseline, weight-losing pancreatic cancer patients (n=7) had lower leptin (P<0.05) but higher cortisol, interleukin-6, resting energy expenditure and fat oxidation than healthy subjects (n=6, P<0.05). Over a 4 h feeding period, the areas under the curve for glucose, cortisol and interleukin-6 were greater (P<0.05), but less for leptin in the cancer group (P<0.05). Therefore, it would appear that low leptin concentrations, increased fat oxidation and insulin resistance are associated with increased concentrations of cortisol and interleukin-6 in weight-losing patients with pancreatic cancer.

Topics: Blood Glucose; Diet; Energy Metabolism; Fats; Female; Humans; Hydrocortisone; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Oxidation-Reduction; Pancreatic Neoplasms; Weight Loss

To assess the main determinant of serum leptin concentration changes in morbidly obese patients treated by banded vertical gastroplasty.. Serum leptin and insulin concentrations, insulin resistance, BMI, body weight, and body fat mass in 18 obese women and 8 obese men treated by vertical banded gastroplasty were studied. Lean women and men subjects were used as controls.. Before surgery, serum leptin and insulin concentrations and insulin resistance index were significantly higher in morbidly obese patients than in control subjects. BMI, body fat mass, and serum triacylglycerol concentrations were also significantly higher in obese than in lean subjects. All of these parameters gradually decreased during 50 weeks after surgery. Univariate regression analysis displayed significant correlations between the following: serum leptin concentration and BMI (and body fat mass), serum leptin concentration and serum insulin concentration, and serum leptin concentration and insulin resistance index. Multivariate regression analysis indicated that only BMI was independently correlated with the decrease in serum leptin concentration.. Obtained data suggest the following: 1) vertical banded gastroplasty causes reduction of body weight, serum leptin and insulin concentration, insulin resistance, and serum triacylglycerol concentration; and 2) BMI is the main determinant of the circulating leptin concentration in morbidly obese women after anti-obesity surgery.

Topics: Adult; Body Composition; Body Mass Index; Female; Gastroplasty; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity, Morbid; Regression Analysis; Triglycerides; Weight Loss

Diurnal variations of adiponectin levels have been studied in normal-weight men and in diabetic and nondiabetic obese subjects, but no data have been reported in obese subjects after weight loss. We collected blood samples at 1-h intervals over 24 h from seven severely obese subjects before and after massive weight loss consequent to surgical operation (bilio-pancreatic diversion [BPD]) to measure adiponectin, insulin, glucose, and cortisol levels. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp (M value). Studies of diurnal variations and pulsatility of adiponectin, insulin, and cortisol were performed. The pulsatility index (PI) of adiponectin increased after BPD from 0.04 to 0.11 microg/min (P = 0.01). Insulin PI significantly increased after the operation (1.50 vs. 1.08 pmol.l(-1).min(-1), P = 0.01), while cortisol PI did not significantly change. The adiponectin clearance rate changed from 0.001 +/- 10(-4).min(-1) before BPD to 0.004 +/- 8. 10(-4).min(-1) after BPD (P = 0.03). Insulin clearance increased from 0.006 +/- 6. 10(-4).min(-1) before BPD to 0.009 +/- 4.10(-4). min(-1) after BPD (P = 0.02). The M value doubled after surgery (27.08 +/- 8.5 vs. 53.34 +/- 9.3 micromol.kg(FFM)(-1).min(-1); P < 0.001) becoming similar to the values currently reported for normal-weight subjects. In conclusion, in formerly severely obese subjects, weight loss paired with the reversibility of insulin resistance restores homeostatic control of the adiponectin secretion, contributing to the reduction of cardiovascular risk already described in these patients.

Topics: Adiponectin; Body Mass Index; Circadian Rhythm; Fasting; Female; Humans; Hydrocortisone; Intercellular Signaling Peptides and Proteins; Leptin; Obesity; Proteins; Weight Loss

Leptin is an adipocyte-derived hormone regulating body weight and energy balance in animals and human being. Although the physiological functions of leptin in human are still unclear, its secretion is closely related to fat mass and energy expenditure in both adults and children. This study investigated whether the plasma leptin level was reduced in connection with the weight loss during the neonatal period and try to find out the role of leptin in body weight regulation and energy balance of premature infants.. The radioimmunoassay was used to determine the plasma leptin concentration. The first blood samples were obtained at the delivered, and then collected the samples every two days until the infants' body weight recovered to the birth weight or above. At the same time, the essential fluid and energy for the patients were supplied to keep their physiological functions. One person was appointed to take responsibility to examine the body weight, body length and head circumference. Then computed out their Kaup index from the first day to the seventh or twelfth day.. A total of 26 premature infants were selected into the study, of which 14 cases were male and 12 female, and their gestational age ranged from 30 to 36 weeks. There was a significantly positive correlation between the premature newborns' body weight loss and their plasma leptin levels (the 1st day: n = 26, r = 0.766; the 3rd day: n = 26, r = 0.636; the 5th day: n = 26, r = 0.629; the 7th day: n = 26, r = 0.717; the 9th-12th day: n = 24, r = 0.587; P < 0.01). The time of body weight loss and the plasma leptin level which declined to extremely low were positively correlated. (r = 0.611, P < 0.01). The time when body weight loss declined to extremely low in 26 premature infants ranged form the 3rd to the 9th day after birth [(5.2 +/- 1.6) day], and that of the plasma leptin levels ranged form the 3rd to the 8th day after birth (4.7 +/- 1.4) day. The maximal ranges of the body weight loss and the plasma leptin decrease in 26 premature infants were (6.5 +/- 3.0)% and (59.6 +/- 11.3)%, respectively. In addition, there were significantly positive correlations among the plasma leptin level, the premature newborns' body length (the 1st day: n = 26, r = 0.609, P < 0.01; the 3rd day: n = 26, r = 0.419, P < 0.05; the 5th day: n = 26, r = 0.583, P < 0.01; the 7th day: n = 26, r = 0.626, P < 0.01; the 9th-12th day: n = 24, r = 0.482; P < 0.05), and the Kaup index (the 1st day: n = 26, r = 0.634; the 3rd day: n = 26, r = 0.534; the 5th day: n = 26, r = 0.542; the 7th day: n = 26, r = 0.611; the 9th-12th day: n = 24, r = 0.539; P < 0.01). Although the head circumference correlated positively with the plasma leptin level at the first week after the delivery (the 1st day: n = 26, r = 0.580, P < 0.01; the 3rd day: n = 26, r = 0.417, P < 0.05; the 5th day: n = 26, r = 0.426; P < 0.01). There was a lower correlation between them one week after the delivery (the 7th day: n = 26, r = 0.369; the 9th-12th day: n = 24, r = 0.323; P > 0.05).. There was a significantly positive correlation between the plasma leptin level and the premature newborns weight loss. Leptin may participate in the regulation of energy balance and body weight of premature infants during neonatal life. Leptin may play an important role in growth and development of premature infants.

Topics: Body Weight; Humans; Infant, Newborn; Infant, Premature; Leptin; Radioimmunoassay; Time Factors; Weight Loss

Genetic mutations in the leptin pathway can be a cause of human obesity. It is still unknown whether leptin can be effective in the treatment of fully established morbid obesity and its endocrine and metabolic consequences in adults. To test the hypothesis that leptin has a key role in metabolic and endocrine regulation in adults, we examined the effects of human leptin replacement in the only three adults identified to date who have genetically based leptin deficiency. We treated these three morbidly obese homozygous leptin-deficient adult patients with recombinant human leptin at low, physiological replacement doses in the range of 0.01-0.04 mg/kg for 18 months. Patients were hypogonadal, and one of them also had type 2 diabetes mellitus. We chose the doses of recombinant methionyl human leptin that would achieve normal leptin concentrations and administered them daily in the evening to model the normal circadian variation in endogenous leptin. The mean body mass index dropped from 51.2 +/- 2.5 (mean +/- SEM) at baseline to 26.9 +/- 2.1 kg/m2 after 18 months of treatment, mainly because of loss of fat mass. We document here that leptin replacement therapy in leptin-deficient adults with established morbid obesity results in profound weight loss, increased physical activity, changes in endocrine function and metabolism, including resolution of type 2 diabetes mellitus and hypogonadism, and beneficial effects on ingestive and noningestive behavior. These results highlight the role of the leptin pathway in adults with key effects on the regulation of body weight, gonadal function, and behavior.

Topics: Adult; Behavior; Body Composition; Body Mass Index; Circadian Rhythm; Diabetes Mellitus, Type 2; Female; Humans; Hypogonadism; Leptin; Phenotype; Weight Loss

Impaired vascular endothelial function may be an important mechanism linking obesity to increased cardiovascular risk. We investigated whether short-term weight loss improves conduit artery endothelial dysfunction in overweight adults. Forty-three otherwise healthy overweight patients with a body mass index > or =27 kg/m(2) completed an open-label 3-month trial consisting of a calorie-restricted diet and 120 mg of orlistat taken 3 times daily with meals. Endothelial function and parameters of the metabolic syndrome were measured before and after intervention. Subjects lost 6.6 +/- 3.4% of their body weight. Low-density lipoprotein cholesterol, low-density lipoprotein concentration, fasting insulin, and leptin decreased significantly (all p <0.009), and C-reactive protein decreased (p = 0.22). Conduit vascular function did not change as assessed by flow-mediated dilation (3.86 +/- 3.54 vs 3.74 +/- 3.78%, p = 0.86) and nitroglycerin-mediated dilation (17.18 +/- 5.89 vs 18.87 +/- 7.11%, p = 0.13) of the brachial artery. A moderate degree of weight reduction over 3 months improved the metabolic syndrome profile but not the vascular dysfunction associated with uncomplicated obesity.

Topics: Adolescent; Adult; Anti-Obesity Agents; C-Reactive Protein; Cholesterol, LDL; Diet, Reducing; Endothelium, Vascular; Female; Humans; Insulin; Lactones; Leptin; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Weight Loss

Topics: Adiponectin; Adipose Tissue; Animals; Body Weight; Brain; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Mice; Proteins; Weight Loss

The current study sought to examine whether leptin injections following a weight reduction in diet-induced obese rats would reduce both the enhanced food intake and body weight (BW) regain observed during the refeeding phase. Female Wistar rats (n = 100, 20 per group) were divided into 5 groups: (1) LEP rats were fed a high-fat (HF) diet (35% wt/wt) for 8 weeks to induce obesity and were then food-restricted (50% ad libitum) with a fortified high-fat diet for 2 weeks to induce a 20% BW loss. These rats were then refed the HF diet ad libtum for another 11 weeks. They were given leptin injections (200 microg/kg BW, twice daily, intraperitoneally ) for 19 days concomitant with the onset of refeeding. (2) SAL rats were treated in the same manner as LEP rats except that they were given saline injections; (3) PF rats were treated like SAL rats except that they were pair-fed with the LEP rats; (4) HFC rats were fed HF diet ad libitum; and (5) LFC rats were fed a low-fat (LF) diet (AIN-93M) ad libitum. Ten rats from each group were killed after leptin treatment and at the end of the study. Food and caloric intakes were monitored, and body composition and plasma glucose, insulin, and leptin levels were assessed at death. Leptin injections after a weight reduction briefly reduced energy intake during the first week only. After 19 days of treatment and to the end of the study, LEP and SAL rats were similar in energy intake, BW (LEP: 393 +/- 11.2 g, SAL: 371 +/- 14.1; difference not significant [NS]) and total body fat percent (LEP: 19.3 +/- 1.5, SAL: 17.6 +/- 1.5; NS). Leptin treatment induced hyperinsulinemia and insulin resistance. All of the metabolic abnormalities observed at the end of treatment period disappeared at the end of the study (8 weeks post-leptin injection). We conclude that bolus leptin injections to manipulate leptin circadian rhythm in diet-induced obese rats after a weight reduction caused temporary insulin resistance and hyperinsulinemia, and were ineffective in influencing food intake, BW, and fat content. Leptin resistance was evident following 1 week of treatment in this study. Leptin treatment had no effect on body fat content both short-term and long-term. Exogenous leptin treatment may, in the long run, increase leptin resistance in diet-induced obese animals. Hence, long-term leptin treatment may not be beneficial to obese individuals consuming a HF diet.

Topics: Animal Feed; Animals; Blood Glucose; Body Composition; Body Weight; Circadian Rhythm; Diet, Fat-Restricted; Dietary Fats; Eating; Energy Intake; Female; Insulin; Leptin; Obesity; Rats; Rats, Wistar; Weight Loss

Severe obesity increases the prevalence of the metabolic syndrome, and moderate acute weight loss with a very low-calorie diet in obese subjects with the metabolic syndrome leads to significant metabolic benefits. Adiponectin has been implicated in both the pathogenesis of obesity-related insulin resistance and increased inflammation. We analyzed the relationship of the adipocyte-derived hormone adiponectin with indices of inflammation, adiposity, and insulin resistance in obese subjects with (MS+, n = 40) and without (MS-, n = 40) the metabolic syndrome and examined the acute effects of rapid weight loss. MS+ subjects had significantly lower adiponectin (7.6 +/- 0.6 vs. 10.4 +/- 0.6 microg/ml; P = 0.003) and significantly higher TNF-alpha (3.3 +/- 0.2 vs. 2.8 +/- 0.3 pg/ml; P = 0.004) levels compared with MS- subjects matched for age and body mass index. Plasma adiponectin and TNF-alpha levels were inversely related to the number of metabolic syndrome factors in a stepwise manner. After 4-6 wk of weight loss, there was marked improvement in glucose, insulin, leptin, and triglycerides, whereas adiponectin and TNF-alpha concentrations did not change. Thus, increases in plasma levels of adiponectin or reductions in TNF-alpha are not required for marked improvements in glucose/insulin and lipid metabolism with acute weight loss.

Topics: Adiponectin; Blood Glucose; Diet, Reducing; Energy Intake; Female; Humans; Inflammation; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Proteins; Triglycerides; Tumor Necrosis Factor-alpha; Weight Loss

Recently, leptin has been suggested as a possible cause of atherosclerotic disease. In the present study, we have investigated in postmenopausal women (n = 60; age: 52 +/- 13) the relationship between circulating levels of leptin, oxidized LDL (Ox-LDL) and other biochemical and anthropometric variables of atherosclerotic risk. In addition, we have evaluated soluble thrombomodulin (sTM) as a marker of endothelial damage. An additional study was conducted in a subgroup of obese subjects to determine the short-term effects of weight loss on selected variables. Ox-LDL showed a positive correlation with leptin circulating levels (r = 0.65, P < 0.0001). A significant association was also found between Ox-LDL and body mass index (r = 0.69, P < 0.0001), waist-to-hip ratio (r = 0.50, P < 0.0001), insulin levels (r = 0.65, P < 0.0001), HOMA index (r = 0.55, p < 0.0001) and sTM (r = 0.74, P < 0.0001) levels. After multivariate regression analysis leptin was still related to Ox-LDL levels (P = 0.007). In obese women who completed the program of weight reduction, leptin changes persisted as a significant predictor of plasma changes in Ox-LDL levels. These findings suggested a novel link between leptin and Ox-LDL, possibly involved in atherosclerotic disease.

Topics: Arteriosclerosis; Female; Humans; Leptin; Lipoproteins, LDL; Middle Aged; Obesity; Postmenopause; Receptors, Leptin; Risk Factors; Thrombomodulin; Weight Loss

Leptin is an adipocyte-derived hormone that plays a key role in energy homeostasis, yet resistance to leptin is a feature of most cases of obesity in humans and rodents. In vitro analysis suggested that the suppressor of cytokine signaling-3 (Socs3) is a negative-feedback regulator of leptin signaling involved in leptin resistance. To determine the functional significance of Socs3 in vivo, we generated neural cell-specific SOCS3 conditional knockout mice using the Cre-loxP system. Compared to their wild-type littermates, Socs3-deficient mice showed enhanced leptin-induced hypothalamic Stat3 tyrosine phosphorylation as well as pro-opiomelanocortin (POMC) induction, and this resulted in a greater body weight loss and suppression of food intake. Moreover, the Socs3-deficient mice were resistant to high fat diet-induced weight gain and hyperleptinemia, and insulin-sensitivity was retained. These data indicate that Socs3 is a key regulator of diet-induced leptin as well as insulin resistance. Our study demonstrates the negative regulatory role of Socs3 in leptin signaling in vivo, and thus suppression of Socs3 in the brain is a potential therapy for leptin-resistance in obesity.

Topics: Animals; Brain Chemistry; Dietary Fats; DNA-Binding Proteins; Eating; Female; Insulin Resistance; Leptin; Male; Mice; Obesity; Phosphorylation; Repressor Proteins; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Trans-Activators; Transcription Factors; Weight Loss

A great deal of attention has focused on the central role of alpha melanocyte-stimulating hormone (alpha-MSH) and its antagonism at the melanocortin-4 receptor (MC4R) by agouti related protein (AgRP) in the regulation of energy balance. However, very little is known regarding the function of circulating AgRP and alpha-MSH in humans. We aimed to determine whether circulating alpha-MSH and AgRP are responsive to long-term perturbations in energy balance, in a manner consistent with their central putative functions.. Circulating alpha-MSH, AgRP and leptin were measured in both lean (n = 11) and obese (n = 18) male volunteers, some of whom (lean n = 11, obese n = 12) were then allocated one of two weight-loss dietary strategies to achieve about 5% weight loss. This was achieved by either total starvation (for 4-6 days) for rapid weight loss or a very low calorie diet (VLCD, 2.6 MJ/day) (11-12 days) for less rapid weight loss, in both the lean and obese volunteers.. At baseline, prior to any weight loss both plasma alpha-MSH (15.8 +/- 1.2 vs. 5.8 +/- 1.0 pmol/l +/- SEM; P < 0.001) and AgRP (49.4 +/- 2.4 vs. 10.1 +/- 0.9 pg/ml +/- SEM; P < 0.001) were elevated in obese subjects compared with lean. In both cases this correlated closely with fat mass (P < 0.001), percentage body fat (P < 0.001) and leptin (P < 0.05). Plasma AgRP increased significantly during a 6-day fast in lean individuals (11.1 +/- 1.6 vs. 21.6 +/- 3.1 pg/ml +/- SEM; P < 0.05) but not in the VLCD subjects or in the obese, while alpha-MSH was not affected by any changes in energy balance in either the lean or the obese volunteers.. We show a difference in alpha-MSH and AgRP in lean and obese subjects that correlates closely with body fat at baseline. We demonstrate an increase in plasma AgRP during a 6-day fast in lean individuals that is coincident with a decrease in plasma leptin. This increase in AgRP was not due to weight loss per se as there was no change in AgRP as a result of the same weight loss in the VLCD intervention in lean individuals. The source of the increase in plasma AgRP and its physiological function in the periphery remains to be elucidated but we suggest that the dynamics of the change in plasma leptin may determine the elevation in fasting plasma AgRP in lean subjects.

Topics: Adult; Agouti-Related Protein; alpha-MSH; Case-Control Studies; Diet, Reducing; Energy Metabolism; Fasting; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Obesity; Proteins; Weight Loss

Serum leptin level is associated with appetite and energy expenditure in healthy individuals. We aimed to evaluate the serum leptin concentration and the other factors which may be associated with weight loss in patients with advanced gastrointestinal cancer.. Forty-four patients with advanced gastrointestinal cancer (25 gastric and 19 colorectal cancer) and 25 healthy controls were enrolled. Serum leptin levels were measured as ng/ml via enzyme linked immuno-sorbent assay (ELISA) method in all subjects. The difference in serum leptin concentration between cancer and control group, the factor associated with its serum level and the relationship between serum leptin concentration and weight loss was evaluated.. Serum leptin concentration of cancer group was significantly lower than controls (p = 0.002). Female subjects had significantly higher serum leptin concentration than male subjects in control group (p = 0.01), while not in cancer group (p > 0.05). Serum leptin concentration was significantly related with gender in controls (p = 0.023, beta = 0.479), while no gender difference was observed in cancer group (p > 0.05). No relationship was found between serum leptin concentration and weight loss percentage in cancer group in linear regression analysis (p > 0.05). No significant difference was observed in serum leptin concentrations between colon and gastric cancer sub-groups (p > 0.05).. Independently from the site of gastrointestinal tract, serum leptin concentration in advanced gastrointestinal cancer is lower than controls and it is not a determinant factor in weight loss. In contrast to healthy subjects, gender does not effect the serum leptin concentration in patients with advanced gastrointestinal cancer.

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Body Mass Index; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Leptin; Male; Middle Aged; Reference Values; Regression Analysis; Sex Distribution; Stomach Neoplasms; Weight Loss

To evaluate interactions among leptin, adiponectin, resistin, ghrelin, and proinflammatory cytokines [tumor necrosis factor receptors (TNFRs), interleukin-6 (IL-6)] in nonmorbid and morbid obesity.. We measured these hormones by immunoenzyme or radiometric assays in 117 nonmorbid and 57 morbidly obese patients, and in a subgroup of 34 morbidly obese patients before and 6 months after gastric bypass surgery. Insulin resistance by homeostasis model assessment, lipid profile, and anthropometrical measurements were also performed in all patients.. Average plasma lipids in morbidly obese patients were elevated. IL-6, leptin, adiponectin, and resistin were increased and ghrelin was decreased in morbidly obese compared with nonmorbidly obese subjects. After adjusting for age, gender, and BMI in nonmorbidly obese, adiponectin was positively associated with HDLc and gender and negatively with weight (beta = -0.38, p < 0.001). Leptin and resistin correlated positively with soluble tumor necrosis factor receptor (sTNFR) 1 (beta = 0.24, p = 0.01 and beta = 0.28, p = 0.007). In the morbidly obese patients, resistin and ghrelin were positively associated with sTNFR2 (beta = 0.39, p = 0.008 and beta = 0.39, p = 0.01). In the surgically treated morbidly obese group, body weight decreased significantly and was best predicted by resistin concentrations before surgery (beta = 0.45, p = 0.024). Plasma lipids, insulin resistance, leptin, sTNFR1, and IL-6 decreased and adiponectin and ghrelin increased significantly. Insulin resistance improved after weight loss and correlated with high adiponectin levels.. TNFalpha receptors were involved in the regulatory endocrine system of body adiposity independently of leptin and resistin axis in nonmorbidly obese patients. Our results suggest coordinated roles of adiponectin, resistin, and ghrelin in the modulation of the obesity proinflammatory environment and that resistin levels before surgery treatment are predictive of the extent of weight loss after bypass surgery.

Topics: Adiponectin; Adult; Blood Glucose; Cholesterol; Cytokines; Female; Gastric Bypass; Ghrelin; Hormones, Ectopic; Humans; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Male; Middle Aged; Obesity, Morbid; Peptide Hormones; Proteins; Resistin; Tumor Necrosis Factor-alpha; Weight Loss

Idiopathic intracranial hypertension (IIH) occurs predominantly in young, obese women. Weight loss may alleviate symptoms of IIH yet may be difficult to achieve. Ghrelin, a gastric hormone, is involved in normal body weight and appetite regulation. Its levels are elevated in syndromes of overeating and decline in simple obesity. We postulated that fasting plasma ghrelin levels are elevated in IIH patients and that the typical postprandial decline in plasma ghrelin may not occur.. Prospective, observational case-control study.. Prospective study.. University hospital and clinic.. Sixty-five patients with a diagnosis of IIH and 25 obese control patients (screened for IIH symptoms). Patients with intracranial abnormalities or a history of gastric surgery were excluded.. Fasting plasma ghrelin, leptin, and insulin levels were assessed between 8 am and 10 am. Subjects were fed a standard breakfast, and postprandial ghrelin levels were measured 30 minutes later.. Fasting plasma ghrelin levels negatively correlated with body mass index in both IIH subjects (r = -.48) and controls; leptin showed a positive correlation with body mass index in both IIH (r =.59) and controls. Levels were not significantly different between the groups. Postprandial ghrelin declined by 71 +/- 31 (95% CI) pg/ml in the IIH group and 71 +/- 35 (95% CI) pg/ml in the control group.. Plasma ghrelin levels, both fasting and postprandial, do not differ between IIH patients and obese controls. Obese IIH patients should be encouraged to lose weight and referred for medical weight loss management to maximize their chances of alleviating their symptoms.

Topics: Adult; Body Constitution; Body Mass Index; Case-Control Studies; Female; Ghrelin; Growth Hormone; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Peptide Hormones; Prospective Studies; Pseudotumor Cerebri; Weight Loss

Generalized lipodystrophy is a rare disorder of adipose tissue, whose etiology remains unknown. Pathophysiology of this disorder is characterized by generalized loss of body fat associated with an infrequent form of diabetes mellitus (lipoatrophic diabetes). Main features of this form of diabetes mellitus are the severe insulin resistance and the absence of ketoacidosis. Lipodystrophy can be congenital or acquired. In the acquired form, metabolic disturbances usually begin in the first years of life and the response to conventional treatment is very poor. Some alterations in serum adipocytokines have been described in this disease. We report the case of a 74-year-old woman with acquired generalized lipodystrophy who presented with low-normal serum concentrations of leptin, low adiponectin and resistin levels, and high serum levels of TNF alpha. Patient was initially treated with fenofibrate, metformin and high doses of subcutaneous insulin achieving an adequate metabolic control. During this period, serum adipocytokines were periodically measured. We comment on the different etiopathogenic mechanisms and the therapeutic modalities of this rare syndrome.

Topics: Adiponectin; Aged; Blood Glucose; Cytokines; Diabetes Mellitus, Lipoatrophic; Diabetes Mellitus, Type 2; Female; Fenofibrate; Hormones, Ectopic; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Metformin; Resistin; Tumor Necrosis Factor-alpha; Weight Loss

Insulin resistance occurs both in obesity and in Cushing's syndrome suggesting a pathogenetic role of cortisol in insulin-resistant obese subjects.. We examined serum cortisol in 81 insulin-resistant (homeostasis model assessment (HOMA) >4) obese children (age in median 12 years) and 151 obese children without insulin resistance (HOMA < or = 4) (age in median 10 years) and compared these to cortisol of 83 healthy children of normal weight (age in median 12 years). Multivariate linear regression analysis was conducted for the dependent variable insulin resistance (HOMA), including weight status (BMI), age, gender, pubertal stage and cortisol concentration as independent variables. Furthermore, we analyzed cortisol and insulin resistance in 45 obese children with significant weight loss (reduction in SDS-BMI > or = 0.5) and in 109 obese children without significant weight loss (reduction in SDS-BMI <0.5) over the time period of 1 year.. Cortisol was significantly (p = 0.006) higher in obese insulin-resistant children (median 14.6 microg/dl) compared to those of normal weight (median 11.4 microg/dl) or obese without insulin resistance (median 11.7 microg/dl). Insulin resistance was significantly influenced by weight status (BMI), age and cortisol using multivariate linear regression analysis. A reduction in overweight showed a significant decrease in cortisol (p = 0.005) and insulin resistance (p = 0.002) in insulin-resistant children, whilst there were no significant changes in children not reducing their overweight and in non-insulin-resistant children.. Cortisol was moderately increased in insulin-resistant, obese children and related to insulin resistance. Weight reduction led to a decrease in cortisol and insulin resistance. These facts point to an association between cortisol and insulin resistance in obesity.

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Hydrocortisone; Insulin Resistance; Leptin; Longitudinal Studies; Male; Obesity; Weight Loss

To evaluate the early effect of Roux-en-Y (RYGB) gastric bypass on hormones involved in body weight regulation and glucose metabolism. SIGNIFICANT BACKGROUND DATA: The RYGB is an effective bariatric procedure for which the mechanism of action has not been elucidated yet. Reports of hormonal changes after RYGB suggest a possible endocrine effect of the operation; however, it is unknown whether these changes are the cause or rather the effect of surgically induced weight loss. We speculated that if the mechanism of action of the RYGB involves an endocrine effect, then hormonal changes should occur early after surgery, prior to substantial body weight changes.. Ten patients with a mean preoperative body mass index (BMI) of 46.2 kg/m (40-53 kg/m) underwent laparoscopic RYGB. Six patients had type 2 diabetes treated by oral hypoglycemic agents. Preoperatively and 3 weeks following surgery, all patients were tested for fasting glucose, insulin, glucagon, insulin-like growth factor 1 (IGF-1), leptin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), corticosterone, and neuropeptide Y (NPY).. Changes in mean BMI were rather minimal (43.2 kg/m; P = not significant), but there was a significant decrease in blood glucose (P = 0.005), insulin (P = 0.02), IGF-1 (P < 0.05), leptin (P = 0.001), and an increase in ACTH levels (P = 0.01). The other hormones were not significantly changed by surgery. All the 6 diabetic patients had normal glucose and insulin levels and did not require medications after surgery. The RYGB reduced GIP levels in diabetic patients (P < 0.01), whereas no changes in GIP levels were found in nondiabetics.. Roux-en-Y gastric bypass determines considerable hormonal changes before significant BMI changes take place. These results support the hypothesis of an endocrine effect as the possible mechanism of action of RYGB.

Topics: Adrenocorticotropic Hormone; Adult; Anastomosis, Roux-en-Y; Biomarkers; Blood Glucose; Body Mass Index; Cholecystokinin; Female; Follow-Up Studies; Gastric Bypass; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Preoperative Care; Probability; Prospective Studies; Sensitivity and Specificity; Somatomedins; Statistics, Nonparametric; Weight Loss

Obesity is demonstrated to be associated with an enhanced inflammatory state, which is suggested to be a cause for the development of obesity-related morbidity. It was hypothesized that a decrease in body weight in morbid obese subjects would lead to a reduction of the inflammatory state in these subjects. Weight loss was achieved by gastric restrictive surgery in 27 morbidly obese patients. Preoperative as well as 3-, 6-, 12-, and 24-month postoperative plasma concentrations of inflammatory mediators macrophage inhibitory factor, plasminogen activator inhibitor-1, lipopolysaccharide binding protein, alpha-1 acid glycoprotein, C-reactive protein, soluble TNFalpha receptors 55 and 75, and leptin were measured. Macrophage inhibitory factor levels remained low normal for 6 months, during weight loss, after which they significantly increased to normal levels at 24 months postoperatively. The other inflammatory mediators remained elevated up to minimally 3 months postoperatively; thereafter they decreased significantly. Both TNFalpha receptors remained elevated up to at least 12 months postoperatively to decrease significantly at 2 yr postoperatively. This study demonstrates that during weight loss, after gastric restrictive surgery, inflammatory mediators remain elevated for at least 3 months postoperatively, suggesting initially an ongoing inflammatory state. However, 2 yr after surgery, the inflammatory mediators reach near normal values.These findings may be an explanation for the reduced comorbidity seen in morbidly obese patients after gastric restrictive surgery.

Topics: Acute-Phase Proteins; Adult; C-Reactive Protein; Carrier Proteins; Gastroplasty; Humans; Leptin; Macrophage Migration-Inhibitory Factors; Membrane Glycoproteins; Obesity, Morbid; Orosomucoid; Plasminogen Activator Inhibitor 1; Postoperative Period; Receptors, Tumor Necrosis Factor; Solubility; Tumor Necrosis Factor-alpha; Weight Loss

The hypothalamus is involved in regulation of food intake (FI) and fat deposition. Molecular mechanisms of weight loss after Roux-en-Y gastric bypass (RYGB) were studied by correlating changes in gene expression profiles in hypothalamic arcuate nucleus (ARC) and subcutaneous abdominal fat (SAF).. Diet-induced obese rats were divided into RYGB, sham-operated (SO-Obese), and sham-operated pair-fed (PF) groups. A non-obese group on a regular chow diet served as control. Body weight (BW) and FI were measured. Rats were killed 10 days after the operation. Plasma was analyzed for biochemical indices, ARC and SAF were analyzed for gene expression profiles. Body SAF was also weighed. Data were analyzed by ANOVA and factor analysis.. BW and FI decreased in RYGB versus SO-Obese, as reflected by decreased SAF (53%). Genes similarly expressed in ARC and SAF after RYGB were limited to several genes that predominantly related to metabolic pathways of carbohydrate, fat, neuropeptide, and cytokines. These expression profiles were similar to those seen in chow control and to those seen in a comparison of PF and SO-Obese.. RYGB-induced weight loss is associated with changes in gene profile expressions that could influence metabolic changes, contributing to weight loss.

Topics: Anastomosis, Roux-en-Y; Animals; Eating; Gastric Bypass; Gene Expression Profiling; Insulin; Interleukin-6; Leptin; Male; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Weight Loss

The aim of our study was to compare serum concentration of leptin and pituitary-thyroid axis hormones in obese/overweight women before and after two levels of energy deficit with those parameters in lean women on adequate energy intake. Additionally, we attempted to elucidate if the effect of weight reduction could be related to anthropometric and hormonal parameters before treatment. Anthropometric and hormonal parameters-serum leptin, TSH, T4, fT4, T3 and leptin to fat mass (Lep/fm), T3/T4, fT4/T4, T4/TSH, fT4/TSH--were compared in two groups of women (n =18 each)--lean women (C: BMI 22.0 +/- 1.2) and overweight/obese (Ov/Ob: BMI 29.9 +/- 3.3). Ov/Ob women were subjected to weight-reducing treatment consisting of energy intake equal to 80% of calculated total energy expenditure for the first 4 wk and to 50% for subsequent 4 wk. All baseline hormone concentrations, Lep/fm, and fT4/T4 were higher in overweight/obese group. After 20% energy deficit decrease in BMI, percent body fat (fm%), leptin, T3, and TSH serum concentrations as well as in Lep/fm and T3/T4 was observed; T4/TSH increased, fT4, fT4/T4 and fT4/TSH did not change significantly. Increase in energy deficit from 20% to 50% resulted in normalization of Lep/fm, on the other hand, it provoked greater decline in thyroid hormone plasma concentration, which could hinder further mass reduction. Leptin and TSH levels were positively correlated after 50% energy deficit treatment. Changes in fm% were directly related to baseline T4/TSH, fT4/TSH, and log TSH. In conclusion, TSH serum concentration and its ratio to T4 and fT4 before weight reduction could be a good predictor of successful weight loss.

Topics: Adipose Tissue; Body Composition; Body Mass Index; Diet, Reducing; Energy Intake; Energy Metabolism; Female; Humans; Leptin; Obesity; Premenopause; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Weight Loss

The rewarding effect produced by electrically stimulating certain sites in the lateral hypothalamus (LH) can be potentiated by food restriction and body weight loss in lean rats. Central leptin and insulin administration can suppress the rewarding impact of the stimulation. To determine whether there are additional peripheral signals that mediate the effect of weight loss on brain reward circuitry, we assessed changes in LH-self-stimulation following food restriction in the obese Zucker rat which develops resistance to circulating leptin and insulin. In addition, we examined the impact of acute food deprivation and leptin administration on LH self-stimulation in lean and obese Zucker rats. The number of brain stimulation rewards earned was measured over a range of LH stimulation frequencies that drove reward rates from zero to asymptotic levels. Restriction reduced frequency thresholds in a subset of lean and obese rats, whereas BSR was unaltered by acute food deprivation. Despite impairment in leptin signaling, intraventricular leptin (4 microg) increased thresholds in most lean and obese rats in which the rewarding effect was sensitive to restriction. These results show that brain reward circuitry in the obese Zucker rat is sensitive to weight loss and leptin.

Topics: Analysis of Variance; Animals; Appetite Regulation; Body Composition; Electric Stimulation; Energy Metabolism; Food Deprivation; Insulin; Leptin; Male; Obesity; Rats; Rats, Zucker; Reinforcement, Psychology; Self Stimulation; Thinness; Weight Loss

Treatment with the anti-inflammatory cytokine, interleukin-11 (IL-11), in rabbits with TNBS-colitis reduces tissue damage but does not normalize body weight loss despite an increase in plasma levels of motilin, known to stimulate food intake. We investigated whether IL-11 could increase plasma levels of the anorectic peptide, leptin in non-inflamed and inflamed rabbits. In addition, the effect of IL-11 and leptin on motilin mRNA expression in the T84 cell line was tested. Five days post-inflammation, weight loss amounted 10.7+/-1.2%, but plasma leptin and motilin levels were unaffected. During IL-11 treatment, weight loss remained and plasma leptin levels dose-dependently increased with 27+/-5% (4 microg/kg day) and 108+/-7% (720 microg/kg day). Motilin levels increased in parallel with 23+/-12% or 256+/-97%. In non-inflamed animals, a prompt decrease in weight (-11.9+/-1%) was observed after treatment with the highest dose of IL-11 and this was associated with an increase in plasma leptin (70+/-18%) and motilin levels (113+/-7%). Both IL-11 and leptin stimulated motilin mRNA expression in T84 cells with a different time profile. In conclusion, the increase in plasma leptin levels during IL-11 treatment induces wasting in normal rabbits and may be one of the major factors involved in the maintenance of body weight loss in rabbits with colitis. Increase of motilin expression by leptin may be part of a feedback mechanism.

Topics: Animals; Cell Line; Colitis; Gene Expression Regulation; Inflammation; Interleukin-11; Leptin; Motilin; Rabbits; RNA, Messenger; Weight Loss

The aim of this study was to evaluate the morphometric changes of adipose tissue of lean and obese rats as assessed by computerized image analysis (IA) system in experimental conditions, with different degrees of adiposity. Moreover, to validate measures obtained by image analysis by correlation with direct measures of adiposity (body weight, epididimal fat, mean fat cell size and serum leptin). Finally to correlate these changes to expression of genes involved in lipid deposition and mobilization in adipose tissue. Lean (Fa/?) and genetically obese (fa/fa) Zucker rats were studied. Obese rats were food-restricted or treated with retinoic acid (ATRA) in order to reduce body weight and fat content. Moreover, gene expression of two key enzymes involved in fat metabolism (HSL and DGAT) were assessed in adipose tissue by RT-PCR. Our results show that HSL expression in adipose tissue was lower in obese compared to lean rats (1.47+/-0.02 vs 0.35+/-0.03, p<0.005) and was upregulated during food restriction in obese rats. DGAT expression was similar in lean and obese rats and was reduced by treatment with ATRA in obese rats. Tissue texture assessed by IA was significantly higher in lean compared to obese rats (23.2+/-0.6 vs 11.6+/-2.4%; p=0.01). Tissue structure highly correlated with adiposity in obese rats with different amount of body fat (area fraction vs epididimal fat depot: p=0.001). Distribution of measures for each sample, an index of spread of adipose tissue texture, as expressed by the standard deviation, correlated with adiposity (standard deviation vs epididimal fat depot: p=0.002) thus suggesting that adipose tissue texture increases its heterogeneity when adiposity is lower. This observation is in agreement with the hypothesis that the process of lipid mobilization from adipose tissue is not uniform, but a subpopulation of slimming adipocytes undergoes a complete release of their fat content while the rest of the tissue is much less affected. Moreover, image analysis system seems a reliable quantitative tool for assessment of adipose tissue texture.

Topics: Adipose Tissue; Animals; Body Weight; Fatty Acids, Nonesterified; Leptin; Male; Obesity; Rats; Rats, Zucker; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Weight Gain; Weight Loss

Leptin and adiponectin are proteins produced and secreted from white adipose tissue and are important regulators of energy balance and insulin sensitivity. Seasonal changes in leptin and adiponectin have not been investigated in mammalian hibernators in relationship to changes in fat cell and fat mass. We sought to determine the relationship between serum leptin and adiponectin levels with seasonal changes in lipid mass. We collected serum and tissue samples from marmots (Marmota flaviventris) in different seasons while measuring changes in fat mass, including fat-cell size. We found that leptin is positively associated with increasing fat mass and fat-cell size, while adiponectin is negatively associated with increasing lipid mass. These findings are consistent with the putative roles of these adipokines: leptin increases with fat mass and is involved in enhancing lipid oxidation while adiponectin appears to be higher in summer when hepatic insulin sensitivity should be maintained since the animals are eating. Our data suggest that during autumn/winter animals have switched from a lipogenic condition to a lipolytic state, which may include leptin resistance.

Topics: Adipocytes; Adiponectin; Analysis of Variance; Animals; Blotting, Northern; Blotting, Western; Body Composition; Colorado; Electric Conductivity; Female; Hibernation; Intercellular Signaling Peptides and Proteins; Leptin; Male; Marmota; Seasons; Weight Gain; Weight Loss

Weight loss in obese insulin-resistant but not in insulin-sensitive persons reduces coronary heart disease risk. To what extent changes in gene expression are related to atherosclerosis and cardiovascular function is unknown.. We studied the effect of diet restriction-induced weight loss on gene expression in the adipose tissue, the heart, and the aortic arch and on atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia, and insulin resistance are associated with hypertension, impaired left ventricular function, and accelerated atherosclerosis in those mice. Compared with lean mice, peroxisome proliferator-activated receptors (PPAR)-alpha and PPAR-gamma expression was downregulated in obese double-knockout mice. Diet restriction caused a 45% weight loss, an upregulation of PPAR-alpha and PPAR-gamma, and a change in the expression of genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress, and inflammation, most of which are under the transcriptional control of these PPARs. Changes in gene expression were associated with increased insulin sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. PPAR-alpha and PPAR-gamma expression was inversely related to plaque volume and to oxidized LDL content in the plaques.. Induction of PPAR-alpha and PPAR-gamma in adipose tissue, heart, and aortic arch is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight loss. Improved lipid metabolism and insulin signaling is associated with decreased tissue deposition of oxidized LDL that increases cardiovascular risk in persons with the metabolic syndrome.

Topics: Adipose Tissue; Animals; Aorta, Thoracic; Arteriosclerosis; Autoantibodies; Circadian Rhythm; Echocardiography; Gene Expression Regulation; Genotype; Glucose; Heart Function Tests; Hypertriglyceridemia; Inflammation; Insulin Resistance; Leptin; Lipoproteins, LDL; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Myocardium; Obesity; Oxidative Stress; PPAR alpha; PPAR gamma; Receptors, LDL; Transcription, Genetic; Up-Regulation; Weight Loss

The high prevalence of obesity and cardiovascular risk factors in hypopituitarism affirms the need for effective weight loss intervention. In this study, we investigated the combined effect of sibutramine, diet, and exercise in obese hypopituitary patients (HPs).. In an open-label prospective intervention trial, 14 obese well-substituted nondiabetic HPs and 14 matched simple obese controls were allocated to 11-month treatment with sibutramine (10 to 15 mg), diet (600 kcal/d deficit), and exercise. Anthropometric indices and body composition (obtained from DXA scan) were assessed monthly for the first 5 months and thereafter every second month for the next 6 months.. Mean (+/-SD) weight loss at 11 months was 11.3 +/- 4.8 kg in patients vs. 10.7 +/- 4.7 kg in controls. The HPs exhibited the same improvements in body composition, waist circumference, blood lipids, and fasting glucose as the simple obese. In a multivariate model, baseline weight, duration of growth hormone replacement therapy, and duration of pituitary disease explained 79% (p = 0.001) of the variation in weight loss at 4 months in the HPs. Only baseline weight and waist circumference could predict weight loss at 11 months.. HPs are not resistant to weight loss therapy. Almost all will achieve at least 5% weight loss, and 60% can lose >10% weight within 11 months. However, the long-term effect on risk factors associated with type 2 diabetes and cardiovascular disease as well as on mortality needs to be established.

Topics: Adult; Anthropometry; Appetite Depressants; Blood Glucose; Body Composition; Cholesterol; Combined Modality Therapy; Cyclobutanes; Exercise; Female; Human Growth Hormone; Humans; Hypopituitarism; Leptin; Lipids; Male; Middle Aged; Obesity; Pregnancy; Weight Loss

Orlistat is an inhibitor of lipase which splits triglycerides into free fatty acides and glycerol. This drug, by inhibiting hydrolysis of triglycerides, is the cause of significant loss of fat in the faeces. 13 obese and 15 nonobese subjects were examined. Obese subjects received orlistat (Xenical, F. Hoffmann La Roche Ltd, Switzerland) 3 x 120 mg/d. Treatment with orlistat for 16 weeks was followed by a significant fall of BMI and MAP, insulinemia, insulin/glucose ratio, leptinemia, serum total cholesterol, triglycerides, HDL-cholesterol and 25-OH-D concentration respectively. Orlistat did not influence significantly serum LDL-cholesterol concentration but unexpectedly increased plasma levels of folic acid, vitamin B12 and NPY.. (1) Monitoring of plasma 25-OH-D levels in obese patients on orlistat therapy seems to be mandatory. (2) In spite of significant changes (in opposite direction) in leptinemia and serum NPY level observed in obese subjects treated with orlistat, presence of a functional relationship between these hormones could not be confirmed.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Carbohydrates; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Enzyme Inhibitors; Female; Hormones; Humans; Hypercholesterolemia; Hyperlipidemias; Insulin; Lactones; Leptin; Lipase; Lipids; Male; Neuropeptide Y; Obesity; Orlistat; Poland; Time Factors; Treatment Outcome; Triglycerides; Vitamins; Weight Loss

In the work presented here, we explored the influence of leptin on the kinetics of experimental autoimmune encephalomyelitis (EAE) onset, in the EAE-associated inflammatory anorexia, and in the development of pathogenic T cell responses. We found that the expression of serum leptin increased before the clinical onset of EAE in disease-susceptible C57BL/6J (H-2(b)) and SJL/J (H-2(s)) strains of mice, which are models of chronic-progressive and relapsing-remitting EAE, respectively. This increase in serum leptin correlated with disease susceptibility, reduction in food intake, and decrease in body weight. Indeed, acute starvation, which is able to prevent the increase in serum leptin, delayed disease onset and attenuated clinical symptoms by inducing a T helper 2 cytokine switch. Furthermore, immunohistochemical analysis revealed a parallel in situ production of leptin in inflammatory infiltrates and in neurons only during the acute/active phase of both chronic-progressive and relapsing-remitting EAE. We also found that leptin secretion by activated T cells sustained their proliferation in an autocrine loop, since antileptin receptor antibodies were able to inhibit the proliferative response of autoreactive T cells in vitro. Given that leptin appears to regulate EAE susceptibility, inflammatory anorexia, and pathogenic T-cell immune function, we postulate that it may offer a potential target in the treatment of multiple sclerosis.

Topics: Animals; Anorexia; Disease Susceptibility; Encephalomyelitis, Autoimmune, Experimental; Female; Leptin; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Th1 Cells; Weight Loss

Pulmonary tuberculosis is the classic cause of "consumption," but the pathogenesis of such wasting is largely unknown. Animal studies in other conditions suggest that leptin may be a mediator between proinflammatory cytokine activity and wasting.. We tested whether the leptin concentration, after control for body fat mass, is higher during active pulmonary tuberculosis than after recovery and whether it correlates with energy metabolism and proinflammatory cytokine activity.. Nondiabetic adults with pulmonary tuberculosis (n = 32) were recruited into a prospective observational study. Patients found to be antibody positive for human immunodeficiency virus were excluded from the study. Dual-energy X-ray absorptiometry, indirect calorimetry, and food intake protocols were performed at baseline and after 1 and 6 mo of tuberculosis treatment. Fasting plasma leptin, tumor necrosis factor alpha and its soluble receptor, and interleukin 6 were measured by enzyme-linked immunosorbent assay.. Resting energy expenditure was close to Harris-Benedict predictions and did not change significantly during treatment, but energy intake increased. Leptin concentration was correlated in a log-linear fashion with percentage body fat but was independent of cytokines and energy intake. There was no significant difference in leptin, corrected for energy balance and fat mass, at baseline and after 1 and 6 mo of treatment.. These data are compatible with recovery from anorexia or starvation without discernible hyper- or hypometabolism. The close correlation of leptin with body fat mass is similar to observations in healthy subjects. No additional influence of disease state or proinflammatory cytokine activity was found. Leptin does not appear to be a component of the immune response to human pulmonary tuberculosis, and thus it cannot account for the weight loss and anorexia associated with tuberculosis.

Topics: Absorptiometry, Photon; Adipose Tissue; Adolescent; Adult; Aged; Aged, 80 and over; Body Composition; Body Water; Calorimetry, Indirect; Chronic Disease; Cytokines; Energy Intake; Energy Metabolism; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Tuberculosis, Pulmonary; Weight Loss

We investigated the effect of repetitive postnatal (2-7 days) intracerebroventricular administration of neuropeptide Y (NPY) on food intake and body weight gain in the 3- to 120-day-old Sprague-Dawley rats. NPY caused a 32% transient increase in body weight gain with elevated circulating insulin concentrations within 24 h. This early intervention led to the persistence of hyperinsulinemia and relative hyperleptinemia with euglycemia in the 120-day-old female alone. This perturbation was associated with 50% suppression in adult female hypothalamic NPY concentrations and a 50-85% decline in NPY immunoreactivity in the paraventricular and arcuate nuclei. This change was paralleled by a approximately 20% decline in food intake and body weight gain at 60 and 120 days. However, when exogenous NPY was stereotaxically reinjected into the paraventricular nucleus of the approximately 120-day-old adult females who were pretreated with NPY postnatally, an increase in food intake and body weight gain was noted, attesting to no disruption in the NPY end-organ responsivity. We conclude that postnatal intracerebroventricular NPY has long-lasting effects that predetermine the resultant adult phenotype in a sex-specific manner.

Topics: Aging; Animals; Animals, Newborn; Blood Glucose; Feeding Behavior; Female; Hypothalamus; Immunohistochemistry; Injections, Intraventricular; Insulin; Leptin; Luteinizing Hormone; Male; Neuropeptide Y; Organ Size; Pregnancy; Rats; Rats, Sprague-Dawley; Sex Characteristics; Time Factors; Weight Loss

Topics: Agouti-Related Protein; alpha-MSH; Animals; Anti-Obesity Agents; Appetite; Arcuate Nucleus of Hypothalamus; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Energy Intake; Ghrelin; Humans; Hunger; Intercellular Signaling Peptides and Proteins; Lactones; Leptin; Mice; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Obesity; Orlistat; Peptide Fragments; Peptide Hormones; Peptide YY; Phentermine; Proteins; Receptors, Corticotropin; Receptors, Melanocortin; Weight Loss

In their efforts to lose weight, obese individuals may be fighting a powerful set of evolutionary forces honed in an environment drastically different from that of today.

Topics: Adipose Tissue; Body Mass Index; Body Weight; Diet; Energy Intake; Energy Metabolism; Feeding Behavior; Female; Genes; Homeostasis; Humans; Hunger; Incidence; Leptin; Life Style; Male; Obesity; Public Health; Selection, Genetic; United States; Weight Loss

This study was performed retrospectively to investigate whether exercise energy expenditure (EE) measured during a standardized treadmill protocol (4.5 km/h at 0% grade) falls below predicted values after body weight loss in obese men. A reference equation was established to predict net exercise EE in a control sample of 83 obese individuals (27 kg/m(2)< or = body mass index <45 kg/m(2)), using age, fat mass and fat-free mass as independent variables. This equation was then used to predict net exercise EE in another group of 11 obese men before and after a 15-week drug-based weight loss programme that was coupled with energy restriction [-2929 kJ/day (-700 kcal/day)]. Body weight and body composition were determined by hydrodensitometry. Net exercise EE, insulin, leptin, 3,3',5-tri-iodothyronine and free thyroxine were measured after an overnight fast at baseline and 2-4 weeks after the end of the programme, when subjects were weight stable. Body weight was significantly reduced (-11%; P <0.01) at the end of the weight loss programme. At baseline, measured net exercise EE was similar to that predicted from the regression equation [19.6 and 19.8 kJ/min (4.69 and 4.74 kcal/min) respectively; not significant]. However, after the end of the intervention, measured net exercise EE was significantly below the predicted value [15.5 and 17.3 kJ/min (3.71 and 4.14 kcal/min) respectively; P <0.01]. The difference between the predicted and the measured fall in net exercise EE was significantly associated with changes in leptin concentration ( r =0.79, P <0.01), even after correction for changes in fat mass and insulin. These observations suggest that net exercise EE falls below predicted values after body weight loss. In addition, this greater than predicted decrease in net exercise EE was associated with changes in leptin.

Topics: Adult; Aged; Analysis of Variance; Body Composition; Energy Metabolism; Exercise; Female; Fenfluramine; Humans; Insulin; Leptin; Male; Middle Aged; Obesity; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Statistics, Nonparametric; Thyroxine; Triiodothyronine; Weight Loss

Leptin resistance is a major cause of obesity in humans. A major component of this resistance is likely an impaired transport of leptin across the blood-brain barrier (BBB). The fattest subgroup of otherwise normal 12-mo-old CD-1 mice have severely impaired transport of leptin across the BBB. However, it is unknown whether these mice are born with a BBB impairment or acquire it with aging and obesity. Here, we found within an otherwise normal population of CD-1 mice that the 10% fattest mice gained weight throughout a 12-mo-life span, whereas the 10% thinnest mice gained little weight after 3 mo of age. The fattest mice acquired a progressive impairment in their ability to transport leptin across the BBB, whereas the thinnest mice had a rate of transport that did not change with age. Fasting fat mice for 24 h or treating them with leptin resulted in modest weight reduction and development of transport rates for leptin across the BBB similar to those of thin mice. These results show that, in obese CD-1 mice, the impaired transport of leptin across the BBB develops in tandem with obesity and is reversible with even modest weight reduction.

Topics: Aging; Algorithms; Animals; Biological Transport, Active; Blood-Brain Barrier; Body Weight; Capillaries; Fasting; Leptin; Male; Mice; Obesity; Weight Loss

Obesity in children is accompanied by increased circulating leptin concentrations. Girls have higher leptin concentrations than boys. The aim of our study was to compare serum leptin levels before and after a five-week weight reduction program and to study the relationship of leptin levels, serum total cholesterol, and androgens (testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate) in 33 obese boys (age: 12.7+/-1.97 years, BMI: 30.46+/-4.54) and 66 obese girls (age: 12.7+/-2.51 years, BMI: 29.31+/-4.62). We found that serum leptin concentrations in obese children were significantly decreased after a weight reduction program (before 20.79+/-9.61 ng/ml, after 13.50+/-8.65 ng/ml in girls; before 12.25+/-10.09 ng/ml and after 5.18+/-3.56 ng/ml in boys, p<0.0001 in both genders). Leptin levels correlated positively with the body mass index before and after weight reduction. There was a positive association in obese boys and a negative one in obese girls between leptin levels and the WHR (waist to hip circumference ratio). Serum leptin also shows a strong relationship to fat distribution (p=0.02 in boys, p<0.0001 in girls). No significant correlation was found between leptin concentrations and total cholesterol or androgens. We confirmed that leptin is a sensitive parameter of body composition and weight reduction in obese children.

Topics: Adolescent; Androgens; Body Composition; Body Mass Index; Child; Cholesterol; Female; Humans; Leptin; Male; Obesity; Sex Characteristics; Weight Loss

Ghrelin is a newly recognized gastric hormone with orexigenic and adipogenic properties, produced primarily by the stomach. Ghrelin is reduced in obesity. Weight loss is associated with an increase in fasting plasma ghrelin. We assessed the effect of massive weight loss on plasma ghrelin concentrations and its correlation with serum leptin levels and the presence of type 2 diabetes mellitus (DM) in severely obese patients.. A prospective study was conducted on 28 morbidly obese women (BMI 56.3 +/- 10.2 kg/m2) who underwent gastric bypass, divided into 2 groups: 14 non-diabetics (NGT) and 14 type 2 diabetics (DM2). Ghrelin and leptin were evaluated before silastic ring transected vertical gastric bypass, and again 12 months postoperatively.. Fasting plasma ghrelin concentrations were 56% lower in NGT and 59% lower in DM2 compared with a lean control group (P < 0.001). There was no difference in ghrelin levels between NGT and DM2 groups before and after surgery (P > 0.05). Ghrelin was negatively correlated with leptin before gastric bypass surgery (r = 0.51, P < 0.01). The mean plasma ghrelin concentration decreased significantly after surgery in both groups (P < 0.001).. Ghrelin was inversely related to leptin concentrations. Presence of diabetes did not affect the ghrelin pattern. Reduced production of ghrelin after gastric bypass could be partly responsible for the lack of hyperphagia and thus for the weight loss.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Ghrelin; Growth Hormone; Homeostasis; Humans; Leptin; Middle Aged; Obesity, Morbid; Peptide Hormones; Postoperative Period; Prospective Studies; Weight Loss

The absence of leptin due to the ob mutation leads to obesity and confers resistance to diet-induced cholesterol gallstone formation in otherwise susceptible C57BL/6J mice. To investigate contributions of obesity and leptin to gallstone susceptibility, C57BL/6J ob/ob mice were treated daily with i.p. saline or recombinant murine leptin at low (1 microgram/g bw) or high (10 microgram/g bw) doses and were pair-fed a lithogenic diet (15% dairy fat, 1.25% cholesterol, 0.5% cholic acid). Weight loss in ob/ob mice increased in proportion to leptin dose, indicating that the lithogenic diet did not impair leptin sensitivity. In a dose-dependent manner, leptin promoted cholesterol crystallization and gallstone formation, which did not occur in saline-treated mice. Notwithstanding, leptin decreased biliary lipid secretion rates without enriching cholesterol in bile. Leptin did not affect bile salt hydrophobicity, but did increase the biliary content of the most abundant molecular species of phosphatidylcholine, 16:0-18:2. Treatment with leptin down-regulated 3-hydroxy-3-methylglutaryl CoA reductase and prevented cholesterol from accumulating in liver. Consistent with increased hepatic clearance, leptin decreased plasma HDL cholesterol concentrations. This was accommodated in liver without up-regulation of cholesterol 7alpha-hydroxylase or Acat. These data suggest that despite the lithogenic diet, endogenous sources constitute a significant proportion of biliary cholesterol during leptin-induced weight loss. Kinetic factors related to cholesterol nucleation, gallbladder contractility, or mucin secretion may have accounted for leptin-induced gallstone formation.

Topics: Animals; Bile; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Dose-Response Relationship, Drug; Gallstones; Genetic Predisposition to Disease; Hydroxymethylglutaryl CoA Reductases; Leptin; Lipid Metabolism; Liver; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Time Factors; Triglycerides; Weight Loss

Loss of body fat by caloric restriction is accompanied by decreased circulating leptin levels, increased ghrelin levels, and increased appetite. In contrast, dietary fat restriction often decreases adiposity without increasing appetite. Substitution of dietary carbohydrate for fat has been shown to increase the area under the plasma leptin vs. time curve (AUC) over the course of 24 h. This effect, if sustained, could explain the absence of a compensatory increase in appetite on a low fat diet. To clarify the effect of dietary fat restriction on leptin and ghrelin, we measured AUC for these hormones in human subjects after each of the following sequential diets: 2 wk on a weight-maintaining 35% fat (F), 45% carbohydrate (C), 20% protein (P) diet (n = 18); 2 wk on an isocaloric 15% F, 65% C, 20% P diet (n = 18); and 12 wk on an ad libitum 15% F, 65% C, 20% P diet (n = 16). AUC for leptin was similar on the isocaloric 15% F and 35% F diets (555 +/- 57 vs. 580 +/- 56 ng/ml.24 h; P = NS). Body weight decreased from 74.6 +/- 2.4 to 70.8 +/- 2.7 kg on the ad libitum 15% F diet (P < 0.001) without compensatory increases in food consumption or AUC for ghrelin. Proportional amplitude of the 24-h leptin profile was increased after 12 wk on the 15% fat diet. We conclude that weight loss early in the course of dietary fat restriction occurs independently of increased plasma leptin levels, but that a later increase in amplitude of the 24-h leptin signal may contribute to ongoing weight loss. Fat restriction avoids the increase in ghrelin levels caused by dietary energy restriction.

Topics: Adipose Tissue; Adult; Body Composition; Circadian Rhythm; Diet, Fat-Restricted; Dietary Carbohydrates; Energy Intake; Female; Food; Ghrelin; Humans; Insulin; Leptin; Male; Middle Aged; Peptide Hormones; Weight Loss

Topiramate is currently used in the treatment of epilepsy, but this anticonvulsant drug has also been reported to exert mood-stabilizing effects and induce weight loss in patients. Neuropeptide Y (NPY) is abundantly and widely distributed in the mammalian central nervous system and centrally administered NPY markedly reduces pharmacologically induced seizures and induces antidepressant-like activity as well as feeding behavior. Two other peptides, galanin and corticotropin-releasing hormone (CRH), have also been proposed to play a modulatory role in mood, appetite, and seizure regulation. Consequently, we investigated the effects of single and repeated topiramate (10 days, once daily: 40 mg/kg i.p.) or vehicle treatment in 'depressed' flinders sensitive line (FSL) and control Flinders resistant line (FRL) rats on brain regional peptide concentrations of NPY, galanin, and CRH. The handling associated with repeated injections reduced hippocampal levels of NPY- and galanin-like immunoreactivities (LI) while NPY- and CRH-LI levels were increased in the hypothalamus, regardless of strain or treatment. In the hippocampus, concentrations of NPY-LI, galanin-LI, and CRH-LI were lower in FSL than FRL animals. Repeated topiramate treatment selectively normalized NPY-LI in this region in the FSL animals. In the hypothalamus, galanin-LI was reduced in FSL compared to FRL animals. Topiramate elevated the hypothalamic concentrations of NPY-LI, CRH-LI, and galanin-LI in both strains. Furthermore, topiramate elevated serum leptin but not corticosterone levels. The present findings show that topiramate has distinct effects on abnormal hippocampal levels of NPY, with possible implications for its anticonvulsant and mood-stabilizing effects. Furthermore, stimulating hypothalamic NPY-LI, CRH-LI and galanin-LI as well as serum leptin levels may be associated with the weight loss-inducing effects of topiramate.

Topics: Affect; Animals; Anticonvulsants; Corpus Striatum; Corticosterone; Corticotropin-Releasing Hormone; Depression; Disease Models, Animal; Drug Administration Schedule; Frontal Lobe; Fructose; Galanin; Hippocampus; Hypothalamus; Leptin; Male; Neuropeptide Y; Occipital Lobe; Radioimmunoassay; Rats; Rats, Inbred Strains; Species Specificity; Topiramate; Weight Loss

The effects of short-term (3 weeks) integrated body weight reduction (BWR) program (including energy-restricted diet, aerobic and strength exercise (5 days/week), nutritional education and psychological counseling) on plasma leptin levels and body composition were investigated in 54 morbidly obese patients (38 females/16 males; mean BMI +/- SE: 41.8 +/- 0.1 kg/m2, range 35-58 kg/m2; mean age: 29.8 +/- 1.0 yr, age range: 18-46 yr). The BWR program induced a significant (p < 0.001) weight loss (BMI reduction: -4.8%) and a significant modification in body composition, consisting in a fat mass (FM) decrease (-7.0 +/- 0.4%, p < 0.001) with a concomitant fat-free (FFM) mass increase (1.8 +/- 0.3%, p < 0.001). On average, plasma leptin levels decreased significantly both in males (from 19.4 +/- 2.6 ng/ml to 11.6 +/- 1.3 ng/ml, p < 0.001) and in females (from 41.1 +/- 3.6 ng/ml to 29.9 +/- 3.0 ng/ml, p < 0.001). Both before and after weight loss, leptin levels were positively correlated (p < 0.001) with BMI and percent fat mass (FM) values. Weight changes after the BWR program were negatively correlated with baseline leptin concentrations both in absolute terms and expressed per unit FM. In conclusion, a short-term diet plus aerobic/strength training effectively induces body composition changes and reduces plasma leptin levels. Body FM reduction appears to be not the unique determinant of leptin levels regulation and the degree of leptin over-expression may negatively affect weight loss in morbidly obese patients.

Topics: Adipose Tissue; Adult; Body Composition; Diet, Reducing; Electric Impedance; Exercise Therapy; Female; Humans; Leptin; Male; Middle Aged; Obesity; Physical Education and Training; Weight Loss

Evidence has accumulated that in both acutely ill and recovered patients with either anorexia or bulimia nervosa circulating leptin levels (LL) are lower than in controls matched for body mass index (BMI; kg/m(2)). It is unknown if these lower leptin levels represent a state or trait marker.. We aimed to confirm the lowered leptin levels in eating disordered females and to identify underlying mechanisms.. We screened 181 female students of the nutritional sciences for eating disorders with the respective module of the M-Composite International Diagnostic Interview and the Cognitive Restraint scale of the Three Factor Eating Questionnaire. The physical assessment included determinations of BMI, body composition and LL. Each case fulfilling lifetime DSM-IV criteria for an eating disorder was BMI matched to two controls. We used a multivariate mixed regression model to evaluate if the observed difference in lg(10)-leptin level between cases and controls is actually due to the influence of restrained eating and/or previous weight loss after adjustment for BMI and percent body fat.. In accordance with our hypothesis the 32 (17.7 %) cases had a lower serum lg(10)-leptin level than the 64 BMI matched controls (one-sided p < 0.001). We were not able to detect an influence of restrained eating or previous weight loss.. We confirm that females with a lifetime history of an eating disorder have lower LL. We were not able to identify an underlying mechanism. Similar to most previous studies we found a high rate of eating disorders among female students of nutritional sciences.

Topics: Adult; Anorexia Nervosa; Body Composition; Body Mass Index; Bulimia; Case-Control Studies; Feeding and Eating Disorders; Female; Humans; Leptin; Psychometrics; Regression Analysis; Weight Loss

Little is known about the determinants of individual variability in body weight and fat loss after gastric bypass surgery or about the effects of massive weight loss induced by this surgery on energy requirements.. The objectives were to determine changes in energy expenditure and body composition with weight loss induced by gastric bypass surgery and to identify presurgery predictors of weight loss.. Thirty extremely obese women and men with a mean (+/- SD) age of 39.0 +/- 9.6 y and a body mass index (BMI; in kg/m(2)) of 50.1 +/- 9.3 were tested longitudinally under weight-stable conditions before surgery and after weight loss and stabilization (14 +/- 2 mo). Total energy expenditure (TEE), resting energy expenditure (REE), body composition, and fasting leptin were measured.. Subjects lost 53.2 +/- 22.2 kg body weight and had significant decreases in REE (-2.4 +/- 1.0 MJ/d; P < 0.001) and TEE (-3.6 +/- 2.5 MJ/d; P < 0.001). Changes in REE were predicted by changes in fat-free mass and fat mass. The average physical activity level (TEE/REE) was 1.61 at both baseline and follow-up (P = 0.98). Weight loss was predicted by baseline fat mass and BMI but not by any energy expenditure variable or leptin. Measured REE at follow-up was not significantly different from predicted REE.. TEE and REE decreased by 25% on average after massive weight loss induced by gastric bypass surgery. REE changes were predicted by loss of body tissue; thus, there was no significant long-term change in energy efficiency that would independently promote weight regain.

Topics: Adult; Body Composition; Energy Metabolism; Exercise; Female; Gastric Bypass; Humans; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity; Postoperative Period; Weight Loss

Presently surgery is the most effective way to obtain a controlled weight reduction in morbidly obese patients. Roux-en-Y gastric bypass (RYGBP) surgery is effective and used worldwide, but the exact mechanism of action is unknown. The effect of RYGBP on ghrelin, insulin, adiponectin, and leptin levels was investigated in 66 obese subjects; mean weight 127 kg (range, 96-195 kg) and mean body mass index (BMI) 45 kg/m(2) (range, 33-64) before and after surgery. Ghrelin levels were also compared in 10 nonoperated and 10 operated obese, BMI-matched women. RYGBP resulted in 22% and 30% weight loss at 6 and 12 months, respectively. Ghrelin increased by 44% and 62% and adiponectin by 36% and 98%, but insulin declined by 57% and 62% and leptin by 60% and 64%. The changes were all related to the reduction in BMI. In addition, ghrelin and insulin were inversely correlated at all time points as were changes of the peptides at 12 months (F = 4.9, P = 0.031), independent of the change in BMI. No evidence for RYGBP surgery per se having an effect on ghrelin levels, independent of weight loss, was obtained. The profound changes in the regulatory peptides are likely to reflect the new state of energy balance achieved. A close inverse association between ghrelin and insulin was observed, supporting an important role for ghrelin in glucose homeostasis.

Topics: Adiponectin; Adipose Tissue; Adult; Bone Density; Female; Gastric Bypass; Ghrelin; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Obesity; Peptide Hormones; Proteins; Regression Analysis; Weight Loss

Biliopancreatic diversion (BPD), a gastrectomy with a long ROUX en Y reconstruction, reduces intestinal absorption by delaying the mixing of food and biliopancreatic juices, and induces persistent weight loss in obese patients unresponsive to medical treatments. The levels of leptin (a plasma protein synthesised in human adipose tissue) are increased in obese subjects and significantly decrease after a major weight loss. A possible role of thyroid hormones in regulating adipose tissue metabolism in humans has been proposed, but it is not universally accepted and the relationship between thyroid function and leptin levels has not yet been clearly defined. We studied serum leptin, TSH, fT4 and fT3 levels in 38 obese patients (26 women and 12 men), before and 12 months after BPD. There was a significant post-surgical decrease in BMI and circulating leptin levels in all of the treated subjects, but thyroid function did not seem to be affected (TSH and fT4 levels were unchanged). However, fT3 levels significantly decreased after surgery. Our data suggest that BPD-induced malabsorption has no direct effect on thyroid function, but possibly reduces the peripheral conversion of thyroxine to T3. Further studies seem to be necessary to clarify the clinical relevance of these observations.

Topics: Adult; Biliopancreatic Diversion; Body Mass Index; Female; Gastrectomy; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Proteins; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Time Factors; Weight Loss

To investigate the tissue factor (TF) pathway in clinical obesity and associated metabolic syndrome.. Thirty-seven morbidly obese patients (4 men; BMI, 48 +/- 7 kg/m(2); range, 42 to 53 kg/m(2)), undergoing elective gastroplasty for the induction of weight loss, were examined for hemostatic, metabolic, and inflammatory parameters at baseline and 14 +/- 5 months postoperatively.. Weight loss significantly reduced circulating plasma TF (314 +/- 181 vs. 235 +/- 113 pg/mL, p = 0.04), coagulation factor VII (130 +/- 22% vs. 113 +/- 19%, p = 0.023), and prothrombin fragment F1.2 (2.4 +/- 3.4 vs. 1.14 +/- 1.1 nM, p = 0.04) and normalized glucose metabolism in 50% of obese patients preoperatively classified as diabetic or of impaired glucose tolerance. The postoperative decrease in plasma TF correlated with the decrease of F1.2 (r = 0.56; p = 0.005), a marker of in vivo thrombin formation. In subgroup analysis stratified by preoperative glucose tolerance, baseline circulating TF (402.6 +/- 141.6 vs. 176.2 +/- 58.2, p < 0.001) and TF decrease after gastroplasty (DeltaTF: 164.7 +/- 51.4 vs. -81 +/- 31 pg/mL, p = 0.02) were significantly higher in obese patients with impaired glucose tolerance than in patients with normal glucose tolerance.. Procoagulant TF is significantly reduced with weight loss and may contribute to a reduction in cardiovascular risk associated with obesity.

Topics: Adult; Blood Glucose; Body Mass Index; C-Reactive Protein; Factor VII; Female; Gastroplasty; Glycated Hemoglobin; Humans; Insulin; Interleukin-6; Leptin; Lipoproteins; Longitudinal Studies; Male; Obesity, Morbid; Prospective Studies; Prothrombin Time; Statistics, Nonparametric; Thromboplastin; Transforming Growth Factor beta; Weight Loss

The purpose of this study was to determine changes in adiponectin levels with moderate weight loss, weight loss plus aerobic exercise, or weight loss plus resistive exercise in overweight and obese, sedentary postmenopausal women.. Longitudinal, clinical intervention study of 6-month (3 x /week) program of either weight loss (WL, n=15), weight loss + aerobic exercise (WL+AEX, n=16), or weight loss + resistive exercise (WL+RT, n=9). We studied 40 sedentary, overweight and obese (body mass index, BMI=32+/-1 kg/m(2), X+/-s.e.m.) postmenopausal (57+/-1y) women.. Fat mass and fat-free mass (FFM) by dual-energy X-ray absorptiometry, plasma insulin, leptin, and adiponectin by radioimmunoassay.. Age, body weight, BMI, waist and hip circumferences, waist-to-hip ratio, VO(2)max, percent fat, total body fat mass, FFM, and fasting plasma glucose, insulin, leptin, and adiponectin concentrations were similar among WL, WL+AEX, and WL+RT groups before the interventions. In all women combined, body weight, BMI, and waist and hip circumferences decreased (P < 0.001). There was a significant absolute decrease in percent body fat from 47 to 44%, representing a 13% decrease in total fat mass and a -1.6% change in FFM. Fasting concentrations of plasma adiponectin did not change (40+/-16%, P=NS), whereas fasting plasma glucose, insulin, and leptin all decreased (P<0.001).. Plasma adiponectin levels do not change with a 6-month moderate weight reduction program even when accompanied by aerobic or resistive exercise training in overweight and obese postmenopausal women.

Topics: Adiponectin; Adipose Tissue; Aged; Blood Glucose; Body Composition; Body Mass Index; Exercise Therapy; Female; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Longitudinal Studies; Middle Aged; Muscle, Skeletal; Obesity; Postmenopause; Proteins; Weight Loss

Leptin treatment of ob/ob mice leads to weight loss appreciably greater than that in pair-fed mice. To test whether this "extra" weight loss is mediated by leptin-induced alterations in nutrient partitioning, the effects in ob/ob mice of subcutaneous leptin infusion (500 ng/h for 0.5 vs. normal C57BL/6J controls). Adipocyte mRNA levels for plasma membrane fatty acid binding protein and fatty acid translocase, putative fatty acid transporters that are up-regulated three- to fourfold in adipocytes from ob/ob mice, had also normalized by d 21. The initial changes in V(max) preceded decreases in food intake and body weight by at least 24 h. In pair-fed mice, insulin levels, V(max) and body weight all declined more slowly than in leptin-treated mice, and all remained significantly elevated compared with normal values at d 21. The data suggest that insulin up-regulates and leptin down-regulates adipocyte fatty acid uptake, leading to alterations in fatty acid partitioning that affect adiposity.

Topics: Adipocytes; Animal Nutritional Physiological Phenomena; Animals; Aspartate Aminotransferases; Body Weight; CD36 Antigens; Cell Size; Eating; Fatty Acids; Insulin; Kinetics; Leptin; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mitochondria; Obesity; Organic Anion Transporters; Osmolar Concentration; Receptors, Leptin; RNA, Messenger; Weight Loss

To investigate whether normal glucose-tolerant and type II diabetic overweight adults differ in response to weight regain with regard to substrate oxidation and metabolic parameters.. A total of 15 overweight-obese subjects: seven normal glucose tolerant (NGT) and eight with type II diabetes (DM) were restudied 5 y after significant weight loss. Prediet, after 28 days calorie restriction and at 5 y, subjects were characterised for weight, height, waist-to-hip ratio (WHR) and body composition by dual-energy X-ray absorptiometry. Fasting glucose, insulin, leptin and lipid levels were measured and subjects underwent euglycaemic-hyperinsulinaemic clamp (insulin 0.25 U/kg/h for 150 min). Indirect calorimetry was performed resting and in the final 30 min of the clamp. Dietary assessment was by 4-day diet-diary.. Both NGT and DM groups regained weight at 5 y and were not different to prediet. Total body fat (%) and WHR were higher at 5 y compared to prediet in both groups. Fasting glucose was increased in NGT subjects at 5 y, and fasting insulin was higher in both groups at 5 y compared to prediet. Insulin sensitivity (GIR) was similar at 5 y compared to prediet, but at 5 y DM subjects were more insulin resistant than NGT subjects. At 5 y, both DM and NGT groups had significantly reduced basal fat oxidation and no significant suppression of fat oxidation with insulin. Clamp respiratory quotient levels at 5 y were significantly higher in NGT compared to DM subjects.. Reduced basal fat oxidation, and reduced variation in substrate oxidation in response to insulin develop with fat regain and fasting hyperinsulinaemia in both NGT and DM obese adults.

Topics: Adipose Tissue; Blood Glucose; Body Composition; Body Constitution; Carbohydrate Metabolism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fasting; Fatty Acids, Nonesterified; Female; Humans; Insulin; Leptin; Lipids; Male; Middle Aged; Obesity; Oxidation-Reduction; Time Factors; Weight Gain; Weight Loss

To investigate whether the changes in vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) concentrations before and after weight reduction in Japanese overweight men are associated with changes in body mass index (BMI), visceral, subcutaneous fat, VO(2) and work rate (WR) at ventilatory threshold (VT).. Cross-sectional and longitudinal clinical intervention study with exercise education.. In total, 30 Japanese overweight men (BMI, 29.0+/-2.2 kg/m(2)) and 31 normal-weight men (BMI, 22.5+/-1.6 kg/m(2)) at baseline were enrolled: 30 overweight men (BMI, 29.0+/-2.2 kg/m(2)) were further enrolled into a 6-month exercise program.. Fat distribution evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, angiogenic peptides including VEGF and bFGF, exercise tests at baseline and after 6 months.. In normal-weight and overweight subjects at baseline, VEGF positively correlated with S area (r=0.350, P=0.007) but not with V area. In contrast, bFGF negatively correlated with BMI (r=-0.619, P<0.001), S (r=-0.457, P<0.001) and V areas (r=-0.466, P<0.001). By intervention with exercise education, 30 overweight subjects showed reduction in BMI (29.0+/-2.2 to 28.0+/-2.0, P<0.001), V and S areas, increase in VO(2) and WR at VT, increase in bFGF (9.21+/-5.82-21.2+/-7.04 ng/ml, P<0.001), and no change in VEGF (1.45+/-0.72-1.88+/-0.52 ng/ml, P=0.016). The stepwise multiple regression analysis revealed that DeltaBMI (beta=-6.052) and DeltaVO(2) (beta=2.806) were independently related to DeltabFGF (P<0.001) and all other variables including DeltaS area, and DeltaV area, and DeltaWR did not enter the equation at significant levels.. The present study indicated a negative correlation between serum bFGF levels and BMI at baseline as well as an association of DeltaBMI and DeltaVO(2) with DeltabFGF after exercise intervention. The exercise-induced elevation of bFGF may be beneficial in the prevention of the atherosclerosis in overweight subjects.

Topics: Adipose Tissue; Adult; Body Composition; Body Mass Index; Cross-Sectional Studies; Endostatins; Exercise Therapy; Fibroblast Growth Factor 2; Humans; Insulin; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity; Vascular Endothelial Growth Factor A; Weight Loss

In this investigation, the feasibility of gene therapy for obesity by electroporational transfer of naked plasmid with leptin cDNA into skeletal muscle was tested. Both young and adult mice were studied.. Human leptin cDNA was attached to the human insulin precursor secretion signal peptide gene. The fused gene was then inserted into the mammalian expression vector pcDNA3.1(-) and transferred into skeletal muscle of normal female mice using electroporation.. During the time of exogenic gene expression, daily food intake of leptin cDNA-treated mice was observed to be lower than the control. The body weight gain was prevented efficaciously regardless of if they were young or adult. At the 7th week after gene transfer, the body weight of both young and adult leptin cDNA-treated mice was about 20% lighter than the control. Although the body weight of pair fed controlled adult mice was close to the leptin cDNA-treated mice at the 8th week, they were always heavier than the leptin cDNA-treated mice before this time. The levels of retroperitoneal fats and serum TG of leptin cDNA-treated mice were markedly lower than that of the control. The relative serum hyperleptinemic level could last for about 2 months. The expression of leptin cDNA in muscle cells was also detected by RT-PCR. The levels of serum insulin and glucose of leptin cDNA-treated mice decreased slightly. Our data also showed that the hyperleptinmia resulted in uterus expansion in young mice, but not in the adults.. The present study provides evidence of successful electroporation of naked plasmid DNA transfer for prevention or treatment of mice obesity.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Temperature; Disease Models, Animal; DNA, Complementary; Eating; Electroporation; Female; Gene Expression; Genetic Therapy; Humans; Insulin; Leptin; Mice; Muscle, Skeletal; Obesity; Plasmids; Radioimmunoassay; Reverse Transcriptase Polymerase Chain Reaction; Triglycerides; Weight Loss

Leptin, a hormone secreted by the adipose tissue, might be a link between obesity and increased morbidity for cardiovascular disease. Leptin exerts proinflammatory, pro-angiogenic actions by activating a specific receptor (Ob-Rb) which is expressed in human endothelial cells. Thus, a link may exist between leptin expression and endothelial dysfunction.. We sought to determine whether in obese women there is a correlation between leptin levels, endothelial perturbation and coagulative activation.. Circulating levels of leptin, von Willebrand Factor (VWF), factor (F)VIIa, prothrombin fragment 1 + 2 (F1+2), were measured in 51 non-diabetic, obese women and in 51 normal-weight subjects, using immunoenzymatic assays.. Obese women had significantly higher levels of leptin, VWF, FVIIa, F1+2 compared with healthy women. Simple correlation coefficients showed significant correlation between leptin and either VWF, FVIIa, or F1+2 concentrations. A multiple linear regression analysis, performed to quantify further the relationship between leptin levels and the above-mentioned variables as well as the inflammatory marker C-reactive protein (CRP) and including age, body mass index (BMI), waist-hip ratio (WHR) and lipid parameters as potential confounders, revealed that only FVIIa and VWF were independently related to leptin levels. Reduction in adipose tissue after weight loss resulted in a decrease in both circulating leptin and endothelial and coagulative activation markers.. We suggest that leptin might have pro-atherogenic effects in vivo, with a mechanism involving endothelial cell activation.

Topics: Adult; Anthropometry; Biomarkers; Blood Coagulation; Case-Control Studies; Endothelium, Vascular; Female; Hemostasis; Humans; Inflammation; Leptin; Middle Aged; Obesity; Thrombophilia; Weight Loss

Progression of breast cancer involves cross-talk between epithelial and stromal cells. This cross-talk is mediated by growth factors and cytokines secreted by both cancer and stromal cells. We previously reported expression of interleukin (IL)-1 alpha in a subset of breast cancers and demonstrated that IL-1 alpha is an autocrine and paracrine inducer of prometastatic genes in in vitro systems. To understand the role of IL-1 alpha in breast cancer progression in vivo, we studied the growth of MCF-7 breast cancer cells overexpressing a secreted form of IL-1 alpha (MCF-7IL-1 alpha) in nude mice. MCF-7IL-1 alpha cells formed rapidly growing estrogen-dependent tumors compared to parental cells. Interestingly, IL-1 alpha expression alone was not sufficient for metastasis in vivo although in vitro studies showed induction of several prometastatic genes and matrix metalloproteinase activity in response to cross-talk between IL-1 alpha-expressing cancer cells and fibroblasts. Animals implanted with MCF-7IL-1 alpha cells were cachetic, which correlated with increased leptin serum levels but not other known cachexia-inducing cytokines such as IL-6, tumor necrosis factor, or interferon gamma. Serum triglycerides, but not blood glucose were lower in animals with MCF-7IL-1 alpha cell-derived tumors compared to animals with control cell-derived tumors. Cachexia was associated with atrophy of epidermal and adnexal structures of skin; a similar phenotype is reported in triglyceride-deficient mice and in ob/ob mice injected with leptin. Mouse leptin-specific transcripts could be detected only in MCF-7IL-1 alpha cell-derived tumors, which suggests that IL-1 alpha increases leptin expression in stromal cells recruited into the tumor microenvironment. Despite increased serum leptin levels, animals with MCF-7IL-1 alpha cell-derived tumors were not anorexic suggesting only peripheral action of tumor-derived leptin, which principally targets lipid metabolism. Taken together, these results suggest that cancer cell-derived cytokines, such as IL-1 alpha, induce cachexia by affecting leptin-dependent metabolic pathways.

Topics: Animals; Cachexia; Cell Division; Cell Line, Tumor; Female; Fibroblasts; Humans; Interleukin-1; Leptin; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Neoplasm Transplantation; Peptides; RNA, Messenger; Severity of Illness Index; Skin Diseases; Transplantation, Heterologous; Weight Loss

A gastric pacemaker has been developed to treat morbid obesity. Patients experience increased satiety, the ability to reduce food intake, and a resultant weight loss. However, the mechanism behind the changed eating behavior in paced patients is still under investigation.. This study was performed on 11 morbidly obese patients (mean BMI, 46.0 kg/m2) treated with gastric pacing. The peripheral blood levels of satiety signals of cholecystokinin (CCK), somatostatin, glucagon-like peptide-1 (GLP-1), and leptin were studied 1 month before gastric pacer implantation, 1 month after implantation, and 6 months after activation of electrical stimulation. Blood samples were drawn 12 hours after fasting and in response to a hypocaloric meal (270 kcal). Patients were followed monthly for vital signs and weight level.. Gastric pacing resulted in a significant weight loss of a mean of 10.4 kg (4.4 BMI units). No negative side effects or complications were observed during the treatment. After activation of the pacemaker, meal-related response of CCK and somatostatin and basal levels of GLP-1 and leptin were significantly reduced (p < 0.05) compared with the tests before gastric pacing. The weight loss correlated significantly with a decrease of leptin levels (R = 0.79, p < 0.01).. Gastric pacing is a novel and promising therapy for morbid obesity. Activation of the gastric pacer was associated with a decrease in plasma levels of CCK, somatostatin, GLP-1, and leptin. More studies are necessary to elucidate the correlations between satiety, weight loss, and digestive neuro-hormone changes.

Topics: Adult; Cholecystokinin; Electric Stimulation Therapy; Female; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Leptin; Male; Obesity, Morbid; Peptides; Satiation; Somatostatin; Stomach; Weight Loss

Leptin, produced by adipose tissue, signals body fat content to the hypothalamus. Serum leptin levels (SLL), elevated in obese humans, decrease with weight loss. This study investigated the reduction of SLL and fat mass following restrictive bariatric surgery.. Obese subjects (body mass index [BMI] >35 kg/m2, n=154) undergoing gastric banding (weight-reduced subjects) were investigated for SLL and body composition before surgery and for 2 years after. Overweight subjects matched for fat mass and gender (fat mass-matched overweight controls, n=194) and subjects who had never been obese (normal weight controls, n=158) were studied for comparison.. SLL were highest in weight-reduced subjects and decreased with weight loss (P <0.001), remaining elevated compared with normal weight controls (P <0.001) but lower than fat mass-matched overweight controls (women: P <0.04). At 2 years, SLL normalized for fat mass (allowing comparison between various levels of adiposity) were lower in weight-reduced subjects compared with fat mass-matched overweight controls (women: P =0.003), yet were similar for weight-reduced subjects at 2 years compared with normal weight controls despite 14 kg greater fat mass. Relative lean mass of extremities in weight-reduced subjects increased with weight loss (P <0.001).. SLL decreased after considerable weight loss more than could be accounted for by fat mass or BMI reduction alone. This disproportionate decrease in SLL might point to a mechanism that evolved as adaptation to starvation during times of famine. Thus, post-obese subjects may be at risk of weight-regain due to disproportionately low SLL and increased appetite via the leptin-melanocortin pathway.

Topics: Adult; Body Composition; Female; Gastroplasty; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Weight Loss

Leptin administration to obese C57BL/6J (ob/ob) mice results in weight loss by reducing body fat. Because adipose tissue is an important storage depot for cholesterol, we explored evidence that leptin-induced weight loss in ob/ob mice was accompanied by transport of cholesterol to the liver and its elimination via bile. Consistent with mobilization of stored cholesterol, cholesterol concentrations in adipose tissue remained unchanged during weight loss. Plasma cholesterol levels fell sharply, and microscopic analyses of gallbladder bile revealed cholesterol crystals as well as cholesterol gallstones. Surprisingly, leptin reduced biliary cholesterol secretion rates without affecting secretion rates of bile salts or phospholipids. Instead, cholesterol supersaturation of gallbladder bile was due to marked decreases in bile salt hydrophobicity and not to hypersecretion of biliary cholesterol per se, such as occurs in humans during weight loss. In addition to regulating bile salt composition, leptin treatment decreased bile salt pool size. The smaller, more hydrophilic bile salt pool was associated with substantial decreases in intestinal cholesterol absorption. Within the liver, leptin treatment reduced the activity of 3-hydroxy-3-methylglutaryl-CoA reductase, but it did not change activities of cholesterol 7alpha-hydroxylase or acyl-CoA:cholesterol acyltransferase. These data suggest that leptin regulates biliary lipid metabolism to promote efficient elimination of excess cholesterol stored in adipose tissue. Cholesterol gallstone formation during weight loss in ob/ob mice appears to represent a pathologic consequence of an adaptive response that prevents absorption of biliary and dietary cholesterol.

Topics: Animals; Bile; Bile Acids and Salts; Cholesterol; Cholesterol, HDL; Cholesterol, VLDL; Enterohepatic Circulation; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Weight Loss

Leptin elicits a metabolic response that cannot be explained by its anorectic effects alone. To examine the mechanism underlying leptin's metabolic actions, we used transcription profiling to identify leptin-regulated genes in ob/ob liver. Leptin was found to specifically repress RNA levels and enzymatic activity of hepatic stearoyl-CoA desaturase-1 (SCD-1), which catalyzes the biosynthesis of monounsaturated fatty acids. Mice lacking SCD-1 were lean and hypermetabolic. ob/ob mice with mutations in SCD-1 were significantly less obese than ob/ob controls and had markedly increased energy expenditure. ob/ob mice with mutations in SCD-1 had histologically normal livers with significantly reduced triglyceride storage and VLDL (very low density lipoprotein) production. These findings suggest that down-regulation of SCD-1 is an important component of leptin's metabolic actions.

Topics: Animals; Body Weight; Crosses, Genetic; Down-Regulation; Eating; Energy Metabolism; Female; Gene Expression; Gene Expression Profiling; Leptin; Lipid Metabolism; Lipids; Lipoproteins, VLDL; Liver; Male; Mice; Mice, Obese; Microsomes, Liver; Mutation; Oligonucleotide Array Sequence Analysis; Oxygen Consumption; RNA, Messenger; Stearoyl-CoA Desaturase; Vacuoles; Weight Loss

Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known enzymes that catalyze the final step in mammalian triglyceride synthesis. We have reported that DGAT1-deficient mice have increased insulin and leptin sensitivity, likely accounting for their protection against diet-induced obesity and insulin resistance. Here we show that DGAT1 deficiency enhanced the response to peripheral leptin infusion in Agouti yellow and leptin-deficient (ob/ob) mice, two genetic models of obesity and insulin resistance. Interestingly, DGAT1 deficiency did not enhance the response to intracerebroventricular leptin infusion. Moreover, DGAT1 deficiency did not alter the expression of key hypothalamic genes involved in leptin signaling or in the regulation of food intake and energy expenditure. Thus, the leptin-sensitizing effect of DGAT1 deficiency is present in both leptin-resistant and leptin-deficient genetic models of obesity and may occur in part by enhancing the effects of leptin in peripheral tissues.

Topics: Acyltransferases; Animals; Diacylglycerol O-Acyltransferase; Disease Models, Animal; Hypothalamus; Leptin; Mice; Mice, Inbred C57BL; Obesity; Weight Loss

Increased cholesterol secretion is a major alteration of biliary function in obese subjects Leptin is a regulator of food intake and is increased in plasma of subjects with low energy expenditure and high adiposity. We investigated the relationship between leptin and the cholesterol saturation of bile in obese women before and after weight reduction by energy restriction (5.02 MJ/d). We studied women (n = 14) with a body mass index (BMI) > or = 30 kg/m(2) who were 35.4 +/- 2.3 y old and who did not have a history of gallstones. They were studied by ultrasound to ensure absence of stones or sludge. BMI, gallbladder bile composition, plasma leptin, serum lipids and lipoproteins cholesterol levels were recorded at baseline and after 6 wk of weight reduction. There were decreases in BMI (33.9 +/- 3.1 to 31.1 +/- 3.6 kg/m(2), P < 0.0001) and leptin levels (16.7 +/- 9.7 to 10.0 +/- 6.7 micro mol/L, P < 0.05) during weight loss. After the experimental period, there were positive correlations between plasma leptin levels and BMI (r = 0.71, P < 0.004); leptin levels and the cholesterol saturation index (CSI) (r = 0.53, P < 0.05); the CSI and LDL cholesterol (r = 0.73, P < 0.003); and negative correlations between leptin levels and HDL cholesterol (r = -0.54, P < 0.05) and LDL cholesterol (r = -0.57, P < 0.03). We have shown relationships among HDL cholesterol, CSI and leptin. This could be useful in understanding the pathophysiology of cholesterol gallstone formation in obese people.

Topics: Adult; Bile; Biomarkers; Body Mass Index; Cholelithiasis; Cholesterol; Female; Humans; Leptin; Lipids; Lipoproteins; Middle Aged; Obesity; Risk Factors; Weight Loss

To determine the influence of weight loss on multiple cardiovascular disease (CVD) risk factors.. Overweight women (n = 12; mean 44.2% fat) and men (n = 10; mean 30.7% fat) participated in an 8 week weight-loss program that included dietary, exercise, multi-vitamin/mineral supplementation, and behavior modification components. Measurement of total and regional body composition assessed using dual energy X-ray absorptiometry (DEXA), circumferences and blood sampling for total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols, homocysteine, insulin and leptin were performed before and after the weight loss intervention.. Subjects increased their physical activity and decreased their energy intake, resulting in a mean decrease in body mass of - 4.3 +/- 3.4 kg in women and -4.7 +/- 3.1 kg in men. Fat accounted for 88 and 58% of the decrease in body mass in men and women, respectively. Proportionally, men lost significantly more fat mass from the trunk region compared to women. Serum total and LDL cholesterol were significantly decreased in men (-11 and -14%, respectively) but not women (-3 and -3%, respectively) and there were no changes in HDL cholesterol and triacylglycerols. Serum leptin was significantly decreased (-36%) and highly correlated to fat mass (r= 0.839). There were no changes in serum insulin and plasma homocysteine.. These data indicate that short-term weight loss resulting from reducing percentage energy from fat, increasing physical activity and vitamin/mineral supplements including folic acid has a favorable effect on regional body composition and total and LDL cholesterol with minimal effects on HDL cholesterol, triacylglycerols, homocysteine and insulin and the effects are greater in men compared to women. Supplementation with folic acid or emphasis on folic acid-rich foods may be an important component of a weight loss program to prevent increases in homocysteine.

Topics: Absorptiometry, Photon; Adult; Body Composition; Body Constitution; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Energy Intake; Exercise; Female; Folic Acid; Homocysteine; Humans; Insulin; Leptin; Lipids; Male; Obesity; Risk Factors; Sex Factors; Weight Loss

Topics: Biomarkers; Body Mass Index; Clinical Trials as Topic; Coronary Disease; Electrocardiography; Humans; Leptin; Obesity, Morbid; Predictive Value of Tests; Risk Factors; Scotland; Weight Loss

Transforming growth factor-beta1 (TGF-beta1) has been demonstrated to be overexpressed in hypertension. Leptin, an adipocyte product, has been shown to play a role in obesity-related hypertension and in vitro studies demonstrated a biologic interaction between leptin and TGF-beta1. Thus, we evaluate a possible in vivo association between TGF-beta1, body mass index (BMI), and leptin circulating levels in hypertensive subjects.. Blood samples for fasting leptin and TGF-beta1, were evaluated in 29 overweight, 46 obese, and 29 nonobese hypertensive patients before and after a 12-week calorie-restricted diet. Monocyte cultures were used for in vitro experiments.. Transforming growth factor-beta1 was significantly elevated in hypertensive obese patients (n = 46) as compared with TGF-beta1 levels of hypertensive patients with normal BMI (n = 29) (8. 9 +/- 3 ng/mL v 4.4 +/- 2; P < .001). The circulating levels of TGF-beta1 were associated with BMI and leptin levels in an univariate analysis (r = 0.59, P < .0001; r = 0.62, P < .0001, respectively) and these associations were still present after stepwise multivariate analysis. Weight loss of 10% produced a parallel decrease in TGF-beta1 (from 8.9 +/- 3 ng/mL to 5.3 +/- 2.8 ng/mL; P < .01) and leptin levels (from 30 +/- 24 ng/mL to 17 +/- 14; P < .05). In vitro experiments showed that leptin is able to induce a dose-dependent increase in TGF-beta1 production and mRNA expression in human monocyte cultures.. Our data indicate that TGF-beta1 levels are positively associated with BMI and leptin levels in hypertensive patients and suggest that adipose tissue may be an important determinant of TGF-beta1 levels possibly by a leptin-dependent pathway.

Topics: Adult; Blood Pressure; Body Mass Index; Female; Gene Expression; Humans; Hypertension; In Vitro Techniques; Leptin; Male; Middle Aged; Obesity; Regression Analysis; RNA, Messenger; Transforming Growth Factor beta; Weight Loss

Little is known about changes in thyroid function in obese children. An influence of leptin on thyroid hormone synthesis has been proposed.. To examine thyroid function and leptin concentrations in obese children.. Triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), and leptin were measured in 118 obese children (aged 4.5-16 years); thyroid function was also determined in 107 healthy children of normal weight. T3, T4, and TSH were analysed in 55 obese children who had achieved weight reduction and in 13 obese children who had not achieved weight reduction after one year based on normal energy diet.. TSH, T3, and T4 were significantly higher in obese children compared to those of normal weight. Twelve per cent of the obese children had TSH, 15% had T3, and 11% had T4 concentrations above the twofold standard deviation of normal weight children. The degree of overweight correlated with T3, T4, and TSH. Thyroid hormones did not correlate significantly with leptin. A reduction in overweight showed a significant decrease in T3, T4, and leptin serum concentrations, but there was no significant change in TSH.. Peripheral thyroid hormones (T3, T4) and TSH are moderately increased in obese children; weight reduction leads to a long term decrease in the peripheral thyroid hormones but not in TSH. There is no necessity to treat the increased serum TSH.

Topics: Adolescent; Body Mass Index; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Leptin; Male; Obesity; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Weight Loss

To determine the relationship between leptin and unintentional weight loss in older adults.. Prospective cohort study over 2 years.. University-affiliated Veterans Affairs Medical Center.. The subjects were 105 community-dwelling male veterans aged 65 and older who had participated in a prospective cohort study on nutrition and health conducted at the Veterans Affairs Puget Sound Health Care System from 1986 to 1989.. Anthropometric data and fasting blood specimens were collected at baseline and annually for the subsequent 2 years. Stored blood specimens were analyzed for leptin, insulin, glucose, C-reactive protein, sex hormone binding globulin, and testosterone levels.. Over 2 years, 75 men were weight stable (weight loss <4% of baseline) and 30 men had unintentional weight loss (weight loss>4% of baseline). The baseline body mass index (BMI) and leptin levels for the two groups were not statistically different. Positive correlations existed between leptin level and BMI at each time point for weight-stable and weight-loss subjects. Furthermore, a significant relationship existed between changes in leptin and changes in BMI over 1 year in multiple regression analysis (r =.436, P <.001 after the first year; and r =.630, P =.027 after the second year).. Like in younger adults, plasma leptin levels remained proportional to BMI, and changes in BMI were accurately reflected by changes in leptin levels in older individuals. Fasting leptin levels did not predict involuntary weight loss over 2 years of follow-up.

Topics: Aged; Blood Glucose; Body Mass Index; C-Reactive Protein; Cohort Studies; Humans; Insulin; Leptin; Male; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone; Weight Loss

The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for the existence of multiple physiological functions of this hormone in rodents. In contrast, information regarding the roles of this hormone in humans is limited. Three morbidly obese children, who were congenitally deficient in leptin, were treated with daily subcutaneous injections of recombinant human leptin for up to 4 years with sustained, beneficial effects on appetite, fat mass, hyperinsulinemia, and hyperlipidemia. Leptin therapy resulted in a rapid and sustained increase in plasma thyroid hormone levels and, through its age-dependent effects on gonadotropin secretion, facilitated appropriately timed pubertal development. Leptin deficiency was associated with reduced numbers of circulating CD4(+) T cells and impaired T cell proliferation and cytokine release, all of which were reversed by recombinant human leptin administration. The subcutaneous administration of recombinant human leptin has major and sustained beneficial effects on the multiple phenotypic abnormalities associated with congenital human leptin deficiency.

Topics: Animals; Child; Child, Preschool; Energy Metabolism; Female; Humans; Leptin; Lymphocyte Activation; Mice; Neurosecretory Systems; Obesity; Phenotype; Recombinant Proteins; T-Lymphocytes; Weight Loss

Obesity-related insulin resistance is closely associated with visceral fat accumulation. Several adipocyte-secreted molecules have been implicated in the development of type 2 diabetes, among them, the recently discovered adiponectin and resistin proteins. Some of these adipocytokines are also present in the immune system, thus suggesting an intriguing functional connection.. We determined adiponectin and resistin expressions in visceral (VAT) and subcutaneous adipose tissue of lean and obese Zucker (fa/fa) rats using reverse-transcription polymerase chain reaction. Moreover, we analyzed the variations after body-weight reduction in food-restricted obese rats.. Resistin and adiponectin expression was significantly lower in VAT of genetically obese in comparison with lean rats; no differences were observed when subcutaneous adipose tissues of the same animals were compared. Weight loss resulted in an increase of adiponectin expression in VAT, whereas a further significant decrease in resistin mRNA level was observed. Resistin is also present and equally expressed in splenocytes of lean and obese rats.. Adiponectin and resistin are down-regulated in VAT of obese rats. Adiponectin expression is restored to normal levels after body-weight reduction, supporting its link with obesity-related insulin resistance. On the contrary, the further decrease of resistin mRNA after weight loss does not support the hypothesis that resistin may play a causative role in insulin resistance in obese rats. Moreover, we demonstrated the presence of resistin in immunocompetent cells in both humans and rats, thus adding another factor to the list of molecules that adipose tissue shares with the immune system.

Topics: Adiponectin; Adipose Tissue; Animals; Fatty Acids, Nonesterified; Gene Expression; Hormones, Ectopic; Humans; Immunocompetence; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Leukocytes, Mononuclear; Male; Nerve Growth Factor; Obesity; Proteins; Rats; Rats, Zucker; Resistin; RNA, Messenger; Spleen; Viscera; Weight Loss

The prospective, cross-sectional study was undertaken to evaluate the relation between the fat mass and serum leptin level in patients with rheumatoid arthritis (RA). Low body mass and anorexia are commonly found in patients with RA. Inflammatory cytokines may significantly influence the secretion of anorectic hormone--leptin--that was confirmed in both experimental and clinical studies. Fifty-two non-diabetic and non-obese patients (38 females, 14 males) were studied. Mean age was 56 +/- 11 years and mean body mass index (BMI) 24.6 +/- 4.1 kg/m2. The disease activity score (DAS) was 3.9 +/- 1.4; range 1.4-7.4, and disease duration 8.1 +/- 6.7 years. Serum leptin was measured by ELISA and body composition by double X-ray densitometry. Mean serum leptin concentration was 2.8 +/- 1.4 ng/ml in patients with RA was lower than in the control group (4.2 +/- 2.0). In a simple regression analysis leptin did not correlate with BMI (R Spearman = 0.01), C-reactive protein (R = 0.08), total fat mass (R = 0.08), trunk fat (R = 0.05), limbs fat (R = 0.09) and DAS (R = -0.17). This relation was also not influenced by gender or type of immunosuppressive therapy. In a multiple regression model none of the independent variables explained the significant portion of variance of serum leptin. It is concluded that the physiologic relation of serum leptin to body fat stores is not present in patients with RA.

Topics: Aged; Arthritis, Rheumatoid; Body Composition; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Middle Aged; Prospective Studies; Regression Analysis; Risk Factors; Weight Loss

Insulin resistance is thought to raise blood pressure. Recently, a significant positive relationship between mean blood pressure and plasma leptin levels, but there have been no reports dealing with the relationship between blood pressure and either insulin resistance or serum leptin levels after weight loss. In the present work, we attempted to clarify the relationship between changes in blood pressure and either the serum leptin level or the insulin level in 102 moderately obese females (mean body mass index (BMI), 29.5 +/- 0.5 kg/m2; age, 47.0 +/- 0.9) during a 3 month period. No differences in age, fat-mass, homeostasis model assessment (HOMA), the summation of insulin (sigmaIRI), plasma renin activity (PRA) or 24 h norepinephrine excretion (24hU-NE) were observed between the hypertensive (HT) group (n = 31) and normotensive (NT) group (n = 71) before weight loss, but the basal serum leptin was significantly higher in the HT (16.8 +/- 1.1 ng/ml) than in the NT group (15.2 +/- 0.8 ng/ml), after adjusting for abdominal total fat. After a 3 month weight reduction program, the total abdominal fat, serum leptin and sigmaIRI significantly decreased in both groups. The systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from 144/84 to 130/77 mmHg only in the HT but not in the NT group. The PRA decreased in both groups, while the 24hU-NE significantly decreased only in the HT group. The changes in the leptin level were significantly correlated with the changes in both sigmaIRI and HOMA after weight loss in the two groups, respectively. Finally, a statistically significant positive correlation was observed between the changes in the leptin and the changes in the mean blood pressure (MBP) (r = 0.412, p < 0.05) only in the HT group. Multiple regression analysis revealed that the changes in MBP were independently associated with the changes in 24hU-NE and the changes in either sigmaIRI or HOMA in all subjects. However, a statistically significant positive correlation was observed between the changes in MBP and the changes in leptin levels even after adjusting for the total abdominal fat, 24hU-NE and either sigmaIRI or HOMA (both expressed as a percentage of the baseline value) in a multiple regression analysis only in the HT group. These results suggest that leptin may play a role in the pathophysiology of obese hypertension.

Topics: Abdomen; Adipose Tissue; Blood Pressure; Body Mass Index; Female; Homeostasis; Humans; Insulin; Leptin; Male; Middle Aged; Norepinephrine; Obesity; Osmolar Concentration; Reference Values; Weight Loss

At present, obesity is considered one of the major health problems. It is a predisposing factor of several chronic diseases including non-insulin dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD). Leptin levels in humans have been found to be highly correlated with total adiposity. We performed statistic analysis in order to identify linkage between leptin levels and anthropometric parameters in a group of 285 Czech obese children (152 girls and 133 boys) aged 7 to 18 years. The children were measured using the standard anthropometric technique according to Martin and Saller [16] at the beginning and end of a five-week therapeutic weight reduction programme. The skin fold thickness at 14 sites was assessed by means of Best calliper. The body composition was evaluated using Matiegka's technique. The leptin levels were investigated on the beginning and end of the reduction programme by direct enzyme linked immunosorbent assay (ELISA). For the evaluation of the grade of obesity, body weight, BMI (body mass index), RI (Rohrer's index), FMI (fat mass index) and normalized body weight, normalized BMI and RI were plotted. Correlation analysis shows relation between leptin concentration and FMI to be the most significant. As to ponderal indexes, normalized RI shows the most significant positive correlation. Leptin concentrations are negatively correlated with the proportion of the weight of skeletal muscles by Matiegka both in girls and boys. Intersexual differences in correlations between leptin concentrations and normalized circumferences are observed, as well as in correlations between leptin and particular skin fold thickness. We also tested relations between the magnitude of leptin decreases and magnitude of decreases of anthropometric parameters. There is a strong endorsement both in girls and boys of positive correlation between decrease of leptin concentration and fat reduction. Interestingly, differences between boys and girls in relations between leptin decrease and change in lean body mass had been observed.

Topics: Adolescent; Anthropometry; Body Composition; Body Mass Index; Child; Female; Humans; Leptin; Male; Obesity; Weight Loss

Acute release of corticotropin-releasing factor (CRF) during repeated restraint (3-h restraint on each of 3 days) causes temporary hypophagia but chronic suppression of body weight in rats. Here we demonstrated that a second bout of repeated restraint caused additional weight loss, but continuing restraint daily for 10 days did not increase weight loss because the rats adapted to the stress. In these two studies serum leptin, which suppresses the endocrine response to stress, was reduced in restrained rats. Peripheral infusion of leptin before and during restraint did not prevent stress-induced weight loss, although stress-induced corticosterone release was suppressed. Restrained rats were hyperthermic during restraint, but there was no evidence that fever or elevated free interleukin-6 caused the sustained reduction in weight. Restraining food-restricted rats caused a small but significant weight loss. Food-restricted rats fed ad libitum after the end of restraint showed a blunted hyperphagia and slower rate of weight regain than their controls. These results indicate that repeated acute stress induces a chronic change in weight independent of stress-induced hypophagia and may represent a change in homeostasis initiated by repeated acute activation of the central CRF system.

Topics: Animals; Body Temperature; Corticosterone; Corticotropin-Releasing Hormone; Eating; Energy Intake; Energy Metabolism; Feedback, Physiological; Leptin; Male; Rats; Rats, Wistar; Restraint, Physical; Stress, Physiological; Weight Loss

Obesity is a frequent cause of insulin resistance and poses a major risk for diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. We tested the hypothesis that dietary lipid deprivation may selectively deplete intramyocellular lipids, thereby reversing insulin resistance. Whole-body insulin sensitivity (by the insulin clamp technique), intramyocellular lipids (by quantitative histochemistry on quadriceps muscle biopsies), muscle insulin action (as the expression of Glut4 glucose transporters), and postprandial lipemia were measured in 20 morbidly obese patients (BMI = 49 +/- 8 [mean +/- SD] kg x m(-2)) and 7 nonobese control subjects. Patients were restudied 6 months later after biliopancreatic diversion (BPD; n = 8), an operation that induces predominant lipid malabsorption, or hypocaloric diet (n = 9). At 6 months, BPD had caused the loss of 33 +/- 10 kg through lipid malabsorption (documented by a flat postprandial triglyceride profile). Despite an attained BMI still in the obese range (39 +/- 8 kg x m(-2)), insulin resistance (23 +/- 3 micromol/min per kg of fat-free mass; P < 0.001 vs. 53 +/- 13 of control subjects) was fully reversed (52 +/- 11 micromol/min per kg of fat-free mass; NS versus control subjects). In parallel with this change, intramyocellular-but not perivascular or interfibrillar-lipid accumulation decreased (1.63 +/- 1.06 to 0.22 +/- 0.44 score units; P < 0.01; NS vs. 0.07 +/- 0.19 of control subjects), Glut4 expression was restored, and circulating leptin concentrations were normalized. In the diet group, a weight loss of 14 +/- 12 kg was accompanied by very modest changes in insulin sensitivity and intramyocellular lipid contents. We conclude that lipid deprivation selectively depletes intramyocellular lipid stores and induces a normal metabolic state (in terms of insulin-mediated whole-body glucose disposal, intracellular insulin signaling, and circulating leptin levels) despite a persistent excess of total body fat mass.

Topics: Adult; Body Mass Index; Diet, Reducing; Female; Gastrectomy; Humans; Insulin Resistance; Leptin; Lipid Metabolism; Male; Muscle, Skeletal; Obesity, Morbid; Postprandial Period; Reference Values; Weight Loss

The present study was conducted in order to analyze the relationship existing between leptin, insulin and neuropeptide Y (NPY) levels in massive weight loss and weight recovery. Twenty-three patients with severe obesity, 23 patients with anorexia nervosa and 28 healthy control subjects were studied. Patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet during 16 weeks, with evaluation taking place before (Body mass index, BMI, 52,1 8 Kg/m2) and after the drastic weight loss (BMI 39,2 6,2 Kg/m2). Patients with anorexia nervosa were treated with nutritional therapy exclusively during 16 weeks, and they were evaluated in the low weight situation (BMI 15,3 1,7 Kg/m2) and after weight recovery (BMI 18,9 2,8 Kg/m2). Normal subjects had a normal BMI from 20 to 27 (average 21,8 2 Kg/m2). BMI, percentage of body fat, and serum levels of leptin, insulin, and NPY, were determined in each patient and normal subjects. In severe obese patients serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 48,8 19,2 to 24,3 9,8 ng/ml; insulin: from 26,2 10,8 to 18 6 U/ml). In patients with anorexia nervosa serum leptin mean levels were significantly higher after weight recovery (3,7 1,9 vs 9,2 5,1 ng/ml). In subjects with morbid obesity NPY levels decreased after weight loss below those of control group (43,5 16,1 vs 57,3 12,8 pmol/l). On the other hand, patients with anorexia nervosa had NPY levels superior to those of control group. In subjects with anorexia, NPY levels decreased after weight recovery (69,1 16,7 a 59,1 20,3 pmol/l). In the whole population, Leptin and NPY plasma levels were correlated with body fat percentage. Leptin was positively correlated with BMI and body fat percentage in obese and anorectic subjects after weight loss or recovery, respectively. NPY was inversely correlated with body fat percentage in controls and obese subjects before treatment. These data reveal that the concentration of serum leptin and NPY correlates significantly with the total adiposity in subjects with a wide weight range and caloric intake. Leptin plasma levels are proportional to fat stores in patients with severe obesity and anorexia nervosa after drastic weight loss or recovery, respectively. NPY serum levels are negatively correlated with de total body fat in normal weight subjects and obese patients in their initial weight.

Topics: Adult; Anorexia Nervosa; Anthropometry; Body Composition; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Female; Gastroplasty; Humans; Insulin; Leptin; Male; Middle Aged; Neuropeptide Y; Obesity, Morbid; Radioimmunoassay; Recurrence; Weight Gain; Weight Loss

To examine the effects of a cafeteria diet and a chronic treatment with melanocortin agonist (MTII) on mature weight-stable female rats.. Ex-breeder Chbb:Thom rats (350 to 400 g) were divided into two groups: highly palatable food (HPF) and normal rat chow (RC). Both groups had ab libitum access to rat chow. The HPF group had access to chocolate bars, cookies, cheese, and nuts (approximately 20 g/d). After 21 days, the rats in each group were then divided into control and treated groups. Mini-pumps delivering saline or MTII (1 mg/kg per day) for minimally 28 days were implanted. Oxygen consumption was measured for 17 days in a second group of rats implanted with mini-pumps containing MTII (1 mg/kg per day) or saline.. HPF rats ate less (<50%) rat chow than RC rats. After 20 days, the HPF group had reached a plateau and weighed significantly more (p < 0.005) than the RC group (411.7 +/- 9.3 g; n = 17 vs. 365.1 +/- 9.4 g; n = 16). HPF rats and RC rats receiving MTII reduced their pellet intake and body weight in the initial 2 weeks of treatment (day 14, RC-saline: -1.6 +/- 1.8 g; RC-MTII, -22.5 +/- 3.7 g; HPF-saline, -7.1 +/- 1.7 g; HPF-MTII, -30.7 +/- 4.8 g). Subsequently, pellet intake returned to pre-implantation values, although body weights remained reduced in both HPF and RC groups. Oxygen consumption was increased in rats treated with MTII.. This suggests that MTII initially reduced body weight by limiting food intake; however, maintenance of weight is most likely due to increased energy expenditure under conditions of normal and highly palatable diets in mature animals.

Topics: alpha-MSH; Animals; Blood Glucose; Calorimetry, Indirect; Disease Models, Animal; Eating; Female; Insulin; Leptin; Male; Obesity; Oxygen Consumption; Rats; Triglycerides; Weight Loss

To investigate whether the changes in IGF-I concentrations after weight reduction in Japanese overweight men are associated with changes in visceral and subcutaneous fat.. Cross-sectional and longitudinal clinical intervention study with exercise education.. One-hundred and twelve Japanese overweight men aged 30-59 y (body mass index (BMI) 28.4+/-2.5 kg/m(2)) and 33 normal-weight men aged 30-39 y (BMI 22.1+/-1.5 kg/m(2)) at baseline. From the participants, 56 randomly selected overweight men (BMI 28.8+/-2.8) were further enrolled into a 1 y exercise program.. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, metabolic parameters and hormones including insulin, leptin and IGF-I at baseline and after 1 y.. In 112 overweight subjects at baseline, insulin (10.5+/-5.0 microU/ml) and leptin (6.4+/-3.7 ng/ml) significantly correlated with both V (r=0.260, P=0.0073; r=0.410, P<0.0001) and S areas (r=0.377, P<0.0001; r=0.613, P<0.0001), respectively. IGF-I (156.8+/-48.7 microU/ml) significantly and negatively correlated with V area (r=-0.242, P=0.0125) and age (r=-0.192, P=0.0480). In normal-weight men aged 30-39 y (n=33) and age-matched subjects (n=30) selected from the 112 overweight men, the serum IGF-I further tightly correlated with V area (r=-0.467, P<0.0001). Visceral fat area and age were independently related to serum IGF-I levels by multiple regression analysis. By intervention with exercise education, 56 overweight subjects showed an increase in daily steps (6224+/-2781 to 7898+/-4141 steps/day) and reduction of BMI (28.8+/-2.8 to 27.7+/-2.9). deltaIGF-I significantly correlated with deltaV area (r=-0.432, P=0.0009) but not with DeltaS area or deltaBMI.. The present study indicated a negative correlation between IGF-I levels and visceral fat at baseline as well as an association between the reduction in visceral fat and increase in IGF-I levels after an exercise intervention.

Topics: Adipose Tissue; Adult; Body Composition; Body Mass Index; Cross-Sectional Studies; Exercise; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Longitudinal Studies; Male; Middle Aged; Regression Analysis; Tomography, X-Ray Computed; Viscera; Weight Loss

To investigate soluble leptin receptor (sLR) in plasma, specific anti-sLR monoclonal antibodies were developed. Western blot analysis and size exclusion fractionation demonstrated sLR in plasma with a molecular mass of approximately 180,000. Next to this, the presence of sLR-leptin complexes in plasma was confirmed. Using the developed monoclonal antibodies, a specific sLR ELISA was developed, which measured in plasma both free and sLR bound to leptin. sLR appeared to inhibit leptin concentrations measured in four different leptin assays indicating that these assays primarily measure free leptin and underestimate the total leptin present in plasma. Furthermore, plasma levels of sLR and leptin were measured in 21 lean individuals and in 30 morbidly obese subjects before and 3, 6, and 12 months after gastric restrictive surgery. Preoperatively, leptin concentrations significantly correlated with body mass index (r = 0.796, P < 0.001). In contrast, sLR significantly inversely correlated with body mass index (r = -0.294, P < 0.05). In lean subjects, the molar ratio of free leptin to sLR was 1:1, whereas in morbidly obese subjects a ratio of 25:1 was found. After weight loss due to surgery, leptin levels rapidly decreased and sLR levels slowly increased to reach normal values at 12 months postoperatively. We conclude that sLR levels are significantly decreased, whereas leptin levels are significantly increased in morbidly obese subjects compared with lean individuals.

Topics: Adult; Antibodies, Monoclonal; Body Mass Index; Carrier Proteins; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Middle Aged; Obesity, Morbid; Receptors, Cell Surface; Receptors, Leptin; Reference Values; Solubility; Thinness; Weight Loss

Obesity is a typical example of a complex multifactorial disease arising from behavioural, environmental and genetic factors that may affect individual responses to dietary intake and physical activity. Observational, longitudinal dietary interventional studies in obese patients present contrasting reports on the predictive value of baseline leptin levels. We report on the effect of a weight reduction programme in three different groups of obese children (82 patients in all) assembled on the basis of their baseline leptin levels adjusted for body mass index (BMI), gender and pubertal development. The effectiveness of this programme was decreased in patients with relative hyperleptinaemia or hypoleptinaemia compared to children with baseline leptin levels appropriate to BMI gender and pubertal development.. Information gained from leptin assays could provide predictive insight into an individual's ability to lose body fat and may therefore have important implications for our approach to the treatment and prevention of childhood obesity.

Topics: Adolescent; Body Mass Index; Child; Female; Humans; Leptin; Obesity; Weight Loss

Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1-deficient mice are resistant to diet-induced obesity through a mechanism involving increased energy expenditure. Here we show that these mice have decreased levels of tissue triglycerides, as well as increased sensitivity to insulin and to leptin. Importantly, DGAT1 deficiency protects against insulin resistance and obesity in agouti yellow mice, a model of severe leptin resistance. In contrast, DGAT1 deficiency did not affect energy and glucose metabolism in leptin-deficient (ob/ob) mice, possibly due in part to a compensatory upregulation of DGAT2 expression in the absence of leptin. Our results suggest that inhibition of DGAT1 may be useful in treating insulin resistance and leptin resistance in human obesity.

Topics: Acyltransferases; Adipocytes; Animals; Cell Size; Diacylglycerol O-Acyltransferase; Energy Metabolism; Humans; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Mice, Obese; Obesity; Tissue Distribution; Triglycerides; Weight Loss

Organochlorine compounds are released from body fat into the bloodstream during weight loss. Because these compounds may impair thyroid status, which is implicated in the control of resting metabolic rate (RMR), the aim of this study was to determine if the augmentation in plasma organochlorine concentrations might be associated with the decrease in serum T(3) concentration and RMR observed in response to body weight loss. Plasma organochlorine concentrations, serum T(3) concentration, and RMR were measured before and after weight loss in 16 obese men who followed a nonmacronutrient-specific energy-restricted diet for 15 weeks. As expected, a significant decrease in serum T(3) concentration and RMR was observed after the program, whereas concentrations of most detected organochlorines were significantly increased. Changes in organochlorine concentrations were negatively associated with changes in serum T(3) concentration (significantly for p,p'-DDT, HCB, Aroclor 1260, PCB 28, PCB 99, PCB 118, and PCB 170) and with changes in RMR adjusted for weight loss (significantly for HCB and PCB 156). In conclusion, organochlorines released in plasma during weight loss are associated with the documented decrease in serum T(3) concentration and RMR. Further studies are needed to verify whether these findings are causally related.

Topics: Basal Metabolism; Diet; Diet, Reducing; History, Modern 1601-; Humans; Hydrocarbons, Chlorinated; Insecticides; Leptin; Male; Obesity; Triiodothyronine; Weight Loss

Maintenance of a reduced body weight is associated with decreased 24-hour energy expenditure, and decreased circulating concentrations of leptin and thyroid hormones. To determine whether these adaptive metabolic and endocrine changes are partly leptin-mediated, we measured body composition, aspects of energy expenditure, and circulating concentrations of leptin and thyroid hormones in 4 subjects at 3 time points: 1.) Usual body weight; 2.) While stable at 10% reduced body weight; and 3.) During a 5-week period at 10% reduced body weight while receiving twice per day leptin injections that restored 8 AM circulating leptin concentrations to those seen at usual body weight. During maintenance of a 10% reduced body weight, circulating T3, T4, and leptin concentrations were decreased. All of these endocrine changes were reversed by administration of "replacement" doses of leptin (r-metHuLeptin). Indirect calorimetry, and subtle changes in body composition associated with leptin administration, were used to calculate the net change in stored calories and in 24-hour energy expenditure. Total energy expenditure increased in all subjects during r-metHuLeptin administration. These data indicate that decrease leptin concentrations resulting from loss of fat mass account for some aspects of the endocrine/metabolic phenotype associated with the weight-reduced state.

Topics: Adult; Body Composition; Calorimetry, Indirect; Dose-Response Relationship, Drug; Energy Metabolism; Female; Humans; Leptin; Male; Osmolar Concentration; Thyroid Hormones; Weight Loss

Weight loss causes changes in appetite and energy expenditure that promote weight regain. Ghrelin is a hormone that increases food intake in rodents and humans. If circulating ghrelin participates in the adaptive response to weight loss, its levels should rise with dieting. Because ghrelin is produced primarily by the stomach, weight loss after gastric bypass surgery may be accompanied by impaired ghrelin secretion.. We determined the 24-hour plasma ghrelin profiles, body composition, insulin levels, leptin levels, and insulin sensitivity in 13 obese subjects before and after a six-month dietary program for weight loss. The 24-hour ghrelin profiles were also determined in 5 subjects who had lost weight after gastric bypass and 10 normal-weight controls; 5 of the 13 obese subjects who participated in the dietary program were matched to the subjects in the gastric-bypass group and served as obese controls.. Plasma ghrelin levels rose sharply shortly before and fell shortly after every meal. A diet-induced weight loss of 17 percent of initial body weight was associated with a 24 percent increase in the area under the curve for the 24-hour ghrelin profile (P=0.006). In contrast, despite a 36 percent weight loss after gastric bypass, the area under the curve for the ghrelin profile in the gastric-bypass group was 77 percent lower than in normal-weight controls (P<0.001) and 72 percent lower than in matched obese controls (P=0.01). The normal, meal-related fluctuations and diurnal rhythm of the ghrelin level were absent after gastric bypass.. The increase in the plasma ghrelin level with diet-induced weight loss is consistent with the hypothesis that ghrelin has a role in the long-term regulation of body weight. Gastric bypass is associated with markedly suppressed ghrelin levels, possibly contributing to the weight-reducing effect of the procedure.

Topics: Adult; Appetite Regulation; Body Composition; Circadian Rhythm; Diet, Reducing; Female; Gastric Bypass; Ghrelin; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Peptide Hormones; Peptides; Postoperative Period; Weight Loss

Human adipose tissue expresses and releases proinflammatory cytokines and these measures of chronic inflammation have recently been associated with obesity.. To test whether the proinflammatory state is reversible in subjects undergoing weight loss by surgical measures.. Twenty morbidly obese women participated in this prospective study. Subjects were examined for fat mass, high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) before and 1 y after Swedish adjustable gastric banding.. Anthropometric measures displayed a significant reduction of the body mass index (BMI) from 41.6+/-5.4 to 30.8+/-6.1 kg/m(2) and the fat mass from 53.9+/-10.3 to 29.8+/-12.1 kg (mean+/-s.d.). Hs-CRP levels decreased significantly from 1.33+/-1.21 mg/dl in pre-gastric banding subjects to 0.40+/-0.61 mg/dl in post-gastric banding subjects, respectively. IL-6 and TNF-alpha levels did not differ significantly between pre- and post-gastric banding subjects.. We speculate that in these patients the marked reduction in C-reactive protein might be beneficial in reducing their cardiovascular risk and is not solely mediated by IL-6 and TNF-alpha.

Topics: Adipose Tissue; Adult; Biomarkers; Body Composition; C-Reactive Protein; Cholesterol; Female; Gastroplasty; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Middle Aged; Obesity; Prospective Studies; Triglycerides; Tumor Necrosis Factor-alpha; Weight Loss

Glucocorticoids are important for normal brain development. Elevation or removal of these hormones can permanently modify the structure and function of the fetal brain. The purpose of this study was to examine the effects of postnatal corticosterone exposure of female pups on metabolic, endocrine and anthropometric variables in adulthood.. Female pups were given subcutaneous injections of corticosterone (5 mg/kg, CORT) or vehicle 3 and 5 days after birth.. From 6 weeks of age, the CORT rats weighed significantly less than did controls, with diminished fat depots, decreased serum levels of leptin and reduced food intake. Adult CORT rats showed increased insulin sensitivity, measured by hyperinsulinemic, euglycemic clamp (5 mU/kg/min), as compared with controls. CORT rats had lower basal corticosterone levels and lower corticosterone levels 15 and 90 min after exposure to stress.. The results indicate that postnatal exposure to corticosterone leads to increased insulin sensitivity, low body weight with diminished fat depots, leptin and food intake. This suggests that postnatal exposure to corticosterone induces specific programming, with consequences in adult life.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Blotting, Western; Body Composition; Corticosterone; Eating; Female; Glucose Clamp Technique; Insulin; Leptin; Locomotion; Rats; Rats, Wistar; Weight Loss

Alcohol consumption is an important risk factor for cancer. Little is known about its effects on cancer progression. Previously, we showed that high ethanol consumption inhibited metastasis of B16BL6 melanoma-bearing mice without affecting primary tumor growth. On the other hand, ethanol-consuming tumor-bearing (TE) mice exhibited decreased survival and decreased body weight as compared to water-drinking, tumor-bearing (TW) mice. The focus of this study was to determine how alcohol promotes weight loss in melanoma-bearing mice.. Female, C57BL/6 mice were given water or 20% w/v ethanol in the drinking water for 3 weeks to 6 months before subcutaneous inoculation of 1 x 10(6) B16BL6 melanoma cells. Mice continued to receive the same fluids. Biochemical parameters were evaluated at various times after tumor inoculation. Body weight, water content, tumor weight and carcass fat content were determined at necropsy.. TW mice elicted a modest weight loss. This response was magnified 2-fold by alcohol consumption. The weight loss in TE mice is not caused by dehydration, decreased energy intake, or loss of skeletal muscle mass. It resulted specifically from loss in body fat. Other alterations associated with the fat loss in TE mice were: (1) decreased glucose, (2) elevated fatty acids, (3) elevated beta-hydroxybutyrate, (4) elevated glucagon, and (5) increased leptin levels in plasma. Body temperature decreased about 2.9 degrees C in TE mice. Metabolic rate increased in TW mice. The fat loss due to alcohol consumption in tumor-bearing mice was not due to increased metabolic rate.. The response elicited by alcohol consumption in tumor-bearing mice is complex and associated with alterations in metabolism and hormones. These findings suggest that alcohol abuse could be a risk factor for cancer patients because it invokes a strong depletion of body fat. This could facilitate wasting and shorten survival time.

Topics: Alcohol Drinking; Animals; Energy Intake; Fatty Acids, Nonesterified; Female; Glucose; Leptin; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Weight Loss

To obtain more information on the possible influence of body mass index (BMI) and weight loss on interleukin-8 (IL-8) in plasma and in the adipose tissue. Tumor necrosis factor-alpha (TNF-alpha) was used for comparison and determined in parallel with IL-8.. The study was divided into three parts: 1) a cross-sectional study that included 89 subjects; 2) a 20-week intervention study in which 34 healthy obese subjects received a dietary intervention for 8 weeks followed by an additional 12 weeks on a weight-stabilization diet; 3) from this latter study, a subgroup of 8 obese subjects was investigated with a subcutaneous adipose-tissue biopsy.. In the cross-sectional study, plasma levels of TNF-alpha (p < 0.01), but not IL-8, was correlated with BMI. However, in a subgroup (BMI, 20 to 30 kg/m(2)), IL-8 was correlated with BMI (p < 0.01). In the intervention study, weight loss and weight maintenance led to an increase in IL-8 by 30% (p < 0.05) and a decrease in TNF-alpha by 40% (p < 0.001), which were paralleled in the adipose tissue, demonstrating a 2- to 3-fold increase (p < 0.01) and a 40% to 80% decrease (p < 0.01) in IL-8 and TNF-alpha, respectively.. Weight loss in obese subjects was associated with opposite changes in the secretion and transcription of IL-8 and TNF-alpha in the adipose tissue, as well as in plasma. This could indicate that plasma IL-8 under some conditions may be related to changes in adipose tissue IL-8 production.

Topics: Adipose Tissue; Adult; Biopsy; Body Mass Index; Cross-Sectional Studies; Culture Techniques; Female; Gene Expression Regulation; Humans; Insulin; Interleukin-8; Leptin; Male; Middle Aged; Obesity; Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Loss

Soluble leptin receptor (sOB-R) represents the main binding site for leptin in human blood. The aim of this study was to investigate the relationship between leptin and soluble leptin receptor and the bound/free ratio after pronounced weight reduction.. A total of 18 morbidly obese women participated in this prospective study. Subjects were examined for fat mass, leptin, and sOB-R concentrations before and 1 year after Swedish adjustable gastric banding.. Anthropomorphic measures displayed a significant reduction of body mass index [(42.9 +/- 5.6 to 32.9 +/- 6.0 kg/m(2) (mean +/- SD)]. Fat mass decreased from 56.3 +/- 9.0 to 33.9 +/- 12.5 kg. Plasma leptin concentration decreased from 44.6 +/- 18.0 to 20.0 +/- 13.1 ng/mL (p < 0.001), whereas the sOB-R levels increased from 11.1 +/- 3.6 to 16.6 +/- 6.0 U/mL after weight-reducing surgery. Thus, the sOB-R bound fraction of leptin increased from 7% to 33%.. This work demonstrates a relationship between weight loss, leptin, and sOB-R concentrations in vivo. During weight loss, leptin levels decreased, whereas sOB-R levels and the receptor bound fraction of leptin increased. Thus, sOB-R may negatively regulate free leptin.

Topics: Adult; Body Composition; Body Mass Index; Gastroplasty; Humans; Leptin; Middle Aged; Obesity, Morbid; Prospective Studies; Protein Binding; Receptors, Cell Surface; Receptors, Leptin; Solubility; Weight Loss

Adipocyte complement-related protein (30 kDa) (Acrp30), a secreted protein of unknown function, is exclusively expressed in differentiated adipocytes; its mRNA is decreased in obese humans and mice. Here we describe novel pharmacological properties of the protease-generated globular head domain of Acrp30 (gAcrp30). Acute treatment of mice with gAcrp30 significantly decreased the elevated levels of plasma free fatty acids caused either by administration of a high fat test meal or by i.v. injection of Intralipid. This effect of gAcrp30 was caused, at least in part, by an acute increase in fatty acid oxidation by muscle. As a result, daily administration of a very low dose of gAcrp30 to mice consuming a high-fat/sucrose diet caused profound and sustainable weight reduction without affecting food intake. Thus, gAcrp30 is a novel pharmacological compound that controls energy homeostasis and exerts its effect primarily at the peripheral level.

Topics: Adipocytes; Adiponectin; Amino Acid Sequence; Animals; Blood Glucose; Blood Proteins; Endopeptidases; Fatty Acids; Glucagon; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Muscle, Skeletal; Oxidation-Reduction; Protein Processing, Post-Translational; Proteins; Triglycerides; Weight Loss

The hormone leptin has been shown to be an afferent signal in a negative-feedback loop regulating body weight, and consequently, the administration of the gene product for the treatment of obesity has recently attracted considerable attention. Leptin is produced by adipocytes in response to increased trigyceride storage, and appears to affect body weight primarily through target cells in the hypothalamus. Although plasma levels of leptin correlate positively with adipose tissue mass in normal humans and animals, recent studies have shown that obese humans and animals appear to be relatively resistant to the increased plasma levels of leptin. Analysis of the levels of leptin in the cerebrospinal fluid suggests that the uptake of leptin across the blood-brain barrier may be saturable. Taken together, these results suggest that therapeutic approaches to deliver leptin through the circulation may prove to be problematic. Although recent clinical trials have suggested that peripherally administered leptin might lead to a reduction in body weight in humans, it is likely that the more effective delivery of leptin to cellular targets within the central nervous system will be necessary in order to fully reveal the therapeutic potential of the gene product. In an effort to provide a means for the delivery of leptin that obviates the need for the gene product to traverse the blood-brain barrier, we have evaluated the use of recombinant adeno-associated vectors to deliver leptin intraventricularly or directly to the hypothalamus.

Topics: Animals; Brain; Cerebral Ventricles; Dependovirus; Genes, Reporter; Genetic Therapy; Genetic Vectors; Green Fluorescent Proteins; Humans; Hypothalamus; Leptin; Luminescent Proteins; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle, Skeletal; Obesity; Recombination, Genetic; Weight Loss

Pathological weight loss is a feature of many diseases and contributes to mortality and morbidity. Although cytokines have been implicated in some models of pathological weight loss, little is known about cellular mechanisms responsible for cachexia in patients with cancer. Leptin is a fat cell product that acts centrally to reduce appetite and decrease metabolism. Leptin synthesis is stimulated by cytokines, and circulating levels of cytokines are elevated in some cancer patients. We hypothesized that cytokine-induced hyperleptinemia contributes to pathological weight loss in patients with pancreatic cancer. To evaluate this hypothesis, fasting serum leptin concentrations were measured in 64 patients undergoing surgery for pancreatic cancer. Preoperative interviews were used to assess body weight and appetite history. Thirty of 64 pancreatic cancer patients had cachexia (weight loss of >10% over the 6 months before surgery). Self-reported loss of appetite was associated with the presence of cachexia. Leptin concentrations, when corrected for body mass index, were lower than levels reported in healthy humans. Six patients had leptin levels more than 2 times those predicted by body mass index. There was no association between patients with increased leptin concentration and weight loss or anorexia. We conclude that a reduced appetite contributes to weight loss in patients with pancreatic cancer. High plasma leptin levels, however, do not appear to contribute to cachexia in these patients.

Topics: Aged; Appetite; Body Mass Index; Cachexia; Humans; Leptin; Middle Aged; Pancreatic Neoplasms; Reference Values; Weight Loss

We investigated the effects of low-dose leptin treatment on restoration of fertility in young adult male leptin deficient obese mice.. MMTV-TGF-alpha Lep(ob) Lep(ob) mice (8--10 weeks old) were treated with recombinant mouse leptin. In experiment 1, four mice (5 microg/g body weight leptin followed by 2.5 microg/g) lost weight and impregnated females (number of pregnancies/number of females, 3/6, 5/6, 5/10, 4/10). In experiment 2, Leptin-Obese (2.5 microg/g) and Control-Lean mice weighed significantly less than Control-Obese mice. Epididymal pad weights of Control-Obese mice were the heaviest, followed by those of Leptin-Obese mice, and Control-Lean mice were the lightest. Testes weight was greater in Control-Lean vs Control-Obese mice. Leptin-Obese mice had testes weight not significantly different from either control group. Four of five Leptin-Obese mice impregnated females (4/10, 5/10, 2/10, 5/12, 0/10).. These results indicate that low-dosage mouse recombinant leptin treatment restored fertility to young Lep(ob) Lep(ob) male mice. Although body weights of Leptin-Obese mice were similar to those of lean age-matched mice, epididymal fat pad weights were heavier. International Journal of Obesity (2001) 25, 95-97

Topics: Animals; Female; Fertility; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Organ Size; Recombinant Proteins; Weight Loss

Ciliary Neurotrophic Factor (CNTF) was first characterized as a trophic factor for motor neurons in the ciliary ganglion and spinal cord, leading to its evaluation in humans suffering from motor neuron disease. In these trials, CNTF caused unexpected and substantial weight loss, raising concerns that it might produce cachectic-like effects. Countering this possibility was the suggestion that CNTF was working via a leptin-like mechanism to cause weight loss, based on the findings that CNTF acts via receptors that are not only related to leptin receptors, but also similarly distributed within hypothalamic nuclei involved in feeding. However, although CNTF mimics the ability of leptin to cause fat loss in mice that are obese because of genetic deficiency of leptin (ob/ob mice), CNTF is also effective in diet-induced obesity models that are more representative of human obesity, and which are resistant to leptin. This discordance again raised the possibility that CNTF might be acting via nonleptin pathways, perhaps more analogous to those activated by cachectic cytokines. Arguing strongly against this possibility, we now show that CNTF can activate hypothalamic leptin-like pathways in diet-induced obesity models unresponsive to leptin, that CNTF improves prediabetic parameters in these models, and that CNTF acts very differently than the prototypical cachectic cytokine, IL-1. Further analyses of hypothalamic signaling reveals that CNTF can suppress food intake without triggering hunger signals or associated stress responses that are otherwise associated with food deprivation; thus, unlike forced dieting, cessation of CNTF treatment does not result in binge overeating and immediate rebound weight gain.

Topics: Adipose Tissue; Animals; Cachexia; Ciliary Neurotrophic Factor; Corticosterone; DNA-Binding Proteins; Hypothalamus; Immunohistochemistry; Interleukin-1; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; STAT3 Transcription Factor; Trans-Activators; Weight Gain; Weight Loss

Leptin deficiency results in a complex obesity phenotype comprising both hyperphagia and lowered metabolism. The hyperphagia results, at least in part, from the absence of induction by leptin of melanocyte stimulating hormone (MSH) secretion in the hypothalamus; the MSH normally then binds to melanocortin-4 receptor expressing neurons and inhibits food intake. The basis for the reduced metabolic rate has been unknown. Here we show that leptin administered to leptin-deficient (ob/ob) mice results in a large increase in peripheral MSH levels; further, peripheral administration of an MSH analogue results in a reversal of their abnormally low metabolic rate, in an acceleration of weight loss during a fast, in partial restoration of thermoregulation in a cold challenge, and in inducing serum free fatty acid levels. These results support an important peripheral role for MSH in the integration of metabolism with appetite in response to perceived fat stores indicated by leptin levels.

Topics: Animals; Appetite; Body Temperature Regulation; Eating; Fasting; Fats; Fatty Acids, Nonesterified; Leptin; Melanocyte-Stimulating Hormones; Mice; Mice, Inbred C57BL; Pro-Opiomelanocortin; Weight Gain; Weight Loss

Topics: Anti-Obesity Agents; Appetite Depressants; Body Mass Index; Counseling; Cyclobutanes; Diet, Reducing; Drug Therapy, Combination; Exercise; Female; Humans; Lactones; Leptin; Life Style; Obesity; Orlistat; Patient Education as Topic; Patient Selection; Primary Health Care; United States; Weight Loss; Women's Health

The adipocyte hormone leptin is thought to serve as a signal to the central nervous system reflecting the status of fat stores. Serum leptin levels and adipocyte leptin messenger RNA levels are clearly increased in obesity. Nevertheless, the factors regulating leptin production are not fully understood. The aim of this study was to determine the effects of in vivo administration of the synthetic glucocorticoid dexamethasone and weight loss on serum leptin levels in two independent protocols. Twenty-five obese subjects were studied (18 women and 7 men, mean age 26.6 +/- 6 years, BMI 31.1 +/- 2.5 kg/m(2), %fat 40.3 +/- 8.3) and compared at baseline to 22 healthy individuals. Serum levels of leptin, insulin, proinsulin and glucose were assessed at baseline and after ingestion of dexamethasone, 4 mg per day (2 mg, twice daily) for two consecutive days. To study the effects of weight loss on serum leptin, 17 of the obese subjects were submitted to a low-calorie dietary intervention trial for 8 weeks and again blood samples were collected. Serum leptin levels were significantly higher in the obese group compared to the control group and a high positive correlation between leptinemia and the magnitude of fat mass was found (r = 0.88, P<0.0001). After dexamethasone, there was a significant increase in serum leptin levels (22.9 +/- 12.3 vs 51.4 +/- 23.3 ng/ml, P<0.05). Weight loss (86.1 +/- 15.1 vs 80.6 +/- 14.2 kg, P<0.05) led to a reduction in leptin levels (25.13 +/- 12.8 vs 15.9 +/- 9.1 ng/ml, P<0.05). We conclude that serum leptin levels are primordially dependent on fat mass magnitude. Glucocorticoids at supraphysiologic levels are potent secretagogues of leptin in obese subjects and a mild fat mass reduction leads to a disproportionate decrease in serum leptin levels. This suggests that, in addition to the changes in fat mass, complex nutritional and hormonal interactions may also play an important role in the regulation of leptin levels.

Topics: Adult; Biomarkers; Clinical Protocols; Dexamethasone; Energy Intake; Female; Glucocorticoids; Humans; Leptin; Male; Obesity; Weight Loss

Patients with cachexia suffer from anorexia, weight loss and hypermetabolism. This study examined the relationship between plasma leptin concentration, leptin gene expression, weight loss and the acute-phase response in a group of surgical patients.. Body composition, plasma leptin, interleukin (IL) 6, soluble tumour necrosis factor receptor (sTNF-R) 55, sTNF-R75 and C-reactive protein were analysed in a cohort of 28 patients undergoing elective surgery. Subcutaneous and omental leptin messenger RNA (mRNA) was analysed in a subgroup of 14 patients.. After adjustment for fat mass (FM), a significant partial correlation coefficient was found between plasma leptin and serum IL-6 concentration (P = 0.037). A positive correlation was found only between plasma leptin and omental leptin mRNA (P = 0.009). Patients with an acute-phase response had a significantly higher level of plasma leptin per unit FM (P = 0.049). Stepwise multiple regression showed that FM (P < 0.0005) and serum IL-6 (P = 0.018) were independent predictors of plasma leptin level.. Plasma leptin levels appear to be influenced by proinflammatory cytokines. Omental fat may have more influence on plasma leptin than subcutaneous fat. Accelerated weight loss in patients with cancer with an ongoing inflammatory response could be mediated in part by inappropriately high plasma levels of leptin.

Topics: Acute-Phase Reaction; Aged; Aged, 80 and over; C-Reactive Protein; Colorectal Neoplasms; Diverticulum, Colon; Elective Surgical Procedures; Etanercept; Female; Humans; Immunoglobulin G; Interleukin-6; Leptin; Male; Middle Aged; Omentum; Receptors, Leptin; Receptors, Tumor Necrosis Factor; RNA, Messenger; Weight Loss

We evaluated the effect of the Magenstrasse and Mill (M & M) operation--a new form of non-banded vertical gastroplasty-on weight loss, plasma leptin levels and insulin resistance.. Fasting plasma glucose, leptin and insulin levels were measured in 12 normal controls, 39 morbidly obese patients and 39 patients a median 3 years after the M & M procedure. Insulin resistance was calculated by the homeostasis model insulin resistance index.. Body mass index mean (s.d.) decreased significantly (p < 0.0001), from 48(7) to 33(5) kg/m2, after the M & M procedure. Fasting plasma leptin concentration in the morbidly obese group was 37.9(15.4) ng/ml, significantly (p < 0.0001) higher than the control group (12.2(8.4)) and the M & M group (19.1(12.7)) ng/ml. Fasting plasma insulin concentrations were also significantly (p < 0.0001) higher in the morbidly obese group compared with than in the M & M group or in the control group: 35.5(22.3) mU/l, 15.5(7.1) mU/l and 13.6(3.4) mU/l, respectively. Insulin resistance was 9.6(7.2) in the morbidly obese group and 3.5(1.9) in the M & M group (p < 0.0001).. This is one of the first studies to show that the decrease in insulin resistance after weight loss achieved by anti-obesity surgery is associated with significantly lower levels of plasma leptin.

Topics: Adult; Blood Glucose; Body Mass Index; Fasting; Female; Gastroplasty; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Obesity, Morbid; Weight Loss

Leptin is involved in the regulation of body weight through a feedback signal between adipose tissue and the satiety center, to decrease food intake and increase energy expenditure. Newborn infants experience physiological weight loss during the first week of life. The leptin level may be decreased to enhance food intake and to decrease energy expenditure for physiological adaptation during early postnatal days. Insulin-like growth factor-I (IGF-I) and insulin are involved in the regulation of perinatal growth. Leptin might be interrelated with IGF-I or insulin, since both of these have adipogenic and somatotropic effects. We therefore hypothesized that leptin, IGF-I and insulin would be decreased during the first week of life, concurrently with physiological weight loss. Thirty preterm AGA infants (birth weight 1.574+/-313 g; GA 31.9+/-2.2 wk) were studied. All infants received parenteral nutrition from the third day after birth. Leptin was significantly decreased during the first week of life, and insulin was significantly increased at day 7 vs. day 1 and day 3. IGF-I did not change during the first week of life. Leptin was positively correlated with body weight (r = 0.368, p<0.01), body mass index (r = 0.267, p<0.05), and serum IGF-I (r = 0.330, p <0.01), but not with serum insulin. The percent of weight reduction during the first week of life was not correlated with the percent of leptin reduction during the first week of life. In conclusion, leptin was significantly decreased and positively correlated with body weight and IGF-I during the first week of life. Changes of leptin and insulin might be related to postnatal adaptation in metabolism, but the exact role of leptin, IGF-I and insulin in postnatal physiological weight loss is not clear.

Topics: Aging; Body Mass Index; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Parenteral Nutrition; Weight Loss

To assess the dominance between hypoinsulinemia and hypoleptinemia as factors in the development of hyperphagia in streptozotocin (STZ)-induced diabetes mellitus (STZ-DM) rodents with respect to hormone-neuropeptide interactions, changes in gene expression of agouti gene-related protein (AGRP) in the arcuate nucleus of the hypothalamus were investigated using STZ-DM rats, fasting Zucker fa/fa rats and STZ-DM agouti (STZ-DM A(y)/a) mice. AGRP mRNA and neuropeptide Y mRNA were both significantly up-regulated in STZ-DM rats, which are associated with body weight loss, hyperglycemia, hypoinsulinemia and hypoleptinemia. We proceeded to analyze whether insulin or leptin played the greater role in the regulation of AGRP using Zucker fa/fa rats. The AGRP mRNA did not differ significantly between fasted fa/fa rats, which have both leptin-insensitivity and hypoinsulinemia, and fed Zuckers, which have leptin-insensitivity and hyperinsulinemia. We further found that up-regulation of AGRP expression was normalized by infusion of leptin into the third cerebroventricle (i3vt), but not by i3vt infusion of insulin, although up-regulation of AGRP was partially corrected by systemic insulin infusion. The latter finding supports hypoleptinemia as a key-modulator of STZ-DM-induced hyperphagia because systemic insulin infusion, at least partially, restored hypoleptinemia through its acceleration of fat deposition, as demonstrated by the partial recovery of lost body weight. After STZ-DM induction, A(y)/a mice whose melanocortin-4 receptor (MC4-R) was blocked by ectopic expression of agouti protein additionally accelerated hyperphagia and up-regulated AGRP mRNA, implying that the mechanism is triggered by a leptin deficit rather than by the main action of the message through MC4-R. Hypoleptinemia, but not hypoinsulinemia per se, thus develops hyperphagia in STZ-DM rodents. These results are very much in line with evidence that hypothalamic neuropeptides are potently regulated by leptin as downstream targets of its actions.

Topics: Agouti Signaling Protein; Animals; Blood Glucose; Cerebral Ventricles; Diabetes Mellitus, Experimental; Feeding Behavior; Food Deprivation; Gene Expression Regulation; Hyperphagia; Hypothalamus; Infusions, Parenteral; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptide Y; Protein Precursors; Proteins; Rats; Rats, Wistar; Rats, Zucker; RNA, Messenger; Transcription, Genetic; Weight Loss

To investigate to what extent serum leptin concentrations in obese humans are influenced by a history of weight cycling.. Cross-sectional study on serum leptin concentrations and body composition in a cohort of obese subjects in whom a retrospective recall of weight and diet history was made.. One hundred and twenty-eight obese patients (89 females and 39 males), aged 18-61 y, body mass index (BMI) 31.2-63.4 kg/m(2).. Serum leptin; various fatness and fat distribution parameters (by anthropometry and bioelectrical impedance analysis); history of overweight at puberty; number, magnitude and timing of previous diet episodes and of consequent weight regain by interview.. By univariate analysis, serum leptin concentrations were significantly correlated with weight, waist-hip ratio, percentage body fat, maximal percentage weight loss in a single diet episode, cumulative percentage weight loss in all diet episodes, cumulative weight regained in all diet episodes, but not with the number of diet episodes. All correlations related to anthropometric and body composition parameters were stronger for men, compared to women, although the male subgroup was smaller. On the contrary, there was a strong positive correlation between weight cycling parameters and serum leptin in women but not in men. Leptin concentrations were significantly higher in patients who were overweight at puberty than in those who were not overweight at puberty. After correction for percentage body fat, presence of overweight at puberty did not correlate any longer with leptin concentrations in either gender. In women, cumulative percentage weight loss in all diet episodes contributed an additional 5% to the variance of serum leptin in the overall model.. The positive correlation between weight cycling and leptin concentration in obesity is mainly accounted for the higher percentage body fat in obese weight cyclers, although in women weight cycling per se independently contributes to the variance of serum leptin.

Topics: Adolescent; Adult; Anthropometry; Body Composition; Body Constitution; Body Mass Index; Body Weight; Cohort Studies; Cross-Sectional Studies; Electric Impedance; Female; Humans; Leptin; Male; Middle Aged; Obesity; Retrospective Studies; Weight Loss

SJL (H-2s) female mice are more susceptible than males to experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin-derived peptides. The reasons for this sexual dimorphism are unclear, but may include such factors as sex-related differences in immune responsiveness, hormonal effects and sex-linked genetic factors. Recent evidence indicates that leptin modifies T cell immunity promoting T helper (Th) 1 pro-inflammatory immune responses. Circulating leptin levels show a marked sexual dimorphism, being higher in females than in males. In the present study, we investigated whether leptin treatment altered the course of relapsing-remitting EAE, induced by the proteolipid protein peptide (PLP(139-151)), in SJL susceptible females and EAE-resistant males. Administration of leptin to female SJL mice before or after disease onset significantly worsened the disease, with a concomitant increase in the PLP(139-151)-specific delayed-type hypersensitivity (DTH) reactivity and in vitro IFN-gamma secretion. Leptin treatment at priming with antigen or before disease onset rendered male SJL mice susceptible to EAE, with the appearance of PLP(139-151)-specific DTH reactivity and a switch from a Th2 to Th1 pattern of cytokine release. Our findings indicate that leptin administration to susceptible females resulted in a more severe disease, and that reduced leptin levels in male SJL mice may contribute to the gender-related differences in the induction phase of EAE.

Topics: Amino Acid Sequence; Animals; Cells, Cultured; Central Nervous System; Disease Susceptibility; Encephalomyelitis, Autoimmune, Experimental; Female; Hypersensitivity, Delayed; Incidence; Interferon-gamma; Leptin; Lymph Nodes; Lymphocyte Activation; Male; Mice; Myelin Proteolipid Protein; Sex Characteristics; Spleen; Th1 Cells; Th2 Cells; Weight Loss

Pineal melatonin secretion has been reported to commonly decrease with aging, whereas intra-abdominal adiposity, plasma insulin and plasma leptin levels tend to increase. We recently demonstrated that daily melatonin administration starting at middle age suppressed male rat intra-abdominal fat, plasma leptin and plasma insulin to youthful levels, suggesting that aging-related changes in pineal melatonin secretion and in energy regulation may be functionally related. Accordingly, we have now investigated the effects of daily melatonin treatment on energy regulation in young versus middle-aged male Sprague Dawley rats. Addition of melatonin to the drinking water (0.2 microg/mL) produced nocturnal and diurnal plasma melatonin concentrations in middle-aged rats (12 months) equivalent to those of young adult (5 months) rats. Administration of this melatonin dosage every day for 10 wk starting at 10 months of age suppressed (P < 0.01) relative intra-abdominal fat, non-fasted plasma insulin and plasma leptin by 27, 39, and 51%, respectively (vs. vehicle-treated controls). In contrast, administration of melatonin for 10 wk starting at 3 months of age did not significantly alter (P> 0.10) any of these parameters. The melatonin administration stimulated (102%, P < 0.001) behavioral responsiveness of the middle-aged rats in a test of response to novelty, restoring youthful levels, but did not significantly alter behavioral responsiveness of the young rats. These results suggest that suppression of intra-abdominal adiposity and plasma leptin and insulin levels and stimulation of behavioral responsiveness in response to daily exogenous melatonin begins at middle age, coincident with and likely dependent upon the aging-associated decline in endogenous pineal melatonin secretion. These results further suggest that appropriate melatonin supplementation may potentially provide therapy or prophylaxis not only for the insulin resistance, increased intra-abdominal fat and resulting pathologies that occur with aging, but also for some aging-associated behavioral changes.

Topics: Adipose Tissue; Aging; Animals; Behavior, Animal; Insulin; Leptin; Male; Melatonin; Pineal Gland; Rats; Rats, Sprague-Dawley; Weight Loss

To examine the relationship between fasting plasma leptin and 24-hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate oxidations, and SPA as predictive markers of success during a standardized weight loss intervention.. Twenty-one nondiabetic obese (body mass index: 33.9 to 43.8 kg/m(2)) and 13 lean (body mass index: 20.4 to 24.7 kg/m(2)) men matched for age and height were included in the study. All obese subjects were reexamined after a mean weight loss of 19.2 kg (95% confidence interval: 15.1-23.4 kg) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability. Twenty-four-hour EE and substrate oxidations were measured by whole-body indirect calorimetry. SPA was assessed by microwave radar.. In lean subjects, leptin adjusted for fat mass (FM) was correlated to 24-hour EE before (r = -0.56, p < 0.05) but not after adjustment for fat free mass. In obese subjects, leptin correlated inversely with 24-hour and resting nonprotein respiratory quotient (r = -0.47, p < 0.05 and r = -0.50, p < 0.05) both before and after adjustments for energy balance. Baseline plasma leptin concentration, adjusted for differences in FM, was inversely related to the size of weight loss after 8 weeks (r = -0.41, p = 0.07), 16 weeks (r = -0.51, p < 0.05), and 24 weeks (r = -0.50, p < 0.05).. The present study suggests that leptin may have a stimulating effect on fat oxidation in obese subjects. A low leptin level for a given FM was associated with a greater weight loss, suggesting that obese subjects with greater leptin sensitivities are more successful in reducing weight.

Topics: Absorptiometry, Photon; Adipose Tissue; Adolescent; Adult; Body Composition; Calorimetry, Indirect; Case-Control Studies; Diet, Reducing; Energy Metabolism; Humans; Leptin; Lipid Metabolism; Male; Middle Aged; Obesity; Oxidation-Reduction; Weight Loss

This study was conducted to clarify the mechanisms involved in the sensitivity for blood pressure (BP) reduction in response to weight loss. In particular, we focused on the contributions of sympathetic nervous system activity and fasting plasma leptin and insulin levels to BP levels during weight loss in obese subjects with weight loss-sensitive and -resistant BP reduction. Sixty-one young, obese untreated hypertensive men (HT) and 52 obese normotensive men (NT) were enrolled in a weight loss program consisting of a low caloric diet and aerobic exercise over a 24-week period. At entry and at week 24, body mass index (BMI), BP, plasma norepinephrine (NE), leptin and insulin were measured. Successful weight loss and BP reduction were respectively defined as a more than a 10% reduction in BMI or mean BP from baseline at week 24. More than 60% of subjects in either group successfully achieved weight loss by this definition. The percentage of subjects who successfully achieved BP reduction was higher (64%) among those subjects who achieved weight loss than among those who did not (22%). Plasma NE level at entry in subjects who failed to achieve BP reduction despite weight loss was significantly higher than that in subjects who succeeded in BP reduction. Plasma leptin and insulin levels were similar between subjects with and without BP reduction. In addition, the absolute decrement and percent decrement in plasma NE in subjects who succeeded in BP reduction were significantly greater than those in subjects who failed to reduce their BP. Absolute and percent decrements in plasma leptin and insulin were similar in both groups. These results suggest that individuals who are resistant to weight loss-induced BP reduction have more sympathetic overactivity both at the outset of and during weight loss.

Topics: Adult; Blood Pressure; Body Mass Index; Humans; Hypertension; Insulin; Leptin; Male; Norepinephrine; Obesity; Sympathetic Nervous System; Weight Loss

Weight loss achieved during weight reduction programme is difficult to maintain. We investigated the possible role of circulating leptin in failure or success in maintaining weight loss.. Serum leptin levels were measured in 30 healthy premenopausal obese women before and after 12 weeks of dietary intervention and after 5 months of follow-up.. After intervention body mass index (BMI) decreased from 30.6 to 25.4 kg/m2 (p < 0.01) and leptin levels decreased from 16.7 to 7.7 ng/ml (p < 0.01). After 5 months follow-up 12 women regained reduced weight and 18 women maintained weight loss. In the regainers leptin levels increased again, but remained low in the maintainers. Baseline leptin concentrations were lower in the regainers than in the maintainers (12.1 vs. 21.2 ng/ml, p = 0.04). During intervention leptin levels decreased three times more in the maintainers than in the regainers, although weight loss was similar in both groups.. This study shows that obese women who regain weight after dieting have significantly lower baseline leptin levels than women who maintain weight loss. Our results suggest that differences in leptin resistance might exist in similarly obese women which could influence the success of dieting.

Topics: Adult; Biomarkers; Body Mass Index; Body Weight; Diet, Reducing; Female; Follow-Up Studies; Humans; Leptin; Middle Aged; Obesity; Predictive Value of Tests; Premenopause; Weight Gain; Weight Loss

Weight loss is typically found during severe infections, e.g. septic arthritis. The aim of our study was to evaluate the role of leptin, regulator of food intake and energy expenditure, for the development of Staphylococcus aureus-triggered arthritis. Leptin production was found to be decreased during murine S. aureus-induced arthritis. Treatment with recombinant leptin neither restored the basal leptin levels nor affected the weight loss during the disease, but it significantly decreased the severity of septic arthritis. Exogenous leptin did not affect the staphylococcal load as measured in blood, joints and kidneys. Preceding the effects on joint manifestations, serum levels of interleukin-6 decreased in leptin-treated mice. In conclusion, the treatment with recombinant leptin reduced both the severity of joint manifestations in S.aureus-induced arthritis and the inflammatory response, as measured by serum IL-6 levels, without affecting the survival of bacteria in vivo.

Topics: Animals; Arthritis, Infectious; Eating; Energy Metabolism; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Staphylococcal Infections; Staphylococcus aureus; Weight Loss

Regulation of growth hormone (GH) receptor expression and hence tissue GH sensitivity may be important for the conflicting results found in treatment studies with recombinant growth hormone in chronic heart failure (CHF). Growth hormone-binding protein (GHBP) corresponds to the extracellular domain of the GH receptor and is closely related to measures of body composition and, specifically, to size of visceral fat tissue. Leptin, the adipocyte specific (ob) gene product, has been proposed as the signal linking adipose tissue and GHBP/GH-receptor expression. CHF has recently been shown to be a hyperleptinaemic and insulin-resistant state regardless of aetiology. This study aimed to examine the influence of leptin on GHBP in CHF patients with and without cardiac cachexia compared with healthy control subjects.. We studied 47 male patients with CHF (mean age 61+/-2 years, New York Heart Association (NYHA)-class 2.7+/-0.1, left ventricular ejection fraction (LVEF) 28+/-2%, peak oxygen consumption 16.8+/-0.9 ml/kg/min) and 21 male healthy controls of similar age. Of the CHF patients, 19 were cachectic (cCHF; non-oedematous weight loss >7.5% over at least 6 months) and 28 non-cachectic (ncCHF; similar for age and LVEF). Insulin sensitivity was assessed by an intravenous glucose tolerance test using the minimal model approach.. Compared with healthy controls, patients had elevated levels of leptin (7.6+/-0.7 vs 4.8+/-0.7 ng/ml, P<0.05), insulin (76.2+/-8.9 vs 41.4+/-6.0 pmol/l, P<0.01), and reduced insulin sensitivity (2.43+/-0.2 vs 3.48+/-0.3 min(-1).microU.ml(-1).10(4), P<0.005) but similar GHBP levels (901+/-73 vs 903+/-95 pmol/l). Leptin levels were increased in ncCHF (9.11+/-1.0 ng/ml, P=0.001) but were not different from normal in cCHF (5.32+/-0.7 ng/ml, P>0.5). After correction for total body fat mass, both ncCHF and cCHF were hyperleptinaemic (41.8+/-3.8 and 37.9+/-0.38 vs 24.4+/-2.1 ng/ml/100 g, ANOVA P=0.001). In both patients and controls there was a direct correlation between leptin levels and GHBP (r=0.70 and r=0.71 respectively, both P<0.0001). This relationship was stronger than between GHBP and several parameters of body composition (body mass index (BMI), total and regional body fat mass or % body fat) and held true when sub-groups were tested individually (ncCHF r=0.62, P<0.001; cCHF r=0.79, P<0.0001). In multivariate regression analysis in all CHF patients, serum leptin levels emerged as the strongest predictor of GHBP, independent of age, BMI, total and regional fat mass or % body fat, fasting insulin level and insulin sensitivity.. Fat mass corrected leptin levels are elevated in CHF patients with and without cachexia. Reduced total fat mass may account for lower leptin levels in cachectic CHF patients compared with non cachectic patients. Leptin strongly predicts GHBP levels in CHF regardless of its hyperleptinaemic state or severely altered body composition as in cardiac cachexia. Leptin could be the signalling link between adipose tissue and GHBP/GH receptor expression in CHF.

Topics: Adipose Tissue; Body Composition; Body Mass Index; Cachexia; Cardiac Output, Low; Carrier Proteins; Chronic Disease; Fasting; Glucose Tolerance Test; Humans; Insulin; Leptin; Male; Middle Aged; Oxygen Consumption; Regression Analysis; Ventricular Function, Left; Weight Loss

We compared serum leptin and satiety measures in 18 Parkinson's disease (PD) patients with unintended weight loss (WL) and 18 PD patients whose weight was stable (WS). Mean serum leptin concentrations tended to be lower in WL than WS patients, but this did not reach statistical significance. Body mass index correlated with serum leptin concentrations. Ratings of hunger, satiety, fullness, and thirst did not differ between groups. However, the mean sensation of fullness before meals correlated with serum leptin in the entire cohort of patients, particularly in the WL group. The results indicate that unintended weight loss in PD patients is unlikely to be due to abnormal serum leptin concentrations.

Topics: Aged; Female; Humans; Leptin; Male; Middle Aged; Parkinson Disease; Satiety Response; Surveys and Questionnaires; Weight Loss

To investigate the effect of short term energy restriction combined with physical activity on serum concentrations of Interleukin-6 (IL-6) in obese children and adolescents.. Longitudinal intervention study of 3.8-5 MJ daily with exercise.. Forty-nine white obese children and adolescents (31 girls, age 11.9+/-1.8 y; 18 boys, age 11.6+/-1.7 y).. Indexes of obesity, IL-6, leptin, estradiol, systolic and diastolic blood pressure, heart rate at baseline and after 3 weeks.. All determined parameters decreased significantly during the 3 week program (IL-6: 3.9+/-4.7 vs 2.0+/-2.2 pg/ml; P<0.05). Body mass index (BMI) fat mass, percentage fat mass (indexes of obesity), and leptin were not related to IL-6 before the program. In contrast, IL-6 concentrations correlated significantly with indexes of obesity and leptin after weight loss. IL-6 concentrations did not correlate with estradiol, systolic and diastolic blood pressure, and heart rate. Changes in IL-6 concentrations correlated significantly with changes in BMI (r=0.25, P<0.05).. An improved body composition induced by restriction of energy intake and increase in physical activity is associated with more favorable serum concentrations of IL-6 in obese children and adolescents.

Topics: Adolescent; Blood Pressure; Body Mass Index; Child; Diet, Reducing; Enzyme-Linked Immunosorbent Assay; Estradiol; Exercise; Female; Heart Rate; Humans; Interleukin-6; Leptin; Male; Obesity; Weight Loss

A longitudinal, clinical intervention study with bariatric surgery was done to investigate the relationship between leptin levels, BMI, and insulin during weight loss across a range of glucose tolerance from normal to diabetes.. 43 morbidly obese patients (BMI: 42-75 kg/m2) undergoing vertical banded gastroplasty Roux-en-Y gastric bypass (VBG-RGB), were divided into 3 groups: 21 normal (NGT), 12 impaired glucose tolerance (IGT) and 10 type 2 diabetes (DM). Leptin, insulin, glucose, lipids and uric acid were measured at baseline and 2, 4, 6, and 12 months following surgery.. BMI fell from 54.1 +/- 9.1 to 34.6 +/- 6.3 kg/m2, similarly in all groups. Leptin decreased from 73.9 +/- 8.7 to 16.9 +/- 10.2 ng/ml and was strongly correlated with BMI during 1-year follow-up (r = 0.78; p < 0.001). Linear univariate analysis for repeated evaluation showed a positive correlation between leptin and glucose, triglycerides, uric acid, and insulin. Multivariate regression analysis indicated that BMI was independently correlated with the decrease in leptin (p < 0.001), accounting for 66% of the variance in leptin levels during weight loss. These results were found in the NGT and IGT groups. In the DM group, a small additional influence in leptin levels was attributed to glucose decrease.. A strong link between leptin and BMI was found after surgery. BMI was the main determinant of the decrease of leptin. In these patients submitted to bariatric surgery, ranging from normal glucose tolerance to diabetes, changes in insulin levels and metabolic parameters, except for glucose in the DM group, did not appear to be correlated with changes in leptin levels.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus; Female; Gastric Bypass; Glucose Intolerance; Humans; Insulin; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity, Morbid; Regression Analysis; Weight Loss

To evaluate the changes of serum leptin levels after weight reduction in diabetic subjects with and without microalbuminuria, we studied 10 obese healthy subjects, 12 obese diabetics with persistent microalbuminuria and 10 obese diabetic subjects without microalbuminuria. Obese diabetic patients with microalbuminuria showed serum leptin levels significantly higher than normoalbuminuric diabetics, while no difference was found between obese diabetics without microalbuminuria and healthy controls. All obese subjects followed a 12-month intensive weight reduction program during which the mean change in body mass index was similar between obese diabetic and obese healthy subjects (obese diabetics without microalbuminuria: 35.2+/-4.3 vs 29.9+/-4.1, p<0.05; obese diabetics with microalbuminuria: 35.7+/-3.9 vs 30.3+/-4.0, p<0.05; obese healthy subjects: 35.5+/-4.0 vs 30.1+/-3.9, p<0.05). The mean changes in serum leptin levels tended to be similar in two groups of subjects studied (obese diabetics without microalbuminuria: 37.6+/-4.1 vs 19.7+/-4.9, p<0.001; obese healthy subjects: 37.1+/-4.3 vs 20.1+/-5.1, p<0.001); obese microalbuminuric subjects showed higher leptin levels (42.4+/-4.0 vs 30.3+/-4.2, p<0.001) than normoalbuminuric diabetic and obese healthy subjects. In conclusion, during weight loss, independently from the quality of metabolic control, serum leptin concentrations declined in both groups of obese diabetics. The changes of leptin in diabetics seem to be similar to those observed in healthy obese subjects.

Topics: Adolescent; Albuminuria; Body Mass Index; Body Weight; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Leptin; Obesity; Weight Loss

Forty-eight morbidly obese patients were placed on a very low calorie (800 kcal) formula diet (OPTIFAST) for a 10-week period with the goal of achieving 10% weight loss within this time. Weekly serum leptin measurements were performed to determine whether changes in this adipose protein would serve as a useful marker of acute and chronic weight loss compliance. In the basal state, serum leptin averaged 56.9 +/- 5.8 ng/ml (SE) in the 24 successful (S) patients, and 67.7 +/- 6.7 ng/ml in the non-successful (N-S) group. During the first week of weight loss there was little change in leptin despite an average weight loss of 2.2%, but after 4 weeks serum leptin decreased by 36% in the S group, and 20% in the N-S group. After 10 weeks, the S group averaged 13.6% weight loss and the serum leptin decreased to 50% of starting levels. In the 24 N-S patients, the mean weight loss was 7.0%, and serum leptin decreased by 22%, remaining unchanged in the final 6 weeks despite a weight loss of 3.6% in this time. On a week-to-week basis serum leptin changed concordantly with weight loss only two-thirds of the time. In a subgroup of 14 patients (8 S+6 N-S), serial assessments of serum leptin, insulin and tumor necrosis factor-alpha (TNF-alpha) were performed. Serum insulin levels decreased with weight loss similar in magnitude to that noted for leptin; however, the insulin changes occurred more rapidly. Serum TNF-alpha also decreased with weight loss, but the weekly changes were more erratic, with a concordance rate of only 48%. In summary, serum leptin, insulin and TNF-alpha all decreased during a rapid weight loss program but at differing rates and variability, precluding their usefulness as markers of week-to-week weight loss compliance.

Topics: Body Mass Index; Diet, Reducing; Female; Humans; Insulin; Leptin; Male; Middle Aged; Obesity, Morbid; Time Factors; Tumor Necrosis Factor-alpha; Weight Loss

Obesity is a prevalent disorder that increases the risk for premature cardiovascular disease. The adipose tissue itself plays an active role in the regulation of fuel metabolism and energy homeostasis by expressing a number of regulatory genes, such as leptin, peroxisome proliferator-activated receptor-gamma (PPARgamma), and CCAAT/enhancer binding protein-alpha (C/EBPalpha). To study the in vivo relationships among these genes and their associations with cardiovascular risk factors, plasma levels of leptin, lipids, apolipoproteins (apo), insulin, and glucose were measured in 216 obese, 165 nonobese, and 36 weight-losing postobese subjects. mRNA expression of leptin, PPARgamma, and C/EBPalpha in the extraperitoneal and intraperitoneal adipose tissue was quantified in subsets of subjects. In obese individuals, plasma leptin was associated with apoA-I (r=0.2346, P<0.001) and insulin (r=0.2125, P<0.002). Leptin and C/EBPalpha mRNA expression in extraperitoneal and intraperitoneal adipose tissue of obese patients was higher than in the respective tissues of nonobese or postobese subjects. No significant differences among the study groups were found for PPARgamma mRNA expression. Leptin, PPARgamma, and C/EBPalpha mRNA levels correlated with each other in the intraperitoneal and extraperitoneal fat of obese subjects, but multivariate analysis revealed that only C/EBPalpha was a predictor of leptin expression in extraperitoneal tissue (partial r=0.6096, P<0.001). Intraperitoneal PPARgamma expression was inversely related to fasting insulin (r=-0.2888, P<0.017) and a fasting insulin resistance index (r=-0.2814, P<0.021) in obese subjects. In postobese patients, intraperitoneal PPARgamma expression was associated with plasma HDL cholesterol (r=0.5695, P<0.018) and apoA-I (r=0.6216, P<0.008) but was inversely related to LDL cholesterol (r=-0.5101, P<0.03) and apoB (r=-0.6331, P<0.007). These findings suggest a relationship between plasma leptin and HDL metabolism as well as adipose-tissue site-dependent associations among leptin, C/EBP-alpha, and PPAR-gamma mRNA expression. Furthermore, our results suggest that C/EBP-alpha enhances leptin expression in vivo and that PPARgamma mRNA expression is inversely associated with cardiovascular risk factors.

Topics: Adipose Tissue; Adult; Body Mass Index; Cardiovascular Diseases; CCAAT-Enhancer-Binding Proteins; DNA-Binding Proteins; Female; Humans; Leptin; Male; Middle Aged; Nuclear Proteins; Obesity; Receptors, Cytoplasmic and Nuclear; Reference Values; Risk Factors; RNA, Messenger; Sex Characteristics; Transcription Factors; Weight Loss

Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women.. Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone-binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0+/-4.5 kg/m2; mean +/- SD), women (60+/-6 years) before and after a 6-month hypocaloric diet (250 to 350 kcal/day deficit).. Body weight decreased by 5.8+/-3.4 kg (7.1%) and leptin levels decreased by 6.6+/-11.9 ng/mL (14.5%) after the 6-month treatment. Insulin levels decreased 10% (p< 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p<0.0001), fat mass (r = 0.38, p<0.01), subcutaneous fat area (r = 0.52, p<0.0001), and with baseline values of SHBG (r = 0.38, p<0.01) and baseline intra-abdominal fat area (r = -0.27, p<0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r2 = 0.24, p<0.01), relative changes in body weight (cumulative r2 = 0.40, p<0.05), and baseline intra-abdominal fat area (cumulative r2 = 0.48, p<0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance.. These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.

Topics: Body Composition; Female; Humans; Hydrocortisone; Insulin; Leptin; Obesity; Postmenopause; Regression Analysis; Sex Hormone-Binding Globulin; Viscera; Weight Loss

To determine the effects of 16 weeks of resistive training alone (RT) and with weight loss (RT+WL) on insulin action, plasma leptin concentrations and leptin's relationship to beta-cell sensitivity to glucose, resting metabolic rate (RMR), and plasma catecholamines in older women.. Fifteen obese postmenopausal women aged 50-69 y.. Body composition (by dual-energy X-ray absorptiometry), RMR (by indirect calorimetry), insulin action (by 2 h hyperglycemic clamps; 7.9 mmol/l above basal plasma glucose levels), plasma leptin and insulin (by RIA), and plasma catecholamines (by enzymatic methods).. RT and RT+WL resulted in significant improvements in muscular strength (P<0.01) with no changes in maximal oxygen consumption. Body weight, fat mass and percent body fat did not change with RT, but decreased with RT+WL (P<0.001). Fat-free mass and RMR increased after training when both groups were combined (P<0.05). The insulin response during the last 20 min of the 2 h hyperglycemic clamps decreased 16% after RT (P=0.05), 43% after RT+WL (P<0.05), and 29% in the entire group (P<0. 01) without any changes in glucose utilization. Plasma leptin levels did not change after RT, but decreased by 36% after RT+WL (P<0.05). Baseline leptin levels correlated with body weight (r=0.68, P<0.01), body fat mass (r=0.77, P<0.001), and RMR (kcal/d; (r=0.69, P<0.005), but not with baseline norepinephrine or epinephrine levels. Plasma leptin levels correlated with basal insulin (r=0.73, P<0.005), and approached significance with the 0-10 min and 100-120 min insulin response to hyperglycemia before training (both r=0.51, P=0.07). In the entire group, the change in insulin response from 100-120 min during the clamp correlated with the change in leptin levels (r=0.60, P<0.05), but this was not independent of changes in fat mass.. Although changes in leptin levels were not related to changes in RMR or plasma catecholamines after RT with and without weight loss, the increase in insulin action after training and weight loss may be related to the decrease in leptin levels that were mediated by the loss of body fat in the obese, postmenopausal women. International Journal of Obesity (2000)24, 27-32

Topics: Aged; Blood Glucose; Body Composition; Calorimetry, Indirect; Catecholamines; Energy Metabolism; Exercise; Female; Humans; Insulin; Leptin; Middle Aged; Obesity; Postmenopause; Weight Loss; Women's Health

Leptin, the product of the ob gene, is an adipocyte-derived hormone that positively correlates with body fat percantage and body mass index (BMI). There are many data which demonstrate a significant relationship between leptin and insulin, but the mechanism underlying the changes of leptin induced by insulin and vice versa remains to be studied in more detail. In this review, we analysed the data on the behaviour of serum leptin levels in non-obese and obese children with type 1 diabetes mellitus. It has been shown that the diminished serum leptin concentrations in patients with newly discovered insulin-dependent diabetes mellitus (IDDM) could be caused by insulin deficiency and/or increased lipolysis. Moreover, while in some studies in diabetic children with good metabolic control the serum leptin levels are similar to those of healthy children, in other studies children with IDDM have leptin levels higher than non diabetic children; it is possible that in some diabetic children intensified insulin therapy could cause chronic hyperinsulinemia with high leptin levels. The mean serum leptin concentrations in the obese diabetic subjects were significantly higher when compared with non-obese diabetics. Obese diabetic patients showed no significant differences in leptin concentrations in comparison to the non diabetic obese group matched by age, sex and BMI. In obese diabetics, during weight loss, independent of the quality of metabolic control, serum leptin concentration declines. The changes of leptin in diabetes seem to be similar to those observed in healthy obese subjects.

Topics: Adult; Age Factors; Child; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Leptin; Male; Obesity; Sex Factors; Weight Gain; Weight Loss

The objective was to determine the effect of central infusion of insulin and (or) glucose on hypothalamic expression of leptin receptor and pituitary secretion of LH in the ewe. Twenty-two ovariectomized ewes (32 wk of age) were fitted with two lateral cerebroventricular (LCV) cannulae and fed 33% of NRC requirements for 8 wk. Ewes (n> or =5/group) were then infused, via LCV cannulae, with artificial cerebrospinal fluid (aCSF) or aCSF containing physiological concentrations of insulin (INS), glucose (GLU), or INS + GLU; the mass of each increasing linearly from Day 0 (mass = 0 units/h) to Day 8 (mass of INS = 80 mIU/hr and GLU = 10 mg/hr). Jugular serum was collected every 12 min for 4 hr on Days 0, 2, and 4. Ewes treated with INS or INS + GLU had greater (P<0.06) mean concentrations of LH than aCSF treated ewes on Day 2 (13.8+/-1.8 and 12.5+/-1.3 > 8.0+/-3.3 ng/ml). Furthermore, on Day 4, concentrations of LH in INS treated ewes exceeded that (P<0.07) of aCSF treated ewes (14.8+/-2.0 > 7.4+/-3.0 ng/ml). Expression of NPY mRNA did not differ between treatments (P = 0.87). Leptin receptor mRNA expression was dramatically reduced (P<0.0002) in INS+GLU versus aCSF treated ewes. These data provide evidence to suggest that insulin may be an important component of hypothalamic mechanisms regulating secretion of LH and expression of leptin receptors in undernourished ruminants.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Carrier Proteins; Female; Food Deprivation; Glucose; Hypothalamus; In Situ Hybridization; Injections, Intraventricular; Insulin; Leptin; Luteinizing Hormone; Neuropeptide Y; Ovariectomy; Pituitary Gland; Pulsatile Flow; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger; Sheep; Weight Loss

Leptin exerts important regulating effects on energy homeostasis and could have a central role in our understanding of obesity, diabetes mellitus and the metabolic syndrome. Leptin circulates in a free and protein bound form. The aim of the present study was to test whether both fractions of the leptin system can be selectively regulated and thus serve independent physiological roles.. Using specific radioimmunoassays we measured both leptin components in relation to BMI in healthy subjects before and after weight reduction and in hyperthyroid patients during correction of thyrotoxicosis. In the latter group body composition and resting energy expenditure was monitored. In addition, we measured serum and cerebrospinal fluid concentrations of free and bound leptin in patients with neurological disorders.. Under all conditions free leptin concentrations reflected body fat mass. Bound leptin concentrations decreased during weight reduction but also after treatment of hyperthyroidism despite an increase in fat mass. Direct measurement of resting energy expenditure and bound leptin in hyperthyroid patients and under thyrostatic treatment showed a significant positive correlation of both variables. In contrast to free leptin whose transport into the cerebrospinal fluid appears to be saturated at low physiological concentrations of serum free leptin, bound leptin concentrations in the cerebrospinal fluid increased in parallel to serum concentrations over the whole physiologically relevant range.. Our data indicate a distinct role of free and bound leptin in the feedback regulating energy intake and expenditure and could have important implications for our understanding of the physiology and pathophysiology of leptin-dependent signalling.

Topics: Adolescent; Adult; Aged; Blood Proteins; Body Composition; Body Mass Index; Child; Energy Metabolism; Female; Homeostasis; Humans; Leptin; Middle Aged; Protein Binding; Weight Gain; Weight Loss

Weight gain and loss increases and decreases energy expenditure, respectively, out of proportion to changes in metabolic mass.. We hypothesized that changes in energy expenditure associated with weight gain or loss were due in part to changes in catecholamine release, thyroid hormones, carbohydrate utilization, or a combination thereof.. Urinary catecholamine excretion, serum thyroid hormone concentrations, and results of 3-h oral-glucose-tolerance tests were examined in obese and never-obese subjects at their usual weights, during weight loss or gain, and at stable weights 10-20% below or 10% above usual.. Urinary norepinephrine excretion decreased significantly during and after weight loss and increased during and after weight gain. Serum concentrations of reverse triiodothyronine increased significantly during and after weight loss, whereas serum concentrations of triiodothyronine increased significantly (by approximately 0%) during and after weight gain. Serum insulin and glucose concentrations during the oral-glucose-tolerance test increased significantly after weight gain in obese subjects. The percentage change in urinary norepinephrine excretion and in serum concentrations of triiodothyronine were significantly correlated with percentage changes in energy expenditure and with each other.. Changes in body weight were associated with changes in catecholamine excretion and thyroid hormones, which might-by virtue of the effects on energy expenditure-have favored a return to usual body weight. Weight gain induced more apparent insulin resistance in the obese than the never-obese subjects, suggesting a threshold effect of total body fat on this phenomenon.

Topics: Adult; Blood Glucose; Body Composition; Carbohydrate Metabolism; Catecholamines; Dopamine; Energy Metabolism; Female; Glucose Tolerance Test; Humans; Insulin; Leptin; Male; Norepinephrine; Obesity; Thyroid Gland; Triiodothyronine; Weight Gain; Weight Loss

The Koletsky ("corpulent) obese rat is homozygous for an autosomal recessive mutation of the leptin receptor (Lepr) that results in hyperphagia, obesity, and hyperlipidemia. Unlike the Lepr mutation that characterizes the fatty Zucker rat (Lepr(fa)), the Koletsky mutation (Lepr(fak)) is null. Because the Lepr(fak) mutation is null, exogenous leptin should have no effect on body weight or food intake in fa(k)/fa(k) rats. We confirmed that prediction: murine leptin, administered into the third ventricle for 5 consecutive days, did not affect daily food intake or body weight in fa(k)/fa(k) rats but produced dose-related inhibitions of food intake and body weight in +/+ and +/fa(k) rats. Although fa(k)/fa(k) rats did not respond to leptin, their response to CCK-8 (4 microg/kg ip) injected before 30-min test meals of 10% sucrose was not different from that of +/+ or +/fa(k) rats. These results demonstrate that the fa(k)/fa(k) rat is a good model in which to analyze the controls of food intake, energy expenditure, and energy storage in the absence of leptin effects.

Topics: Animals; Carrier Proteins; Dietary Sucrose; Disease Models, Animal; Eating; Injections, Intraventricular; Leptin; Obesity; Rats; Rats, Mutant Strains; Receptors, Cell Surface; Receptors, Leptin; Satiation; Sincalide; Weight Gain; Weight Loss

The aim of this study was to evaluate the relationship between changes in abdominal fat areas and the baseline serum leptin levels of Japanese obese women during weight reduction. The study was performed on 100 obese female Japanese volunteers. We measured the BMI and abdominal fat areas (visceral, subcutaneous and total) by magnetic resonance imaging and determined the fasting serum leptin levels before and after a 3 month weight reduction program. We examined whether or not a relationship exists between the baseline leptin levels and the subsequent changes in the abdominal fat areas after a weight reduction program. Multiple linear regression analysis was performed to examine the relationship between the baseline leptin levels and changes in abdominal visceral, subcutaneous, and total fat areas, and demonstrated that the baseline leptin level was a significant predictive factor for changes in the abdominal visceral fat area in both pre and postmenopausal Japanese obese women. We thus concluded the relatively higher baseline leptin levels in Japanese obese women to be associated with a relatively smaller reduction in the amount of abdominal visceral fat after undergoing a weight reduction program.

Topics: Abdomen; Adult; Fats; Female; Humans; Leptin; Obesity; Weight Loss

The management of food animals prior to slaughter influences both profitability and animal well-being. This experiment was conducted as a split-unit design to determine live weight shrink and stress responses in goats due to differences in stocking density during transportation and holding. A total of 150 Spanish does were transported on two different days (replicate) and held overnight (18 h) without feed in low- (LD) or high-density (HD) groups. On each day, 75 does were transported 2.5 h with floor spaces of .18 m2 and .37 m2/animal in LD (25 does) and HD (50 does) groups, respectively. The average temperatures in the trailer during transportation were 34.6 and 35 degrees C, respectively, on d 1 and 2. All animals were blood-sampled before loading (PRELOAD) and four does from each treatment were sampled immediately after loading (POSTLOAD). Animals were blood-sampled in holding pens either at 0, 1, 2, 3, 4, or 18 h after transportation (time) to assess the time course (n = 8 does per time per replicate) of stress responses. Individual animals were weighed just before loading onto a trailer and after overnight holding to assess shrinkage. Treatment or treatment x time did not have a significant effect on any of the dependent variables studied. There were significant effects of time (P < .01) on plasma cortisol, glucose, and urea nitrogen (PUN) concentrations. Time also had significant effects (P < .01) on plasma creatine kinase (CK) activity, differential leukocyte counts (neutrophils, lymphocytes, monocytes, and eosinophils), and ratio of neutrophils to lymphocytes (N:L). However, plasma leptin concentrations were not influenced by time. Cortisol concentrations increased at POSTLOAD sampling, peaked at 0 h, and decreased thereafter before spiking again at 18 h of holding. The PUN was higher at 18 h than at other time periods studied. Plasma glucose concentrations increased and remained at higher levels at 0, 1, and 2 h and began decreasing at 3 h, reaching PRELOAD levels at 18 h. Plasma CK kinase activity peaked at approximately 2 h after transportation. The N:L ratio was higher at all time periods after transportation than prior to starting the journey, indicating a prolonged effect of transportation stress on the immune system. The mean (+/- SE) shrinkage losses were 10.2 +/- .68 and 9.8 +/- .68 in HD and LD treatment groups, respectively. The results indicate that the stress responses of goats due to transportation begin decreasing within 3 h after

Topics: Animals; Blood Glucose; Blood Urea Nitrogen; Creatine Kinase; Goat Diseases; Goats; Hydrocortisone; Leptin; Stress, Physiological; Transportation; Weight Loss

With the escalation of obesity-related disease, there is great interest in defining the mechanisms that control appetite and body weight. We have identified a link between anabolic energy metabolism and appetite control. Both systemic and intracerebroventricular treatment of mice with fatty acid synthase (FAS) inhibitors (cerulenin and a synthetic compound C75) led to inhibition of feeding and dramatic weight loss. C75 inhibited expression of the prophagic signal neuropeptide Y in the hypothalamus and acted in a leptin-independent manner that appears to be mediated by malonyl-coenzyme A. Thus, FAS may represent an important link in feeding regulation and may be a potential therapeutic target.

Topics: Acetyl-CoA Carboxylase; Animals; Appetite; Appetite Depressants; Cerulenin; Dose-Response Relationship, Drug; Eating; Enzyme Inhibitors; Fasting; Fatty Acid Synthases; Female; Hypothalamus; Injections, Intraventricular; Leptin; Liver; Male; Malonyl Coenzyme A; Mice; Mice, Inbred BALB C; Neurons; Neuropeptide Y; RNA, Messenger; Weight Loss

The aim of the present study was to determine the impact of weight loss on appetite as measured by visual analog scale (VAS).. Seventeen subjects (10 men and seven women) took part in a 15 week weight loss program which consisted of drug therapy (fenfluramine 60 mg/day) or placebo coupled to an energy restriction (-2930 kJ/day; phase 1) followed by an 18 week low-fat diet-exercise follow-up (phase 2). Subjects were given a standardized breakfast before and after phase 1 as well as after phase 2. Individuals were asked to fill out VAS before and at 0, 10, 20, 30, 40, 50 and 60 min after this test meal. Blood samples were drawn before the meal and at 0, 30 and 60 min postprandially and analyzed for glucose and insulin. Fasting plasma cortisol and leptin were also determined.. An increase in the fasting desire to eat, hunger and prospective food consumption (PFC) was observed after phase 1 and to an even greater extent after phase 2 in both men and women. In the fasting state, positive correlations were observed between changes in the desire to eat (r=0.76; P<0.05) as well as changes of PFC (r=0. 82; P<0.05) and changes in cortisol at the end of phase 1 for women. In response to phase 1, statistically significant correlations were found between changes of hunger (r=0.64; P<0.05) and desire to eat (r=0.67; P<0.05) as measured by AUC in response to the meal and changes of fasting plasma cortisol in men. The most consistent predictor of changes of baseline desire to eat (r=0.68 P<0.05), fullness (r=-0.78, P<0.05) and PFC (r=0.91, P<0.01) during phase 2 was the change in fasting cortisol in men. Changes of fullness were also associated with changes of fasting leptin in men (r=0.68; P<0. 05) during phase 2.. These results suggest that weight loss is accompanied by an increase of baseline appetite in both men and women and that the most consistent predictor of these changes in appetite seems to be changes in fasting plasma cortisol.

Topics: Adult; Appetite; Area Under Curve; Diet, Fat-Restricted; Energy Intake; Exercise; Fasting; Female; Fenfluramine; Glucose; Humans; Hydrocortisone; Insulin; Leptin; Male; Middle Aged; Obesity; Postprandial Period; Weight Loss

Ciliary neurotrophic factor (CNTF), a cytokine of the interleukin-6 superfamily, has been shown to induce hypophagia and weight loss. Neuropeptide Y (NPY) and orexin are potent orexigenic signals in the hypothalamus. Anorexia, normally seen in response to infection, injury and inflammation, may result from diminished hypothalamic orexigenic signalling caused by persistently elevated cytokines, including CNTF. To test this hypothesis, we first examined the effects of chronic intracerebroventricular (i.c.v.) infusion of CNTF for 6-7 days on food intake and body weight as well as hypothalamic NPY and orexin gene expression in male rats. Subsequently, the effectiveness of NPY replacement to counteract the effects of CNTF by coinfusion of NPY and CNTF was evaluated. Chronic i.c.v. infusion of CNTF (2.5 microg/day) reduced body weight (14.3% vs control) at the end of 7 days. Food intake remained suppressed for 5 days postinfusion and subsequently gradually returned to the control range by day 7. Serum leptin concentrations in these rats were in the same range seen in control rats. Chronic i.c.v. infusion of higher doses of CNTF (5.0 microg/day) produced sustained anorexia and body weight loss (29% vs controls) through the entire duration of the experiment. This severe anorexia was accompanied by markedly suppressed serum leptin concentrations. Furthermore, CNTF infusion alone significantly reduced hypothalamic NPY gene expression (P < 0. 05) without affecting orexin gene expression. As expected, in fusion of NPY alone (18 microg/day) augmented food intake (191.6% over the initial control, P < 0.05) and produced a 25.1% weight gain in conjunction with a 10-fold increase in serum leptin concentrations at the end of the 7-day period. Interestingly, coinfusion of this regimen of NPY with the highly effective anorectic and body reducing effects of CNTF (5.0 microg/day) not only prevented the CNTF-induced anorexia and weight loss, but also normalized serum leptin concentrations and hypothalamic NPY gene expression. These results demonstrate that chronic central infusion to produce a persistent elevation of the cytokine at pathophysiological levels (a situation that may normally manifest during infection, injury and inflammation) produced severe anorexia and weight loss in conjunction with reduction in both serum leptin concentrations and hypothalamic NPY gene expression. Reinstatement of hypothalamic NPY signalling by coinfusion of NPY counteracted these CNTF-induced

Topics: Animals; Anorexia; Brain; Ciliary Neurotrophic Factor; Eating; Gene Expression; Hypothalamus; Leptin; Male; Neuropeptide Y; Neuropeptides; Rats; Rats, Sprague-Dawley; RNA, Messenger; Weight Loss

Topics: Adipose Tissue; Animals; Carrier Proteins; Fatty Acids, Nonesterified; Food; Food Deprivation; Gene Expression; Ion Channels; Leptin; Mitochondrial Proteins; Muscle, Skeletal; Rats; Rats, Zucker; RNA, Messenger; Uncoupling Protein 3; Weight Loss

We compared the effects of hypothalamic obesity induced by neonatal monosodium glutamate (MSG) treatment between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Newborn WKY and SHR were injected intraperitoneally with 4 mg/kg body weight of MSG daily for 5 days. At 6 months of age, the obesity of SHR was more advanced than that of WKY, but at 14 months of age the severity of obesity was similar between the two strains. Hypertriglyceridemia was enhanced in MSG-treated SHR as compared with MSG-treated WKY. Systolic blood pressure measured by the tail-cuff method was consistently lower in MSG-treated SHR than in control SHR, whereas blood pressure was not affected by neonatal MSG treatment in WKY. Food restriction reduced body weight more in control SHR than in control WKY, with the former also showing enhanced ketogenesis. Neonatal MSG treatment abolished the accelerated reduction of body weight in SHR. Serum leptin concentration was markedly increased in MSG-treated obese rats, though no differences were seen between WKY and SHR in the control or MSG-treated groups. Serum leptin was closely correlated with both Lee obese index and mesenteric fat weight over the strain. Blood flow in interscapular brown adipose tissue (BAT) measured by Laser Doppler flowmetry was significantly increased in response to beta3-adrenoceptor agonist BRL26830A in both the control and MSG-treated rats. However, the response of blood flow was not affected by MSG treatment or strain difference. The present study demonstrated some strain differences in response to neonatal MSG treatment between WKY and SHR. These differences could not be explained by the difference in serum leptin level or beta3-adrenergic reactivity in BAT.

Topics: Adipose Tissue, Brown; Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Agonists; Animals; Blood Pressure; Disease Models, Animal; Energy Intake; Ethanolamines; Female; Food Additives; Hypertension; Leptin; Male; Obesity; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Regional Blood Flow; Sodium Glutamate; Weight Loss

Striking the delicate balance between energy intake in the form of food and energy expenditure in the form of metabolic activity keeps the body extremely busy. As Schwartz explains in his enlightening Perspective, the finding that insulin signals the brain to promote weight loss (Brüning et al.) flies in the face of the notion that insulin is involved solely in glucose storage, its conversion to fat, and weight gain.

Topics: Adipocytes; Animals; Blood Glucose; Body Weight; Brain; Eating; Female; Insulin; Leptin; Male; Mice; Neurons; Obesity; Receptor, Insulin; Signal Transduction; Weight Loss

The present study was conducted in order to analyze the relationship existing between leptin and insulin levels in massive weight loss and weight recovery. Thirteen patients with severe obesity, 14 patients with anorexia nervosa and 13 healthy control subjects were studied. The patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet for 12 weeks. They were evaluated prior to (body mass index [BMI] 51.2 +/- 8.8 Kg/m2) and after drastic weight loss (BMI 40.6 +/- 6.7 Kg/m2). Patients with anorexia nervosa were treated exclusively with nutritional therapy during 12 weeks, and they were evaluated at their lowest weight status (BMI 16.2 +/- 2.2 Kg/m2) and after weight recovery (BMI 17.9 +/- 2.3 Kg/m2). The BMI of the normal subjects was in the normal range of 20 to 27 Kg/m2 (average 22.8 +/- 2.6 Kg/m2). BMI, percentage of body fat, waist circumference, and serum levels of leptin, insulin, and C-peptide were determined in each patient and normal subject. In severely obese patients, serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 51.8 +/- 22.3 to 23.7 +/- 10.2 ng/ml; insulin: from 27.1 +/- 13.3 to 17.2 +/- 7.2 mU/ml). In patients with anorexia nervosa, the mean serum leptin levels were significantly higher after weight recovery (5.5 +/- 3.2 vs 7.6 +/- 6 ng/ml). Serum leptin in the severe obesity group correlated positively with BMI, percentage body fat and waist circumference before and after weight loss. In those patients suffering from anorexia nervosa, serum leptin correlated positively with the BMI, percentage of body fat, and waist circumference in the low weight state and after weight recovery. In addition, their serum insulin correlated with BMI and waist circumference after weight recovery. These data reveal that serum leptin concentration correlates significantly with the BMI and body fat content 1) in subjects with a range of weight and caloric intake, 2) in obese patients after drastic weight loss; 3) in anorexic patients after weight gain; and that hyper- or normoinsulinemia do not seem to have any influence on the leptin changes caused by weight loss or gain.

Topics: Adipose Tissue; Adolescent; Adult; Anorexia Nervosa; Anthropometry; Body Mass Index; C-Peptide; Combined Modality Therapy; Female; Gastroplasty; Humans; Hyperinsulinism; Insulin; Leptin; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Weight Gain; Weight Loss

The aim of the present study was to identify predictors of weight loss in obese men participating in a 2-year behaviour modification programme.. Longitudinal, clinical intervention study of a behaviour modifying weight loss program.. University Hospital, Stockholm, Sweden.. Forty-four obese men (age, 42.7 +/- 1.1 years: BMI, 37.1 +/- 0.6 kg m(-2), mean +/- SEM) followed for 2 years.. Behaviour modification weight loss programme.. Associations between plasma leptin and thyroid function tests, insulin resistance by homeostatic model assessment (HOMA), dietary recall and anthropometrically determined body composition.. At baseline, there were significant correlations between plasma leptin and body mass index (BMI), fat-free mass (FFM) and insulin resistance. Median weight loss over 2 years was 4.9 kg (range, -27.2 to +11.9). Baseline serum leptin concentrations adjusted for BMI (leptin/BMI ratio) were significantly correlated with 2-year weight change (r = 0.34, P = 0.04). A subset of seven of the 44 men gained weight over the 2 years. These 'gainers' differed significantly in initial leptin/BMI ratio (0.62 +/- 0.07) compared with the 37 'losers' (0.42 +/- 0.03, P < 0.05). In a multiple regression model, baseline leptin, insulin and age predicted 22% of the variance in weight change with no additional significant contribution from BMI, FFM, waist:hip ratio, thyroid function tests or energy intake. There was a strong correlation between the change in leptin concentrations and the change in insulin resistance from baseline to 2-year follow-up (r = 0.54; P < 0.001).. Baseline plasma leptin concentrations predicted long-term weight loss. Inappropriate leptin secretion or disposal, corrected for BMI, was associated with failure to maintain weight loss in obese men in a behaviour modification weight loss programme.

Topics: Adult; Age Factors; Behavior Therapy; Body Composition; Body Mass Index; Diet, Reducing; Energy Metabolism; Humans; Insulin Resistance; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity; Predictive Value of Tests; Regression Analysis; Retrospective Studies; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine; Weight Loss

A role for leptin to predict weight gain is still controversial.. To determine the relationship between baseline serum leptin values and responsiveness to an educational-based weight excess reduction program (WERP), 418 (241 males and 185 females) obese subjects, aged 9-15 y, were recruited. WERP required 2 y of follow-up. Body mass index (BMI) was evaluated at baseline and at each semester of follow-up. The obese subjects were subdivided into responsives and non-responsives, according to reduction or not of their BMI Z-scores during the WERP. Leptin concentrations were assayed at baseline and were included together with other independent variables in statistical multiple regression analysis.. At a preliminary multiple regression analysis, a significant positive correlation between leptin values and BMI Z-score reduction at the second, third and fourth semester of follow-up was registered. To determine the odds ratio of the subjects who were responsive or non-responsive at the various semesters of WERP follow-up, a stepwise logistic regression was used incorporating the same predictors, with the serum leptin values subdivided into quintiles and responsiveness and non-responsiveness as a binary outcome variable. The model offered a satisfying goodness of fit as shown by the sensitivity and specificity. The odds ratio of being responsive were significantly increased by greater quintiles of leptin serum concentrations. Furthermore, such odds ratios were much higher in pubertal than in prepubertal subjects.. These findings support a significant role for serum leptin concentration in predicting BMI changes as a response to an educational excess weight reduction program.

Topics: Adolescent; Behavior Therapy; Body Mass Index; Child; Exercise; Female; Humans; Leptin; Linear Models; Male; Obesity; Odds Ratio; Patient Education as Topic; Treatment Outcome; Weight Loss

Short stature can be a severe side-effect of bone marrow transplantation (BMT). Because of the effect of weight changes on growth rate and on plasma insulin-like growth factor (IGF I), we analyzed changes in height and body mass index (BMI) in 53 patients given BMT. Group 1 (n = 22) was given 12 Gy total body irradiation (TBI) as six fractions, group 2 (n = 14) 10 Gy TBI (one dose), group 3 (n = 8) 6 Gy total lymphoid irradiation (one dose), and group 4 (n = 9) chemotherapy alone. At the first evaluation, 13/36 patients in groups 1 and 2 had low growth hormone (GH) peaks after stimulation. The mean plasma IGF I concentrations (z score) were similar in groups 1 (-2.9 +/- 0.3) and 2 (-2.5 +/- 0.3), and in groups 3 (-1.4 +/- 0.3) and 4 (-1.4 +/- 0.7), but those of group 1 were lower than those of groups 3 (P < 0.01) and 4 (P < 0.05), and those of group 2 than those of group 3 (P < 0.05). BMI during the 5 years after BMT did not change in groups 1 and 2, decreased in group 3, and increased in group 4. However, these changes were not significant. Most of the patients given TBI had BMI below the mean at 2 (66%) and 5 (57%) years later. Their BMI and leptin concentrations correlated positively with each other (P = 0.005), and negatively with GH peak (P = 0.02 for BMI and 0.007 for leptin). In conclusion, this study suggests that TBI actually decreases GH secretion and is followed by a persistent low BMI. The negative relationship between GH peak and leptin may indicate that both are markers of a TBI-induced hypothalamic-pituitary lesion.

Topics: Adolescent; Adult; Body Height; Body Mass Index; Body Weight; Bone Marrow Transplantation; Child; Child, Preschool; Female; Follow-Up Studies; Growth Disorders; Human Growth Hormone; Humans; Infant; Insulin-Like Growth Factor I; Leptin; Male; Middle Aged; Transplantation Conditioning; Weight Loss; Whole-Body Irradiation