leptin and Weight-Gain

Topics: Breast Feeding; Female; Ghrelin; Humans; Infant; Leptin; Milk, Human; Weight Gain

Although numerous studies investigated the effect of UASMS2 polymorphism in leptin gene on cattle production, a consensus has not yet been reached. Therefore, we reviewed and meta-analyzed the effects of UASMS2 on cattle. We searched potentially relevant studies from seven databases (to December 25, 2019). Standard mean difference along with 95% confidence intervals was calculated to assess the strength of association through the random-effects model. Six published articles containing 1378 cattle samples were included in our meta-analysis. We found UASMS2 was not related to carcass weight, dressing percentage and loin muscle area in the recessive genetic model, but there was a significant association between UASMS2 and average daily weight gain, dry matter intake, body weight, marbling score, and backfat thickness. This meta-analysis indicated that UASMS2 was associated with growth and meat quality traits of cattle, implying that this SNP can be used reliably in beef cattle breeding. This study may provide valuable information on improving beef yield and quality in cattle production.

Topics: Animals; Cattle; Leptin; Meat; Phenotype; Polymorphism, Single Nucleotide; Weight Gain

Obesity, which has long since reached epidemic proportions worldwide, is associated with long-term stress to a variety of organs and results in diseases including type 2 diabetes. In the brain, overnutrition induces hypothalamic stress associated with the activation of several signalling pathways, together with central insulin and leptin resistance. This central action of nutrient overload appears very rapidly, suggesting that nutrition-induced hypothalamic stress is a major upstream initiator of obesity and associated diseases. The cellular response to nutrient overload includes the activation of the stress-activated c-Jun N-terminal kinases (JNKs) JNK1, JNK2 and JNK3, which are widely expressed in the brain. Here, we review recent findings on the regulation and effects of these kinases, with particular focus on the hypothalamus, a key brain region in the control of energy and glucose homeostasis. JNK1 blocks the hypothalamic-pituitary-thyroid axis, reducing energy expenditure and promoting obesity. Recently, opposing roles have been identified for JNK1 and JNK3 in hypothalamic agouti gene-related protein (AgRP) neurons: while JNK1 activation in AgRP neurons induces feeding and weight gain and impairs insulin and leptin signalling, JNK3 (also known as MAPK10) deletion in the same neuronal population produces very similar effects. The opposing roles of these kinases, and the unknown role of hypothalamic JNK2, reflect the complexity of JNK biology. Future studies should address the specific function of each kinase, not only in different neuronal subsets, but also in non-neuronal cells in the central nervous system. Decoding the puzzle of brain stress kinases will help to define the central stimuli and mechanisms implicated in the control of energy balance. Graphical abstract.

Topics: Agouti-Related Protein; Animals; Brain; Endoplasmic Reticulum Stress; Energy Metabolism; Feeding Behavior; Glucose; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Insulin; JNK Mitogen-Activated Protein Kinases; Leptin; Metabolic Diseases; Mitogen-Activated Protein Kinase 10; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase 9; Neurons; Obesity; Thyroid Gland; Weight Gain

There are different changes observed before and after diet therapy, and also after weight regain. However, there is not sufficient information regarding weight regain and hormonal changes.. The purpose of this study was to review the connection between weight regain and leptin concentration levels.. MEDLINE, SCOPUS, Web of Science, and the Cochrane Library were searched for interventional articles published from January 1, 1980, to June 30, 2020. Randomized clinical trials with parallel or cross over design assessing leptin concentrations at the baseline and at the end of study were reviewed. Two independent reviewers extracted data related to study design, year of publication, country, age, gender, body mass index (BMI), duration of the following up period and mean ± SD of other intended variables.. Four articles were included, published between 2004 and 2016. Three of them were conducted in the US and one of them in Netherland. Sample size of the studies ranged between 25 and 148 participants. The range of following up period was from13 to 48 weeks. The age range of participants was from 34 to 44 years. Our analysis shows that weight regain could reduce leptin levels, but this change is not statistically significant.. This review suggests that weight regain may induce a non-significant reduction in leptin level. However, the limited number and great heterogeneity between the included studies may affect the presented results and there are still need to well-designed, large population studies to determine the relationship between weight regain and leptin levels.

Topics: Adult; Humans; Leptin; Publication Bias; Risk; Weight Gain

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

Antipsychotic-induced weight gain is the most prevalent somatic adverse event occurring in patients treated by antipsychotics, especially atypical antipsychotics. It is of particular interest because of its repercussion on cardiovascular morbidity and mortality especially now that the use of second-generation antipsychotics has been extended to other mental health illnesses such as bipolar disorders and major depressive disorder. The mechanism underlying antipsychotics-induced weight gain is still poorly understood despite a significant amount of work on the topic. Recently, there has been an on-going debate of tremendous research interest on the relationship between antipsychotic-induced weight gain and body weight regulatory hormones such as leptin. Given that, researchers have brought to light the question of leptin's role in antipsychotic-induced weight gain. Here we summarize and discuss the existing evidence on the link between leptin and weight gain related to antipsychotic drugs, especially atypical antipsychotics.

Topics: Antipsychotic Agents; Depressive Disorder, Major; Female; Humans; Leptin; Male; Weight Gain

Epidemiological evidence indicates the presence of dysregulated homeostatic biological pathways in depressed patients, such as increased inflammation and disrupted energy-regulating neuroendocrine signaling (e.g., leptin, insulin). Alterations in these biological pathways may explain the considerable comorbidity between depression and cardiometabolic conditions (e.g., obesity, metabolic syndrome, diabetes) and represent a promising target for intervention. This review describes how immunometabolic dysregulations vary as a function of depression heterogeneity by illustrating that such biological dysregulations map more consistently to atypical behavioral symptoms reflecting altered energy intake/expenditure balance (hyperphagia, weight gain, hypersomnia, fatigue, and leaden paralysis) and may moderate the antidepressant effects of standard or novel (e.g., anti-inflammatory) therapeutic approaches. These lines of evidence are integrated in a conceptual model of immunometabolic depression emerging from the clustering of immunometabolic biological dysregulations and specific behavioral symptoms. The review finally elicits questions to be answered by future research and describes how the immunometabolic depression dimension could be used to dissect the heterogeneity of depression and potentially to match subgroups of patients to specific treatments with higher likelihood of clinical success.

Topics: Depression; Humans; Leptin; Metabolic Syndrome; Obesity; Weight Gain

Antipsychotics, especially most of the second-generation antipsychotics, have a high risk for metabolic syndrome and antipsychotic-induced weight gain (AIWG). A promoter variant of the leptin (LEP) gene, -2548G/A (rs7799039), has been associated with AIWG in several studies. The aim of this study was to evaluate this association in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sample, followed by meta-analysis.. We investigated the association between rs7799039 and AIWG in a sub-sample of European (N = 164) individuals from the CATIE study. Body mass index (BMI) change and weight gain (presence or absence) was analyzed using ANCOVA and logistic regression, respectively. For the meta-analysis, a literature search was conducted using MEDLINE, Embase, and PsycINFO up to October 2019. The pooled odds ratio was calculated for presence or absence of weight gain (≥7% weight change) using a random effects model.. We did not detect an association between rs7799039 and BMI change or weight gain (presence or absence) in the CATIE sample. As for the meta-analysis, we included 12 studies. No significant associations between the LEP rs7799039 polymorphism and AIWG were observed under the allelic genetic model (allele A vs. allele G) (OR = 1.10 [0.71, 1.70], p = .68). In the subgroup analyses of first-episode schizophrenia patients, a significant association between the A-allele and weight gain was observed, respectively (OR = 2.32 [1.41, 3.82], p = .0009).. The present meta-analysis showed no significant effect of rs7799039 on AIWG. However, this variant may influence AIWG in first-episode schizophrenia patients. Further investigation of a larger and more homogenous sample is required to elucidate the role of the LEP gene in AIWG.

Topics: Alleles; Antipsychotic Agents; Body Mass Index; Humans; Leptin; Polymorphism, Genetic; Schizophrenia; Weight Gain

Leptin, a hormone that is capable of effectively reducing food intake and body weight, was initially considered for use in the treatment of obesity. However, obese subjects have since been found to have high levels of circulating leptin and to be insensitive to the exogenous administration of leptin. The inability of leptin to exert its anorexigenic effects in obese individuals, and therefore, the lack of clinical utility of leptin in obesity, is defined as leptin resistance. This phenomenon has not yet been adequately characterized. Elucidation of the molecular mechanisms underlying leptin resistance is of vital importance for the application of leptin as an effective treatment for obesity. Leptin must cross the blood-brain barrier (BBB) to reach the hypothalamus and exert its anorexigenic functions. The mechanisms involved in leptin transportation across the blood-brain barrier continue to be unclear, thereby preventing the clinical application of leptin in the treatment of obesity. In recent years, new strategies have been developed to recover the response to leptin in obesity. We have summarized these strategies in this review.

Topics: Adiposity; Anti-Obesity Agents; Blood-Brain Barrier; Brain; Capillary Permeability; Feeding Behavior; Humans; Leptin; Obesity; Signal Transduction; Weight Gain

Decreased mineral density is one of the major complications of anorexia nervosa. The phenomenon is even more pronounced when the disease occurs during adolescence and when the duration of amenorrhoea is long. The mechanisms underlying bone loss in anorexia are complex. Oestrogen deficiency has long been considered as the main factor, but cannot explain the phenomenon on its own. The essential role of nutrition-related factors-especially leptin and adiponectin-has been reported in recent studies. Therapeutic strategies to mitigate bone involvement in anorexia are still a matter for debate. Although resumption of menses and weight recovery appear to be essential, they are not always accompanied by a total reversal of bone loss. There are no studies in the literature demonstrating that oestrogen treatment is effective, and the best results seem to have been obtained with agents that induce bone formation-such as IGF-1-especially when associated with oestrogen. As such, bone management in anorexia remains difficult, hence, the importance of early detection and multidisciplinary follow-up.

Topics: Absorptiometry, Photon; Adiponectin; Amenorrhea; Anorexia Nervosa; Bone Density; Bone Density Conservation Agents; Drug Therapy, Combination; Estrogens; Exercise; Female; Humans; Insulin-Like Growth Factor I; Leptin; Lipolysis; Osteoporosis; Recombinant Proteins; Treatment Outcome; Weight Gain

Epidemiological studies suggested an association between obesity and sleep disturbances. Obstructive sleep apnea is the most prevalent type of obesity-related sleep disorder that lead to an increased risk for numerous chronic health conditions. In addition the increased visceral adipose tissue might be responsible for the secretion of inflammatory cytokines that could contribute to alter the sleep-wake rhythm. Unhealthy food characterized by high consumption of fat and carbohydrate seems to negatively influence the quality of sleep while diet rich of fiber is associated to more restorative and deeper sleep. Although obesity could cause through several pathogenetic mechanisms an alteration of sleep, it has been reported that subjects suffering from sleep disorders are more prone to develop obesity. Experimental laboratory studies have demonstrated that decreasing either the amount or quality of sleep increase the risk of developing obesity. Experimental sleep restriction also causes physiological, hormonal and food behavioral changes that promote a positive energy balance and a compensatory disproportionate increase in food intake, decrease in physical activity, and weight gain. Thus, the aim of this review is to provide observational evidence on the association of obesity with sleep disturbances and

Topics: Diet; Endocannabinoids; Energy Metabolism; Exercise; Ghrelin; Humans; Hydrocortisone; Leptin; Melatonin; Obesity; Sleep Apnea, Obstructive; Sleep Wake Disorders; Weight Gain

Changes in added sugar intake have been associated with corresponding changes in body weight. Potential mechanisms, particularly the impact of added sugar intake on appetite, warrant exploration. A systematic literature review of randomised controlled trials investigated the association between added sugar consumption and appetite in overweight and obese adults. A systematic search of Medline, Cochrane CENTRAL, Web of Science and CINAHL included studies that examined the relationship between added sugar intake and appetite markers, in comparison with a group with lower added sugar intake. A total of twenty-one articles describing nineteen studies were included in the review. The effect of added sugar on appetite was explored separately by reported comparisons of added sugar type and their effect to three study outcomes: energy consumption (n 20 comparisons); satiety (n 18); and appetite hormones, leptin (n 4) or ghrelin (n 7). Increased added sugar consumption did not impact subsequent energy intake (n 9), nor did it influence satiety (n 12) or ghrelin levels (n 4). Differences in the total daily energy intake were comparable with the differences in energy values of tested products (n 3). Added sugar intake was reported to increase leptin levels (n 3). This review did not find a consistent relationship between added sugar intake and appetite measures, which may be partially explained by variations in study methodologies. There is a need for randomised controlled trials examining a range of added sugar sources and doses on appetite in overweight and obese adults to better understand implications for weight gain.

Topics: Adult; Appetite; Body Mass Index; Diet; Dietary Sugars; Energy Intake; Female; Ghrelin; Humans; Leptin; Male; MEDLINE; Middle Aged; Obesity; Overweight; Satiation; Weight Gain

Breastfed infants have a growth pattern that is different from formula-fed infants, which is regarded as the optimal growth pattern. Breastfed infants increase more in weight, length, and BMI during the first 2-3 months of life and then have a slower growth velocity up to 12 months. They also have a higher accumulation of fat during early infancy. Breastfed infants have lower levels of circulating IGF-I and insulin, which could be part of the explanation of their growth pattern. Many studies and meta-analyses have examined the association between breastfeeding and later obesity. Most find a moderate reduction in the risk of later obesity, but it has been argued that this could be biased due to residual confounding and reverse causation. From studies in low- and middle-income countries randomizing women to breastfeeding promotion, there was only little effect on early growth. Recent studies have found associations between breast milk composition (total fat, protein, human milk oligosaccharides, adiponectin, leptin, and insulin) and growth. However, the studies are few, and the results are inconsistent. More studies, including studies of maternal factors influencing breast milk composition, are needed to better understand how breastfeeding influences current and later growth and thereby short- and long-term health.

Topics: Adiponectin; Body Composition; Body Height; Body Mass Index; Body Weight; Breast Feeding; Child; Child, Preschool; Fats; Female; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Leptin; Milk Proteins; Milk, Human; Obesity; Oligosaccharides; Poverty; Somatomedins; Weight Gain

Obesity is a global health problem even among pregnant women. Obesity alters quality of labor, such as preterm labor, prolonged labor, and higher oxytocin requirements in pregnant women. The most important factors to play a role in the altered gestational period and serve as drug targets to treat the consequences are female sexual hormones, calcium channels, adrenergic system, oxytocin, and prostaglandins. However, we have limited information about the impact of obesity on the pregnant uterine contractility and gestation time. Adipose tissue, which is the largest endocrine and paracrine organ, especially in obesity, is responsible for the production of adipokines and various cytokines and chemokines, and there are no reliable data available describing the relation between body mass index, glucose intolerance, and adipokines during pregnancy. Recent data suggest that the dysregulation of leptin, adiponectin, and kisspeptin during pregnancy contributes to gestational diabetes mellitus and pre-eclampsia. A preclinical method for obese pregnancy should be developed to clarify the action of adipokines and assess their impact in obesity. The deeper understanding of the adipokines-induced processes in obese pregnancy may be a step closer to the prevention and therapy of preterm delivery or prolonged pregnancy. Gestational weight gain is one of the factors that could influence the prenatal development, birth weight, and adiposity of newborn.

Topics: Adipokines; Adiponectin; Birth Weight; Body Mass Index; Female; Gestational Age; Humans; Infant, Newborn; Kisspeptins; Leptin; Obesity; Pregnancy; Uterus; Weight Gain

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

Topics: Abdominal Fat; Adiponectin; Body Composition; Body Mass Index; Breast Feeding; Child; Child, Preschool; Dietary Proteins; Growth; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Leptin; Maternal Health; Milk, Human; Obesity; Pediatric Obesity; Risk Factors; Weight Gain; Young Adult

Topics: Adolescent; Amino Acids; Animals; Body Height; Child; Child Nutrition Disorders; Child, Preschool; Dietary Supplements; Gastrointestinal Microbiome; Growth; HIV Infections; Humans; Infant; Infant Nutrition Disorders; Insulin-Like Growth Factor I; Leptin; Nutritional Physiological Phenomena; Puberty; Randomized Controlled Trials as Topic; Rats; Weight Gain

Leptin protein consists of 167 amino acids, which is mainly secreted from the white adipose tissue. This protein acts on the hypothalamic regions of the brain which control eating behavior, thus playing a significant role in maintaining body's metabolism. Leptin receptors belong to glycoprotein 130 (gp130) family of cytokine receptors and exist in six isoforms (LEPR a-f), and all the isoforms are encoded by LEPR gene; out of these isoforms, the LEPR-b receptor is the 'longest form,' and in most of the cases, mutations in this isoform cause severe obesity. Also, mutations in the leptin gene (LEP) or its receptors gene can lead to obesity. Some biochemical pathways affect the bioactivity of leptin and/or its receptors. To date, eleven pathogenic mutations have been reported in the LEP which are p.L72S, p.N103K, p.R105W, p.H118L, p.S141C, p.W121X c.104_106delTCA, c.135del3bp, c.398delG, c.481_482delCT, and c.163C>T. Different mutations in the LEPR have also been reported as c.2396-1 G>T, c.1675 G>A, p.P316T, etc. In some studies, where leptin was deficient, leptin replacement therapy has shown positive impact by preventing weight gain and obesity.

Topics: Genetic Predisposition to Disease; Humans; Leptin; Mutation; Obesity; Receptors, Leptin; Weight Gain

Weight gain is a major side effect of antipsychotics (APs), which contributes to poor treatment adherence and significant morbidity. The mechanisms involved in AP-induced weight gain are incompletely understood. Recently, it has been proposed that changes in leptin, an cadipocyte-derived hormone exerting anorexigenic effects, may be involved in AP-induced weight gain. Thus far, studies on leptin changes during AP treatment have produced inconsistent results, prompting our group to perform a meta-analysis.. A search of the literature was performed using PubMed and Embase. Studies were included only if reporting peripheral levels of leptin before and after AP treatment in schizophrenia. Effect size estimates were calculated with Hedges g and were aggregated using a random effects model as results were heterogeneous (P<0.10). Meta-regression analyses were performed using study length and changes in body mass index (BMI) as moderator variables.. Twenty-eight studies were retrieved, including 39 comparisons. A moderate and positive effect size was observed across studies. Olanzapine, clozapine, and quetiapine produced moderate leptin elevations, whereas haloperidol and risperidone were associated with small (nonsignificant) leptin changes. Across studies, BMI changes were significantly associated with increases in leptin levels. There was no effect of sex on AP-induced changes in leptin.. A physiological role of leptin in AP-induced weight gain is supported because the most significant leptin increases were observed with APs inducing the most weight gain and because of the observed association between leptin increases and BMI changes. The overall increase in leptin levels suggests that leptin acts as a negative feedback signal in the event of fat increase.

Topics: Antipsychotic Agents; Humans; Leptin; Schizophrenia; Weight Gain

Recent epidemiological and ecological trends in humans indicate a possible causal relationship between sleep duration and energy balance. We aimed to find experimental evidence that has tested this relationship between sleep duration and measures of body composition, food intake or biomarkers related to food intake. We conducted a systematic literature review using six databases throughout 7 August 2014. We sought reports of randomized controlled trials where sleep duration was manipulated and measured outcomes were body weight or other body composition metrics, food intake, and/or biomarkers related to eating. We found 18 unique studies meeting all criteria: eight studies with an outcome of body weight (4 - increased sleep, 4 - reduced sleep); four studies on food intake; four studies of sleep restriction on total energy expenditure and three of respiratory quotient; and four studies on leptin and/or ghrelin. Few controlled experimental studies have addressed the question of the effect of sleep on body weight/composition and eating. The available experimental literature suggests that sleep restriction increases food intake and total energy expenditure with inconsistent effects on integrated energy balance as operationalized by weight change. Future controlled trials that examine the impact of increased sleep on body weight/energy balance factors are warranted.

Topics: Adiposity; Body Composition; Body Weight; Energy Intake; Energy Metabolism; Female; Humans; Leptin; Male; Obesity; Randomized Controlled Trials as Topic; Sleep; Sleep Deprivation; Weight Gain

Accumulating data suggest that food supplementation with seaweeds which traditionally are an important part of food culture in South-East Asian countries might lead to essential health benefits. In this short review, we summarize findings from experimental studies on the effects of fucoxanthin (a carotenoid derived from brown seaweeds) on lipid metabolism, adiposity, and related conditions and discuss the possible underlying mechanisms.. Supplementation of fucoxanthin or its derivatives consistently attenuated body and visceral fat weight gain, lipid accumulation in the liver, decreases insulin resistance, and improves the plasma lipid profile in rodents fed a high-fat diet. It should however be noted that in diabetic/obese KK-Ay mice with genetically compromised insulin signaling, fucoxanthin might increase the plasma levels of cholesterol and low-density lipoproteins. The anti-obesity effects of fucoxanthin are apparently mediated by the hormones leptin and adiponectin through their common target AMK-activated protein kinase, resulting in downregulation of lipogenic enzymes and upregulation of lipolytic enzymes. Fucoxanthin also suppresses adipocyte differentiation and induces the expression of uncoupling proteins in visceral adipose tissue.. The results of experimental studies suggest that consumption of fucoxanthin and its derivatives as nutritional supplements is a promising option for prevention and treatment of obesity and a wide variety of related pathologies, including metabolic syndrome, type 2 diabetes, and heart disease. Yet, clinical trials are warranted to assess a therapeutic value of fucoxanthin.

Topics: Adipocytes; Adiponectin; Animals; Anti-Obesity Agents; Cell Differentiation; Diet, High-Fat; Humans; Ion Channels; Leptin; Lipid Metabolism; Lipids; Lipogenesis; Lipolysis; Liver; Mice; Mitochondrial Proteins; Rats; Uncoupling Protein 1; Weight Gain; Xanthophylls

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

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

Leptin, a hormone secreted by adipocytes, plays a crucial role in regulating energy balance. Estrogen, like leptin, reduces food intake and adiposity while increasing energy expenditure in animals and humans of both sexes through its actions on the central nervous system. We reviewed the literature for studies of the effects of exogenously administered estrogen on serum leptin concentrations and adiposity in women.. Using PubMed/Medline, we searched for studies of hormone therapy that enrolled healthy postmenopausal women. Studies were further evaluated to determine if leptin and adiposity were monitored both at baseline and throughout a treatment period of at least 2 months.. Twenty articles met inclusion criteria. We found no consistent effects of exogenous estrogen on serum leptin concentrations, adiposity, or weight gain.. Despite suggestive data from animal studies, the current literature does not provide compelling evidence that estrogen therapy attenuates weight gain, alters circulating leptin levels, or improves leptin action in postmenopausal women.

Topics: Adiposity; Animals; Body Mass Index; Estrogen Replacement Therapy; Estrogens; Female; Humans; Leptin; MEDLINE; Obesity; Randomized Controlled Trials as Topic; Weight Gain

Anorexia nervosa is a frequent disorder especially among adolescent girls and young women, with high morbidity, mortality, and relapse rates. To date, no single therapeutic approach has proved to be superior to others (Herpertz et al., 2011). It remains unclear how its etiology and pathology are encoded within cognitive, neural, and endocrinological processes that modulate important mechanisms in appetitive processing and weight regulation. Yet, several trait characteristics have been identified in AN which might reflect predisposing factors. Further, altered levels of neuropeptides and hormones that regulate appetite and feeding behavior have been found during both the acute and the recovered state, pointing to dysfunctional mechanisms in AN that persist even after malnutrition has ceased. Researchers are also hoping that brain imaging techniques will allow for a more detailed investigation of the neural basis of reward and punishment sensitivity that appears to be altered in AN. The integration and extension of recent findings in these areas will hopefully provide a more comprehensive understanding of the disorder and hence enable the development of more effective treatments.. Anorexia nervosa ist eine psychosomatische Erkrankung mit hoher Morbidität und Mortalität, die meist bei Mädchen und jungen Frauen auftritt. Bisher gibt es keine Hinweise auf die Überlegenheit eines bestimmten Therapieverfahrens (Herpertz et al., 2011). Während der klinische Phänotyp bislang im Fokus stand, werden immer häufiger Methoden und Ansätze verwendet, die in der Anorexieforschung bisher unterrepräsentiert waren. Diese beinhalten zum einen die Untersuchung endokrinologischer Merkmale wie z. B. Hormone und andere Mediatoren, die wichtige Vorgänge der Gewichts- und Appetitregulation beeinflussen, aber auch die Erforschung von kognitiven Veränderungen und Persönlichkeitsmerkmalen, die oft auch nach Ende der akuten Krankheitsphase noch messbar sind. Dabei ist es vor allem wichtig, prädisponierende und die Krankheit aufrechterhaltende Faktoren zu identifizieren und zu unterscheiden. Nicht zuletzt ermöglichen bildgebende Verfahren seit einigen Jahren die genauere Untersuchung von funktionellen Zusammenhängen verschiedener Gehirnareale, die diesen prädisponierenden und aufrechterhaltenden Faktoren zugrunde liegen könnten. Letztendlich ist es das Ziel, mit Hilfe dieser neurowissenschaftlichen Methoden langfristig neuropsychologische und biologische Merkmale zu ermitteln, die ein besseres Verständnis der zugrundeliegenden Mechanismen von Anorexia nervosa ermöglichen und damit zur Verbesserung der Behandlung beitragen.

Topics: Adolescent; Anorexia Nervosa; Appetitive Behavior; Brain; Cognition Disorders; Female; Humans; Hypothalamus; Leptin; Magnetic Resonance Imaging; Neuropsychological Tests; Neurotransmitter Agents; Protein-Energy Malnutrition; Sense of Coherence; Weight Gain; Young Adult

Clozapine is, and will remain in the coming years, an irreplaceable drug in psychiatry which has elective indication in treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson's disease, prevention and treatment of tardive dyskinesia. Unfortunately, the drug is largely underused for many and serious side effects. Only a good knowledge of these side effects and of the main strategies to prevent their occurrence or minimize their impact can allow overcoming the underutilization of this valuable therapy. The article describes the clinical and epidemiological features of the non-motor side effects of clozapine including blood dyscrasias, constipation, diabetes, enuresis, fever, hepatitis, hypersalivation, ileus, myocarditis, nephritis, priapism, seizures, serositis, weight gain and metabolic syndrome. The paper suggests several strategies, supported by scientific evidence, in the management of these side effects. The neuropsychiatric side effects of clozapine are not discussed in this review.

Topics: Antipsychotic Agents; Clozapine; Diabetes Mellitus, Type 2; Electroencephalography; Humans; Leptin; Metabolic Syndrome; Paraproteinemias; Receptor, Serotonin, 5-HT2C; Seizures; Weight Gain

The leptin -2548G/A (rs7799039) gene polymorphism has been implicated in susceptibility to antipsychotic-induced weight gain (AIWG), but study results are still controversial. The present meta-analysis was performed to investigate the relationship between the leptin -2548G/A gene polymorphism and AIWG.. Electronic databases were searched for eligible articles in English and Chinese and seven separate studies on the association of the leptin -2548G/A gene polymorphism with AIWG were analyzed.. The meta-analysis involved 451 AIWG patients and 568 controls. The pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated by a fixed or random effect. Overall, our meta-analysis suggests that the leptin -2548G/A gene polymorphism was not significantly associated with AIWG risk under various genetic models. But, in the subgroup analysis by ethnicity, significant association was found between leptin -2548A allele and the AIWG risk in Asian populations under additive, dominant, recessive, and homozygote genetic model. On the contrary, in European populations, the -2548A allele seemed to decrease the risk of AIWG when compared with the -2548G allele under various genetic models, even though they were not statistically significant.. Our meta-analysis suggests that the correlation between leptin -2548G/A gene polymorphism and AIWG risk has significant racial differences.

Topics: Antipsychotic Agents; Humans; Leptin; Weight Gain

With rising rates of obesity, research continues to explore the contributions of homeostatic and hedonic mechanisms related to eating behaviour. In this Review, we synthesize the existing information on select biological mechanisms associated with reward-related food intake, dealing primarily with consumption of highly palatable foods. In addition to their established functions in normal feeding, three primary peripheral hormones (leptin, ghrelin and insulin) play important parts in food reward. Studies in laboratory animals and humans also show relationships between hyperphagia or obesity and neural pathways involved in reward. These findings have prompted questions regarding the possibility of addictive-like aspects in food consumption. Further exploration of this topic may help to explain aberrant eating patterns, such as binge eating, and provide insight into the current rates of overweight and obesity.

Topics: Adult; Animals; Behavior, Addictive; Brain; Bulimia; Dopamine; Eating; Feeding Behavior; Female; Ghrelin; Homeostasis; Humans; Insulin; Leptin; Male; Obesity; Receptors, Dopamine; Reward; Weight Gain

Short sleep duration has been shown to be associated with elevated body mass index (BMI) in many epidemiological studies. Several pathways could link sleep deprivation to weight gain and obesity, including increased food intake, decreased energy expenditure, and changes in levels of appetite-regulating hormones, such as leptin and ghrelin. A relatively new factor that is contributing to sleep deprivation is the use of multimedia (e.g. television viewing, computer, and internet), which may aggravate sedentary behavior and increase caloric intake. In addition, shift-work, long working hours, and increased time commuting to and from work have also been hypothesized to favor weight gain and obesity-related metabolic disorders, because of their strong link to shorter sleep times. This article reviews the epidemiological, biological, and behavioral evidence linking sleep debt and obesity.

Topics: Appetite; Body Mass Index; Energy Intake; Energy Metabolism; Ghrelin; Humans; Leptin; Obesity; Sedentary Behavior; Sleep; Sleep Deprivation; Weight Gain

To discuss recent research on the role of ghrelin in the regulation of carbohydrate and lipid metabolism in the context of its wider role in regulating energy balance.. Ghrelin possesses a range of centrally and peripherally mediated metabolic actions influencing insulin glucose homeostasis and fatty acid metabolism and appetite. Although acyl ghrelin was previously thought to be the active hormone, recent evidence suggests that des-acyl ghrelin also possesses activity, and the enzyme ghrelin-O-acyl transferase regulates their interconversion. In partnership with insulin and leptin, ghrelin defends against energy deficit by enhancing hunger, conserving carbohydrate and promoting fat oxidation. In the postprandial state, it contributes to satiety, energy storage and favours glucose oxidation. New research suggests a range of new roles including addictive behaviours, cardiovascular protection, neuroprotection and regeneration and perhaps the ageing process.. Ghrelin functions primarily as a short-term metabolic switch at the onset of fasting, gearing the fuel economy away from glucose uptake, conserving glucose for vital functions, favouring fatty acid oxidation and triggering food-seeking behaviour. The ghrelin system is a potential target for a range of pharmacological interventions, but its pleiotropic nature makes selective treatments challenging.

Topics: Adipogenesis; Appetite; Energy Metabolism; Ghrelin; Glucose; Homeostasis; Humans; Insulin; Leptin; Lipid Metabolism; Postprandial Period; Satiation; Weight Gain

Classically, leptin resistance has been associated with increased body fat and circulating leptin levels, and the condition is believed to contribute to the onset and/or maintenance of obesity. Although a great deal is known about the central nervous system mechanisms mediating leptin resistance, considerably less is known about the role of diet in establishing and maintaining this altered hormonal state. An exciting new finding has recently been published demonstrating the existence of leptin resistance in normal-weight rats with lean leptin levels by feeding them a high-concentration-fructose diet. This finding has opened the possibility that specific macronutrients may be capable of inducing leptin resistance, independently of the amount of body fat or circulating leptin present in the treated animals. This review describes several lines of research that have recently emerged indicating that specific types of dietary sugars and fats are capable of inducing leptin resistance in experimental rodent models. The results further show that diet-induced leptin resistance is capable of increasing energy intake and elevating body weight gain under appropriate dietary challenges. It appears that biological mechanisms on multiple levels may underlie the dietary induction of leptin resistance, including alterations in the leptin blood-to-brain transport system, in peripheral glucose metabolism, and in central leptin receptor signaling pathways. What is clear from the findings reviewed here is that diet-induced leptin resistance can occur in the absence of elevated circulating leptin levels and body weight, rendering it a potential cause and/or predisposing factor to excess body weight gain and obesity.

Topics: Adipose Tissue; Animals; Brain; Diet; Dietary Fats; Dietary Sucrose; Energy Intake; Glucose; Humans; Leptin; Metabolic Diseases; Obesity; Weight Gain

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

Treatment of epileptic patients with valproic acid (VPA) may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. VPA-induced weight gain seems to be associated with many metabolic disturbances; the most frequent are hyperinsulinemia and insulin resistance, hyperleptinemia and leptin resistance. Patients who gain weight during VPA therapy can develop dyslipidemia and metabolic syndrome that are associated with long-term vascular complications such as hypertension and atherosclerosis. Moreover, an elevation in the levels of uric acid and homocysteine, together with oxidative stress, may contribute to atherosclerotic risk in patients under long-term therapy with VPA. The aim of this review is to discuss the metabolic and endocrine effects of VPA chronic treatment in patients with epilepsy.

Topics: Anticonvulsants; Epilepsy; Humans; Hyperinsulinism; Insulin Resistance; Leptin; Metabolic Syndrome; Valproic Acid; Weight Gain

Antipsychotic medications are used to effectively treat various symptoms for different psychiatric conditions. Unfortunately, antipsychotic-induced weight gain (AIWG) is a common side effect that frequently results in obesity and secondary medical conditions. Twin and sibling studies have indicated that genetic factors are likely to be highly involved in AIWG. Over recent years, there has been considerable progress in this area, with several consistently replicated findings, as well as the identification of new genes and implicated pathways. Here, we will review the most recent genetic studies related to AIWG using the Medline database (PubMed) and Google Scholar. Among the steadiest findings associated with AIWG are serotonin 2C receptors (HTR2C) and leptin promoter gene variants, with more recent studies implicating MTHFR and, in particular, MC4R genes. Additional support was reported for the HRH1, BDNF, NPY, CNR1, GHRL, FTO and AMPK genes. Notably, some of the reported variants appear to have relatively large effect sizes. These findings have provided insights into the mechanisms involved in AIWG and will help to develop predictive genetic tests in the near future.

Topics: Antipsychotic Agents; Genetic Predisposition to Disease; Genotype; Humans; Leptin; Obesity; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; PubMed; Receptor, Serotonin, 5-HT2C; Weight Gain

Obesity is a major worldwide health problem. Excess weight gain is the most significant preventable cause of increased blood pressure (BP) in patients with essential hypertension and increases the risk for cardiovascular and renal diseases. Our goal is to review the mechanisms that link obesity with hypertension, with special emphasis on the role of leptin and the brain melanocortin system in driving sympathetic activation in obesity.. Despite increased interest in obesity as a major risk for developing hypertension, the precise mechanisms linking excess weight gain with increases in BP are still elusive. Current evidence suggests that increased sympathetic nervous system (SNS) activity contributes to impaired renal-pressure natriuresis and sodium retention in obesity. Recent findings indicate that the adipocyte-derived hormone, leptin, activates brain centers that regulate SNS activity through a melanocortin-system-dependent pathway. The interaction of leptin and the brain melanocortin system represents an important area of research to further our understanding of the mechanisms leading to sympathetic activation in obesity.. Sympathetic overactivity is an important link between excess weight gain and increased BP. Hormones and cytokines secreted by the adipose tissue that interact with neural pathways (e.g. melanocortin system) appear to play a key role in contributing to sympathetic activation in obesity and represent potential new targets for therapies.

Topics: Adipocytes; Animals; Blood Pressure; Central Nervous System; Humans; Hypertension; Leptin; Melanocortins; Obesity; Receptor, Melanocortin, Type 4; Signal Transduction; Sympathetic Nervous System; Weight Gain

Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation and chemotherapy) or to primary tumor together with lifestyle modifications and genetic factors could affect long-term outcomes. Nevertheless, the etiology of obesity in acute lymphoblastic leukemia is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.

Topics: Body Mass Index; Child; Comorbidity; Energy Metabolism; Growth Hormone; Humans; Hypothalamus; Leptin; Life Style; Metabolic Syndrome; Obesity; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiotherapy; Risk Factors; Survivors; Weight Gain

Topics: Animals; Brain; Diet; Dietary Fats; Dietary Sucrose; Energy Intake; Humans; Leptin; Obesity; Weight Gain

Obesity and its associated co-morbidities represent one of the biggest public health challenges facing the western world today. Although environmental factors have driven the recent rise in the prevalence of obesity, the heritability of body weight is high and there is evidence that genetic variation plays a major role in determining the susceptibility to weight gain.. Genetic approaches can be used to investigate the mechanisms underlying the regulation of weight and the development of obesity.. The discovery that leptin, a hormone that is secreted by adipocytes, could regulate weight through effects on food intake and energy expenditure represented a major breakthrough in our understanding of the molecular components of the systems involved in energy homeostasis.. I discuss how the identification of humans with mutations in the genes encoding leptin and its downstream targets has provided insights into the role of leptin responsive pathways in the regulation of body weight, neuroendocrine axes and immunity.

Topics: Animals; Appetite; Body Weight; Energy Metabolism; Female; Genetic Variation; Humans; Leptin; Male; Obesity; Rats; Risk Factors; Weight Gain

Adipose tissue secretes a variety of adipokines, including leptin and adiponectin, which are involved in endocrine processes regulating glucose and fatty metabolism, energy expenditure, inflammatory response, immunity, cardiovascular function, and reproduction. The present article describes the fluctuations in circulating leptin and adiponectin as well as their patterns of secretion in women from birth to menopause. During pregnancy, leptin and adiponectin seem to act in an autocrine/paracrine fashion in the placenta and adipose tissue, playing a role in the maternal-fetal interface and contributing to glucose metabolism and fetal development. In newborns, adiponectin levels are two to three times higher than in adults. Full-term newborns have significantly higher leptin and adiponectin levels than preterms, whereas small-for-gestational-age infants have lower levels of these adipokines than adequate-for-gestational-age newborns. However, with weight gain, leptin concentrations increase significantly. Children between 5 and 8 years of age experience an increase in leptin and a decrease in adiponectin regardless of body mass index, with a reversal of the newborn pattern for adiponectin: plasma adiponectin levels at age five are inversely correlated with percentage of body fat. In puberty, leptin plays a role in the regulation of menstrual cycles. In adults, it has been suggested that obese individuals exhibit both leptin resistance and decreased serum adiponectin levels. In conclusion, a progressive increase in adiposity throughout life seems to influence the relationship between leptin and adiponectin in women.

Topics: Adiponectin; Adiposity; Adolescent; Adult; Age Factors; Aged; Child; Child Development; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Leptin; Middle Aged; Postmenopause; Pregnancy; Puberty; Weight Gain; Young Adult

Second-generation antipsychotics can greatly improve symptoms of psychosis-spectrum disorders. Unfortunately, these drugs are associated with weight gain, which increases a patient's risk for developing chronic diseases including Type 2 diabetes, cardiovascular diseases or other obesity-related complications. There are interindividual differences in weight gain resulting from antipsychotic drug use that may be explained by pharmacodynamic characteristics of these agents as well as clinical factors. In addition, genetic variations in pathways associated with satiety are increasingly recognized as potential contributors to antipsychotic-associated weight gain. Polymorphisms in the leptin gene, as well as the leptin receptor gene, are potential pharmacogenetic markers associated with these outcomes. This article summarizes evidence for the associations of the leptin gene and the leptin receptor gene polymorphisms with antipsychotic-induced weight gain, potential mechanisms underlying these relationships, and discusses areas for future pharmacogenetic investigation.

Topics: Antipsychotic Agents; Humans; Leptin; Obesity; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2C; Receptors, Dopamine; Receptors, Leptin; Schizophrenia; Weight Gain

This review presents the findings of pharmacogenetic studies exploring the influence of gene variants on antipsychotic treatment response, in terms of both symptom improvement and adverse effects, in patients with schizophrenia. Despite numerous studies in the field, replicating findings across different cohorts that include subjects of different ethnic groups has been challenging. It is clear that non-genetic factors have an important contribution to antipsychotic treatment response. Differing clinical, demographic and environmental characteristics of the cohorts studied have added substantial complexity to the interpretation of the positive and negative findings of many studies. Pharmacogenomic genome-wide investigations are beginning to yield interesting data although they have failed to replicate the most robust findings of candidate gene studies, and are limited by the sample size, especially given the need for studying homogeneous cohorts. Most of the studies conducted on cohorts treated with single antipsychotics have investigated clozapine, olanzapine or risperidone response. These studies have provided some of the most replicated associations with treatment efficacy. Serotonergic system gene variants are significantly associated with the efficacy of clozapine and risperidone, but may have less influence on the efficacy of olanzapine. Dopamine D3 receptor polymorphisms have been more strongly associated with the efficacy of clozapine and olanzapine, and D2 genetic variants with the efficacy of risperidone. Serotonin influences the control of feeding behaviour and has been hypothesized to have a role in the development of antipsychotic-induced weight gain. Numerous studies have linked the serotonin receptor 2C (5-HT2C) -759-C/T polymorphism with weight gain. The leptin gene variant, -2548-G/A, has also been associated with weight gain in several studies. Pharmacogenetic studies support the role of cytochrome P450 enzymes and dopamine receptor variants in the development of antipsychotic-induced movement disorders, with a contribution of serotonergic receptors and other gene variants implicated in the mechanism of action of antipsychotics. Clozapine-induced agranulocytosis has been associated with polymorphisms in the major histocompatibility complex gene (HLA).

Topics: Antipsychotic Agents; Leptin; Pharmacogenetics; Polymorphism, Genetic; Precision Medicine; Schizophrenia; Treatment Outcome; Weight Gain

Determining the effect of hypothalamic inflammatory signals on energy balance presents a paradox. On the one hand, a large body of work has identified inflammatory signaling in the hypothalamus as an essential mediator of the sickness response--the anorexia, cachexia, fever, inactivity, lethargy, anhedonia and adipsia that are triggered by systemic inflammatory stimuli and promote negative energy balance. On the other hand, numerous recent studies implicate inflammatory activation within the hypothalamus as a key factor whereby high-fat diets--and saturated fats in particular--cause central leptin and insulin resistance and thereby promote the defense of elevated body weight. This paradox will likely remain unresolved until several issues have been addressed. Firstly, the hypothalamus--unlike many peripheral inflamed tissues--is an extremely heterogeneous tissue comprised of astrocytes, oligodendrocytes, microglia, endothelial cells, ependymal cells as well as numerous neuronal subgroups. Determining exactly which cells activate defined inflammatory signals in response to a particular stimulus--i.e. sepsis vs. nutrient excess--may yield critical clues. Secondly, for the sake of simplicity many studies evaluate inflammation as an on/off phenomenon. More realistically, inflammatory signaling occurs as a cascade or cycle that changes and progresses over time. Accordingly, even within the same cell type, the low-grade, chronic signal induced by nutrient excess may invoke a different cascade of signals than a strong, acute signal such as sepsis. In addition, because tolerance can develop to certain inflammatory mediators, physiological outcomes may not correlate with early biochemical markers. Lastly, the neuroanatomical location, magnitude, and duration of the inflammatory stimulus can undoubtedly influence the net CNS response. Rigorously evaluating the progression of the inflammatory signaling cascade within specific hypothalamic cell types is a key next step towards resolving the paradox surrounding the effect of inflammatory signaling on energy homeostasis.

Topics: Animals; Dietary Fats; Eating; Energy Metabolism; Homeostasis; Humans; Hypothalamus; Inflammation; Insulin Resistance; Leptin; Melanocortins; Obesity; Signal Transduction; Weight Gain

To correctly diagnose a patient with anorexia nervosa, medical history according to DSM-IV or ICD-10 criteria and the physical examination is essential. Furthermore, it is useful for a physician to have knowledge regarding typical alteration in laboratory parameters of anorectic patients to realize diagnostical hints. Typical laboratory changes, although not exclusively seen in anorexia nervosa, include hyponatremia, hypokalemia, hypochloremia, liver enzyme elevation, and low red and white blood cell count. The hormones leptin, neuropeptide Y (NPY), triiodothyronine (T3), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and oestrogen are usually below the normal range, whereas ghrelin, pancreatic polypeptide (PP), tumor necrosis factor-alpha (TNF-alpha) and cortisol levels are reported to be typically elevated.

Topics: Anorexia Nervosa; Appetite; Blood Chemical Analysis; Body Mass Index; Diagnosis, Differential; Female; Ghrelin; Gonadal Steroid Hormones; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leptin; Male; Neuropeptide Y; Pituitary-Adrenal System; Thinness; Tumor Necrosis Factor-alpha; Weight Gain

Obesity induced by high-fat (HF) feeding is associated with low-grade inflammation in peripheral tissues that predisposes to insulin resistance. Recent evidence suggests the occurrence of a similar process in the hypothalamus, which favors weight gain through impairment of leptin and insulin signaling. In addition to its implications for obesity pathogenesis, this hypothesis suggests that centrally targeted antiinflammatory therapies may prove effective in prevention and treatment of this disorder. This article highlights molecular and cellular mechanisms by which hypothalamic inflammation predisposes to diet-induced obesity.

Topics: Animals; Glucose Intolerance; Humans; Hypothalamus; Inflammation; Insulin Resistance; Leptin; Models, Biological; Obesity; Weight Gain

Epidemiological studies have shown a positive relationship between dietary fat intake and obesity. Since rats and mice show a similar relationship, they are considered an appropriate model for studying dietary obesity. The present paper describes the history of using high-fat diets to induce obesity in animals, aims to clarify the consequences of changing the amount and type of dietary fats on weight gain, body composition and adipose tissue cellularity, and explores the contribution of genetics and sex, as well as the biochemical basis and the roles of hormones such as leptin, insulin and ghrelin in animal models of dietary obesity. The major factors that contribute to dietary obesity - hyperphagia, energy density and post-ingestive effects of the dietary fat - are discussed. Other factors that affect dietary obesity including feeding rhythmicity, social factors and stress are highlighted. Finally, we comment on the reversibility of high-fat diet-induced obesity.

Topics: Adipose Tissue; Animals; Body Composition; Dietary Fats; Disease Models, Animal; Energy Intake; Feeding Behavior; Ghrelin; Humans; Hyperphagia; Insulin; Leptin; Obesity; Sex Factors; Social Environment; Stress, Psychological; Weight Gain

The prevalence of Diabetes Mellitus (DM) is becoming a serious public health problem. The use of atypical antipsychotics has been associated with disruption of the glucose metabolism and therefore with causing DM. The underlying mechanisms are unknown, but knowledge of the differences between the pharmacological features of various antipsychotics combined with their diabetogenic profile might help us to understand those mechanisms. This article describes how the binding of various essential receptors or transporters in essential body tissues, adipose tissue, pancreatic tissue and liver and skeletal muscle tissue can cause disruption of the glucose metabolism. With such knowledge in mind one can try to explain the differences between the diabetogenic propensities of various antipsychotics. It is well known that clozapine and olanzapine cause weight gain and DM, whereas aripiprazole and ziprasidone have much less disruptive clinical profiles. The most significant risk factor for adiposity seems to be strong blocking of histaminergic receptors. An agonistic activity on serotonergic-1a receptors, with a very low affinity for muscarinergic-3 receptors, might protect against the development of DM. More data will become available which may help to solve the puzzle.

Topics: Adiponectin; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Clozapine; Diabetes Mellitus; Humans; Leptin; Obesity; Olanzapine; Piperazines; Quinolones; Receptor, Muscarinic M3; Receptor, Serotonin, 5-HT1A; Receptors, Dopamine D2; Receptors, Histamine; Serotonin 5-HT1 Receptor Agonists; Thiazoles; Weight Gain

Recent data suggest that obstructive sleep apnea syndrome (OSAS) is an independent risk factor for asthma exacerbations. Neuromechanical reflex bronchoconstriction, gastroesophageal reflux, inflammation (local and systemic), and the indirect effect on dyspnea of OSAS-induced cardiac dysfunction have been suggested as mechanisms that lead to worsening asthma control in patients with concomitant OSAS. Vascular endothelial growth factor-induced airway angiogenesis, leptin-related airway changes, and OSAS-induced weight gain also may play a common mechanistic role linking both disorders. Several studies have confirmed that asthmatic patients are more prone to develop OSAS symptoms than are members of the general population. The common asthmatic features that promote OSAS symptoms are nasal obstruction, a decrease in pharyngeal cross sectional area, and an increase in upper airway collapsibility. Clarifying the nature of the relationship between OSAS and asthma is a critical area with important therapeutic implications.

Topics: Animals; Asthma; Bronchi; Bronchoconstriction; Comorbidity; Dyspnea; Gastroesophageal Reflux; Glottis; Heart Failure; Humans; Inflammation; Laryngeal Nerves; Leptin; Neovascularization, Pathologic; Reflex, Abnormal; Risk Factors; Sleep Apnea, Obstructive; Vagus Nerve; Vascular Endothelial Growth Factor A; Weight Gain

Amylin is a pancreatic B-cell hormone that plays an important role in the control of nutrient fluxes because it reduces food intake, slows gastric emptying, and reduces postprandial glucagon secretion. These actions seem to depend on a direct effect on the area postrema (AP). Subsequent to area AP activation, the amylin signal is conveyed to the forebrain via distinct relay stations. Within the lateral hypothalamic area, amylin diminishes the expression of orexigenic neuropeptides. Recent studies suggest that amylin may also play a role as a long term, adiposity signal. Similar to leptin or insulin, an infusion of amylin into the brain resulted in lower body weight gain than in controls, irrespective of the starting body weight. Interestingly, preliminary data also suggest that rats fed an energy-dense diet develop resistance to central amylin. In addition to amylin's action to control meal termination and to act as a potential adiposity signal, amylin and its agonist salmon calcitonin have recently been shown to increase energy expenditure under certain conditions. In summary, amylin may be an interesting target as a body weight lowering drug. In fact, recent studies provide evidence that amylin, especially when combined with other anorectic hormones (for example, peptide YY and leptin) has beneficial long-term effects on body weight.

Topics: Adiposity; Amyloid; Animals; Appetite Depressants; Appetite Regulation; Area Postrema; Dose-Response Relationship, Drug; Energy Metabolism; Feeding Behavior; Humans; Islet Amyloid Polypeptide; Leptin; Obesity; Peptide YY; Proto-Oncogene Proteins c-fos; Rats; Satiety Response; Weight Gain

Obesity is the most serious long-term health risk currently facing America's adolescents. Weight gain during adolescence carries a higher risk for adult obesity and the metabolic syndrome. This review highlights early adolescence as a particularly high-risk time for weight gain due to the synergy of naturally occurring metabolic changes along with increasing behavioral risk factors. One of the first potential health effects of abnormal weight gain during this period is earlier puberty, usually manifested as thelarche. The obesity epidemic is clearly implicated in the national trend toward earlier thelarche, although the data are not as strong in relation to menarche. Leptin activation of the hypothalamic-pituitary axis, combined with insulin resistance, and increased adiposity may result in the higher estrogen levels that are linked to breast development. Young adolescents also experience a sharp decline in their level of physical activity, worsening nutritional habits, and other important psychosocial and developmental risk factors that may contribute to obesity and estrogen-dependent disease in later life, including polycystic ovary syndrome and breast cancer. Unfortunately, the very psychosocial factors that contribute to abnormal weight gain during early adolescence make prevention and treatment in this population particularly challenging. Therefore, intervening prior to pubertal onset becomes even more important given the risk factors present once puberty begins.

Topics: Adolescent; Adult; Breast Neoplasms; Estrogens; Female; Humans; Hypothalamo-Hypophyseal System; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Puberty; Risk Factors; Weight Gain

Roux-en-Y gastric bypass (RYGB) produces rapid and dramatic weight loss in very heavy obese patients. Up to 20% cannot sustain their weight loss beyond 2 to 3 y after surgery.. To identify putative etiologic factors producing post-RYGB weight regain, a literature survey of metabolic changes in very obese and a review of our diet-induced obese RYGB rat model data was done.. Weight regain suggests an imbalance in physiologic mechanisms regulating appetite and metabolic rate. Weight regain occurred in 25% of our rats, produced by return to presurgical energy intake levels. The 75% of rats that sustained weight loss secreted a significantly larger amount of peptide YY (PYY) while suppressing leptin secretion; those that failed were unable to develop or sustain a sufficiently large plasma PYY:leptin ratio. Metabolic consequences of this failure included reversal of initial postsurgical increases in peripheral fatty acid oxidation, anorexigenic activity in the hypothalamic arcuate nucleus and paraventricular nucleus, and the expression of uncoupling protein-2 in adipose tissues, and decreases in hepatic lipogenesis, free tri-iodothyronine secretion, expression of orexigenic activity in the arcuate nucleus and paraventricular nucleus, expression of adenosine monophosphate kinase in adipose tissues, skeletal muscle mitochondrial mass, and endocannabinoid content and appetite.. Weight regain after RYGB occurs in approximately 20% of patients and constitutes a serious complication. Weight regain-promoting consequences are attributed to a failure to sustain elevated plasma PYY concentrations, indicating that combining RYGB with pharmacologic stimulation of PYY secretion in patients after RYGB who exhibit inadequate PYY concentration may increase long-term success of surgical weight reduction in morbidly obese adults.

Topics: Adipose Tissue; Animals; Energy Metabolism; Fatty Acids; Feeding Behavior; Gastric Bypass; Humans; Hypothalamus; Leptin; Peptide YY; Rats; Recurrence; Weight Gain

Several population-based studies have shown a significant association between TSH-level and BMI (body mass index). About 30% of the rest energy expenditure are regulated by thyroid hormones, which generated the hypothesis that thyroid hormone substitution with TSH-titration into the lower reference levels may prevent body weight gain. The opposite effect of thyroid hormones is appetite stimulation, which may be responsible for body weight gain in case of substitutive medication. The association between TSH and BMI has become a complex topic in the light of the endocrine activity of adipocytes. Adipocytes are not a silent fat mass, but increase the hormone level of leptin, which influences neurones in the hypothalamus, the thyreotropic axis and TSH secretion. BMI is positively correlated with serum leptin. Elevated leptin levels, endogenous in individuals with high BMI or exogenous after leptin injection for treatment of hypothalamic amenorrhoea, shift TSH in the upper reference level. Borderline elevated TSH levels are reversible in case of body weight reduction in obese persons. It remains unclear whether high TSH levels or high leptin level are responsible for obesity or represent secondary phenomenon. Recommendation for daily practice: Borderline elevated TSH-levels in obese patients will decrease in case of body weight reduction without hormone medication. After definitive treatment of hyperthyroidism patient's history for use of carbohydrates (increased during hyperthyroidism) should be noticed and substitution with thyroid hormones aims at TSH in the lower reference level. As body weight gain is observed in all TSH groups, a special concept for prevention and therapy of obesity (diet, daily exercise, behaviour training) should be initiated early and additionally to medication.

Topics: Adipose Tissue; Behavior Therapy; Body Mass Index; Diet, Reducing; Exercise; Humans; Leptin; Obesity; Reference Values; Thyroid Function Tests; Thyrotropin; Weight Gain

Our laboratory has investigated 2 hypotheses regarding the effects of fructose consumption: 1) the endocrine effects of fructose consumption favor a positive energy balance, and 2) fructose consumption promotes the development of an atherogenic lipid profile. In previous short- and long-term studies, we showed that consumption of fructose-sweetened beverages with 3 meals results in lower 24-h plasma concentrations of glucose, insulin, and leptin in humans than does consumption of glucose-sweetened beverages. We have also tested whether prolonged consumption of high-fructose diets leads to increased caloric intake or decreased energy expenditure, thereby contributing to weight gain and obesity. Results from a study conducted in rhesus monkeys produced equivocal results. Carefully controlled and adequately powered long-term studies are needed to address these hypotheses. In both short- and long-term studies, we showed that consumption of fructose-sweetened beverages substantially increases postprandial triacylglycerol concentrations compared with glucose-sweetened beverages. In the long-term studies, apolipoprotein B concentrations were also increased in subjects consuming fructose, but not in those consuming glucose. Data from a short-term study comparing consumption of beverages sweetened with fructose, glucose, high-fructose corn syrup, and sucrose suggest that high-fructose corn syrup and sucrose increase postprandial triacylglycerol to an extent comparable with that induced by 100% fructose alone. Increased consumption of fructose-sweetened beverages along with increased prevalence of obesity, metabolic syndrome, and type 2 diabetes underscore the importance of investigating the metabolic consequences of fructose consumption in carefully controlled experiments.

Topics: Animals; Beverages; Blood Glucose; Dietary Sucrose; Energy Intake; Energy Metabolism; Fructose; Glucose; Humans; Insulin; Leptin; Lipid Metabolism; Macaca mulatta; Sweetening Agents; Weight Gain

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

Anorexia nervosa (AN) initiates an adaptive response at the level of the hypothalamus, which results in a complex interplay involving most elements of the neuroendocrine axis. Consequences of onset of disease in adolescence include amenorrhoea, pubertal arrest with potential loss of target height, and osteoporosis with reduced capacity for future attainment of peak bone mass. With recovery, delay in restoration of menses is common. Hormonal therapies for restoration of bone mineral density (BMD) in adolescents have shown limited efficacy. This review will discuss the reproductive endocrine effects of AN in adolescence, and discuss new investigative tools for monitoring restoration of reproductive function and BMD in this population.

Topics: Adolescent; Anorexia Nervosa; Bone Density; Bone Density Conservation Agents; Bone Diseases; Bone Resorption; Calcium; Dehydroepiandrosterone; Diphosphonates; Estrogen Replacement Therapy; Exercise Therapy; Female; Ghrelin; Humans; Hypothalamo-Hypophyseal System; Insulin-Like Growth Factor I; Leptin; Ovary; Peptide YY; Pituitary-Adrenal System; Reproductive Medicine; Vitamin D; Weight Gain

Growing evidence suggests that food intake, energy expenditure and endogenous glucose production are regulated by hypothalamic areas that respond to a variety of peripheral signals. Therefore, in response to a reduction in energy stores or circulating nutrients, the brain initiates responses in order to promote positive energy balance to restore and maintain energy and glucose homeostasis. In contrast, in times of nutrient abundance and excess energy storage, key hypothalamic areas activate responses to promote negative energy balance (i.e. reduced food intake and increased energy expenditure) and decreased nutrient availability (reduced endogenous glucose production). Accordingly, impaired responses or 'resistance' to afferent input from these hormonal or nutrient-related signals would be predicted to favour weight gain and insulin resistance and may contribute to the development of obesity and type 2 diabetes.

Topics: Animals; Diabetes Mellitus, Type 2; Eating; Energy Metabolism; Feedback, Physiological; Glucose; Homeostasis; Humans; Hypothalamus; Insulin Resistance; Leptin; Liver; Obesity; Signal Transduction; Weight Gain

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

Among the atypical antipsychotics, clozapine and olanzapine are known to cause significant weight gain. Along with quetiapine, they may impair glucose metabolism and increase the risk for type 2 diabetes. They are also associated with a rise in triglyceride levels and an increased risk for coronary artery disease. Clinicians should take these risks seriously in prescribing these antipsychotics and employ intelligent safeguards if and when they use them.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Hypertriglyceridemia; Leptin; Neurotransmitter Agents; Olanzapine; Weight Gain

Recent studies reveal that sleep loss in humans leads to metabolic disorders. A new study reports the development of metabolic syndrome in mice with altered circadian timing brought about by a mutation in a gene that functions in the biological clock. An intriguing and unanswered question is the relation between a healthy biological clock and normal appetite and weight regulation.

Topics: Animals; Appetite; Circadian Rhythm; CLOCK Proteins; Feeding Behavior; Humans; Leptin; Mammals; Metabolic Syndrome; Mice; Obesity; Sleep; Sleep Wake Disorders; Trans-Activators; Weight Gain

The authors presents the state of knowledge on the prevalence and proposed mechanisms leading to weight gain during treatment with atypical antipsychotics. A short review on the therapeutic approaches is also supplied.

Topics: Antipsychotic Agents; Body Weight; Clozapine; Dibenzothiazepines; Humans; Hyperlipidemias; Leptin; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles; Weight Gain

An abundant and compelling literature supports the existence of a homeostatic system that dynamically adjusts energy intake and energy expenditure to promote stability of body fat mass. In the context of this system, the ease with which many individuals gain weight is difficult to explain. Some have argued that energy homeostasis operates primarily to defend against weight loss and that, over the course of evolution, biological defense against weight gain was not selected for. According to this Absence of Protection model, obesity is seen as the natural result of living in an obesigenic environment. An alternative hypothesis, termed the Central Resistance model, proposes that under normal circumstances, the energy homeostasis system provides an effective defense against weight gain as well as weight loss and that common forms of obesity involve genetic or acquired defects (or interactions between them) that impair the function of this system. Here, we discuss these dichotomous possibilities within the context of current literature regarding energy homeostasis and suggest a strategy for distinguishing between them.

Topics: Animals; Central Nervous System; Drug Resistance; Energy Metabolism; Genotype; Homeostasis; Humans; Insulin; Leptin; Models, Biological; Obesity; Signal Transduction; Weight Gain

Topics: Appetite; Body Mass Index; Ghrelin; Humans; Leptin; Obesity; Peptide Hormones; Public Health; Sleep; Sleep Deprivation; Weight Gain

Ghrelin a novel peptide consisting of 28 amino acids was first identified in the stomach in 1999. It is mainly produced in endocrine cells of the human gastric mucosa, but it was also found in several other tissues e. g. in the pituitary, the hypothalamus and the pancreas. The functional receptor belongs to the family of the 7-transmembrane G-protein receptors and is predominantly detected in the pituitary and at lower levels in hypothalamic nuclei, the stomach, heart, lungs, kidneys, gut, the adipose and many other tissues. According to the widespread distribution of the peptide and its receptor, ghrelin has multiple biological effects: it stimulates the release of growth hormone in the pituitary and induces a rise in the serum concentration of ACTH, cortisol, catecholamines and prolactin. Ghrelin causes an increase of food intake and body weight by stimulating the production of neuropeptide Y (NPY) and agouti-related protein (AGP) in the nucleus arcuatus. It further leads to elevated concentrations of plasma glucose. A physiological antagonism between ghrelin and GLP-1 in the hypothalamic regulation of appetite is being discussed. The basic serum level of ghrelin depends on the state of nutrition and is negatively correlated with the body-mass-index. It shows a certain pattern of variation before and after food intake with a preprandial increase and a postprandial decrease. Ghrelin modulates gastric acid secretion and the gastrointestinal motility via vagal cholinergic pathways. The discovery of ghrelin definitely contributes to the understanding of the growth-hormone secretion and of the regulation of appetite and food intake.

Topics: Adrenocorticotropic Hormone; Animals; Appetite Regulation; Blood Glucose; Body Mass Index; Body Weight; Catecholamines; Eating; Gastrointestinal Motility; Ghrelin; Growth Hormone; Homeostasis; Humans; Hydrocortisone; Hypothalamus; Leptin; Neuropeptide Y; Nutritional Status; Peptide Hormones; Prolactin; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Stomach; Tissue Distribution; Weight Gain

Leptin, the ob gene product, is related to the onset of puberty in animal models, but its role in human puberty is still rather undefined. In prepubertal girls and boys, leptin concentrations increase slowly with age and body-fat mass. In boys, this increase is interrupted in early puberty, when testosterone and lean body mass increase. In girls, leptin, along with the body-fat mass, continue to increase during puberty. Plasma leptin concentrations are significantly correlated with fat mass at all Tanner stages in males and females. The diurnal variation of leptin concentrations seen in adults is apparent for all age groups with no significant changes in the pattern across puberty. Leptin is bound in blood by a high-affinity binding protein identical with the soluble leptin receptor (sOB-R). In the first year of life, the concentration of sOB-R is high, and then a continuous decline of sOB-R follows until midpuberty. The therapeutic response to leptin treatment in a child with leptin deficiency confirms the importance of leptin in the regulation of body weight in humans, and establishes an important role for this hormone in the regulation of appetite. Still no evidence is available that would indicate leptin is a primary signal that initiates the onset of human puberty. Instead, it may act in a permissive way as one of several metabolic factors to allow pubertal maturation to proceed and later reproduction to occur.

Topics: Adipose Tissue; Adolescent; Animals; Body Mass Index; Cross-Sectional Studies; Female; Humans; Leptin; Longitudinal Studies; Male; Mice; Obesity; Puberty; Receptors, Cell Surface; Receptors, Leptin; Sensitivity and Specificity; Sexual Maturation; Weight Gain

Obesity and arterial hypertension are important public health problems. Both overweight and hypertension predispose to cardiovascular diseases, such as myocardial infarction, stroke and renal failure. Moreover, overweight clearly predisposes to hypertension, and thus to an increased prevalence of cardiovascular diseases. This in turn favors inactivity and further weight gain, leading to an exacerbation of cardiovascular disorders. Obesity, hypertension and cardiovascular diseases thus contribute to three corners of a vicious triangle. It is within this conceptual framework that this paper reviews the pathogenesis of obesity-related hypertension, which is highly complex. Many factors act together to promote vasoconstriction and sodium retention. Leptin, free fatty acids and insulin, whose levels are increased in obesity, may act synergistically to stimulate sympathetic activity and vasoconstriction. In addition, obesity-induced insulin resistance and endothelial dysfunction may operate as amplifiers of the vasoconstrictor response. Finally, increased renal tubular reabsorption of sodium may also occur, caused by an increased renal sympathetic nerve activity, the direct effect of insulin, hyperactivity of the renin-angiotensin system and possibly by an alteration of intrarenal physical forces. All together, these factors will lead to sustained hypertension. Because the prevalence of obesity was steadily increasing in the last decades, leading to an increased prevalence of hypertension and cardiovascular disorders, obesity and hypertension will most likely become the health challenges of the twenty-first century.

Topics: Adult; Aged; Fatty Acids, Nonesterified; Humans; Hypertension; Insulin Resistance; Kidney; Leptin; Middle Aged; Obesity; Sodium; Sympathetic Nervous System; Tumor Necrosis Factor-alpha; Weight Gain

To critically review published literature on the causal association between leptin, cytokines, and excessive body weight gain (BWG) induced by antipsychotic drugs (APs).. We completed a Medline search using the words leptin, cytokines, antipsychotic drugs, neuroleptics, psychotropic drugs, weight gain, and obesity. We also included our empirical research on this topic in the discussion. We examined the relation between leptin, cytokines (mainly tumour necrosis factor alpha [TNF-alpha] and its soluble receptors), and AP-induced BWG, using the biological sciences' current theories of causality.. In the general field of weight regulation, there is scarce experimental evidence that leptin or TNF-alpha by themselves can induce obesity. Serum levels of leptin and TNF-alpha rather increase simultaneously as BWG occurs. This has also been reported during AP-induced BWG, with the equivocal exception of a study with clozapine. Some researchers have suggested that the absence of the expected correlation between leptin and body mass index (BMI) or serum insulin levels, and the lack of sex-related differences in leptin levels in AP-treated patients, may point to a causal relation. This contention requires more experimental support. In addition, future clinical studies must carefully control for sex and BMI.. No conclusive evidence has been provided that leptin or TNF-alpha may induce obesity either in drug-free subjects or in AP-treated patients. In most cases, the elevated serum levels of these hormones appear to be a consequence rather than a cause of obesity. That does not mean that such an elevation is innocuous, since it may impair blood pressure and also carbohydrate and lipid metabolism regulation. Hence, all efforts should be made to prevent or attenuate BWG during treatment with APs.

Topics: Animals; Antipsychotic Agents; Cytokines; Humans; Leptin; Obesity; Psychotic Disorders; Tumor Necrosis Factor-alpha; Weight Gain

The estimated percentage of persons with schizophrenia who are overweight is higher than the percentage of persons in the general population who are overweight. The increased mortality rate for persons with schizophrenia is largely due to obesity-related diseases. The atypical antipsychotics offer an improved therapeutic index when compared with the conventional agents, but may impart serious adverse events such as weight gain. This brief review is intended to provide the practicing clinician with an update of disparate research paradigms under investigation in an attempt to delineate the biological mechanisms that presage weight gain. Research success in this area may invite novel prevention strategies and hint at potential mechanisms of antipsychotic drug action.

Topics: Antipsychotic Agents; Cytokines; Energy Intake; Energy Metabolism; Female; Gonadal Steroid Hormones; Histamine; Humans; Leptin; Male; Neuropeptides; Neurotransmitter Agents; Obesity; Schizophrenia; Weight Gain

Food intake (eating) is a form of behavior that is subject to conscious control. In practice, many obese and weight-gaining individuals claim that their eating is out of (their) control. Mechanistic models describe the interplay of biological and environmental forces that control food intake. However, because human food intake is characterized by individuals intervening to adjust their own patterns of behavior, food intake should reflect interactions among biology, environment, and attempted self-imposed control of behavior. In general, humans display a system of weight regulation that is asymmetrical--a reduction in body weight is strongly defended but weight gain is not. The body seems to tolerate a positive energy balance. There is no mechanism that can detect a positive energy balance per se or that can implement a sufficiently strong correction to behavior to maintain body weight in an environment that promotes consumption. The evolutionary process has favored biological traits associated with preferences for high energy density (sweet and/or fatty) energy-yielding foods. The control of food intake in obese or weight-gaining individuals may display various risk factors that favor an increase in energy. These include the preference for high energy-dense over low energy-dense foods, weak postprandial inhibitory signaling, strong hunger traits associated with low leptin levels after weight loss, and the consumption of fatty foods. In addition, many individuals (up to 47% of some samples) display binge eating patterns, whereas approximately 16% show either night eating or nocturnal eating. Because energy expenditure is only loosely coupled to energy intake, sedentariness does not down-regulate food intake.

Topics: Appetite Regulation; Behavior; Eating; Energy Intake; Energy Metabolism; Food Preferences; Humans; Leptin; Obesity; Weight Gain

The rapidly increasing prevalence of obesity, in spite of an unchanged gene pool, makes it interesting to search for biological factors which increase the susceptibility at the individual level as well as searching for the responsible environmental factors. Among the identified metabolic factors is a low resting metabolic rate for given body size and composition, a high respiratory quotient (RQ) indicating a low fat oxidation and a low spontaneous physical activity, all factors which are regarded as being under substantial genetic influence. Among the environmental factors, it is low levels of physical activity, increasing inactivity and a high fat diet that are probably the most important ones. In this review we have focused on controversies in this area. Understanding the interaction between the constitutional biological factors and the environmentally determined lifestyle factors it is important to produce better options for both the prevention and treatment of obesity.

Topics: Animals; Behavior; Dietary Fats; Energy Intake; Energy Metabolism; Environment; Exercise; Humans; Leptin; Life Style; Obesity; Oxidation-Reduction; Sympathetic Nervous System; Weight Gain

A loop system exists between hypothalamic neuropeptide Y (NPY) and peripheral adipose tissue leptin to maintain normal body homeostasis. When hypothalamic NPY levels are increased by fasting or by intracerebroventricular (i.c.v.) infusion, food intake and body weight increase. NPY has genuine hormono-metabolic effects. It increases insulin and corticosterone secretion relative to controls. These hormonal changes, acting singly or combined, favor adipose tissue lipogenic activity, while producing muscle insulin resistance. They also promote leptin release from adipose tissue. When infused i.c.v. to normal rats to mimic its central effects, leptin decreases NPY levels, thus food intake and body weight. Leptin i.c.v. has also genuine hormono-metabolic effects. It decreases insulinemia and adipose tissue storage ability, enhancing glucose disposal. Leptin increases the expression of uncoupling proteins (UCP-1, -2, -3) and thus energy dissipation. Leptin-induced changes favor oxidation at the expense of storage. Circadian fluctuations of NPY and leptin levels maintain normal body homeostasis. In animal obesity, defective hypothalamic leptin receptor activation prevent leptin from acting, with resulting obesity, insulin and leptin resistance.

Topics: Adipose Tissue; Animals; Brain; Eating; Energy Metabolism; Fasting; Leptin; Neuropeptide Y; Uncoupling Agents; Weight Gain

The prevalence of obesity is increasing in westernized societies. In the USA the age-adjusted prevalence of BMI > 30 kg/m2 increased between 1960 and 1994 from 13% to 23% for people over 20 years of age. This increase in the prevalence of obesity has been attributed to an increased fat intake and a decreased physical activity. However, the role of the impact of the level of dietary fat intake on human obesity has been challenged. High-fat diets, due to their high energy density, stimulate voluntary energy intake. An increased fat intake does not stimulate its own oxidation but the fat is stored in the human body. When diet composition is isoenergetically switched from low to high fat, fat oxidation only slowly increases, resulting in positive fat balances on the short term. Together with a diminished fat oxidation capacity in pre-obese subjects, high-fat diets can therefore be considered to be fattening. Another environmental factor which could explain the increasing prevalence of obesity is a decrease in physical activity. The percentage of body fat is negatively associated with physical activity and exercise has pronounced effects on energy expenditure and substrate oxidation. High-intensity exercise, due to a lowering of glycogen stores, can lead to a rapid increase in fat oxidation, which could compensate for the consumption of high-fat diets in westernized societies. Although the consumption of high-fat diets and low physical activity will easily lead to the development of obesity, there is still considerable inter-individual variability in body composition in individuals on similar diets. This can be attributed to the genetic background, and some candidate genes have been discovered recently. Both leptin and uncoupling protein have been suggested to play a role in the prevention of diet-induced obesity. Indeed, leptin levels are increased on a high-fat diet but this effect can be attributed to the increased fat mass observed on the high-fat diet. No effect of a high-fat diet per se on leptin levels is observed. Uncoupling proteins are increased by high-fat diets in rats but no data are available in human subjects yet. In conclusion, the increased intake of dietary fat and a decreasing physical activity level are the most important environmental factors explaining the increased prevalence of obesity in westernized societies.

Topics: Animals; Dietary Fats; Energy Intake; Exercise; Female; Humans; Leptin; Male; Obesity; Oxidation-Reduction; Prevalence; Rats; Uncoupling Agents; Weight Gain

Human obesity is the result of both environmental and genetic factors. In this manuscript, we briefly review the metabolic factors predicting body weight gain in Pima Indians, a population prone to obesity. The metabolic predictors of weight gain are: 1) a low metabolic rate, 2) low levels of physical activity, 3) low rates of fat oxidation, 4) insulin sensitivity, 5) low sympathetic nervous system activity, and 6) low plasma leptin concentrations. In contrast, obesity is associated with high metabolic rate, high fat oxidation, low insulin sensitivity and high plasma leptin concentration. This observation emphasizes the need to conduct prospective studies to obtain a better understanding of the etiology of obesity. In addition, genetic studies will help to identify new pathways involved in the pathophysiology of obesity.

Topics: Basal Metabolism; Dietary Fats; Energy Metabolism; Exercise; Female; Humans; Insulin Resistance; Leptin; Male; Obesity; Oxidation-Reduction; Proteins; Sympathetic Nervous System; Weight Gain

Experimental animal studies demonstrate the effects of leptin on appetite, weight gain and metabolism. The biological effects of leptin in human adults are still to be determined, but recent reports show that congenital leptin deficiency leads to hyperphagia and excessive weight gain from early infancy as well as failure of pubertal onset in adolescence. Our recently reported data from two longitudinal cohorts suggest a role for leptin in the normal regulation of childhood weight gain, maturation and the development of secondary sexual features and body composition. Low leptin levels in cord blood closely reflected decreased adiposity at birth and strongly predicted high rates of weight gain in infancy and catch-up growth. In adolescents, leptin levels rose gradually with age prior to puberty, suggesting that a threshold effect may trigger puberty. In girls, low leptin levels at the start of puberty predicted large gains in the percentage of fat mass, perhaps suggesting a role in the preparation for childbearing.

Topics: Adipose Tissue; Adolescent; Animals; Body Composition; Child; Child Development; Humans; Infant; Leptin; Puberty; Weight Gain

Obesity results from a chronic imbalance between energy intake and energy expenditure. However, the biological mechanism(s) underlying possible alterations of energy balance is(are) still poorly defined. Advances in the understanding of body weight regulation in humans are represented by the discovery of: a) metabolic risk factors of body weight gain (i.e. low resting energy expenditure, low level of physical activity, high carbohydrate-to-lipid oxidation rate); b) the role of the autonomic nervous system in the control of energy metabolism and nutrient partitioning; and c) leptin, a previously unknown hormone produced by the adipocyte which seems to be quite involved in the complex neurohormonal regulation of energy balance. In view of these discoveries, current models of human body weight regulation concord on the existence of crosstalks between central nervous system and peripheral tissues. The brain monitors the nutritional status of the body (using several peripheral afferent signals including leptin) and reacts to nutritional changes by modulating the activity of its neurohormonal efferent signaling systems (autonomic nervous systems and endocrine organs). A low sympathetic nervous system (SNS) activity and a relative plasma leptin deficiency have been shown to predict body weight gain. Furthermore, plasma concentration of leptin and activity of the SNS seem to regulate each other. This paper reviews the evidence that previously described metabolic risk factors of body weight gain (i.e., low resting energy expenditure, low level of physical activity, and high carbohydrate-to-lipid oxidation rate) may in fact be the phenotypic expression of a dysfunctional leptin-SNS activity body weight regulatory loop.

Topics: Basal Metabolism; Energy Metabolism; Humans; Leptin; Neurosecretory Systems; Obesity; Proteins; Risk Factors; Sympathetic Nervous System; Weight Gain

Topics: Appetite Regulation; Feeding Behavior; Humans; Leptin; Obesity; Proteins; Receptors, Adrenergic, beta; Receptors, Histamine; Receptors, Neuropeptide; Receptors, Neurotransmitter; Receptors, Serotonin; Weight Gain

Reviewed are reports on factors, identified by risk analysis, involved in the genesis of primary malnutrition in children. Data are compared with the sequence of factors in a flow diagram, based on the natural history of malnutrition, proposed 3 decades ago. Susceptibility to malnutrition is analyzed in light of observations related to inheritance, the ob gene and leptin.

Topics: Adipose Tissue; Child; Disease Susceptibility; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Leptin; Maternal Exposure; Nutrition Disorders; Pregnancy; Proteins; Risk Factors; Socioeconomic Factors; Weight Gain

Berberine could improve antipsychotic-induced weight gain in obese cell lines and animal models. This study aimed to exam the effect of berberine on weight gain in patients with schizophrenia.. Each subject who met DSM-IV-TR criteria for schizophrenia had been on stable dose of a single antipsychotic for at least one month. In an 8-week randomized, double-blind, placebo-controlled study, subjects received either berberine (900 mg per day) or placebo. Anthropometric parameters, leptin and adiponectin were measured at baseline, week 4, and week 8.. A total of 65 patients were enrolled, 49 of which completed the treatment. At the 8th week, the mean weight of patients in the berberine group (N = 27) lost 1.10 kg, while in the placebo group (N = 22) gained 1.45 kg. There were significant differences in body weight (F. This study suggests that berberine is a potential weight loss and weight maintenance drug for patients with schizophrenia. The effect of berberine on weight gain may be related to the regulation of leptin, but not adiponectin.

Topics: Adiponectin; Antipsychotic Agents; Berberine; Body Mass Index; Double-Blind Method; Humans; Leptin; Schizophrenia; Weight Gain

Offspring of obese rodents develop a metabolic phenotype that favors fat deposition. Data regarding the impact of maternal obesity programing of offspring fuel usage in humans is scarce.. The objective of this study was to explore the association between maternal weight status and dietary palmitate oxidation (DPO) in 2-y-old offspring, taking into consideration potential confounders and modifiers.. Women (n = 56) were enrolled by the first trimester of gestation. Maternal physical activity (PA; measured with accelerometers) at enrollment and gestational weight gain (GWG) were measured. Offspring sex, race, and breastfeeding (BF) duration were self-reported. Human milk (HM) composition was determined at 6 mo postpartum. At age 2 y, dietary quality [healthy eating index (HEI)] and parental feeding practices [Child Feeding Questionnaire (CFQ)] were assessed. DPO in 2-y-olds (2-yo-DPO) was measured using deuterated palmitic acid. Generalized linear regression analysis was used to model the associations of 2-yo-DPO with maternal weight status [normal weight (NW), BMI <25 (in kg/m2) compared with excessive weight (EW), BMI ≥25].. DPO was higher in offspring of women with EW compared with NW (2.1 ± 1.2%/h compared with 1.4 ± 0.7%/h, P = 0.03). Maternal weight status interacted with BF duration in association with 2-yo-DPO (log ß: 0.05, P = 0.04). Specifically, 2-yo-DPO was higher in the EW compared with NW group if BF duration was ≥9 mo. HM insulin (log ß: 0.35, P = 0.002) and HM leptin (log ß: 0.81, P = 0.001) concentrations directly associated with 2-yo-DPO. PA (log ß: 0.06, P = 0.013), parental feeding restriction (log ß: 0.05, P < 0.0001), and male sex (log ß: 0.54, P < 0.001) were positively associated with 2-yo-DPO. HEI was negatively associated with 2-yo-DPO (log ß:-0.03, P < 0.0001).. Higher 2-yo-DPO in offspring of women with EW compared with NW were driven by BF duration. Higher HM insulin and leptin concentrations in women with EW may explain these finding. More studies are needed to confirm these results. This trial was registered at clinicaltrials.gov as NCT03281850.

Topics: Body Mass Index; Breast Feeding; Child; Child, Preschool; Female; Humans; Insulin; Leptin; Male; Palmitates; Pregnancy; Weight Gain

C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration.. For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration.. In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 - 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 - 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 - 0.42, p < 0.001; and Coef.= 0.34, 95% CI: 0.06 - 0.63, p = 0.02, respectively).. UC blood concentration of C-peptide is significantly associated with the incidence of maternal GDM and neonatal macrosomia. Using stratification for maternal BMI and gestational weight gain (GWG) and investigating molecular markers like Leptin and IGF-1 in the future might lay the ground to better understand the link between metabolic disturbances of pregnancy and UC blood C-peptide concentration.

Topics: Birth Weight; Body Mass Index; C-Peptide; Cesarean Section; Child; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Iran; Leptin; Pregnancy; Pregnancy Outcome; Weight Gain

This study investigated the effects of growth rates and compensatory growth on puberty attainment in Nellore heifers. Nellore heifers (n = 120), weaned at 8 ± 0.75 mo of age, were blocked by sire and BW (180 ± 8.6 kg) and assigned randomly to receive 1 of 4 treatments over a 10-mo period. Treatments included ad libitum feeding (high gain, HG), feed intake to gain 0.6 kg/d (medium gain, MG), restricted feeding (0.2 kg/d) for 4 mo followed by ad libitum feeding for 6 mo (compensatory gain, CG), and alternating periods of ad libitum and restricted feeding for 2 mo each throughout the trial (alternated CG, ACG). Puberty was assessed weekly by transrectal ultrasonography. Blood samples were collected at 8, 11, and 18 mo of age and at puberty to determine circulating concentrations of leptin. At 18 mo of age, nonpubertal heifers were treated with a puberty induction protocol using an intravaginal progestin device. There was no treatment effect (P = 0.17) on the percentage of heifers pubertal by 18 mo of age (HG: 66, MG: 40, CG: 58, and ACG: 52%), BW at puberty, and age at puberty. However, HG heifers had higher ADG (P < 0.01), dry matter intake (P < 0.01), and leptin concentrations (P = 0.03) than heifers from other groups. The response to the puberty induction protocol was similar (P = 0.90) among treatments. Regarding sire effects (genetic effects), there was an effect (P = 0.03) on the percentage of heifers pubertal by 18 mo of age and a tendency (P = 0.07) of sire effect in response to the puberty induction protocol. Compensatory growth appears to be an effective managerial approach to decrease feeding costs and stimulate puberty in Nellore heifers.

Topics: Aging; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Caloric Restriction; Cattle; Diet; Female; Gene Expression Regulation; Leptin; Sexual Maturation; Weight Gain

Chemically-interesterified (CIE) fats are

Topics: Adiposity; Adult; Apolipoprotein A-I; Apolipoprotein B-100; Blood Glucose; Body Mass Index; Cholesterol; Diet; Dietary Fats; Double-Blind Method; Fatty Acids; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Overweight; Palm Oil; Patient Compliance; Snacks; Stearic Acids; Triglycerides; Weight Gain; Young Adult

It has been clearly demonstrated that the maternal nutritional status during pregnancy and lactation has long-term effects on offspring health. In mammals, milk represents the first maternal support provided to the newborns so that its composition may play a major role in long-term programming. We therefore assessed the effects of maternal high-fat/high-sugar obesogenic (OD) or control (CD) diets on offspring growth and adiposity in the rabbit. Between 7 and 20 wk of age, the BW gain of OD milk-fed rabbits was higher than that of CD milk-fed rabbits ( < 0.05). Body fat mass measurements at 21 wk of age revealed a significant increase in body adiposity as a function of milk ingested during the neonatal period, in both female and male offspring ( < 0.05). A marked weight gain difference was observed according to the milk in both female and male offspring. Moreover, we investigated the composition in major proteins and leptin levels in milk from OD or CD diet-fed dams. Liquid chromatography-mass spectrometry analysis of individual CD skimmed milk samples enabled identification and quantification of the rabbit main milk proteins and of their main phosphorylated isoforms at 2 different stages of lactation (3 and 10 d). Here we show that the OD diet induced a reduction in the whey acidic protein content concomitantly with both an increase in serum albumin and lactoferrin contents and in the phosphorylated isoforms of the main milk proteins. Furthermore, a sharp rise in leptin levels was observed in the milk of OD diet-fed dams on Day 10 of lactation when compared with CD diet animals ( < 0.05). Taken together, these findings provide evidence that lactation is a critical window of development during which exposure to a deleterious diet is highly detrimental to long-term outcomes. Moreover, these insights suggest that it may be possible to prevent at least some of the adverse effects of inadequate maternal nutrition on the long-term metabolic outcomes of the offspring through nutritional interventions applied during the lactation period.

Topics: Adiposity; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Diet; Dietary Carbohydrates; Dietary Fats; Eating; Female; Lactation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Milk; Obesity; Pregnancy; Rabbits; Time; Weight Gain

A bolus administration of 0.15 mg nonivamide has previously been demonstrated to reduce energy intake in moderately overweight men. This 12-week intervention investigated whether a daily consumption of nonivamide in a protein-based product formulation promotes a reduction in body weight in healthy overweight subjects and affects outcome measures associated with mechanisms regulating food intake, e.g. plasma concentrations of (an)orexigenic hormones, energy substrates as well as changes in fecal microbiota.. Nineteen overweight subjects were randomly assigned to either a control (C) or a nonivamide (NV) group. Changes in the body composition and plasma concentrations of satiating hormones were determined at fasting and 15, 30, 60, 90, and 120 min after a glucose load. Participants were instructed to consume 0.15 mg nonivamide per day in 450 mL of a milk shake additionally to their habitual diet. After treatment, a group difference in body fat mass change (-0.61 ± 0.36% in NV and +1.36 ± 0.38% in C) and an increase in postprandial plasma serotonin were demonstrated. Plasma metabolome and fecal microbiome read outs were not affected.. A daily intake of 0.15 mg nonivamide helps to support to maintain a healthy body composition.

Topics: Adiponectin; Adiposity; Adult; Blood Glucose; Body Composition; Body Mass Index; Body Weight; Capsaicin; Cholesterol; Diet; Dietary Fats; Female; Gastrointestinal Hormones; Gastrointestinal Microbiome; Humans; Insulin; Leptin; Male; Overweight; Postprandial Period; Satiation; Sensory System Agents; Serotonin; Triglycerides; TRPV Cation Channels; Weight Gain; Young Adult

Offspring of obese mothers have increased risk of developing obesity and related short- and long-term disease. The cause is multifactorial and may partly be explained by the unfavorable intrauterine environment. Intervention during pregnancy leading to a healthier lifestyle among obese may alter this.. To assess the effect of lifestyle intervention on markers of maternal metabolism and inflammation in 'the TOP (Treatment of Obese Pregnant Women) study', a randomized controlled trial.. In the TOP-study 425 participants with body mass index ⩾30 kg/m. Median levels of hsCRP in gestational week 28-30 were lower in each of the intervention groups (8.3 mg/l in PA+D group, P=0.03; and 8.8 mg/l in PA group, P=0.02) versus the control group (11.5 mg/l). Obtaining 11 000 steps per day as aimed for resulted in a 21% lower hsCRP compared to non-compliant women. Women reporting high carbohydrate intake had around 30% higher hsCRP concentrations in late gestation than women reporting the lowest intake. There were no differences in lipid profile or any of the metabolic markers in gestational week 28-30 when comparing the intervention and control groups.. Lifestyle intervention in obese women can reduce hsCRP representing a marker of inflammation during pregnancy. The effect may partly be mediated by more physical activity and partly by changes in intake of carbohydrates and the glycaemic load.

Topics: Adult; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Energy Intake; Exercise; Female; Glucose Tolerance Test; Humans; Inflammation; Insulin; Interleukin-6; Leptin; Netherlands; Obesity; Pregnancy; Pregnancy Complications; Risk Reduction Behavior; Weight Gain

Adiponectin exerts beneficial effects by reducing inflammation and improving lipid metabolism and insulin sensitivity. Although the adiponectin level is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans.. Forty-four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8 weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8±1.2 kg resulted in increased adiponectin level (P=0.03), whereas weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (P=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, whereas a leptin antagonist had opposite effects. To understand the role of leptin in established obesity, we compared adipose tissue samples obtained from normal-weight versus obese subjects. We noted, first, that leptin activated cellular signaling pathways and increased adiponectin mRNA in the adipose tissue from normal-weight participants, but did not do so in the adipose tissue from obese participants. Second, we noted that obese subjects had increased caveolin-1 expression, which attenuates leptin-dependent increases in adiponectin.. Modest weight gain in healthy individuals is associated with increases in adiponectin levels, which correlate positively with changes in leptin. In vitro, leptin induces adiponectin expression, which is attenuated by increased caveolin-1 expression. In addition, the adipose tissue from obese subjects shows increased caveolin-1 expression and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin levels in obese subjects despite their high levels of leptin. Therefore, impaired leptin signaling may contribute to low adiponectin expression in obesity and may provide a target for increasing adiponectin expression, hence improving insulin sensitivity and cardio-metabolic profile in obesity.

Topics: Adiponectin; Adipose Tissue; Aging; Body Mass Index; Caveolin 1; Female; Humans; Leptin; Lipid Metabolism; Longitudinal Studies; Male; Obesity; Prevalence; Signal Transduction; United States; Up-Regulation; Weight Gain

To determine the effect of serial weighing and dietary advice compared with standard antenatal care on obstetric outcomes.. Randomised controlled clinical trial.. Australian tertiary obstetric hospital.. Three hundred and eighty-two overweight or obese non-diabetic pregnant women at less than 20 weeks gestation with a singleton pregnancy.. Women were randomised to targeted, serial self-weighing and simple dietary advice, (intervention), or standard antenatal care (control).. The primary outcome was a reduction in a composite of obstetric complications: gestational hypertension, pre-eclampsia, diabetes, assisted or caesarean birth, shoulder dystocia, severe perineal trauma, postpartum haemorrhage and maternal high dependency care. Secondary outcomes were gestational weight gain at 36 weeks' gestation, quality of life (QOL) and maternal serum levels of 28-week leptin, adiponectin and C-reactive protein (CRP).. There was no difference in the rate of the primary composite outcome of obstetric complications: 124/184 (67% control), 124/187 (66% intervention) [relative risk 0.98 (95% confidence interval (CI) 0.85-1.14)]. There was no difference in mean gestational weight gain [-0.9 kg (95% CI -2.0, 0.25)], QOL or leptin, adiponectin or CRP levels between intervention and control groups.. This low-cost, pragmatic intervention failed to prevent obstetric complications or modify maternal biochemistry or gestational weight gain in overweight or obese pregnant women. Participation in the study did not impair participants' QOL.. Serial self-weighing and dietary advice failed to reduce obstetric complications in overweight pregnant women.

Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Diet; Directive Counseling; Female; Gestational Age; Humans; Leptin; Obesity; Obstetric Labor Complications; Pregnancy; Prenatal Care; Quality of Life; Self Care; Weight Gain

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

Increasing physical activity in pregnancy may improve pregnancy outcomes for obese women. Exercise could reduce gestational weight gain, improve the maternal circulating lipid profile as well as alter leptin, Interleukin-8 (IL-8) and Monocyte Chemoattractant Protein-1 (MCP-1) levels.. The aim of this study was to investigate the effects of exercise on gestational weight gain, maternal circulating lipids, IL-8, MCP-1 and leptin levels in obese pregnant women.. The analysis was performed in the 35 obese women enrolled in the pilot BAMBINO randomised controlled trial who provided blood samples at 12- and 28-weeks gestation. Women in the exercise intervention arm received an individualised exercise plan. Blood samples, exercise diary and pedometer data were obtained at 12-, 20-, 28- and 36-weeks' gestation. Cord blood was obtained at delivery.. Women in the exercise arm exercised more than those in the control arm (P = 0.038). There was no difference in gestational weight gain, excess gestational weight gain, MCP-1 and leptin levels between women in the exercise intervention (n = 19) or the control arm (n = 16). IL-8 was not detectable. Exercise did not alter the maternal lipid profile.. The low level of physical activity achieved in obese women in the exercise intervention arm was insufficient to alter gestational weight gain, MCP-1, leptin or circulating lipid levels.

Topics: Adult; Chemokine CCL2; Exercise; Female; Humans; Interleukin-8; Leptin; Obesity; Pilot Projects; Pregnancy; Pregnancy Complications; Weight Gain; Young Adult

The objective of this experiment was to determine the association of serum leptin concentrations with production measures including DMI, ADG, and G:F as well as carcass characteristics in genetically diverse finishing beef steers. Three cohorts of steers ( = 473 total) were individually fed a finishing ration for 92, 64, and 84 d for cohort 1, 2, and 3, respectively. Serum was collected on d 42, 22, and 19 of the experiment for cohort 1, 2, and 3, respectively. Leptin concentrations were positively correlated to DMI ( = 0.21, < 0.01) but negatively correlated to grams DMI per kilogram initial BW ( = -0.21, < 0.01). Leptin concentrations were also negatively correlated to ADG and G:F ( < 0.01). Leptin concentrations were positively correlated to 12th-rib fat thickness, yield grade, and marbling score ( < 0.01) and negatively correlated to LM area ( < 0.01). Using a mixed model analysis (SAS 9.3; SAS Inst. Inc., Cary, NC) to account for breed effects, leptin concentrations were positively associated with DMI ( = 0.01) and accounted for 1.10% of the variance. However, if initial BW and yield grade were included as covariates to account for body size and fatness, leptin was negatively associated with DMI ( = 0.02) and accounted for 0.54% of the variance. Regardless of covariates included in the model, leptin was negatively associated with ADG ( < 0.01) and G:F ( < 0.01) and accounted for 2.62 and 7.87% of the variance for ADG and G:F, respectively. Leptin concentrations were also positively associated with 12th-rib fat thickness, yield grade, and marbling score ( < 0.01) and accounted for 14.74, 12.74, and 6.99% of the variance for 12th-rib fat, yield grade, and marbling score, respectively. Leptin concentrations could be a useful physiological marker for growth and feed efficiency of finishing beef cattle. Genetic influences on the biology of leptin also need to be considered when using leptin as physiological marker for production measures.

Topics: Animal Feed; Animals; Biomarkers; Body Composition; Cattle; Cohort Studies; Eating; Leptin; Male; Weight Gain

Large for gestational age infants have an increased risk of obesity, cardiovascular and metabolic complications during life. Knowledge of the key predictive factors of neonatal adiposity is required to devise targeted antenatal interventions. Our objective was to determine the fetal metabolic factors that influence regional neonatal adiposity in a cohort of women with previous large for gestational age offspring.. Data from the ROLO [Randomised COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analysed in the ROLO Kids study. Neonatal anthropometric and skinfold measurements were compared with fetal leptin and C-peptide results from cord blood in 185 cases. Analyses were performed to examine the association between these metabolic factors and birthweight, anthropometry and markers of central and generalised adiposity.. Fetal leptin was found to correlate with birthweight, general adiposity and multiple anthropometric measurements. On multiple regression analysis, fetal leptin remained significantly associated with adiposity, independent of gender, maternal BMI, gestational age or study group assignment, while fetal C-peptide was no longer significant.. Fetal leptin may be an important predictor of regional neonatal adiposity. Interventional studies are required to assess the impact of neonatal adiposity on the subsequent risk of childhood obesity and to determine whether interventions which reduce circulating leptin levels have a role to play in improving neonatal adiposity measures.

Topics: Adiposity; Adult; Anthropometry; Birth Weight; Body Mass Index; C-Peptide; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Leptin; Male; Pediatric Obesity; Pregnancy; Weight Gain

Leptin and ghrelin appear to play a role in weight regain after a successful weight loss. The pre-treatment plasma levels of leptin/ghrelin ratio (L/G) could have power to predict this clinically relevant issue in the obesity treatment.. To evaluate the ability of the L/G as a non-invasive tool for the early discrimination of obese patients who are more likely to regain weight after an energy restriction program (regainers) from those who maintain the lost weight (non-regainers).. Fasting leptin and ghrelin levels were evaluated in 88 overweight/obese patients who followed an 8-week hypocaloric diet program and were categorized as regainers (≥10 % weight-lost regain) and non-regainers (<10 % weight-lost regain) 6 months (32 weeks) after finishing the dietary treatment. A receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic value of the L/G ratio and to establish a cut-off point to differentiate regainers from non-regainers.. Regainers showed a statistically higher baseline (week 0) and after treatment (week 8) L/G ratio than non-regainers. The baseline L/G ratio was associated with an increased risk for weight regain (odds ratio 1.051; p = 0.008). Using the area under the ROC curve (AUC), the L/G ratio significantly identified female (AUC = 0.69; p = 0.040) and male regainers (AUC = 0.68; p = 0.030). The maximum combination of sensitivity and specificity was shown at the cut-off point of 26.0 for women and 9.5 for men.. The pre-intervention fasting leptin/ghrelin ratio could be a useful non-invasive approach to personalize obesity therapy and avoid unsuccessful treatment outcomes.

Topics: Adult; Biomarkers; Caloric Restriction; Diet, Reducing; Female; Ghrelin; Humans; Leptin; Male; Obesity; Overweight; Prognosis; Treatment Failure; Weight Gain

To compare maternal characteristics, obstetric outcomes and insulin resistance in a cohort of women subdivided into those who did and those who did not exceed the Institute of Medicine (IOM) gestational weight gain guidelines.. This is a prospective study of 621 women without diabetes. Concentrations of glucose, insulin and leptin were measured in early pregnancy and at 28 weeks. Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall width (AAW). At delivery birthweight was recorded and fetal glucose, C-peptide and leptin measured in cord blood. Insulin resistance was calculated using the HOMA equation. Outcomes in those who did and did not exceed IOM guidelines were compared.. Overall, 267 women (43%) exceeded IOM guidelines and 354 (57%) did not. On 34-week ultrasound women with excessive weight gain had higher fetal weights (2681 ± 356 g vs. 2574 ± 331, P = 0.001) and fetal adiposity (AAW) (5.29 ± 1.3 vs. 4.8 ± 1.2, P = 0.001). Infant birthweight and birthweight centiles were also higher in those who exceeded the guidelines. There was no difference between the two groups in maternal insulin resistance in early pregnancy, but by 28 weeks those with excessive weight gain had higher maternal HOMA indices and higher maternal leptin concentrations.. Excessive maternal gestational weight gain has significant implications for infant growth and adiposity, with potential implications for later adult health.

Topics: Adiposity; Adult; Birth Weight; Body Mass Index; C-Peptide; C-Reactive Protein; Female; Fetal Blood; Humans; Infant, Newborn; Insulin; Leptin; Pregnancy; Prospective Studies; United States; Weight Gain

We sought to determine: (1) if early weight regain between 1 and 2 years after Roux-en-Y gastric bypass (RYGB) is associated with worsened hepatic and peripheral insulin sensitivity, and (2) if preoperative levels of ghrelin and leptin are associated with early weight regain after RYGB.. Hepatic and peripheral insulin sensitivity and ghrelin and leptin plasma levels were assessed longitudinally in 45 subjects before RYGB and at 1 month, 6 months, 1 year, and 2 years postoperatively. Weight regain was defined as ≥5% increase in body weight between 1 and 2 years after RYGB.. Weight regain occurred in 33% of subjects, with an average increase in body weight of 10 ± 5% (8.5 ± 3.3 kg). Weight regain was not associated with worsening of peripheral or hepatic insulin sensitivity. Subjects with weight regain after RYGB had higher preoperative and postoperative levels of ghrelin compared to those who maintained or lost weight during this time. Conversely, the trajectories of leptin levels corresponded with the trajectories of fat mass in both groups.. Early weight regain after RYGB is not associated with a reversal of improvements in insulin sensitivity. Higher preoperative ghrelin levels might identify patients that are more susceptible to weight regain after RYGB.

Topics: Adult; Anastomosis, Roux-en-Y; Female; Ghrelin; Humans; Insulin Resistance; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity; Postoperative Period; Recurrence; Weight Gain

The present study is a secondary analysis of the ROLO study, a randomised control trial of a low-glycaemic index (GI) diet in pregnancy to prevent the recurrence of fetal macrosomia. The objectives of the present study were to identify which women are most likely to respond to a low-GI dietary intervention in pregnancy with respect to three outcome measures: birth weight; maternal glucose intolerance; gestational weight gain (GWG). In early pregnancy, 372 women had their mid-upper arm circumference recorded and BMI calculated. Concentrations of glucose, insulin and leptin were measured in early pregnancy and at 28 weeks. At delivery, infant birth weight was recorded and fetal glucose, C-peptide and leptin concentrations were measured in the cord blood. Women who benefited in terms of infant birth weight were shorter, with a lower education level. Those who maintained weight gain within the GWG guidelines were less overweight in both their first and second pregnancies, with no difference being observed in maternal height. Women who at 28 weeks of gestation developed glucose intolerance, despite the low-GI diet, had a higher BMI and higher glucose concentrations in early pregnancy with more insulin resistance. They also had significantly higher-interval pregnancy weight gain. For each analysis, women who responded to the intervention had lower leptin concentrations in early pregnancy than those who did not. These findings suggest that the maternal metabolic environment in early pregnancy is important in determining later risks of excessive weight gain and metabolic disturbance, whereas birth weight is mediated more by genetic factors. It highlights key areas, which warrant further interrogation before future pregnancy intervention studies, in particular, maternal education level and inter-pregnancy weight gain.

Topics: Adiposity; Adult; Birth Weight; Body Mass Index; Cohort Studies; Diet, Carbohydrate-Restricted; Educational Status; Female; Fetal Blood; Fetal Macrosomia; Glucose Intolerance; Glycemic Index; Humans; Insulin; Insulin Resistance; Leptin; Maternal Nutritional Physiological Phenomena; Patient Education as Topic; Pregnancy; Pregnancy Complications; Secondary Prevention; Weight Gain

Smokers have a lower body weight compared to non-smokers. Smoking cessation is associated with weight gain in most cases. A hormonal mechanism of action might be implicated in weight variations related to smoking, and leptin might be implicated. We made secondary analyses of an RCT, with a hypothesis-free exploratory approach to study the dynamic of leptin following smoking cessation.. We measured serum leptin levels among 271 sedentary smokers willing to quit who participated in a randomized controlled trial assessing a 9-week moderate-intensity physical activity intervention as an aid for smoking cessation. We adjusted leptin for body fat levels. We performed linear regressions to test for an association between leptin levels and the study group over time.. One year after smoking cessation, the mean serum leptin change was +3.23 mg/l (SD 4.89) in the control group and +1.25 mg/l (SD 4.86) in the intervention group (p of the difference < 0.05). When adjusted for body fat levels, leptin was higher in the control group than in the intervention group (p of the difference < 0.01). The mean weight gain was +2.91 (SD 6.66) Kg in the intervention and +3.33 (SD 4.47) Kg in the control groups, respectively (p not significant).. Serum leptin levels significantly increased after smoking cessation, in spite of substantial weight gain. The leptin dynamic might be different in chronic tobacco users who quit smoking, and physical activity might impact the dynamic of leptin in such a situation. Clinical trial registration number: NCT00521391.

Topics: Adult; Biomarkers; Body Weight; Exercise; Female; Humans; Leptin; Male; Research Design; Smoking Cessation; Weight Gain

High intake of cow-milk protein in formula-fed infants is associated with higher weight gain and increased adiposity, which have led to recommendations to limit protein intake in later infancy. The impact of protein from meats for breastfed infants during complementary feeding may be different.. We examined the effect of protein from meat as complementary foods on growth and metabolic profiles of breastfed infants.. This was a secondary analysis from a trial in which exclusively breastfed infants (5-6 mo old from the Denver, CO, metro area) were randomly assigned to receive commercially available pureed meats (Meat group; n = 14) or infant cereal (Cereal group; n = 28) as their primary complementary feedings for ∼ 5 mo. Anthropometric measures and diet records were collected monthly from 5 to 9 mo of age; intakes from complementary feeding and breast milk were assessed at 9 mo of age.. The Meat group had significantly higher protein intake, whereas energy, carbohydrate, and fat intakes from complementary feeding did not differ by group over time. At 9 mo of age, mean (± SEM) intakes of total (complementary feeding plus breast milk) protein were 2.9 ± 0.6 and 1.4 ± 0.4 g · kg(-1) · d(-1), ∼ 17% and ∼ 9% of daily energy intake, for Meat and Cereal groups, respectively (P < 0.001). From 5 to 9 mo of age, the weight-for-age z score (WAZ) and length-for-age z score (LAZ) increased in the Meat group (ΔWAZ: 0.24 ± 0.19; ΔLAZ: 0.14 ± 0.12) and decreased in the Cereal group (ΔWAZ: -0.07 ± 0.17; ΔLAZ: -0.27 ± 0.24) (P-group by time < 0.05). The change in weight-for-length z score did not differ between groups. Total protein intake at 9 mo of age and baseline WAZ were important predictors of changes in the WAZ (R(2) = 0.23, P = 0.01).. In breastfed infants, higher protein intake from meats was associated with greater linear growth and weight gain but without excessive gain in adiposity, suggesting that potential risks of high protein intake may differ between breastfed and formula-fed infants and by the source of protein.

Topics: Adiposity; Biomarkers; Blood Glucose; Body Weight; Breast Feeding; Child Development; Cholesterol, HDL; Diet Records; Dietary Proteins; Energy Intake; Female; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Insulin; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Linear Models; Male; Meat; Milk, Human; Triglycerides; Tumor Necrosis Factor-alpha; Weight Gain

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

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

To assess the effect of massage on weight gain and body fat deposition in preterm infants.. Preterm infants (29-32 weeks) were randomized to the massage group (n = 22, 12 girls, 10 boys) or the control group (n = 22, 12 girls, 10 boys). Treatment was masked with massage or control care administered twice-daily by licensed massage therapists (6 d/wk for 4 weeks). Body weight, length, Ponderal Index (PI), body circumferences, and skinfold thickness (triceps, mid-thigh, and subscapular [SSF]) were measured. Circulating insulin-like growth factor I, leptin, and adiponectin levels were determined by enzyme-linked immunosorbent assay. Daily dietary intake was collected.. Energy and protein intake as well as increase in weight, length, and body circumferences were similar. Male infants in the massage group had smaller PI, triceps skinfold thickness, mid-thigh skinfold thickness, and SSF and increases over time compared with control male infants (P < .05). Female infants in the massage group had larger SSF increases than control female infants (P < .05). Circulating adiponectin increased over time in control group male infants (group × time × sex interaction, P < .01) and was correlated to PI (r = 0.39, P < .01).. Twice-daily massage did not promote greater weight gain in preterm infants. Massage did, however, limit body fat deposition in male preterm infants. Massage decreased circulating adiponectin over time in male infants with higher adiponectin concentrations associated with increased body fat. These findings suggest that massage may improve body fat deposition and, in turn, growth quality of preterm infants in a sex-specific manner.

Topics: Adiponectin; Anthropometry; Body Fat Distribution; Body Weight; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant, Newborn; Infant, Premature; Insulin-Like Growth Factor I; Leptin; Male; Massage; Weight Gain

Treatment with several psychopharmacological agents has been associated with increased leptin plasma concentrations. We measured leptin plasma concentrations in 76 adult depressed patients after a 6-day washout phase and again after 35 days of treatment with amitriptyline or paroxetine, as well as in 73 depressed patients after 28 days of treatment with either mirtazapine or venlafaxine. Leptin plasma concentrations increased during treatment with amitriptyline and mirtazapine, even after controlling for increased body mass index and irrespective of response to treatment [14.5 (13.8) vs 20.3 (18.7) ng/mL, and 12.2 (15.8) vs 14.4 (16.5) ng/mL in the 2 cohorts, respectively]. In contrast, paroxetine and venlafaxine treatment was not associated with changes in leptin plasma concentrations [14.8 (12.0) vs 13.6 (10.6); 15.9 (17.3) vs 13.5 (14.6) ng/mL] nor with weight gain. We conclude that treatment with amitriptyline or mirtazapine is associated with an increase in leptin secretion beyond change in weight. Thus, high leptin levels apparently are ineffective in the control of weight gain, indicating leptin resistance. Leptin resistance may be mediated by an antihistaminergic effect on hypothalamic nuclei integrating signals relevant for energy balance.

Topics: Adult; Aged; Aged, 80 and over; Amitriptyline; Analysis of Variance; Antidepressive Agents; Biomarkers; Body Mass Index; Cyclohexanols; Depression; Female; Humans; Leptin; Male; Mianserin; Middle Aged; Mirtazapine; Paroxetine; Time Factors; Treatment Outcome; Up-Regulation; Venlafaxine Hydrochloride; Weight Gain; Young Adult

Rheumatoid arthritis (RA) is a chronic inflammatory disease that damages the synovial joints, and patients with it are often anorexic and cachectic with high morbidity and mortality. Biological therapy with anti-tumor necrosis factor (TNF)-α has been proven effective as a treatment for RA. However, the long-term effects of anti-TNF-α therapy on body weight, appetite, plasma gut hormones and leptin have not been investigated.. Twenty RA patients received subcutaneous injections of etanercept, a chimeric protein of human IgG1 Fc and TNF receptor p75, twice weekly for 12 consecutive months. Sequential changes in body weight, body fat, appetite rating, lipid profiles, gut hormones and leptin were measured at baseline and at 3 and 12 months after treatment. Ten RA patients who received non-biological disease modifying anti-rheumatic drugs were enrolled as the controls and were appraised at baseline and at 12 months after treatment (a nonrandomized study).. Significant weight gain, hyperuricemia, decreased fasting plasma glucose-dependent insulinotropic polypeptide (GIP) levels, and loss of post-oral glucose suppression of plasma leptin concentration were found in the patients after the 12-month course of etanercept therapy, but not in the controls. A transient decrease in fasting plasma acyl ghrelin occurred at 3 months during etanercept treatment. Appetite score and serum lipid profiles did not change in either group.. Long-term therapy with anti-TNF-α is promising in ameliorating body mass decrease in patients with active RA. Plasma levels of ghrelin, GIP and leptin may play significant roles in maintaining energy homeostasis in the anti-inflammatory responses during RA remission.

Topics: Adult; Antirheumatic Agents; Appetite; Arthritis, Rheumatoid; Body Composition; Body Mass Index; Cachexia; Etanercept; Female; Gastrointestinal Hormones; Humans; Immunoglobulin G; Leptin; Male; Middle Aged; Receptors, Tumor Necrosis Factor; Weight Gain

Some but not all second-generation antipsychotics can induce considerable weight gain and metabolic syndrome. Although the exact biochemical mechanisms for these adverse effects are unclear, appetite-regulating neuropeptides of the central nervous system are thought to be implicated in this process. The hypothalamic mediator Agouti-related protein (AGRP) is inhibited by leptin and was shown to increase food intake. The aim of the present study was to investigate the trajectory of AGRP levels during antipsychotic-induced weight gain.. As part of a controlled prospective clinical study, we determined indicators of body fat mass, plasma AGRP, and leptin levels in 16 patients with schizophrenia treated with ziprasidone and 21 patients with schizophrenia treated with olanzapine. Measurements by enzyme-linked immunosorbent assay were obtained before treatment (T0), after 4 weeks (T1), and after 3 months (T2) of treatment.. Whereas body mass index and leptin levels increased in patients treated with olanzapine compared to patients treated with ziprasidone, plasma AGRP levels did not differ among the treatment groups and did not change over time. Associations between AGRP and fat mass as well as appetite were disrupted in the olanzapine-treated patients but not in the ziprasidone group.. Future studies are needed to test whether the lack of a decrease in AGRP levels during weight gain in patients treated with olanzapine could perpetuate adverse metabolic long-term effects.

Topics: Adult; Agouti-Related Protein; Antipsychotic Agents; Biomarkers; Cohort Studies; Female; Follow-Up Studies; Humans; Leptin; Longitudinal Studies; Male; Prospective Studies; Schizophrenia; Weight Gain

Over 75% of obese subjects fail to maintain their weight following weight loss interventions. We aimed to identify phenotypic and genetic markers associated with weight maintenance/regain following a dietary intervention.. In the 2-year Dietary Intervention Randomized Controlled Trial, we assessed potential predictors for weight changes during the 'weight loss phase' (0-6 months) and the 'weight maintenance/regain phase' (7-24 months). Genetic variation between study participants was studied using single-nucleotide polymorphisms in the leptin gene (LEP).. Mean weight reduction was -5.5% after 6 months, with a mean weight regain of 1.2% of baseline weight during the subsequent 7-24 months. In a multivariate regression model, higher baseline high-molecular-weight adiponectin was the only biomarker predictor of greater success in 0- to 6-month weight loss (β = -0.222, P-value = 0.044). In a multivariate regression model adjusted for 6-month changes in weight and various biomarkers, 6-month plasma leptin reduction exhibited the strongest positive association with 6-month weight loss (β = 0.505, P-value < 0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (β = -0.131, P-value < 0.013). Weight regain was higher among participants who had a greater (top tertiles) 6-month decrease in both weight and leptin (+3.4% (95% confidence interval 2.1-4.8)) as compared with those in the lowest combined tertiles (+0.2% (95% confidence interval -1.1 to 1.4)); P-value < 0.001. Weight regain was further significantly and independently associated with genetic variations in LEP (P = 0.006 for both rs4731426 and rs2071045). Adding genetic data to the phenotypic multivariate model increased its predictive value for weight regain by 34%.. Although greater reduction in leptin concentrations during the initial phase of a dietary intervention is associated with greater weight loss in the short term, plasma leptin reduction, combined with the degree of initial weight loss and with genetic variations in the LEP gene, constitutes a significant predictor of subsequent long-term weight regain.

Topics: Biomarkers; Body Mass Index; Diet, Reducing; Female; Genetic Variation; Humans; Leptin; Male; Middle Aged; Obesity; Phenotype; Weight Gain

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

The objective of this study was to investigate the effects of foetal undernutrition on the metabolism in growing lambs. Seven-month-old lambs whose mothers had been fed either restrictively (RN; n = 14) or adequately (AN; n = 6) in late gestation were fasted for three days. One hour before fasting and after 48 h and 72 h fasting, changes in plasma concentrations of metabolites, i.e. glucose, nonesterified fatty acids (NEFA), 3-beta-hydroxybutyrate (BOHB) and urea as well as hormones, i.e. insulin, the insulin-like growth factor (IGF-I) and leptin, were determined. Blood glucose, NEFA, urea, insulin, IGF-I and leptin were not different between the two groups of lambs. Unexpectedly, at the end of the 3 d fasting, in spite of lower NEFA concentration (1.6 +/- 0.03 vs. 1.9 +/- 0.05 mM in Groups RN and AN, respectively), the BOHB concentration in RN lambs (0.94 +/- 0.02 mM) was significantly higher than that in AN lambs (0.78 +/- 0.04 mM). This higher rate of BOHB production might be interpreted as perturbations in ketone body metabolism potentially induced by undernutrition during foetal life. However, more investigations are necessary to clarify this interrelationship.

Topics: Animals; Blood Glucose; Body Composition; Energy Metabolism; Female; Fetal Nutrition Disorders; Food Deprivation; Insulin; Leptin; Male; Malnutrition; Pregnancy; Sheep; Urea; Weight Gain

Data from species other than cattle indicate that ghrelin and GH secretagogue receptor (GHS-R) could play a key role in fat deposition, energy homeostasis, or glucose metabolism by directly affecting liver and adipose tissue metabolism. Beef steers (n = 72) were used to test the hypothesis that plasma ghrelin and leptin concentrations and abundance of the GHS-R in liver, muscle, and adipose tissues differ in steers exhibiting differences in composition of gain. At trial initiation (d 0), 8 steers were slaughtered for initial carcass composition. The remaining 64 steers were stratified by BW, allotted to pen, and treatment was assigned randomly to pen. Steers were not implanted with anabolic steroids. Treatments were 1) a low-energy (LE) diet fed during the growing period (0 to 111 d) followed by a high-energy (HE) diet during the finishing period (112 to 209 d; LE-HE) or 2) the HE diet for the duration of the trial (1 to 209 d; HE-HE). Eight steers per treatment were slaughtered on d 88, 111, 160, and 209. Carcass ninth, tenth, and eleventh rib sections were dissected for chemical composition and regression equations were developed to predict compositional gain. Liver, muscle, and subcutaneous adipose tissues were frozen in liquid nitrogen for subsequent Western blotting for GHS-R. Replicate blood samples collected before each slaughter were assayed for ghrelin and leptin concentrations. When compared at a common compositional fat end-point, the rate of carcass fat accretion (g·kg of shrunk BW(-1)) was greater (P < 0.001) in HE-HE steers whereas the rate of carcass protein accretion (g·kg of shrunk BW(-1)) was less (P < 0.001) compared with LE-HE steers. When compared at a common compositional fat end-point, plasma leptin, ghrelin, and insulin concentrations were greater (P < 0.05) for HE-HE compared with LE-HE steers. Abundance of the GHS-R, to which ghrelin binds, increased over time in liver and adipose tissue but did not differ as a result of treatment. Plasma ghrelin concentrations were increased for cattle continuously fed the HE diet as they became increasingly fatter; however, abundance of the GHS-R in liver, muscle, and subcutaneous adipose tissue was not different between treatment groups. The role of ghrelin in cattle metabolism warrants further investigation as it could have a significant effect on composition of BW gain, feed efficiency, and metabolic disorders such as ketosis and fatty liver.

Topics: Adipose Tissue; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Body Composition; Cattle; Diet; Fatty Acids, Nonesterified; Gene Expression Regulation; Ghrelin; Growth Hormone; Insulin; Leptin; Liver; Muscle, Skeletal; Receptors, Ghrelin; Weight Gain

Atypical antipsychotic medications like olanzapine (OLZ) induce weight gain and increase the risk of diabetes in patients with schizophrenia. The goal of this study was to assess potential mechanisms of OLZ-induced weight gain and accompanying metabolic effects. Healthy, lean, male volunteers received OLZ and placebo (PBO) in a randomized, double-blind, crossover study. In periods 1 and 2, subjects received OLZ (5 mg for 3 days then OLZ 10 mg for 12 days) or matching PBO separated by a minimum 12-day washout. Twenty-four hour food intake (FI), resting energy expenditure (REE), activity level, metabolic markers, and insulin sensitivity (IS) were assessed. In total, 30 subjects were enrolled and 21 completed both periods. Mean age and BMI were 27 years (range: 18-49 years) and 22.6 +/- 2.2 kg/m(2), respectively. Relative to PBO, OLZ resulted in a 2.62 vs. 0.08 kg increase in body weight (P < 0.001) and 18% (P = 0.052 or 345 kcal) increase in FI. Excluding one subject with nausea and dizziness on the day of OLZ FI measurement, the increase in FI was 547 kcal, (P < 0.05). OLZ increased REE relative to PBO (113 kcal/day, P = 0.003). Significant increases in triglycerides, plasminogen activator inhibitor-I (PAI-I), leptin, and tumor necrosis factor-alpha (TNF-alpha) were observed. No significant differences in activity level or IS were observed. This study provides evidence that OLZ pharmacology drives the early increase in weight through increased FI, without evidence of decreased energy expenditure (EE), activity level, or short-term perturbations in IS.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Metabolism; Benzodiazepines; Biomarkers; Double-Blind Method; Energy Intake; Exercise; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Olanzapine; Plasminogen Activator Inhibitor 1; Reference Values; Triglycerides; Tumor Necrosis Factor-alpha; Weight Gain; Young Adult

To document prospective weight and anthropometric changes in children and adolescents during the first 12 weeks of treatment with risperidone and evaluate metabolic outcomes including plasma leptin levels.. Eight patients with psychotic disorders (ages 11-17) who had started risperidone (mean: 1.80 mg/day; sd = 1.04) in the prior 4 weeks participated in this observational study. Fasting morning blood samples were obtained at baseline and week 8 to assess glucose, leptin, cortisol, insulin, and triglycerides. Measures of body mass index (BMI), weight, waist and hip circumference, blood pressure, and heart rate were obtained weekly.. Participants increased in mean weight (4.16 kg; sd = 4.36; p = 0.03) and BMI (1.47 kg/m(2); sd = 1.53; p = 0.03) with five out of eight gaining at least 7% of baseline body weight. They had a 4.03 cm (sd = 3.82; p = 0.02) increase in waist circumference and a 5.17 cm (sd = 3.68; p = 0.01) increase in hip circumference. Leptin trended higher, but did not reach statistical significance. There were no significant changes in glucose, insulin, cortisol, blood pressure, or heart rate.. Subjects experienced significant increases in weight, BMI, hip and waist circumference during the first 3 months of treatment. Better powered research with more advanced anthropometric assessment is warranted to further elucidate mechanisms of antipsychotic associated weight gain in youth.

Topics: Adolescent; Anthropometry; Antidepressive Agents, Second-Generation; Body Mass Index; Body Size; Body Weight; Child; Day Care, Medical; Diagnostic and Statistical Manual of Mental Disorders; Female; Hip; Humans; Insulin Resistance; Leptin; Male; Pilot Projects; Psychotic Disorders; Risperidone; Waist Circumference; Weight Gain

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

Leptin and peroxisome proliferator-activated receptor gamma (PPARγ) are adipogenic proteins that are actively involved in metabolic homeostasis of fat. Recently, it was reported that fat tissue in humans and rodents differs in metabolic activity relative to anatomical location of the fat tissue (i.e. depots) and animal age. Hence, we hypothesized that leptin and PPARγ production in various fat depots in female pigs differs in response to acute fasting, and that these responses vary with physiological maturity of the animal. Sixteen intact crossbred immature female pigs [prepubertal (PP); 132.2 ± 4.1 days] and 16 sexually mature female pigs (M; 224 ± 7.4 days) housed in an open-air, concrete slab, sheltered barn were randomly assigned to either Control or Fasted treatments. Control pigs (PP, n = 8; M, n = 8) had ad libitum access to feed, while Fasted pigs (PP, n = 8; M, n = 8) were denied access to feed from the onset of the study (0 h) to euthanasia at 72 h. Immediately post-mortem, fat samples were collected from the subcutaneous, pelvic, kidney, and heart (M pigs only) fat depots and analysed for leptin and PPARγ mRNA and protein content. Acute fasting decreased mean leptin mRNA tissue content in a depot specific manner in M pigs (p < 0.01), while mean leptin protein concentrations in fat tissues did not differ with fat depot or age of the pig. Furthermore, acute fasting did not affect mean PPARγ mRNA tissue content in a fat depot or age dependent manner. Mean concentrations of PPARγ protein in fat depots tended to be greater in M vs. PP pigs (p = 0.07). We suggest that these data provide evidence that acute fasting has a greater effect on leptin than PPARγ production in a fat depot dependent manner in M pigs, which may be indicative of changing physiological demands as an animal matures.

Topics: Adipogenesis; Adipose Tissue; Aging; Animals; Energy Intake; Female; Food Deprivation; Leptin; Male; PPAR gamma; Sexual Maturation; Swine; Weight Gain

The purpose of the study was to test prospectively whether healthy individuals with a family history of type 2 diabetes are more susceptible to adverse metabolic effects during experimental overfeeding.. We studied the effects of 3 and 28 days of overfeeding by 5,200 kJ/day in 41 sedentary individuals with and without a family history of type 2 diabetes (FH+ and FH- respectively). Measures included body weight, fat distribution (computed tomography) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp).. Body weight was increased compared with baseline at 3 and 28 days in both groups (p < 0.001), FH+ individuals having gained significantly more weight than FH- individuals at 28 days (3.4 +/- 1.6 vs 2.2 +/- 1.4 kg, p < 0.05). Fasting serum insulin and C-peptide were increased at 3 and 28 days compared with baseline in both groups, with greater increases in FH+ than in FH- for insulin at +3 and +28 days (p < 0.01) and C-peptide at +28 days (p < 0.05). Fasting glucose also increased at both time points, but without a significant group effect (p = 0.1). Peripheral insulin sensitivity decreased in the whole cohort at +28 days (54.8 +/- 17.7 to 50.3 +/- 15.6 micromol min(-1) [kg fat-free mass](-1), p = 0.03), and insulin sensitivity by HOMA-IR decreased at both time points (p < 0.001) and to a greater extent in FH+ than in FH- (p = 0.008). Liver fat, subcutaneous and visceral fat increased similarly in the two groups (p < 0.001).. Overfeeding induced weight and fat gain, insulin resistance and hepatic fat deposition in healthy individuals. However, individuals with a family history of type 2 diabetes gained more weight and greater insulin resistance by HOMA-IR. The results of this study suggest that healthy individuals with a family history of type 2 diabetes are predisposed to adverse effects of overfeeding.. ClinicalTrials.gov NCT00562393. The study was funded by the National Health and Medical Research Council (NHMRC), Australia (no. #427639).

Topics: Adult; Analysis of Variance; Australia; Body Composition; C-Peptide; Diabetes Mellitus, Type 2; Feeding Behavior; Female; Genetic Predisposition to Disease; Glucose; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Overnutrition; Risk Factors; Sedentary Behavior; Weight Gain

Weight gain is one of the major adverse effects of antipsychotics. Although mechanisms remain unclear, genetic susceptibility has become increasingly attractive as a potential mechanism that could explain a significant part of interindividual variability. Most investigations have explored genes related with the mechanism of action of antipsychotic drugs. An alternative approach to investigate the role that genetic factors play in weight gain secondary to antipsychotic treatment is to study those genetic variants that have been found associated with obesity. The aim of this study was to determine whether the fat mass and obesity-associated gene (FTO) rs9939609 variant, the single nucleotide polymorphism that has shown the strongest association with common obesity in different populations, influences weight gain during the first year of antipsychotic treatment. We investigated also the genetic variants in other 3 strong candidates genes involved in the leptin-signaling pathway including leptin, leptin receptor, and Src homology 2. We carried out a prospective study on 239 patients with first-episode psychosis. Two hundred five patients completed the follow-up at 1 year (85.8%). Before antipsychotic treatment, the homozygous subjects for the risk allele A of the FTOrs9939609 variant had a higher body mass index at baseline (24.2 T 3.8 kg/m²) than the AT/TT group (22.82 T 3.3 kg/m2; F = 5.744; P = 0.018). After 1 year, the magnitude of weight increase was similar in the 3 genotypes defined by the rs9939609 variant. These results suggest that the pharmacological intervention accompanied by changes in energy intake and expenditure could suppress the genetic susceptibility conferred by the FTO genotype. None of the other single nucleotide polymorphisms evaluated were associated with weight gain during the first 12 months of antipsychotic therapy.

Topics: Adaptor Proteins, Signal Transducing; Adult; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Antipsychotic Agents; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Humans; Leptin; Longitudinal Studies; Male; Polymorphism, Single Nucleotide; Prospective Studies; Proteins; Psychotic Disorders; Receptors, Leptin; Schizophrenia; Weight Gain; Young Adult

The second generation antipsychotics clozapine and olanzapine are known to cause weight gain. However, only clozapine is associated with drug-induced fever. Cytokines have been linked to the induction of both weight gain and drug-induced fever. We investigated these potential side effects of clozapine and olanzapine and studied their differential effects on cytokine secretion. Thirty patients suffering from schizophrenia, schizophreniform disorder or schizoaffective disorder were treated with either clozapine (mean modal dose: 266.7+/-77.9mg) or olanzapine (21.2+/-2.5mg) in a randomized, double-blind, 6-week study. Body mass index (BMI), tympanic temperature, and plasma levels of leptin and cytokines (tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 and 2 (sTNFR-1/2), soluble interleukin-2 receptors (sIL-2R), interleukin-6) were determined weekly. BMI, leptin and cytokines significantly increased over time, except interleukin-6 and sTNFR-1 in the olanzapine group. All cytokines numerically increased compared to baseline already during the first week of treatment in both groups. Leptin, TNF-alpha, sTNFR-1, sTNFR-2 and sIL-2R levels correlated with the BMI. Five patients who received clozapine (33%) developed drug-induced fever (>/=38 degrees C). In these, interleukin-6 peak levels were significantly (p<0.01) higher than in those patients treated with clozapine who did not develop fever. In conclusion, increase of BMI appears to be related to clozapine's and olanzapine's similar effects on cytokine systems, whilst drug-induced fever appears to be related to clozapine's differential effects on interleukin-6.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Cytokines; Double-Blind Method; Female; Fever; Humans; Leptin; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Weight Gain

Weight regain in subjects with anorexia nervosa is associated with an increase in serum leptin concentrations that is hypothesized to impair full weight restoration. As diets rich in n-3 polyunsaturated fatty acids (PUFA) have been described to lower serum leptin concentrations, we tested the hypothesis that consumption of a hypercaloric diet rich in n-3 PUFA is associated with an attenuated increase in serum leptin and a higher efficiency of body weight gain in subjects with anorexia nervosa. Twenty-five female subjects with anorexia nervosa were enrolled into this controlled dietary intervention study. Four subjects discontinued therapy or participation in the study prematurely, and six were excluded. 15 subjects completed the study. Subjects consumed hypercaloric diets rich in either saturated fatty acids (SFA, n = 8) or n-3 PUFA (n = 7) for 5 weeks. Primary endpoints were the change in serum leptin concentrations and body weight gain relative to energy consumed. Serum leptin concentrations increased distinctly throughout the study (P < .001), and to a similar extend in both groups [+2.9 (SD 2.4) vs. +2.8 (SD 3.4) ng/mL in the SFA- and n-3 PUFA group, respectively; P = .487]. The efficiency of body weight gain also did not differ significantly between groups, with a body weight gain of 63.1 (SD 12.4) vs. 79.2 (SD 26.0) g per 4.2 MJ (1000 kcal) consumed in the SFA- and n-3 PUFA group, respectively (P = .132). Hypercaloric diets rich in either SFA or n-3 PUFA do not differ in their effects on serum leptin concentrations and the efficiency of body weight gain in female subjects with anorexia nervosa.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet; Dietary Fats; Energy Intake; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Ghrelin; Humans; Insulin; Leptin; Middle Aged; Triglycerides; Weight Gain; Young Adult

In contrast to the general population, a higher body mass index is associated with better survival among hemodialysis patients. Theoretically, high energy supplementation in these patients ought to lead to weight gain over time, but the benefits of this strategy are unclear.. The objective was to assess whether high energy supplementation in nondiabetic hemodialysis patients might adversely affect insulin resistance -- a known risk factor for cardiovascular disease.. We first investigated the association between body fat mass and insulin resistance (homeostasis model assessment of insulin resistance; HOMA-IR) in nondiabetic hemodialysis patients in a cross-sectional analysis (study 1). Of the 106 individuals studied, 55 were randomly assigned to either high energy supplementation (an extra 475 kcal/d; n = 28) or not (n = 27) for 12 wk to assess prospective changes in body fat mass and insulin resistance (study 2).. In study 1, body fat mass (P < 0.05) and C-reactive protein (CRP) (P < 0.05) each contributed independently to HOMA-IR. In study 2, 41 patients completed the study. The 20 patients who received high energy supplementation had a significantly greater increase in body fat mass (P < 0.05), CRP (P < 0.05), and HOMA-IR (P < 0.001) than did the 21 controls.. Body fat mass and CRP are primary determinants of insulin resistance in nondiabetic hemodialysis patients. High energy supplementation, because it increases adiposity and inflammation, exacerbates insulin resistance. A long-term study is needed to clarify the metabolic effects of high energy supplementation on cardiovascular disease outcomes in hemodialysis patients.

Topics: Adipose Tissue; Adiposity; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; C-Reactive Protein; Cross-Sectional Studies; Dietary Supplements; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Patient Selection; Renal Dialysis; Serum Albumin; Weight Gain

To compare the changes in body composition and in leptin levels in postmenopausal women receiving hormone therapy (HT) or tibolone.. Prospective comparative study.. Menopause Unit in a tertiary Hospital.. One hundred twenty women were recruited.. Women were assigned into a control group, HT, and tibolone group.. Anthropometric indices, leptin levels, tissue fat percentage, total fat, and lean mass measurements were performed at baseline and after 6 months.. The serum leptin levels were in strong correlation with the total fat percentage and total fat mass at baseline. Untreated women had weight gain and a gradual decrease in leptin levels. Women receiving HT had significantly increased leptin levels. Women in the tibolone group, however, had a significant decrease in leptin levels accompanied by decreased total fat mass, fat percentage, and increased total lean mass. The changes in leptin levels were more pronounced in lean women.. Postmenopausal women tend to gain weight accompanied with a reduction in leptin concentrations. Hormone therapy administration increases leptin levels while maintaining body weight and body fat distribution, whereas tibolone use decreases leptin levels, total fat percentage, and total fat mass.

Topics: Adiposity; Adult; Body Mass Index; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Humans; Leptin; Medroxyprogesterone Acetate; Middle Aged; Norpregnenes; Postmenopause; Time Factors; Treatment Outcome; Waist-Hip Ratio; Weight Gain

Olanzapine is an efficacious drug often used as a first-line medication in the treatment for schizophrenia. However, weight gain is a notable adverse drug reaction of this medication in a proportion of patients and a major cause of noncompliance. Several hypotheses, including a contribution from hormonal, physiological and environmental factors, have been postulated. In this study, we aimed to analyze a possible association of genetic polymorphisms at four important candidate genes involved in appetite regulation and antipsychotic-induced metabolic syndrome with olanzapine-induced weight gain.. A total of 154 schizophrenia subjects were recruited in a systematic, 6-week, open-label trial of olanzapine. We investigated the contribution of 14 polymorphisms from four genes, namely, leptin, lipoprotein lipase, tri-acyl-glycerol lipase and citrate lyase using a binary logistic regression analysis towards olanzapine-induced weight gain.. rs 4731426 C/G SNP, a variant in the leptin gene, was moderately associated with median weight gain (Delta weight(m); [p = 0.05; OR: 2.2; 95% CI: 0.99-4.90]) and significantly associated with extreme weight gain (Delta weight(e) [p = 0.019; OR: 11.43; 95% CI: 1.49-87.55]) when average drug dose was included in a regression model. Using in silico analysis, we found that this associated intronic SNP in the leptin gene alters the binding of zinc finger 5, a transcription factor.. The leptin gene may be a promising candidate for olanzapine-induced weight gain. As the associations are modest, replicate studies are warranted. This approach may facilitate rationalized drug regimens.

Topics: Adult; Benzodiazepines; Female; Genetic Linkage; Humans; India; Leptin; Male; Metabolic Networks and Pathways; Middle Aged; Olanzapine; Polymorphism, Genetic; Schizophrenia; Weight Gain

Can gestational weight gain in obese women be restricted by 10-h dietary consultations and does this restriction impact the pregnancy-induced changes in glucose metabolism?. A randomized controlled trial with or without restriction of gestational weight gain to 6-7 kg by ten 1-h dietary consultations.. Fifty nondiabetic nonsmoking Caucasian obese pregnant women were randomized into intervention group (n=23, 28+/-4 years, prepregnant body mass index (BMI) 35+/-4 kg m(-2)) or control group (n=27, 30+/-5 years, prepregnant BMI 35+/-3 kg m(-2)).. The weight development was measured at inclusion (15 weeks), at 27 weeks, and 36 weeks of gestation. The dietary intakes were reported in the respective weeks by three 7-day weighed food records and blood samples for analyses of fasting s-insulin, s-leptin, b-glucose, and 2-h b-glucose after an oral glucose tolerance test were collected.. The women in the intervention group successfully limited their energy intake, and restricted the gestational weight gain to 6.6 kg vs a gain of 13.3 kg in the control group (P=0.002, 95% confidence interval (CI): 2.6-10.8 kg). Both s-insulin and s-leptin were reduced by 20% in the intervention group compared to the control group at week 27, mean difference: -16 pmol l(-1) (P=0.04, 95% CI: -32 to -1) for insulin and -23 ng ml(-1) (P=0.004, 95% CI: -39 to -8) for leptin. At 36 weeks of gestation, the s-insulin was further reduced by 23%, -25 pmol l(-1) (-47 to -4, P=0.022) and the fasting b-glucose were reduced by 8% compared with the control group (-0.3 mmol l(-1), -0.6 to -0.0, P=0.03).. Restriction of gestational weight gain in obese women is achievable and reduces the deterioration in the glucose metabolism.

Topics: Adult; Blood Glucose; Body Mass Index; Counseling; Diet; Diet Records; Energy Intake; Female; Glucose Tolerance Test; Humans; Insulin; Leptin; Obesity; Pregnancy; Weight Gain

Formula-fed infants have growth and plasma amino acid patterns different from those of breastfed infants.. alpha-Lactalbumin is a major protein in human milk, and the addition of bovine alpha-lactalbumin to infant formula has been proposed to modify the plasma amino acid pattern of the recipient infant, possibly allowing a reduction in the protein content of the formula, which may affect growth.. We compared breastfed infants and infants fed standard formula or alpha-lactalbumin-enriched formulas (25% of protein) with glycomacropeptide accounting for 15% or 10% of the protein. The protein content of each formula was 13.1 g/L. Ninety-six infants aged 6 +/- 2 wk were recruited. Anthropometric measures were recorded, and interviews were conducted at enrollment and monthly until 6 mo of age. Blood samples were collected at enrollment and at 4 and 6 mo.. Formula intake did not differ between groups, and weight gain in the alpha-lactalbumin-enriched formula groups were similar to that of the breastfed infants. The standard formula group gained significantly more weight than did the breastfed infants. All formula-fed infants had significantly higher plasma concentrations of most essential amino acids at 4 and 6 mo than did the breastfed infants, and serum urea nitrogen was also higher in the formula-fed infants. Insulin and leptin concentrations did not differ between groups.. Compared with standard formula-fed infants, infants fed formula with a modified protein composition had growth patterns more similar to those of breastfed infants. All formula-fed groups had plasma amino acid concentrations similar to or higher than those of breastfed infants. This indicates that the protein content of alpha-lactalbumin-enriched formula can be further reduced, which should be evaluated.

Topics: Amino Acids, Essential; Blood Urea Nitrogen; Child Development; Female; Food, Fortified; Glycopeptides; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Insulin; Lactalbumin; Leptin; Male; Milk, Human; Weight Gain

Short sleep appears to be strongly associated with obesity and altered metabolic function, and sleep and growth hormone (GH) secretion seems interlinked. In obesity, both the GH-insulin-like-growth-factor-I (GH-IGF-I) axis and sleep have been reported to be abnormal, however, no studies have investigated sleep in relation to the GH-IGF-I axis and weight loss in obese subjects. In this study polygraphic sleep recordings, 24-h GH release, 24-h leptin levels, free-IGF-I, total-IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), cortisol and insulin sensitivity were determined in six severely obese subjects (BMI: 41+/-1 kg/m(2), 32+/-2 years of age), cross-sectional at baseline, and longitudinal after a dramatically diet-induced weight loss (36+/-7 kg). Ten age- and gender-matched nonobese subjects served as controls. Sleep duration (360+/-17 vs. 448+/-15 min/night; P<0.01), 24-h GH (55+/-9 vs. 344+/-55 mU/l.24 h; P<0.01), free-IGF-I (2.3+/-0.42 vs. 5.7+/-1.2 microg/l; P<0.01), and total-IGF-I (186+/-21 vs. 301+/-18 microg/l; P<0.01) were significantly decreased and 24-h leptin levels were increased (35+/-5 vs. 12+/-3 microg/l; P<0.01) in obese subjects at pre-weight loss compared with nonobese subjects After diet-induced weight loss the differences in GH, free IGF-I, and leptin were no longer present between previously obese and nonobese subjects, whereas a significant difference in sleep duration and total IGF-I levels persisted. Rapid eye movement (REM) sleep, non-REM sleep, IGFBP-3, ALS, and cortisol levels were similar in obese and nonobese subjects. Sleep duration, 24-h GH, and IGF-I levels were decreased and 24-h leptin levels were increased in obese subjects. We conclude that hyposomatotropism and hyperleptinemia in obesity are transient phenomena reversible with weight loss, whereas short sleep seems to persist after weight has been reduced dramatically.

Topics: Adult; Carrier Proteins; Case-Control Studies; Circadian Rhythm; Energy Intake; Female; Glycoproteins; Human Growth Hormone; Humans; Hydrocortisone; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Male; Obesity; Polysomnography; Prospective Studies; Severity of Illness Index; Sleep; Sleep Wake Disorders; Sleep, REM; Treatment Outcome; Weight Gain

Weight gain has become one of the most common and concerning side effects of antipsychotic treatment. The mechanisms whereby antipsychotics induce weight gain are not known. It has been suggested that peptides related to food intake and energy balance could play a role in weight gain secondary to antipsychotic therapy. To better understand the pathophysiology of antipsychotic-induced weight gain, we studied the effects of 3 antipsychotic drugs (haloperidol, olanzapine, and risperidone) on peptides involved in energy balance (insulin, ghrelin, leptin, adiponectin, visfatin, and resistin) in a population of drug-naive patients with first episode of psychosis.A significant increase in weight (10.16 kg [SD, 8.30 kg]; P < 0.001), body mass index (3.56 kg/m [SD, 2.89 kg/m]; P < 0.001), and fasting insulin (3.93 muU/mL [SD, 3.93 muU/mL]; P = 0.028), leptin (6.76 ng/mL [SD, 7.21 ng/mL]; P < 0.001), and ghrelin (15.47 fmol/mL [SD, 47.90 fmol/mL]; P = 0.009) plasma levels were observed. The increments in insulin and leptin concentrations were highly correlated with the increment in weight and body mass index and seem to be a consequence of the higher fat stores. The unexpected increase in ghrelin levels might be related with the causal mechanism of weight gain induced by antipsychotics. Finally, the 3 antipsychotics had similar effects in all parameters evaluated.

Topics: Adiponectin; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Body Composition; Body Mass Index; Dose-Response Relationship, Drug; Energy Metabolism; Female; Ghrelin; Haloperidol; Humans; Insulin; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Olanzapine; Prospective Studies; Psychotic Disorders; Resistin; Risperidone; Schizophrenia; Weight Gain

Olanzapine (OLA) administration has been reported to induce weight gain in experimental animals and humans, through not yet fully defined mechanisms of action. Aim of this study was to determine whether in patients with Anorexia Nervosa (AN) OLA induces weight gain through the modulation of the hunger-satiety regulatory peptides leptin and ghrelin.. Twenty anorexic probands received a 3 months course of cognitive-behavioral psychotherapy and programmed nutritional rehabilitation, combined with OLA PO (2.5 mg for 1 month and 5 mg for 2 months) in ten patients and with placebo PO (PL) in the other 10. Weight, measured as body mass index (BMI), leptin and ghrelin plasma values were monitored before starting the therapy and then monthly for 3 months. Plasma leptin was measured by ELISA, and plasma ghrelin by radioimmunoassay.. BMI increased significantly but not differently in both treatment groups. Leptin and ghrelin secretion did not change during the course of the treatments. No correlations were observed between BMI values and leptin and ghrelin levels.. Our data suggest that the weight gain observed in our OLA-treated patients was not linked to drug administration. Moreover, leptin and ghrelin secretions were not responsible for BMI changes.

Topics: Adult; Anorexia Nervosa; Benzodiazepines; Body Mass Index; Double-Blind Method; Female; Ghrelin; Humans; Leptin; Olanzapine; Peptide Hormones; Placebos; Selective Serotonin Reuptake Inhibitors; Weight Gain

Weight gain is a problem commonly encountered with antipsychotic treatment and has become more apparent with increasing use of the newer atypical antipsychotics. The adipocyte-derived hormone, leptin, has been associated with body weight and energy homeostasis, and abnormal regulation of leptin could play a role in weight gain induced by antipsychotics. We investigated whether a leptin gene promoter variant affected weight gain after long-term treatment with clozapine in chronic schizophrenia. Leptin G2548A polymorphism was genotyped in 102 Chinese Han inpatients with chronic schizophrenia treated with clozapine. Weight gains, expressed as change in body mass index (BMI), were monitored after long-term clozapine treatment. We found a significant relationship between the 3 leptin G/A genotypes and mean BMI gain (F(2,99) = 3.35, P = 0.039, r(2) = 0.09). Moreover, genotype had a strong effect on BMI gain in male (P = 0.004, r(2) = 0.16), but not in female patients (P > 0.05). Thus, variation in the leptin gene may be a risk factor for weight gain in male patients with schizophrenia on long-term clozapine treatment.

Topics: Antipsychotic Agents; Asian People; Body Mass Index; China; Chronic Disease; Clozapine; Female; Genotype; Humans; Leptin; Male; Middle Aged; Pharmacogenetics; Polymorphism, Genetic; Promoter Regions, Genetic; Schizophrenia; Weight Gain

Melkersson proposed leptin dysregulation as a factor in the olanzapine-induced metabolic dysfunction. Their suggestion was based on the absence of the expected positive correlation between serum leptin levels and the BMI, and the loss of the sex-dependent difference in leptin levels, which are higher in women. Although subsequent studies did not confirm that proposal, few of them assessed basal leptin levels and corrected for body fat percentage. Along with these variables, we added a precise definition of participants out of the expected positive correlation in a large sample of schizophrenia patients. Sixty patients (26 women and 34 men) with severe schizophrenia undergoing chronic hospitalization and conventional antipsychotic treatment were switched to olanzapine (10-20 mg/day). We assessed at baseline, and at weeks 8 and 16 of treatment, the percentage of participants with abnormal correlation (out of the 95% confidence interval in the regression line) between leptin levels and the BMI, and the correlation between leptin and insulin, glucose, the insulin resistance index, c-reactive protein (CRP) and treatment response. Leptin levels were higher in women than in men (P<0.01). The positive correlation between leptin levels, BMI and percentage of fat were preserved. After olanzapine, 3.8% of women and 2.9-5.8% of men were out the 95% confidence interval, and the proportion was similar at baseline. Glucose, insulin, the insulin resistance index and the CRP levels significantly increased after olanzapine. The impact of olanzapine on leptin regulation appears discrete and limited to a small number of participants. Additional studies must clarify the features that render them to metabolic dysregulation.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; C-Reactive Protein; Female; Humans; Insulin; Insulin Resistance; Leptin; Linear Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Schizophrenia; Sex Factors; Weight Gain

We investigated ghrelin, leptin, glucose, and insulin response to an oral glucose tolerance test among children receiving antipsychotics. Hormone concentrations were assayed at fasting, 30, 60, and 120 minutes. The sample was composed of 9 obese (defined as at or above the 95th percentile for age) and 10 overweight/normal children (defined as less than the 95th percentile in weight) based on National Institutes of Health criteria. Ages of the obese (10.7 +/- 3.4 years) and the overweight/normal (13.1 +/- 1.6 years) did not differ. Leptin was significantly higher among the obese group and did not change consequent to glucose. Ghrelin did not differ between the groups, and when the values were combined, ghrelin decreased at 30 minutes and approached fasting concentrations at 120 minutes. To further explore our data, we constituted separate groups based upon z score changes. When weight gain defined as an increase in z score (X = 0.4), the nongainers showed leptin concentrations to decrease over time. Findings encourage further oral glucose tolerance test studies to explain the leptin response to weight gain seen among children receiving antipsychotic medication.

Topics: Administration, Oral; Adolescent; Age Factors; Analysis of Variance; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Blood Glucose; Body Mass Index; Child; Chlorpromazine; Fasting; Female; Ghrelin; Glucose; Glucose Tolerance Test; Humans; Insulin; Leptin; Male; Piperazines; Quinolones; Risperidone; Sex Factors; Time Factors; Weight Gain

Ghrelin is a major hormone, regulating the energy balance of the body. Weight gain is a significant side effect of valproic acid, which has not been clearly identified pathogenetically. The aim of this study was to investigate the effect of valproic acid on ghrelin and its potential effects on weight gain and growth. Each patient and control group consisted of 35 children aged 3 to 15 years. Fasting serum glucose, insulin, C-peptide, leptin, ghrelin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels were measured in patients treated with valproic acid before and at month 6 of treatment. A significant increase in body weight, body mass index, height, and height standard deviation scores was observed in all patients after 6 months of treatment. Significant increases in growth velocity and weight gain were observed in the patient group compared with controls at 6 months of therapy. A significant increase in serum ghrelin levels (P < .01) was detected at the same time in the study group. A negative correlation of ghrelin with insulin-like growth factor-1 and insulin-like growth factor binding protein-3 was detected. Serum ghrelin levels were significantly increased (P < .05), and insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels were significantly decreased (P < .01 and P < .05, respectively) in the prepubertal group at 6 months of treatment, but no significant change was observed in the pubertal group. Consequently, ghrelin levels significantly increase in the prepubertal children treated with valproic acid. The weight gain in using valproic acid may be associated with the increase in ghrelin level in the early treatment period.

Topics: Adolescent; Anticonvulsants; Blood Glucose; Body Height; Body Mass Index; Body Weight; C-Peptide; Child; Child, Preschool; Epilepsy; Female; Ghrelin; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Puberty; Valproic Acid; Weight Gain

In mammals, triacylglycerol (TAG) accumulation in nonadipose tissue, termed lipotoxicity, develops with obesity and can provoke insulin resistance, overt diabetes, and ovarian dysfunction. Leptin, an adipose tissue hormone, may mediate these effects. Feed-satiated broiler breeder hens manifest lipotoxicity-like symptoms. Changes in body and organ weights, hepatic and plasma TAG, nonesterified fatty acids (NEFA), ovarian morphology, and egg production in response to acute voluntary increases of feed intake were measured in 2 studies with Cobb 500 broiler breeder hens provided with either 145 or > or = 290 g of feed/d per hen for 10 d. In both studies, no hen fed 145 g of feed/d exhibited ovarian abnormalities, whereas approximately 50% of feed-satiated hens did. Egg production in feed-satiated hens was reduced from 73.3 to 55.8% (P = 0.001). Morphology indicated that apoptosis-induced atresia occurred in the hierarchical follicles. Fractional weight of yolk increased from 29.3 to 30.6% (P = 0.016) and no longer correlated to egg weight. Body, liver, and abdominal adipose weights were significantly greater (P < 0.05) in feed-satiated hens, as were plasma concentrations of glucose, NEFA, TAG, insulin, and leptin (P < 0.05). Feed-satiated hens with abnormal ovaries had significantly more liver and abdominal fat, greater plasma leptin and TAG concentrations, and more saturated fatty acids in plasma NEFA than did feed-satiated hens with normal ovaries. Differences in severity of lipotoxic metabolic and hormonal responses among feed-satiated hens were closely linked to the incidence of ovarian abnormalities and granulosa cell susceptibility to apoptosis and necrosis.

Topics: Adiposity; Animal Feed; Animals; Apoptosis; Blood Glucose; Egg Yolk; Female; Insulin; Leptin; Lipid Metabolism; Lipids; Liver; Ovarian Diseases; Ovary; Oviposition; Poultry Diseases; Triglycerides; Weight Gain

1. Three experiments were conducted to study the effects of leptin on weight gain and body composition in laying hens. 2. The effects of immunisation against chicken leptin on feed intake (FI), fat deposition and laying rate were observed in laying Guangdong yellow-feathered hens. Ten hens were inoculated with leptin immunogen on d 3, 31, 63 and 84, together with 10 control hens immunised with bovine serum albumin (BSA). In the 100-d experiment, immunisation against leptin increased blood anti-leptin antibody titres, slightly reduced plasma T3 concentrations, slightly decreased FI and increased live weight; however, laying rate was significantly depressed and abdominal fat mass was increased by the end of the 100-d experiment. 3. Passive immunisation of 50-d-old pullets with yolk extract containing anti-leptin antibody IgY significantly increased FI within 6 h of treatment compared with physiological saline treated controls. 4. In growing 70-d-old pullets, inoculation with 0.5 (group 1) or 1 (group 2) ml leptin immunogen on d 1 and 28 of the experiment slightly increased FI and significantly increased daily gain compared with BSA-immunised control pullets. Abdominal fat mass on d 49 increased from 48+/-4.5 g in controls to 66+/-3.5 and 80+/-3.1 g in groups 1 and 2, respectively. 5. It was suggested that immunisation against leptin mimicked loss of leptin bioactivity and might become a novel technique to stimulate fat growth in certain types of animal production.

Topics: Adipose Tissue; Animals; Antibodies; Antigens; Chickens; Egg Yolk; Feeding Behavior; Female; Immunization; Immunoglobulins; Leptin; Oviposition; Recombinant Proteins; Weight Gain

To evaluate the effects of improved glycaemic control on the abdominal visceral and subcutaneous fat in type 1 diabetes.. Sixteen subjects were enrolled for this 6-month study. The goal was to achieve normal haemoglobin A1c (HbA1c <5.6% in our laboratory). T1-weighted magnetic resonance imaging was used to measure the abdominal subcutaneous and visceral fat areas at the L2-L3 disk level. Activity and energy intake were assessed using a weekly recall and food diary respectively. Plasma leptin, ghrelin and adiponectin levels were measured at baseline and at 6 months.. Twelve subjects completed the study. HbA1c was 10.4 +/- 2.2% at baseline, and abdominal visceral to subcutaneous fat ratio was 0.29 +/- 0.15. HbA1c dropped to 8.0 +/- 1.4% at 6 months (p = 0.009). There was a +1.85 kg weight change in 6 months (p = 0.30), whereas the visceral to subcutaneous fat ratios changed to 0.36 +/- 0.18 (p = 0.22). Daily metabolic equivalents (METs) of activity at 6 months correlated with a decrease in the visceral to subcutaneous fat ratios (r = -0.80, p = 0.01). Ghrelin level changes correlated negatively with the changes in the visceral to subcutaneous fat ratio (p < 0.01).. The visceral to subcutaneous fat changes had a negative correlation with the physical activity METs at 6 months but not with HbA1c changes in this study. The correlation between the changes in ghrelin and the visceral to subcutaneous fat ratios is intriguing, but a larger study may be needed to confirm this finding.

Topics: Adiponectin; Adult; Body Composition; Cholesterol, HDL; Diabetes Mellitus, Type 1; Eating; Female; Ghrelin; Glycated Hemoglobin; Hemoglobins; Humans; Hypoglycemic Agents; Insulin; Intra-Abdominal Fat; Leptin; Magnetic Resonance Imaging; Male; Peptide Hormones; Physical Exertion; Pilot Projects; Prospective Studies; Subcutaneous Fat; Weight Gain

Weight gain is a common adverse effect associated with olanzapine treatment. Another side effect of olanzapine treatment is a significant increase in circulating leptin levels. This preliminary study monitored the changes in leptin levels for 2 weeks after olanzapine treatment had been initiated. The relationship between the changes in circulating leptin levels and alterations in body weight in 9 patients with schizophrenia who received olanzapine was examined. The results showed that olanzapine may cause a surge in circulating leptin levels before weight gain is manifested. Moreover, higher pretreatment circulating leptin levels predicted lower weight gains after olanzapine treatments (r = -0.93; p < 0.05) after controlling for the effect of sex.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Leptin; Male; Olanzapine; Schizophrenia; Sex Factors; Weight Gain

Increased appetite and weight gain are frequently reported in treatment with olanzapine. However, the mechanism behind this appetite gain remains unclear. Ghrelin is a newly discovered appetite-stimulating peptide that has a role in the regulation of feeding behavior. Ghrelin is synthesized principally in the stomach, and the concentration of circulating ghrelin is negatively correlated with leptin and body fat mass. To elucidate the mechanism of appetite and weight gain during olanzapine treatment, we investigated the circulating ghrelin levels.. Seven patients with schizophrenia were examined before and after 6-month administration of olanzapine. The concentrations of circulating ghrelin, leptin, glucose and lipid metabolic parameters were measured.. Body fat percentage (P=0.0121) and serum leptin (P=0.0284) were significantly increased after 6-month administration of olanzapine. Both plasma total ghrelin (P=0.0188) and active ghrelin levels (P=0.0057) were significantly increased. Six of the seven patients reported increased appetite during olanzapine treatment. Other glucose and lipid parameters were not altered significantly.. Although, the leptin level and body fat percentage were significantly increased, the concentration of circulating ghrelin was also significantly increased. Olanzapine may directly act on the secretion of ghrelin and induce appetite, resulting in weight gain.

Topics: Adult; Aged; Antipsychotic Agents; Appetite; Benzodiazepines; Body Composition; Body Mass Index; Body Weight; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Olanzapine; Peptide Hormones; Radioimmunoassay; Schizophrenia; Weight Gain

Alterations in plasma leptin have been reported in schizophrenia patients treated with antipsychotics, suggesting the hypothesis that impairments in leptin secretion or signaling might play a role in antipsychotic-induced weight gain. Plasma leptin was measured in 72 schizophrenia patients chronically treated with olanzapine (n=27), risperidone (n=24) or typical antipsychotics (n=21) and 124 healthy adult control subjects. ANCOVA was used to test effects of adiposity (body mass index kg/m2; BMI), subject group (treated patients vs untreated controls), and treatment group (specific medication groups and untreated controls) on plasma leptin concentrations. Additional analyses were performed in a subset of patients and controls individually matched for BMI to further assess group differences in plasma leptin independent of adiposity. BMI strongly predicted plasma leptin concentrations in the overall sample. In addition, a significant three-way interaction between BMI, subject group, and gender was observed. In the individually BMI-matched sample, modestly reduced plasma leptin levels (effect size 0.4 SD) were observed in treated patients in comparison to the BMI-matched healthy controls, with both groups including males and females. However, no differences in plasma leptin levels were observed in the matched sample when separately comparing male patients vs untreated male controls and female patients vs untreated female controls. Plasma leptin in chronically treated patients with schizophrenia is strongly predicted by adiposity, similar to untreated healthy individuals despite adequate power to detect a difference. The results argue against a role for defective leptin secretion or sensitivity in the weight gain induced by antipsychotic medications.

Topics: Adipose Tissue; Adult; Antipsychotic Agents; Body Composition; Body Mass Index; Female; Humans; Leptin; Male; Middle Aged; Psychiatric Status Rating Scales; Satiety Response; Schizophrenia; Sex Characteristics; Weight Gain

Weight gain during treatment with psychotropic drugs is frequently observed and is assumed to be responsible for non-compliance and for an elevated risk to develop a number of somatic co-morbidities including cardiovascular disorders and type 2 diabetes. Absence of weight inducing effects is therefore a major objective for the development of new compounds. Recently, R121919, the first corticotropin releasing hormone receptor 1 (CRH1R) antagonist, was tested in major depression. Clinical efficacy, safety, and tolerability of this compound could be demonstrated. Since CRH is discussed to be involved in the regulation of appetite and weight, directly and via interaction with leptin, CRH1R antagonists are suspected to influence body weight. Effects of 30 days of treatment with the CRH1R antagonist R121919 on weight and leptin levels in 20 patients suffering from major depression were investigated. No significant weight changes during treatment with R121919 were observed. Furthermore, noeffects on plasma leptin concentrations were found. We conclude that treatment with the CRH1R antagonist R121919 does not affect weight or plasma leptin concentrations in patients with major depression. Together with previous findings indicating safety, tolerability, and clinical efficacy CRH1R antagonists are highly promising as a new treatment option in depression.

Topics: Adult; Depressive Disorder, Major; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Male; Middle Aged; Pyrimidines; Receptors, Corticotropin-Releasing Hormone; Receptors, Leptin; Risk Factors; Weight Gain

The objective was to determine whether increased energy and protein intake between 2 and 14 wk of age would increase growth rates of heifer calves without fattening. At 2 wk of age, Holstein heifer calves were assigned to 1 of 4 treatments in a 2 x 2 factorial arrangement with 2 levels of protein and energy intake (moderate [M]; high [H]) in period 1 (2 to 8 wk of age) by 2 levels of protein and energy intake (low [L]; high [H]) in period 2 (8 to 14 wk of age) to produce similar initial BW for all 4 treatments. Treatments were ML, MH, HL, and HH, indicating moderate or high energy and protein intake during the first period and low or high intake during the second period. The M diet consisted of a standard milk replacer (21.3% CP, 21.3% fat) fed at 1.1% of BW on a DM basis and a 16.5% CP grain mix fed at restricted intake to promote 400 g of average daily gain (ADG), whereas the L diet consisted only of the grain mix. The H diet consisted of a high-protein milk replacer (30.3% CP, 15.9% fat) fed at 2% of BW on a DM basis and a 21.3% CP grain mix available ad libitum. Calves were weaned gradually from milk replacer by 7 wk and slaughtered at 8 (n = 11) or 14 wk of age (n = 41). In periods 1 and 2, ADG and the gain:feed ratio were greater for calves fed the H diet. Calves fed the H diet were taller after both periods 1 and 2. No difference was observed in carcass composition at 8 wk, but at 14 wk calves fed MH and HH had less water and more fat than calves fed ML and HL. Plasma IGF-I concentrations were greatest for calves fed the H diet during either period. Plasma leptin concentrations were increased in calves fed the H diet during period 1 from 4 to 6 wk of age. Increasing energy and protein intake from 2 to 8 wk and 8 to 14 wk of age increased BW, withers height, and gain:feed ratio. Calves fed the H diet from 8 to 14 wk of age had more body fat than calves fed the L diet. Increased energy and protein intake can increase the rate of body growth of heifer calves and potentially reduce rearing costs.

Topics: Adipose Tissue; Animal Feed; Animals; Biometry; Body Composition; Body Weight; Cattle; Costs and Cost Analysis; Diet; Dietary Proteins; Energy Intake; Female; Health Status; Insulin-Like Growth Factor I; Leptin; Weight Gain

It has been shown that leptin is present in breast milk and human mammary epithelial cells are able to synthesize leptin. It has been suggested that leptin in human milk might be involved in the regulation of postnatal nutrition and growth.. To investigate whether there is a relationship between leptin levels in human milk and weight gain in the postnatal period and to compare variations of milk-borne maternal leptin concentrations for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) infants.. Forty-seven healthy lactating women aged from 17-38 years and their infants were included in the study. The infants were separated into three groups according to birth weight as SGA (n = 11), LGA (n = 14) and AGA (n = 22). All infants were fed with breast milk during the study period. Anthropometric measurements were performed on the 15th day of life and at 1, 2, and 3 months of age, and the body mass index (BMI) of the infants' mothers was calculated. Breast milk leptin levels were analyzed by radioimmunoassay.. Breast milk leptin levels were found reduced in the SGA group and increased in the LGA group compared to the AGA group at 15 days of life (13.4 +/- 2.2, 28.5 +/- 4.4 and 18.4 +/- 2 ng/ml, respectively; p <0.05). At 1 month of age, leptin levels in breast milk were significantly lower in the LGA group than in the AGA group (15.5 +/- 4.9, 19.4 +/- 1.7 ng/ml, respectively; p<0.05). There was no difference among the three groups at 2 and 3 months of age (p>0.05). There was a positive correlation between birth Weight and breast milk leptin levels on the 15th day (r = 0.47, p = 0.001). A negative correlation was found between weight gain during the first 15 days and 1 month of life and breast milk leptin levels on the 15th day (r = -0.44, p = 0.002; r = -0.40, p = 0.005, respectively). No relationship could be determined between breast milk leptin levels and BMI of the mothers.. Maternal milk of SGA, LGA and AGA infants had different leptin levels, especially during the first month of life. More rapid growth was shown in the SGA infants during the first postnatal 15 days compared to AGA and LGA infants, and human milk leptin levels were significantly reduced in the SGA group. However, LGA infants gained more weight during the second 15 days of life and breast milk leptin levels were dramatically decreased in LGA and increased in SGA infants at the end of first month of life. These findings suggest that the presence of leptin in breast milk might have a significant role in growth, appetite and regulation of nutrition in infancy, especially during the early lactation period, and the production of leptin in breast tissue by human mammary epithelial cells might be regulated physiologically according to necessity and state of the infant.

Topics: Adolescent; Adult; Anthropometry; Breast Feeding; Child Development; Female; Follow-Up Studies; Gestational Age; Growth; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Leptin; Milk, Human; Weight Gain

We investigated serum ghrelin levels (SGL) in 12 patients with schizophrenia over a 10-week period after initiation of clozapine treatment. In contrast to increments of body mass indices (BMI, kg/m2) and serum leptin levels (SLL), no significant change in SGL was detected. Inverse correlations between delta SGL and delta SLL did not reach statistical significance. Linear mixed model analysis could not detect effects of age, sex, BMI, SLL and serum clozapine levels on SGL. Our results do not support a causal involvement of ghrelin in clozapine-related weight gain.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Clozapine; Female; Ghrelin; Humans; Leptin; Longitudinal Studies; Male; Peptide Hormones; Prospective Studies; Schizophrenia; Schizophrenia, Catatonic; Schizophrenia, Disorganized; Schizophrenia, Paranoid; Weight Gain

A 2-yr study using primiparous and multiparous, spring-calving, crossbred beef cows was conducted to evaluate the effects of supplemental whole corn germ on reproductive performance, calf performance, and serum leptin concentrations. Each year, cows were blocked by age and BCS and assigned randomly to one of three treatments: PRE (n = 115) cows received 1.14 kg/d (DM basis) of whole corn germ for approximately 45 d before calving; POST (n = 109) cows were fed 1.14 kg/d of whole corn germ for approximately 45 d after calving; and control cows (n = 118) were fed similar energy and protein from dry-rolled corn (1.82 kg of DM/d) for 45 d before and after calving. Additionally, PRE cows were grouped with controls after calving, and POST cows were grouped with control cows before calving, so that corn germ-supplemented cows received the control supplement in the alternate feeding period. Cow BW (538 +/- 13 kg) and BCS (5.4 +/- 0.13) did not differ among treatments at any time during the experiment. Calf birth weight (39 +/- 2 kg), weaning weight (225 +/- 7 kg), and age-adjusted weaning weight (234 +/- 8 kg) did not differ because of dam supplementation regimen. Treatment did not affect the proportion of cows exhibiting ovarian luteal activity before the start of the breeding season (67%) or pregnancy rate (91%). The interval from exposure to bulls until subsequent calving did not differ (P = 0.16) among PRE (298 +/- 2.3 d), POST (303 +/- 2.6 d), and control (304 +/- 2.3 d) cows. Leptin concentrations did not differ among treatments and were 2.15 +/- 0.75, 1.88 +/- 0.76, and 1.91 +/- 0.75 ng/mL for control, POST, and PRE cows, respectively. Age and week relative to calving influenced leptin concentration. Primiparous cows had similar leptin concentrations to 3-yr-old and mature cows for wk -7 and -6 relative to calving, but lower (P < 0.10) concentrations than mature cows for wk -5, and lower (P < 0.05) concentrations than either 3-yr-old or mature cows for wk -4 to +7 relative to calving. Serum leptin was correlated with BCS (P < 0.0001; r = 0.35) at initiation of the feeding period and was correlated with BCS (P = 0.02; r = 0.12) and weight (P < 0.01; r = 0.14) at the completion of the supplement period, but it was not correlated with initial BW or interim BCS. Calving interval was not correlated (P > 0.12) with weekly measures of serum leptin concentration. Supplementing beef cows with whole corn germ had no effect on cow performance, calf performance, or ser

Topics: Aging; Animal Feed; Animals; Cattle; Dietary Supplements; Female; Leptin; Parity; Pregnancy; Reproduction; Weight Gain; Zea mays

The tricyclic antidepressant amitriptyline (AMT) and the calcium channel blocker flunarizine are frequently used in the preventive treatment of migraine, but the side-effect of prominent weight gain that frequently emerges during preventive treatment of migraine with these agents often leads to the discontinuation of therapy. In this study, we aimed to investigate the possible relationship between the weight gain associated with the use of these agents and serum levels of leptin, C-peptide and insulin in patient with migraine. Forty-nine migraine patients with a body mass index (BMI) < 25 and without any endocrinological, immunological or chronic diseases were randomly divided into two groups, receiving AMT or flunarizine. There was a statistically significant increase in serum levels of leptin, C-peptide, insulin and measures of BMI in both groups when measured at the 12th week of therapy compared to their respective basal levels. To our knowledge this is the first study investigating the effects of AMT and flunarizine on serum leptin levels in preventive use of migraine treatment. A result from this study indicates that AMT and flunarizine may cause leptin resistance possibly by different mechanisms and thereby result in increase in serum leptin levels and BMI.

Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Body Mass Index; C-Peptide; Female; Flunarizine; Humans; Insulin; Leptin; Male; Migraine Disorders; Vasodilator Agents; Weight Gain

Weight gain is a common side effect of valproate treatment. The potential mechanisms of valproate-associated weight gain are not yet clear. Decreased blood glucose level, impairment of beta-oxidation of fatty acids, and increased insulin levels are some of the possible mechanisms. The aim of the present study is to evaluate the role of insulin, leptin, and neuropeptide Y in valproate-related weight gain in epileptic children. In 20 epileptic children treated with valproate before treatment and after a follow-up period of 3 and 6 months, body mass index and fasting insulin glucose ratio were calculated and serum glucose, insulin, cortisol, leptin, and neuropeptide Y levels were measured. At the end of 3 months, the mean body mass index values and the mean serum insulin, fasting insulin glucose ratio, and neuropeptide Y levels increased, whereas the serum glucose levels decreased. After 6 months of treatment, the mean serum cortisol and leptin levels were high, in addition to the body mass index, neuropeptide Y, and fasting insulin glucose ratio. These results suggest that weight gain during valproate treatment might be related to low glucose and high insulin, cortisol, leptin, and neuropeptide Y levels.

Topics: Anticonvulsants; Blood Glucose; Body Mass Index; Child; Child, Preschool; Epilepsy; Female; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin; Leptin; Male; Neuropeptide Y; Valproic Acid; Weight Gain

It has been reported that nizatidine may reduce weight gain in schizophrenic patients on olanzapine treatment. Leptin has been reported to be associated with antipsychotic-induced weight gain. Thus, the purpose of the study was to evaluate whether nizatidine might be useful for the treatment of quetiapine-induced weight gain. Among the patients on the quetiapine monotherapy, 47 participated in the study for the two and half months of the open-label screening period. However, 28 patients who gained considerable weight in this period entered the 8-week, double-blind and placebo-controlled phase. These patients were randomly divided into two groups; quetiapine plus nizatidine (group I) and quetiapine plus placebo (group II) for the 8-week double-blind phase. The patients were evaluated at the baseline and at week 8 with respect to the positive and negative syndrome scale, body mass index, weight and serum leptin levels. The mean weight and leptin levels exhibited modest increases in both groups for the open-label screening period. In the double-blind period, in group I, a minimal, but not statistically significant, decrease in weight was observed, with a mean of 1.0 +/- 0.6 kg. The weight increased in group II. The leptin levels decreased by a mean of 0.6 +/- 0.6 ng/ml in group I, and increased by 1.0 +/- 0.9 ng/ml in group II. At evaluation at week 8, a trend toward statistical significance in the mean serum leptin levels between groups was detected. The results suggest that nizatidine treatment may stop but not reduce the weight gain and is correlated with leptin levels in patients with schizophrenia on quetiapine treatment.

Topics: Adult; Age Factors; Antipsychotic Agents; Appetite Depressants; Body Mass Index; Dibenzothiazepines; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Male; Nizatidine; Quetiapine Fumarate; Schizophrenia; Sex Factors; Treatment Outcome; Weight Gain

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

The authors examined the developmental impact and temporal characteristics of risperidone-associated weight change.. Weight change was measured for 63 children and adolescents with autism treated with risperidone for 6 months. Change in serum leptin levels after 2 months was examined as a predictor of final weight gain in mixed regression models that controlled for site, gender, age, and risperidone dose.. Age- and gender-standardized weight increased after 6 months of treatment (gross: mean=5.6 kg [SD=3.9]; standardized: mean=0.6 z [SD=0.5]) and was positively correlated with weight gained after 1 month. Change in leptin levels after 2 months of treatment (mean=-0.3 ng/ml, SD=6.2) (N=48) did not predict final weight gain.. Chronic risperidone exposure in children with autism causes weight gain in excess of developmentally expected norms that follows a curvilinear trajectory and decelerates over time. Serum leptin change does not reliably predict risperidone-associated weight gain.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Autistic Disorder; Body Mass Index; Body Weight; Child; Child, Preschool; Female; Humans; Leptin; Male; Prospective Studies; Risperidone; Weight Gain

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

Megestrol acetate (MA) has been used to stimulate weight gain in elderly populations with the majority of the gain being adipose tissue. Significant inverse correlations have been reported between weight gain with MA and reductions in circulating the tumor necrosis factor (TNF) alpha receptors. In addition, MA has been shown to reduce circulating interleukin 6 (IL-6) concentrations. We attempted to increase gains in fat-free mass with MA using resistance training and/or testosterone replacement and examined the effects on circulating IL-6, TNF alpha, and leptin in elderly men.. All subjects received MA and were randomly assigned to one of these four groups: placebo (P) injections; resistance training and P (RT+P); weekly injections of testosterone (T; 100 mg/wk); or RT and T (RT+T). Cytokines were measured by enzyme-linked immunosorbent assay Preinterventions, Midinterventions, and after 12 weeks of the interventions (Post).. IL-6 decreased ( p =.03) over time for the T and P groups when compared to the RT+T and RT+P groups. A time effect ( p =.013) was observed for TNF alpha with Mid and Post both being lower than Pre. A hormone by time interaction ( p =.03) was observed for plasma leptin with individuals not on T exhibiting higher concentrations Post than those individuals on T. A positive correlation was observed (r =.60; p <.05) between changes in fat mass and the change in leptin.. IL-6 was reduced by MA except when RT was undertaken; TNF alpha was reduced over time regardless of group; leptin was higher in individuals not on T than those on T; and the change in plasma leptin was correlated with the change in fat mass.

Topics: Aged; Analysis of Variance; Appetite; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Exercise; Humans; Injections, Intramuscular; Interleukin-6; Leptin; Male; Megestrol Acetate; Middle Aged; Physical Education and Training; Probability; Reference Values; Sensitivity and Specificity; Testosterone; Treatment Outcome; Tumor Necrosis Factor-alpha; Weight Gain

Novel antipsychotics impart substantial weight gain. Persons with bipolar disorder are frequently treated with these and other agents known to impart substantial weight gain. We sought to describe the influence of adjunctive risperidone and olanzapine on body weight, body mass index (BMI, kg/m2) and serum leptin levels over a prospective observation period of 6 months. Throughout the 6-month investigation, significant increases from baseline to end point in weight were noted with both agents; with significantly greater weight gain with olanzapine (t(10) = 2.761, P = 0.023; t(9) = 4.783, P = 0.001). Leptin levels were highly correlated with increases in weight and were significantly elevated from baseline at 4 months (r = 0.658, P < 0.05). Significant increases in weight and body mass index were apparent at 3 months (P < 0.05). The temporal association between weight increase and leptin changes does not support the notion that leptin is a primary promoter of antipsychotic-induced weight gain; however, a secondary perpetuating role cannot be ruled out.

Topics: Adolescent; Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Female; Humans; Leptin; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Risperidone; Valproic Acid; Weight Gain

It has been reported that nizatidine may reduce the weight gain in schizophrenic patients receiving olanzapine treatment. Previous studies have demonstrated a relation between olanzapine-induced weight gain and serum leptin levels. Therefore, in the present study, it was planned to investigate the efficacy of nizatidine on the treatment of olanzapine-induced weight gain, and if available, whether leptin levels were associated with reductions in weight gain. Of the patients with schizophrenia on olanzapine treatment, 59 who gave informed consent entered a 3 month open-label screening period. Of them, 35 patients (59%) showed weight gain in excess of 2.5 kg. These patients were randomly divided into two groups; olanzapine plus nizatidine (group I) and olanzapine plus placebo (group II) for an 8-week double-blind phase. The patients were evaluated at the baseline and at week 8 with respect to the positive and negative syndrome scale, body mass index, weight and serum leptin levels. In the open-label period, olanzapine led to a considerable marked increase in weight and in serum leptin levels. There was no statistically significant difference between the groups with respect to weight at the beginning of the 8-week double-blind treatment period. Throughout the 8 week double-blind period, in group I, the weight decreased by 4.5 +/- 2.2 kg ( p<0.05). In contrast, weight increased in group II by a mean of 2.3 +/- 0.9 kg ( p>0.05). The leptin levels decreased by 4.4 +/- 2.3 ng/ml in group I ( p<0.01), and increased by 1.8 +/- 0.6 ng/ml in group II ( p>0.05). These changes were accompanied by changes in the leptin levels in both groups I and II. It is concluded that leptin seems to be strongly associated with olanzapine-induced weight gain and that nizatidine treatment may reduce the weight gain and the correlated leptin levels in patients with schizophrenia on olanzapine treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Histamine H2 Antagonists; Humans; Leptin; Male; Nizatidine; Obesity; Olanzapine; Pirenzepine; Schizophrenia; Treatment Outcome; Weight Gain

Circulating concentrations of leptin are exceedingly low in severe malnutrition as seen in the acute state of anorexia nervosa (AN). During refeeding therapy plasma leptin levels increase to normal and in some cases peak at values in excess of the BMI of matched controls even before a normal body weight has been achieved. Peak leptin levels are possibly the cause of an increased energy expenditure during this stage of the disorder and might predispose to renewed weight loss (rebound phenomenon). In this study we investigated the role of leptin fluctuations as a prognostic factor of therapeutic success in AN. In 11 anorectic female patients serum leptin levels, BMI and body fat percentage were evaluated in four-week intervals during a conventional refeeding program over three months (group 1). The results of the first two measurements were used to determine a range of increases in leptin levels in relation to increases in BMI. The values between the 25th and 75th percentiles determined the reference range. In a second group of 9 anorectic female patients serum leptin levels, BMI, body fat percentage and the increase in the leptin level in relation to the BMI of each subject were investigated for three months every two weeks. These patients were also treated according to the same conventional refeeding program, but the caloric intake was reduced or increased (+/-250 kcal/d) if the increase in the leptin level, in relation to the increase in the BMI, had exceeded or fallen short of the reference range. During the refeeding therapy every subject of each group experienced increases in serum leptin levels, BMI and body fat percentage. Six subjects of group 1 and six subjects of the second group had an increase in leptin levels in relation to the increase of the BMI out of the reference range at least once. To investigate the therapeutic outcome of leptin monitoring and the following alteration of caloric intake, weight gain of the patients of both groups during the whole treatment was compared. No significant difference was found. Our results probably do not support the findings that high leptin levels predispose to a renewed loss of weight. The outcome in our patients whose caloric intake was modified due to their serum leptin levels was not significantly improved.

Topics: Adipose Tissue; Anorexia; Biomarkers; Body Mass Index; Body Weight; Energy Intake; Fasting; Female; Humans; Leptin; Monitoring, Physiologic; Predictive Value of Tests; Prognosis; Reference Values; Time Factors; Weight Gain

Weight gain is an important side effect of antipsychotic (AP) treatment. Weight is regulated by multiple systems, including leptin, neuropeptide Y (NPY) and gonadal steroids. The aim was to investigate whether AP-induced weight gain was related to leptin and NPY abnormalities and whether these were associated with a disruption of gonadal steroid production.. Twenty two female patients with schizophrenia receiving standard AP treatment were studied over a 3-month period. Plasma leptin, NPY, gonadal steroids and their regulators were measured along with weight and BMI.. Weight, leptin and testosterone levels increased over time. There were significant relationships between a change in oestrogen levels and both a change in NPY levels and a change in BMI. Change in BMI, weight and leptin all correlated strongly with a change in the testosterone/luteinizing hormone ratio.. AP treatment results in increase in weight over time and this increase is accompanied by increased leptin levels. AP-induced weight gain is also associated with disruption of the hypothalamic-pituitary-gonadal axis. Altered regulation of NPY, either through abnormal leptin control or serotonin blockade, is a possible explanation for the effects of AP medication on both weight and gonadal steroid levels.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Gonadal Steroid Hormones; Humans; Leptin; Middle Aged; Neuropeptide Y; Olanzapine; Pirenzepine; Radioimmunoassay; Risperidone; Schizophrenia; Time Factors; Weight Gain

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

The aim of this study was to investigate the effect of postnatal systemic dexamethasone on serum leptin, insulin and hormones of the hypothalamic-pituitary-adrenal (HPA) axis in preterm, very low birthweight (VLBW) infants. Nineteen VLBW infants who received a 3 wk dose tapering course of dexamethasone for treatment of bronchopulmonary dysplasia were prospectively enrolled. Blood for hormone assays was collected immediately before the start of the dexamethasone course (T(d-per)), 3 wk after commencement of the drug (T(d-end)) and 2 wk after dexamethasone treatment had been stopped (T(d-post)). In addition, 28 VLBW infants who participated in a concurrent longitudinal leptin study within the same period but did not receive corticosteroid had their serum leptin and insulin concentrations serially monitored. Blood specimens for the latter group of infants were obtained at 2 (T(wk-2)), 5 (T(wk-5)) and 7 (T(wk-7)) wk of postnatal age. Serum leptin and insulin at T(d-end) were significantly increased, whereas plasma ACTH and serum cortisol were significantly suppressed compared with the pretreatment (T(d-pre)) levels in the corticosteroid group (p < 0.0001 for leptin and insulin; p < 0.05 and p < 0.001 for ACTH and cortisol, respectively). In contrast, serum leptin and insulin at weeks 5 (T(wk-5)) and 7 (T(wk-7)) did not differ significantly from their respective levels at week 2 (T(wk-2)) in the non-treatment group.. The administration of systemic corticosteroid resulted in significant increases in serum leptin and insulin, but marked suppression of hormones of the HPA axis. The effect of dexamethasone on the "adipoinsular" and HPA axes was transient and reversible. The adipoinsular axis in preterm infants is likely to be functional and active at an early stage of human development, and leptin may regulate energy balance in VLBW infants in the early postnatal period. Corticosteroids may, through the adipoinsular axis or its associated pathways, mediate in the regulation of body weight in preterm neonates.

Topics: Adrenocorticotropic Hormone; Bronchopulmonary Dysplasia; Dexamethasone; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hydrocortisone; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Infusions, Intravenous; Insulin; Intensive Care Units, Neonatal; Leptin; Male; Probability; Prospective Studies; Reference Values; Statistics, Nonparametric; Weight Gain

Weight gain is a frequent adverse effect associated with lithium use. Leptin is an adipocyte hormone, regulating food intake and energy balance providing the hypothalamus with information on the amount of body fat. Therefore, we planned to evaluate whether lithium administration was associated with weight gain, and leptin levels. The study consisted of 15 consecutive inpatients with bipolar I disorder according to DSM-III-R. The fasting serum leptin levels were measured. The patients were evaluated at baseline and at the eighth week according to the body mass index, weight, Young Mania Rating (YMRS) and Hamilton Depression Rating (HAM-D) scales, and serum leptin levels. With respect to the leptin levels, a significant difference was observed after lithium treatment. There was a significant positive correlation between the changes in leptin levels and the duration of illness. The change in total YMRS scores correlated with change in leptin levels and that in weight. In conclusion, our result suggest that leptin may be associated with lithium-induced weight gain.

Topics: Adult; Bipolar Disorder; Body Mass Index; Diet; Female; Humans; Leptin; Lithium; Male; Psychiatric Status Rating Scales; Weight Gain

Abnormal regulation of the adipocyte-derived hormone leptin could play a role in body weight gain induced by antipsychotics.. To study the effects of long-term antipsychotic treatment on leptin levels in patients with schizophrenia.. Serum leptin levels were determined in 59 out-patients with chronic schizophrenia and in the same number of healthy subjects controlled by gender, age and body mass index.. Leptin levels did not differ between patients and controls. Leptin levels in patients with schizophrenia correlated with weight gain, even after controlling for current weight, but did not show any association with clinical variables. Antipsychotic class tended to exert different effects over leptin levels (among atypicals, olanzapine induced a greater increase).. Elevation of leptin levels induced by chronic antipsychotic treatment can be attributed to weight gain, but other mechanisms could be involved.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Chronic Disease; Female; Humans; Leptin; Male; Schizophrenia; Weight Gain

The goal of this study was to explore the pathophysiology of weight gain during treatment with olanzapine for schizophrenia.. The authors used a prospective, controlled, open study comparing body weight, body mass index, and related biological measures in mentally and physically healthy volunteers and olanzapine-treated patients with schizophrenia. Weight, eating behavior, leptin serum levels, body mass index, and body composition were assessed over an 8-week observation period.. A significant increase in body weight, leptin serum levels, and percentage of body fat was seen in patients treated with olanzapine, but the drug-free comparison group did not show any significant changes. The weight gain during antipsychotic treatment with olanzapine was mainly attributable to an increase in body fat; patients' lean body mass did not change.. In addition to the original finding that an increase in body fat is mainly responsible for olanzapine-induced weight gain, these findings confirm results obtained in other studies showing increases in body weight and serum leptin levels during treatment with second-generation antipsychotics.

Topics: Adipose Tissue; Adult; Antipsychotic Agents; Benzodiazepines; Body Composition; Body Mass Index; Feeding Behavior; Female; Humans; Leptin; Male; Olanzapine; Pirenzepine; Prospective Studies; Schizophrenia; Weight Gain

Excessive body weight gain, hyperprolactinemia and low gonadal steroid serum levels are often observed during chronic administration of antipsychotic drugs (AP). Clinical and experimental findings suggest that leptin, the peptidic hormone involved in long-term body weight regulation, and reproductive hormones are interrelated. Therefore, we assessed circulating leptin levels in healthy, lean women (n = 12) and men (n = 7) before and after short-term administration of the AP sulpiride (SUL, 200 mg/day). In addition, we studied psychotic obese (n = 9) and lean women (n = 13) under chronic treatment with diverse AP. No significant weight changes were observed after SUL administration in healthy women--initial weight: 54.9+/-2.6 Kg; final weight: 55.04+/-2.6, NS. Leptin levels did not change either: 11.9+/-1.5 ng/ml. vs. 10.6+/-1.3, NS. By contrast, a small, but significant weight gain was found in SUL-treated men--60.6+/-1.9 Kg. vs. 61.3+/-2.1, p = 0.004. Leptin and insulin levels were significantly higher after SUL administration--leptin: 2.77+/-0.22 ng/ml. vs. 13.9+/-2.5, p=0.035; insulin: 3.59+/-0.17 mIU/ml vs. 8.81+/-0.81, p = 0.0001. In these subjects, leptin levels positively correlated with body weight change (p = 0.006), and serum prolactin change (p = 0.001). Obese psychotic women (Body Mass Index, BMI, Kg/m2 = 31.5+/-1.03) displayed higher leptin levels than non-obese psychotic women (BMI = 25.5+/-0.52): 26.8+/-4.8, vs. 12.8+/-3.4 ng/ml, p = 0.006. In these women, a significant positive correlation was found between leptin levels and BMI (p = 0.0001), and between leptin and basal insulin levels (p = 0.001). These results show that the expected circulating leptin elevation which is observed when body weight raises, is preserved in people treated with AP drugs.

Topics: Adult; Antipsychotic Agents; Estradiol; Female; Follicle Stimulating Hormone; Hormones; Humans; Insulin; Leptin; Luteinizing Hormone; Male; Progesterone; Prolactin; Psychotic Disorders; Reference Values; Regression Analysis; Sulpiride; Weight Gain

We investigated the dynamics of the leptin concentration throughout the perinatal period. Serum leptin concentrations in venous cord blood at different gestational ages were measured in 20 preterm and 139 term newborns, as well as in 143 pregnant women and 24 term newborns at approximately 6 d of life. Leptin concentrations in preterm newborns (mean 4.6+/-6.9 ng/mL) were lower than those in term newborns (mean 19.6+/-14.3 ng/mL) and tended to increase according to gestational age and birth weight, especially from the late stage of gestation. Leptin concentrations in pregnant women increased from the first trimester and then remained higher than those in non-pregnant women throughout the remainder of pregnancy even after controlling for body mass index. The leptin concentrations of newborns declined rapidly and were extremely low by approximately 6 d of life (mean 1.9+/-1.1 ng/mL). These results suggest that fetuses might produce a part of circulating leptin in their own adipocytes and that the relatively high leptin concentrations at birth and their rapid decline in the early neonatal period might reflect the dramatic changes of the hormonal and nutritional state during the perinatal period.

Topics: Body Mass Index; Embryonic and Fetal Development; Energy Intake; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Leptin; Obesity; Pregnancy; Proteins; Weight Gain

Leptin and oestrogen are both involved in the regulation of adipose tissue deposition and feeding behaviour. We investigated whether 5 years of hormone replacement therapy (HRT) affected serum leptin and body composition differently in 89 postmenopausal women treated with HRT compared with 178 controls. At baseline, leptin was significantly correlated with oestradiol (r=0.13, P<0.05) and in multiple backward regression analysis including oestradiol and any estimate of body fat, oestradiol remained a significant determinant of leptin levels. In the control group, all estimates of body fat determined by dual energy X-ray absorptiometry (DEXA) or anthropometry were increased (3.6-16.9%) and leptin increased 31.3% (16.03+/-1.02 to 20.84+/-1.2 ng/ml (s.e.m.), P<0.001). In the HRT group all estimates of body composition also increased during the 5-year observation but to a lesser extent than observed in the control group (1.0-8.5%). Leptin was raised by 19.7% (17.81+/-1.32 to 20.57+/-1.65 ng/ml, P<0.001). However, the DEXA scans revealed that the control group gained 2.4-fold more fat during the 5-year observation (1.9+/-0.3 vs 0.8+/-0.4 kg, P<0.05), and especially the trunk fat increased (1.4+/-0.2 vs 0.7+/-0.3 kg, P<0.05). This was reflected in the increase in leptin levels, which were increased by 7.4% in the control group compared with the HRT group (4.81+/-0.60 vs 2.76+/-0.87 ng/ml, P<0.05). Adjusting for the difference in adipose tissue revealed that HRT had no independent effect on leptin levels. Comparisons between obese (body mass index>25 kg/m(2)) and non-obese (<25 kg/m(2)) subjects by stratifying for HRT treatment using multiple linear regression revealed that the change in fat mass was significantly less among treated subjects (P=0.038) and especially in the non-obese subjects (P=0.001). The change in trunk fat was similarly correlated with treatment status (P=0.029) and with the degree of obesity (P=0.006). In conclusion, 5 years of HRT treatment significantly reduced fat mass accumulation, especially in the trunk region. This effect of HRT was more pronounced in non-obese as compared with obese subjects. The HRT-induced reduction in fat mass seems not to be mediated by leptin.

Topics: Body Composition; Body Mass Index; Estradiol; Estrogen Replacement Therapy; Estrogens; Female; Follow-Up Studies; Humans; Leptin; Linear Models; Middle Aged; Obesity; Postmenopause; Progesterone; Weight Gain

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

Single nucleotide polymorphisms are commonly associated with changes in quantitative traits, and have been considered useful markers for improving different traits in livestock. The current study aimed to explore the effect of three SNPs located in

Topics: Animals; Body Weight; Leptin; Polymorphism, Single Nucleotide; PPAR gamma; Rabbits; Receptor, Insulin; Weight Gain

Off-label treatment of a 15-year-old female patient with anorexia nervosa (AN) with human recombinant leptin (metreleptin) for nine days was associated with self-reported increments of appetite and hunger resulting in rapid weight gain and substantial improvement of eating disorder cognitions and of depression. The results further substantiate the effects of metreleptin on both AN and depression. We contrast these results with the widespread view that leptin is an anorexigenic hormone. Randomized controlled trials are warranted to confirm the described effects.

Topics: Adolescent; Anorexia Nervosa; Appetite; Feeding and Eating Disorders; Female; Humans; Hunger; Leptin; Off-Label Use; Weight Gain

Perinatal nutrition is a key player in the susceptibility to developing metabolic diseases in adulthood, leading to the concept of "metabolic programming". The aim of this study was to assess the impact of maternal protein restriction during gestation and lactation on glucose homeostasis and eating behaviour in female offspring. Pregnant rats were fed a normal or protein-restricted (PR) diet and followed throughout gestation and lactation. Body weight, glucose homeostasis, and eating behaviour were evaluated in offspring, especially in females. Body weight gain was lower in PR dams during lactation only, despite different food and water intakes throughout gestation and lactation. Plasma concentration of leptin, adiponectin and triglycerides increased drastically before delivery in PR dams in relation to fat deposits. Although all pups had identical birth body weight, PR offspring body weight differed from control offspring around postnatal day 10 and remained lower until adulthood. Offspring glucose homeostasis was mildly impacted by maternal PR, although insulin secretion was reduced for PR rats at adulthood. Food intake, satiety response, and cerebral activation were examined after a lipid preload and demonstrated some differences between the two groups of rats. Maternal PR during gestation and lactation does induce extrauterine growth restriction, accompanied by alterations in maternal plasma leptin and adiponectin levels, which may be involved in programming the alterations in eating behaviour observed in females at adulthood.

Topics: Adiponectin; Animals; Body Weight; Brain; Diet, Protein-Restricted; Female; Glucose; Lactation; Leptin; Maternal Nutritional Physiological Phenomena; Pregnancy; Rats; Triglycerides; Weight Gain

To determine if the leptin, adiponectin, and leptin/adiponectin ratio (LAR) can predict weight gain at the end of GnRH analogs (GnRHa) treatment in girls with central precocious puberty (CPP).. Study design: prospective cohort. Serum levels of leptin and adiponectin were determined at diagnosis of CPP. Anthropometry was performed at diagnosis of CPP and every six-months, until treatment with GnRHa was discontinued and they presented menarche. Patients were divided according to BMI<94 and BMI>95 percentile at diagnosis of CPP. The outcome was the increased in weight gain (e.g., from normal weight to overweight) at the end of follow-up. Statistical analysis: repeated measures ANOVA test and Student's t-test were used to compare groups. Logistic regression analysis was used to evaluate the association of leptin and adiponectin levels, as well as LAR values with increased weight gain.. In patients with CPP, leptin levels and higher LAR values appear to be associated with significantly greater weight gain during GhRHa treatment, particularly in girls starting with BMI < 94 percentile.

Topics: Adiponectin; Body Mass Index; Female; Humans; Leptin; Overweight; Prognosis; Prospective Studies; Puberty, Precocious; Weight Gain

Topics: Female; Humans; Hypoglycemic Agents; Leptin; Metformin; Polycystic Ovary Syndrome; Pregnancy; Weight Gain

Topics: Child; Child Development; Child, Preschool; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Leptin; Male; Weight Gain

Topics: Clinical Relevance; Craniopharyngioma; Humans; Leptin; Obesity; Pituitary Neoplasms; Prospective Studies; Receptors, Leptin; RNA, Messenger; Weight Gain

An imbalance between adipokines and micronutrient concentrations, such as those of copper (Cu), has been linked to dysregulation of energy homeostasis leading to weight gain and the development of other comorbidities; however, information on this issue remains limited. Our aim was to investigate the correlation between Cu status and serum adipokine levels and their relationship in normal-weight, overweight, and obese adult women.. Sixty patients were evaluated and classified according to their body mass index (BMI) and biochemical parameters; adipokines and Cu were measured at fasting.. Leptin (Lep) and resistin (Res) levels were elevated, whereas adiponectin (Adpn) and ghrelin (Ghr) values were decreased in overweight and obese women (p = 0.001). The mean Adpn/Lep ratio was <0.5 in overweight and obese subjects, while the Lep/Ghr ratio increased significantly in relation to weight gain, suggesting an inverse link between the ratios of these hormones in the regulation of obesity. The analysis revealed a positive association between BMI and Cu levels in obese women. Moreover, a negative association between Cu and Res in normal-weight subjects was found.. Circulating fasting Res levels are negatively associated with serum Cu concentration in normal-weight adult women. We also observed a close relationship between Adpn/Lep and Lep/Ghr ratios with obesity. However, more observational studies are required to confirm these results in future research.

Topics: Adipokines; Adiponectin; Adult; Anti-Inflammatory Agents; Body Mass Index; Copper; Female; Humans; Leptin; Obesity; Overweight; Weight Gain

Obesity consists in the accumulation of adipose tissue accompanied by low grade chronic inflammation and is considered a pandemic disease. Recent studies have observed that obesity affects females and males in a sex-dependent manner. In addition, several works have demonstrated that parental obesity increases the risk to develop obesity, insulin resistance, diabetes, and reproductive disorders. Considering that intergenerational effects of obesity may occur in a sex-dependent manner, we studied male. Five-week-old female and male. HFD altered plasma fasting glucose, insulin and leptin levels, glucose tolerance, adiposity, and beta-cell expression of p16 in F0 rats. Particularly, HFD showed sexual dimorphic effects on body weight gain and insulin sensitivity. Moreover, we observed that parental HFD feeding exerts parental-sex-specific metabolic impairment in the male progeny. Finally, parental metabolic dysfunction could be in part attributed to the increased beta-cell expression of p16; other mechanisms could be involved in the offspring glucose homeostasis.

Topics: Animals; Diet, High-Fat; Female; Glucose; Homeostasis; Insulin; Insulin Resistance; Leptin; Male; Obesity; Rats; Rats, Wistar; Weight Gain

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly to the development of obesity and associated metabolic disorders. By suppressing the rise in leptin through the use of a monoclonal leptin-neutralizing antibody, we effectively prevented weight gain, restored glucose tolerance, and preserved adipose tissue and liver function in antipsychotic drug-treated mice. Mechanistically, suppressing excess leptin resolved local tissue and systemic inflammation typically associated with antipsychotic drug treatment. We conclude that hyperleptinemia is a key contributor to antipsychotic drug-associated weight gain and metabolic deterioration. Leptin suppression may be an effective approach to reducing the undesirable side effects of antipsychotic drugs.

Topics: Animals; Antipsychotic Agents; Humans; Leptin; Metabolic Diseases; Mice; Obesity; Weight Gain

To determine and compare the mean maternal serum leptin levels, the prevalence of high serum leptin levels and mean gestational weight gain at term among obese and non-obese pregnant women in Enugu, Nigeria.. This cross-sectional comparative study enrolled obese and non-obese pregnant women. The serum leptin levels of the women were determined using an enzyme-linked immunosorbent assay kit. Anthropometric and sociodemographic data were obtained and compared. Mean weight gain during pregnancy was determined.. A total of 170 pregnant women were included in the study. The mean ± SD serum leptin level (99.39 ± 50.2 ng/ml) and the prevalence of hyperleptinaemia (81 of 85 patients; 95.3%) among the obese pregnant women at term were significantly higher than those of the non-obese pregnant women (48.98 ± 30.35 ng/ml/65 of 85 patients; 76.5%). The mean percentage weight gain was significantly higher in the non-obese women compared with the obese women at term. The predictors of high maternal serum leptin level at term among the participants were the employment status and levels of education of the participants.. Maternal serum leptin level, maternal weight gain and prevalence of hyperleptinaemia at term were significantly higher in the obese compared with the non-obese pregnant women.

Topics: Body Mass Index; Cross-Sectional Studies; Female; Gestational Weight Gain; Humans; Leptin; Nigeria; Obesity; Pregnancy; Pregnant Women; Weight Gain

Fetal overgrowth "programs" an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health.. This work aimed to evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants.. In the Canadian 3D birth cohort, we studied 70 LGA (birth weight > 90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) infants matched by maternal ethnicity, smoking, and gestational age at delivery. The primary outcomes were fasting leptin, and total and high-molecular-weight (HMW) adiponectin concentrations at age 2 years.. LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, and total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0 to 24 months, current BMI, and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and White ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0 to 24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only.. This study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weight gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA individuals.

Topics: Adiponectin; Adiposity; Birth Weight; Canada; Case-Control Studies; Child, Preschool; Female; Fetal Macrosomia; Follow-Up Studies; Gestational Age; Humans; Infant; Infant, Newborn; Insulin Resistance; Leptin; Male; Sex Factors; Weight Gain

The purpose of this study is to evaluate the relationship between body composition, basal metabolic rate (BMR), and serum concentrations of leptin with long-term weight regain after Roux-en-Y gastric bypass (RYGB) and compare it with obesity before surgery.. Prospective longitudinal analytical study. Three groups were formed: individuals 60 months post RYGB, with weight regain (G1) and without it (G2), and individuals with obesity who had not undergone bariatric surgery (G3). Body fat (BF), body fat mass (BFM), visceral fat (VF), fat-free mass (FFM), skeletal muscle mass (SMM), and BMR were assessed by octapolar and multi-frequency electrical bioimpedance. Fasting serum concentrations of leptin were measured.. Seventy-two individuals were included, 24 in each group. Higher means of BF, BFM, VF, and leptin levels were observed in G1, when compared to G2 (BF: 47.5 ± 5.6 vs. 32.0 ± 8.0, p < 0.05; FBM: 47.8 ± 11.6 vs. 23.9 ± 7.0, p < 0.05; VF: 156.8 ± 30.2 vs. 96.1 ± 23.8, p < 0.05; leptin: 45,251.2 pg/mL ± 20,071.8 vs. 11,525.7 pg/mL ± 9177.5, p < 0.000). G1 and G2 did not differ in FFM, SMM, and BMR. G1 and G3 were similar according to BF, FFM, BMR, and leptin levels. Body composition, but not leptin, was correlated with %weight regain in G1 (FBM: r = 0.666, p < 0.000; BF: r = 0.428, p = 0.037; VF: r = 0.544, p = 0.006).. Long-term weight regain after RYGB is similar to pre-surgical obesity in body composition, BMR, and leptin concentrations, indicating relapse of metabolic and hormonal impairments associated with excessive body fat.

Topics: Basal Metabolism; Body Composition; Gastric Bypass; Humans; Leptin; Obesity; Obesity, Morbid; Prospective Studies; Weight Gain

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder characterized by high androgen levels. The aim of this study was to evaluate the effects of hyperandrogenism on the hypothalamus and subsequently on the food intake and obesity in females.. A dihydroxy testosterone (DHT)-induced rat model was established to recapitulate the hyperandrogenism features of PCOS patients. Body weight and food intake of the rats were recorded. The food intake of DHT-induced rats was restricted by pair feeding to exclude possible effects of weight gain on the hypothalamus. The expression levels of relevant proteins and mRNAs in the hypothalamus and primary hypothalamic neurons exposed to DHT were analyzed by Western blotting and RT-PCR, respectively. The leptin levels in the serum and cerebrospinal fluid (CSF) were measured, and leptin was injected via the intracerebroventricular (ICV) route to test the leptin sensitivity of the hypothalamus.. The excessive prepuberty androgen levels in the DHT-induced rats markedly elevated food intake prior to weight gain. Consistent with this, the expression of neuropeptide Y and agouti-related peptide mRNAs was upregulated, which occurred prior to obesity and even with restricted food intake. In addition, the hypothalamic sensitivity to insulin and leptin was also impaired in the DHT-induced rats before obesity and with restricted food intake. DHT significantly reduced the leptin levels in the CSF, and ICV injection of leptin inhibited the DHT-induced increase in food intake.. Androgen excess increased food intake in rats and promoted obesity by downregulating insulin and leptin signaling in the hypothalamus, most likely by suppressing leptin levels in the CSF.

Topics: Androgens; Animals; Body Weight; Eating; Female; Humans; Hyperandrogenism; Hypothalamus; Insulin; Leptin; Neuropeptide Y; Obesity; Polycystic Ovary Syndrome; Rats; RNA, Messenger; Signal Transduction; Testosterone; Weight Gain

This study aimed to investigate the effect of maternal high-fat (HF) diet and exercise during gestation and lactation on hypothalamic neural projection development in the offspring. Pregnant Sprague-Dawley rats were fed a CHOW or HF diet during gestation and lactation, and further divided into two subgroups: voluntary exercised and sedentary. Offspring's brains and tissue were collected at weaning and 16 weeks of age. Maternal exercise downregulated dams' body weight and food intake during lactation, but failed to normalize increased fat weight, plasma and milk leptin levels of HF dams at weaning. Maternal HF diet significantly increased offspring's body weight, adipose depots, plasma insulin, and leptin at weaning and had long-term effect on body weight of male offspring, while maternal exercise decreased offspring's body weight from 3 to 5 weeks of age in both sexes. At weaning, maternal exercise decreased αMSH fiber density and maternal HF diet impaired agouti-related peptide fiber density in the paraventricular nucleus of hypothalamus of male pups, while maternal HF diet disrupted αMSH fiber density in the paraventricular nucleus of hypothalamus of female pups. The impaired αMSH fiber density was consistent with reduced STAT3 signaling in the arcuate nucleus of hypothalamus, while the reduced agouti-related peptide fiber density was consistent with reduced ERK1/2 signaling in the arcuate nucleus of hypothalamus. The impaired hypothalamic projections were compensated in adulthood in both sexes. Our findings suggest that maternal HF diet and exercise exerts different effects on hypothalamic neural projections development through distinct signaling pathways in a sex-specific manner.

Topics: Adiposity; Adult; Animals; Body Weight; Diet, High-Fat; Female; Humans; Hypothalamus; Lactation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Weight Gain

Alteration of the perinatal nutritional environment is an important risk factor for the development of metabolic diseases in later life. The hormone leptin plays a critical role in growth and development. Previous studies reported that postnatal overnutrition increases leptin secretion during the pre-weaning period. However, a direct link between leptin, neonatal overnutrition, and lifelong metabolic regulation has not been investigated.. We used the small litter mouse model combined with neonatal leptin antagonist injections to examine whether attenuating leptin during early life improves lifelong metabolic regulation in postnatally overnourished mice.. Postnatally overnourished mice displayed rapid weight gain during lactation and remained overweight as adults. These mice also showed increased adiposity and perturbations in glucose homeostasis in adulthood. Neonatal administration of a leptin antagonist normalized fat mass and insulin sensitivity in postnatally overnourished mice. These metabolic improvements were associated with enhanced sensitivity of hypothalamic neurons to leptin.. Early postnatal overnutrition causes metabolic alterations that can be permanently attenuated with the administration of a leptin antagonist during a restricted developmental window.

Topics: Animals; Female; Hypothalamus; Leptin; Mice; Obesity; Overnutrition; Pregnancy; Weight Gain

This study prospectively investigated the levels of energy metabolism hormones in very preterm neonates to identify their change over time and association with intake of maternal milk as well as weight gain velocity.. We measured and compared the leptin, adiponectin, ghrelin, and insulin-like growth factor I (IGF-1) levels in the urine of 70 very preterm neonates, before the initiation of any enteral feeding (baseline level) and twice within 14 days on full enteral feeding (FEF). Regression models identified the role of intake of maternal milk on the levels of the tested energy metabolism hormones in the enteral-fed infants. We also analyzed the adequacy of the weight gain velocity defined by the fetal-infant growth reference (FIGR). Additionally, we collected and analyzed the infants' clinical and feeding characteristics during the birth hospitalization.. The preterm infants' baseline levels of the energy metabolism hormones significantly predicted their increase at the end of two weeks of observation on FEF. The leptin level was associated with increased intake of maternal milk, whereas the feeding volume was associated with increased ghrelin and IGF-1, and decreased leptin and adiponectin. Infants with comparable FIGR had higher leptin levels than those with inadequate weight gain velocity.. Early postnatal levels of leptin, adiponectin, ghrelin, and IGF-1 predicted the increase of these hormones in the fully enteral fed very preterm neonates. Moreover, greater intake of maternal milk by the study infants contributed to an increased leptin-associated weight gain velocity.

Topics: Adiponectin; Breast Feeding; Energy Metabolism; Female; Ghrelin; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Insulin-Like Growth Factor I; Leptin; Milk, Human; Weight Gain

Topics: Animals; Anorexia; Blood Pressure; Body Weight; Eating; Female; Leptin; Male; Mice; Mice, Knockout; Obesity; TRPC6 Cation Channel; Weight Gain

Monogenic obesity is a severe, genetically determined disorder that affects up to 1/1000 newborns. Recent reports on potential new therapeutics and innovative clinical approaches have highlighted the need for early identification of individuals with rare genetic variants that can alter the functioning of the leptin-melanocortin signalling pathway, in order to speed up clinical intervention and reduce the risk of chronic complications. Therefore, next-generation DNA sequencing of central genes in the leptin-melanocortin pathway was performed in 1508 children and adolescents with and without obesity, aged 2-19 years. The recruited cohort comprised approximately 5% of the national paediatric population with obesity. The model-estimated effect size of rare variants in the leptin-melanocortin signalling pathway on longitudinal weight gain between carriers and non-carriers was derived. In total, 21 (1.4%) participants had known disease-causing heterozygous variants (DCVs) in the genes under investigation, and 62 (4.1%) participants were carriers of rare variants of unknown clinical significance (VUS). The estimated frequency of potential genetic variants associated with obesity (including rare VUS) ranged between 1/150 (VUS and DCV) and 1/850 (DCV) and differed significantly between participants with and without obesity. On average, the variants identified would result in approximately 7.6 kg (7.0-12.9 kg at the 95th percentile of body weight) (girls) and 8.4 kg (8.2-14.4 kg) (boys) of additional weight gain in carriers at age 18 years compared with subjects without obesity. In conclusion, children with a genetic predisposition to obesity can be promptly identified and may account for more than 6% of obesity cases. Early identification of genetic variants in the

Topics: Adolescent; Child; Female; Genes, Recessive; Humans; Infant, Newborn; Leptin; Male; Melanocortins; Obesity, Morbid; Pediatric Obesity; Receptor, Melanocortin, Type 4; Receptors, Leptin; Weight Gain

Nutrient excess, such as the intake of a high-fat diet, reduces hypothalamic responses to exogenously administered leptin and induces dietary obesity; however, orally active components that attenuate neural leptin dysregulation have yet to be identified. We herein demonstrated that YHIEPV, derived from the pepsin-pancreatin digestion of the green leaf protein Rubisco, increased the leptin-induced phosphorylation of STAT3 in ex vivo hypothalamic slice cultures. We also showed that YHIEPV mitigated palmitic acid-induced decreases in leptin responsiveness. Furthermore, orally administered YHIEPV promoted leptin-induced reductions in body weight and food intake in obese mice. In addition, dietary-induced body weight gain was significantly less in mice orally or centrally administered YHIEPV daily than in saline-control mice. Cellular leptin sensitivity and the levels of proinflammatory-related factors, such as IL1β and Socs-3, in the hypothalamus of obese mice were also restored by YHIEPV. YHIEPV blocked cellular leptin resistance induced by forskolin, which activates Epac-Rap1 signaling, and reduced the level of the GTP-bound active form of Rap1 in the brains of obese mice. Collectively, the present results demonstrated that the orally active peptide YHIEPV derived from a major green leaf protein increased neural leptin responsiveness and reduced body weight gain in mice with dietary obesity.

Topics: Animals; Body Weight; Hypothalamus; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Ribulose-Bisphosphate Carboxylase; Weight Gain

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

Obesity is an abnormal or excessive accumulation of fat in the body that exacerbates metabolic and inflammatory processes, and impairs the health of afflicted individuals. β-caryophyllene is a natural sesquiterpene that is a dietary cannabinoid with anti-inflammatory properties and potential activity against metabolic diseases. In the present study, we evaluated the effect of β-caryophyllene on C57BL/6 mice using a diet-induced obesity model. Male mice were randomly assigned to the following groups over a 16-week period: (1) standard diet as lean control, (2) high-fat diet (HFD) as obese control, and (3) HFD + β-caryophyllene with β-caryophyllene at 50 mg/kg. Treatment with β-caryophyllene improved various metabolic parameters including increased total body weight, fasting glucose levels, oral-glucose tolerance, insulin tolerance, fasting triglycerides, adipocyte hypertrophy, and liver macrovesicular steatosis. β-caryophyllene also modulated the levels and expression of immune response factors including adiponectin, leptin, insulin, interleukin-6, tumor necrosis factor-a, and Toll-like receptor-4. Our data indicate that chronic supplementation with β-caryophyllene can improve relevant metabolic and immunological processes in obese mice. This protocol was approved by the Institutional Committee for Care and Use of Laboratory Animals from the University of Guadalajara with protocol code CUCEI/CINV/CICUAL-01/2022.

Topics: Adiponectin; Animals; Anti-Inflammatory Agents; Blood Glucose; Cannabinoids; Diet, High-Fat; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Polycyclic Sesquiterpenes; Triglycerides; Tumor Necrosis Factors; Weight Gain

Weight gain is the one of the most important factors which increases global burden of psychiatric disorder. Second-generation antipsychotics, olanzapine (Olz) and valproic acid (Vpa) in particular, are held responsible for weight gain. However, it is still uncertain how these drugs cause this. Thus, the rats selected for the experiment were randomly divided into 3 groups. The 1st group received only 0.5 ml saline solution intraperitoneally (n = 20, control group); the second group was given 200 mg / kg Vpa intraperitoneally (n = 20, Vpa group) and 2 mg / kg Olz was given intraperitoneally to the 3rd group (n = 20, Olz group) between 8 and 10 am for 30 days. We examined serum leptin, adiponectin, resistin, TNF-α, IL-6, ghrelin level and, the amount of ghrelin secreting cells in the stomach and growth hormone secretagogue receptor-1a (GHSR-1a, ghrelin receptor) expression in the hypothalamus. The hypothalamic GHS-1a receptor index was significantly higher in the Olz group compared with the control group and Vpa group (p = 0.036 and p = 0.016 respectively). Ghrelin immune positive cell index in stomach was statistically significantly lower in the Vpa group compared with the control and Olz groups (p = 0.028 and p = 0.013 respectively) There was no difference between the groups in terms of serum leptin, resistin, IL-6 and ghrelin levels. In the Vpa group, a statistically significant increase was found in serum adiponectin level compared with both the control group and the Olz group (p = 0009 and p = 0024 respectively) and, significant decrease was found in serum TNF-α level compared to Olz group (p = 0007). In conclusion, we found that the main cause of weight gain in Olz use was the increase in the number of hypothalamic ghrelin receptors. Investigating the mechanism by which Olz increases the number of ghrelin receptors may help to develop effective treatment strategies in preventing obesity in psychiatric patients.

Topics: Adiponectin; Animals; Ghrelin; Hypothalamus; Interleukin-6; Leptin; Olanzapine; Rats; Receptors, Ghrelin; Resistin; Tumor Necrosis Factor-alpha; Valproic Acid; Weight Gain

Children born small for gestational age (SGA) are at risk of future obesity and associated comorbidities. Therefore the identification of risk factors and novel biomarkers which are associated with this risk are needed for early detection and to improve preventive strategies. Spexin (SPX), a novel neuropeptide that is involved in the regulation of obesity and fat metabolism, is a candidate biomarker for predicting obesity and related comorbidities at an early age. The aim of this study was to investigate serum levels of SPX in term infants born small, appropriate, and large for gestational age (LGA) and its association with newborn anthropometric measurements.. One hundred and twenty term newborn babies classified as SGA, appropriate for gestational age (AGA), or LGA and their mothers were included. SPX, leptin and visfatin were measured in cord blood and maternal serum by enzyme-linked immunosorbent assay.. Fifty-six (46.7%) neonates were girls and 64 (53.3%) were boys. The mean birth weight was 3170.70±663 g, birth length was 48.9±2.79 cm, and head circumference was 34.5±1.67 cm. Birth weights, lengths, and head circumferences of the neonates in the SGA, AGA, and LGA groups were significantly different. Cord blood SPX and leptin levels in the SGA groups were significantly lower than those of both the LGA and AGA groups. Cord blood visfatin levels were significantly lower in the AGA group than the LGA and SGA groups. Maternal SPX levels of SGA babies were significantly lower than those of the mothers in both the LGA and AGA groups, but no significant difference was observed between the SGA and LGA groups. Maternal visfatin levels of the AGA babies were significantly higher than the maternal levels of SGA and LGA groups. There was no difference in terms of maternal leptin levels. Cord blood SPX and leptin levels were positively correlated with birth weight, length and head circumference. Birth weight increased significantly in line with maternal pregestational body mass index.. The lowest SPX levels were found in the SGA babies and cord SPX level was significantly correlated with newborn length, weight, and head circumference.

Topics: Birth Weight; Female; Fetal Blood; Fetal Growth Retardation; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Obesity; Peptide Hormones; Weight Gain

To explore the differences of serum fibroblast growth factor-21 (FGF-21) levels in pregnant women with normal glucose tolerance and gestational diabetes mellitus (GDM), and to analyze the relationship between FGF-21 and glucose and lipid metabolic indicators, leptin, retinol binding protein 4 (RBP-4) and adiponectin in GDM, in order to provide basis for the prevention and treatment of GDM.. Total of 120 women were included, and divided into normal glucose tolerance group (58 cases) and GDM group (62 cases) according to the 75 g oral glucose tolerance test results. General information were recorded; height, weight and blood pressure, blood glucose, lipids, insulin, FGF-21, leptin, RMP-4, and adiponectin were measured, and body mass index (BMI), homeostasis model assessment-IR, homeostasis model assessment-β and area under glucose curve were calculated. The t-test, Pearson analysis and multiple linear regression analysis were used to evaluate the differences and related factors of FGF-21 in GDM.. The pre-pregnancy BMI, pregnancy BMI, weight gain during pregnancy and FGF-21 levels were higher in GDM group, whereas there were no statistically significant differences in leptin, RBP-4 and adiponectin. Correlation analysis suggested that FGF-21 level was correlated with age, pre-pregnancy BMI, weight gain during pregnancy, high-density lipoprotein cholesterol, leptin, RBP-4 and adiponectin, and the results of multiple linear regression showed that serum FGF-21 was related to pre-pregnancy BMI, weight gain during pregnancy, leptin, RBP-4 and adiponectin in GDM.. There were higher serum FGF-21 levels in GDM, which might be related to pre-pregnancy BMI, weight gain during pregnancy, leptin, RBP-4 and adiponectin.

Topics: Adipokines; Adiponectin; Blood Glucose; Body Mass Index; Diabetes, Gestational; Female; Fibroblast Growth Factors; Humans; Leptin; Pregnancy; Weight Gain

Undernutrition is responsible for up to 45% of deaths in children under five, with low- and middle-income countries disproportionately affected. Adipokines are known modulators of metabolism and have been linked to growth rates and neurocognition during infancy. We examined the relationship(s) between cord blood adiponectin and leptin and both longitudinal growth and cognition during the first year of life using generalized estimating equations. Infants were classified as underweight (weight-for-age z-score [WAZ]), stunted (height-for-age z-score [HAZ]) or wasted (weight-for-height z-score [WHZ]) using WHOAnthro software. Cord blood adiponectin and leptin levels were highly correlated (r = 0.35, P < 0.0001) and positively associated with birth WAZ (r = 0.34 and r = 0.45, P < 0.0001, respectively). Adipokines were independently, inversely associated with weight gain. Infants in the highest quintile of adipokine production had a lower risk of being stunted, while neither was associated with lower WAZ or WHZ in final adjusted models. Cognition was not found to be independently related to cord blood leptin or adiponectin. The negative association with adipokines and rate of weight gain during infancy may reflect heightened nutritional status at birth rather than a direct hormonal influence. The relationship between leptin or adiponectin and longitudinal length gains suggests that both adipokines may promote linear growth during infancy.

Topics: Adipokines; Adiponectin; Child; Fetal Blood; Growth Disorders; Humans; Infant; Infant, Newborn; Leptin; Weight Gain

Egg-derived peptides play important roles in insulin secretion and sensitivity, oxidative stress, and inflammation, suggesting their possible involvement in obesity management. Hence, the aim of this study is to explore the alleviating effects of IRW (lle-Arg-Trp) and IQW (lle-Gln-Trp) on obesity via the mouse model induced by a high-fat diet. The entire experimental period lasted eight weeks. The results demonstrated that IQW prevented weight gain (6.52%), decreased the glucose, low-density lipoprotein (LDL), malonaldehyde, triglycerides, total cholesterol (TC), and leptin levels, and increased the concentration of adiponectin (p < 0.05, n = 8). Although IRW failed to prevent weight gain, it reduced the concentration of glucose, high-density lipoprotein (HDL), LDL, and leptin, and increased the concentration of adiponectin (p < 0.05, n = 8). Moreover, IRW and IQW increased glucose tolerance and insulin resistance based on the results of the intraperitoneal glucose test and insulin tolerance test (p < 0.05, n = 8). The quantitative polymerase chain reaction results revealed that IRW and IQW downregulated the mRNA expression of DGAT1 (Diacylglycerol O-Acyltransferase 1), DGAT2 (Diacylglycerol O-Acyltransferase 2), TNF-α, IL-6, and IL-1β of liver tissue (p < 0.05, n = 8). The results of the 16S ribosomal RNA amplicon sequencing showed that IQW and IRW tended to reduce the relative abundance of Firmicutes and Parabacteroides, and that IRW enhanced the abundance of Bacteroides (p < 0.05, n = 8). Collectively, IRW and IQW supplementation could alleviate the progression of obesity due to the fact that the supplementation reduced lipid deposition, maintained energy balance, and reprogrammed gut microbiota.

Topics: Adiponectin; Animals; Cholesterol; Diacylglycerol O-Acyltransferase; Diet, High-Fat; Disease Models, Animal; Egg Proteins; Gastrointestinal Microbiome; Glucose; Insulins; Interleukin-6; Leptin; Lipoproteins, HDL; Lipoproteins, LDL; Malondialdehyde; Membrane Proteins; Mice; Mice, Inbred C57BL; Obesity; Peptides; RNA, Messenger; RNA, Ribosomal, 16S; Transferrin; Triglycerides; Tumor Necrosis Factor-alpha; Weight Gain

Biological sex and aging impact obesity development and type 2 diabetes, changing the secretion of leptin and adiponectin. The balance between these factors has been propounded as a reliable biomarker of adipose tissue dysfunction. Our proposal was to study sexual differences and aging on the adiponectin/leptin (Adpn/Lep) ratio in order to acquire a broader view of the impact of consuming an high-fat diet (HFD) on energy metabolism according to sex and age. Male and female C57BL/6J mice were fed a normal chow diet or an HFD for 12 or 32 weeks (n = 7−10 per group) and evolution of body weight, food intake and metabolic profile were registered. The HFD triggered an increase in body weight (p < 0.001), body weight gain (p < 0.01) and adiposity index (p < 0.01) in both sexes at 32 weeks of age, but female mice fed the HFD exhibited these changes to a significantly lower extent than males. Aged female mice showed an increase (p < 0.01) in the Adpn/Lep ratio, which was negatively correlated with body weight gain, changes in different fat depots and insulin resistance. Females were more metabolically protected from obesity development and its related comorbidities than males regardless of age, making the Adpn/Lep ratio a relevant factor for body composition and glucose metabolism.

Topics: Adiponectin; Animals; Body Weight; Diabetes Mellitus, Type 2; Diet, High-Fat; Female; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Weight Gain

Psoriasis is a chronic inflammatory disease associated with obesity and metabolic syndrome. Adipokines are thought to be a link between psoriasis and obesity. Leptin, adiponectin, and omentin are bioactive adipokines thought to play a role in both metabolic comorbidities and inflammation. Anti-tumour necrosis factor alfa (anti-TNF-α) agents are effective for psoriasis treatment, although significant weight gain has been reported during anti-TNF-α therapy. The interleukin 12/23 (IL 12/23) inhibitor ustekinumab is also effective for psoriasis treatment. We compared the effects of three anti-TNF-α drugs and an IL-12/23 inhibitor on adipokines and weight gain during treatment.. This prospective study included 80 patients (37 women, 43 men) with moderate to severe plaque psoriasis whose age and weight were matched. The patients were divided into four equal groups: etanercept, infliximab, adalimumab, and ustekinumab treatment groups. Psoriasis Area Severity Index (PASI) score, body weight (muscle and fat compartments), and leptin, adiponectin, and omentin levels were evaluated at baseline and weeks 4, 12, 24, and 48 of treatment.. There were no differences between drug groups in terms of weight parameters or biochemical parameters at baseline. At the end of 48 weeks, there was significant weight gain in the adalimumab group. Patients who received infliximab showed significant weight gain by week 12, but in the following weeks they returned to their initial weight. Body weight reached a maximum level by week 12 in patients using etanercept, but they lost weight in the following weeks and finished the study below their initial weight. Patients using ustekinumab did not demonstrate significant weight change during the 48 weeks except at week 12. At the end of week 48, PASI75 (improvement in PASI ≥75%) response rates were approximately 85% for the ustekinumab group, 80% for the adalimumab group, 75% for the infliximab group, and 50% for the etanercept group. Leptin, adiponectin, and omentin levels were higher in the ustekinumab group at all weeks except baseline. The lowest levels were observed in the etanercept group. The treatment response rate was also lower in the etanercept group.. We did not evaluate visfatin and resistin levels, insulin sensitivity, and cardiovascular risk that may be associated with weight gain and adipokine levels.. Unlike TNF inhibitors, ustekinumab does not cause significant weight changes and it increases adipokine levels more than TNF inhibitors. Adipokine levels seem to be related to the treatment response.

Topics: Adalimumab; Adipokines; Adiponectin; Body Weight; Etanercept; Female; Humans; Infliximab; Interleukin-12; Interleukin-23; Leptin; Male; Obesity; Prospective Studies; Psoriasis; Severity of Illness Index; Tumor Necrosis Factor Inhibitors; Ustekinumab; Weight Gain

Prediabetes is a strong predictor of type 2 diabetes and its associated cardiovascular complications, but few studies explore sexual dimorphism in this context. Here, we aim to determine whether sex influences physiological response to high-fat high-sucrose diet (HFS) and myocardial tolerance to ischemia-reperfusion injury. Male and female Wistar rats were subjected to standard (CTRL) or HFS diet for 5 months. Then, ex-vivo experiments on isolated perfused heart model were performed to evaluate tolerance to ischemia-reperfusion injury. HFS diet induced fasting hyperglycemia and increased body fat percent to a similar level in both sexes. However, glucose intolerance was more pronounced in female HFS. Cholesterol was increased only in female while male displayed higher level of plasmatic leptin. We observed increased heart weight to tibia length ratio only in males, but we showed a similar decrease in tolerance to ischemia-reperfusion injury in female and male HFS compared with respective controls, characterized by impaired cardiac function, energy metabolism and coronary flow during reperfusion. In conclusion, as soon as glucose intolerance and hyperglycemia develop, we observe higher sensitivity of hearts to ischemia-reperfusion injury without difference between males and females.

Topics: Animals; Cholesterol; Diabetes Mellitus, Type 2; Diet, High-Fat; Dietary Sucrose; Energy Metabolism; Female; Glucose Intolerance; Humans; Hyperglycemia; Leptin; Male; Myocardial Reperfusion Injury; Myocardium; Oxidative Stress; Prediabetic State; Rats; Rats, Wistar; Sex Factors; Weight Gain

Lithium-treated patients often suffer from weight gain as a common adverse event. In an earlier investigation, we found an impact of two single-nucleotide polymorphisms (rs10487506 and rs2278815) at the leptin gene on weight gain but not on leptin protein levels in serum under lithium augmentation. A recent genome-wide association study identified a polymorphism at the leptin gene locus (rs10487505) associated with circulating leptin protein levels. To characterize potential effects of this variant in acute major depressive disorder, we investigated body mass indices from 180 lithium-augmented patients and serum concentrations of leptin protein from 89 patients using linear mixed model analyses and rs6979832, a proxy SNP of rs10487505. Body mass index was measured before and after 4 weeks of lithium augmentation, in a subsample also after 4 and 7 months. Leptin serum levels were measured before and during lithium augmentation. G-allele homozygotes of rs6979832 had a significantly lower body mass index increase during observation compared to A-allele hetero- and homozygotes. However, we found no influence on leptin serum levels. Joint analyses of rs6979832 with the previously investigated polymorphisms rs10487506 and rs2278815, and expressed quantitative trait data, suggest a complex interplay between SNP alleles at the leptin locus. These results strongly support our earlier findings that common genetic variation at the leptin gene locus may be involved in lithium augmentation-associated weight gain in major depressive disorder.

Topics: Body Mass Index; Depression; Depressive Disorder, Major; Genome-Wide Association Study; Humans; Leptin; Lithium; Polymorphism, Single Nucleotide; Weight Gain

The unfolded protein response (UPR) is involved in the pathogenesis of metabolic disorders, yet whether variations in the UPR among individuals influence the propensity for metabolic disease remains unexplored. Using outbred deer mice as a model, we show that the intensity of UPR in fibroblasts isolated early in life predicts the extent of body weight gain after high-fat diet (HFD) administration. Contrary to those with intense UPR, animals with moderate UPR in fibroblasts and therefore displaying compromised stress resolution did not gain body weight but developed inflammation, especially in the skin, after HFD administration. Fibroblasts emerged as potent modifiers of this differential responsiveness to HFD, as indicated by the comparison of the UPR profiles of fibroblasts responding to fatty acids in vitro, by correlation analyses between UPR and proinflammatory cytokine-associated transcriptomes, and by BiP (also known as HSPA5) immunolocalization in skin lesions from animals receiving HFD. These results suggest that the UPR operates as a modifier of an individual's propensity for body weight gain in a manner that, at least in part, involves the regulation of an inflammatory response by skin fibroblasts. This article has an associated First Person interview with the first author of the paper.

Topics: Animals; Biomarkers; Cytokines; Diet, High-Fat; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Fatty Acids; Fibroblasts; Inflammation; Leptin; Models, Biological; Organ Size; Peromyscus; Skin; Transcriptome; Unfolded Protein Response; Weight Gain

Changes in functionality and composition of gut microbiota (GM) have been associated and may contribute to the development and maintenance of obesity and related diseases. The aim of our study was to investigate for the first time the impact of

Topics: Adipocytes; Adipose Tissue, White; Animal Feed; Animals; Biodiversity; Blood Glucose; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; DNA, Bacterial; Feces; Gastrointestinal Microbiome; Leptin; Lipid Metabolism; Lipoproteins, LDL; Liver; Male; Obesity; Probiotics; Rats; Rats, Sprague-Dawley; RNA, Ribosomal, 16S; Weight Gain

Obesity has become a common rising health care problem, especially in "modern" societies. Obesity is considered a low-grade systemic inflammation, partly linked to leaky gut. Circadian rhythm disruption, a common habit in modern life, has been reported to cause gut barrier impairment. Abnormal time of eating, defined by eating close to or during rest time, is shown to cause circadian rhythm disruption. Here, using a non-obesogenic diet, we found that abnormal feeding time facilitated weight gain and induced metabolic dysregulation in mice. The effect of abnormal time of eating was associated with increased gut permeability, estimated by sucralose and/or lactulose ratio and disrupted intestinal barrier marker. Analysis of gut microbiota and their metabolites, as important regulators of barrier homeostasis, revealed that abnormal food timing reduced relative abundance of butyrate-producing bacteria, and the colonic butyrate level. Overall, our data supported that dysbiosis was characterized by increased intestinal permeability and decreased beneficial barrier butyrate-producing bacteria and/or metabolite to mechanistically link the time of eating to obesity. This data provides basis for noninvasive microbial-targeted interventions to improve intestinal barrier function as new opportunities for combating circadian rhythm disruption induced metabolic dysfunction.

Topics: Animal Husbandry; Animals; Biomarkers; Blood Glucose; Cadherins; Circadian Rhythm; Colon; Food; Gastrointestinal Microbiome; Glucose; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Random Allocation; Time Factors; Weight Gain

The aim of this study was to investigate the effects of feed efficiency classifications on live animal measurements, circulating IGF-1 and leptin concentrations, and carcass, non-carcass and meat quality traits of lambs. One-hundred and two lambs approximately 70 days-old with initial live weight of 24.6 ± 3.71 kg (mean ± SD) were individually fed for 56 days to determine residual feed intake (RFI) and residual feed intake and gain (RIG). Lambs were then classified as phenotypically Low-, Medium- or High-RFI and Low-, Medium- or High-RIG phenotypes. Circulating leptin and IGF-1 concentrations were higher in more efficient lambs (Low-RFI or High-RIG). Variation in RFI and RIG did not affect meat redness or tenderness, but High-RIG lambs had darker meat. These findings show that the phenotypically more efficient Low-RFI and High-RIG lambs produced carcasses with similar characteristics and meat quality as the less efficient High-RFI and Low-RIG lambs but have a strategic advantage of lower feed intake to achieve similar production outcomes.

Topics: Animal Nutritional Physiological Phenomena; Animals; Eating; Food Quality; Insulin-Like Growth Factor I; Leptin; Male; Red Meat; Sheep, Domestic; Weight Gain

Human milk contains hormones that regulate metabolism. Extrauterine growth restriction remains common among preterm infants, but the effect of ingesting milk hormones on preterm infant growth is poorly understood.. To quantify associations of longitudinal exposure to leptin, adiponectin, and insulin in milk with physical growth of preterm infants.. In 50 preterm neonates (median gestational age 29.4 weeks), we sampled maternal milk on day-of-life 7, 14, 21, and 28 and measured hormone levels in whole milk by ELISA. Milk leptin levels were available for a subset of 18 infants. We calculated milk hormone doses by multiplying the hormone level by the milk volume ingested on each day and estimated the area under the curve (AUC) to reflect longitudinal exposure. We analyzed associations of milk hormone exposure with growth outcomes in generalized estimated equations.. Weight gain velocity and z-scores in weight, length, head circumference, and body mass index at 36 weeks' postmenstrual age (PMA).. Higher leptin intake was associated with greater weight gain (2.17g/kg/day [95% CI, 1.31, 3.02]) and weight z-score at 36 weeks' PMA (0.30 [0.08, 0.53] higher z-score per tertile). Higher adiponectin intake was associated with greater length z-score (0.41 [0.13, 0.69]), however, this association was nullified after adjustment of protein and calorie intake. Higher adiponectin was associated with smaller head circumference z-score (-0.36 [-0.64, -0.07]). Insulin was not associated with growth outcomes.. Milk leptin and adiponectin exposures may affect growth of preterm infants. The long-term effects of milk hormones warrant further investigation.

Topics: Adiponectin; Child Development; Cohort Studies; Eating; Female; Hormones; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Leptin; Longitudinal Studies; Male; Massachusetts; Milk, Human; Weight Gain

The brain renin-angiotensin system (RAS) has been recently involved in the homeostatic regulation of energy. Our goal was to analyse the influence of a diet rich in saturated fatty acids (butter) against one enriched in monounsaturated fatty acids (olive oil) on hypothalamic RAS, and their relationship with the metabolism of fatty acids. Increases in body weight and visceral fat, together with an increase in aminopeptidase A expression and reductions in AngII and AngIV were observed in the hypothalamus of animals fed with the butter diet. In this group, a marked reduction in the expression of genes related to lipid metabolism (LPL, CD36, and CPT-1) was observed in liver and muscle. No changes were found in terms of body weight, total visceral fat and the expression of hepatic genes related to fatty acid metabolism in the olive oil diet. The expressions of LPL and CD36 were reduced in the muscles, although the decrease was lower than in the butter diet. At the same time, the fasting levels of leptin were reduced, no changes were observed in the hypothalamic expression of aminopeptidase A and decreases were noted in the levels of AngII, AngIV and AngIII. These results support that the type of dietary fat is able to modify the hypothalamic profile of RAS and the body energy balance, related to changes in lipid metabolism.

Topics: Angiotensin II; Angiotensin III; Animals; Body Weight; Butter; CD36 Antigens; Diet, High-Fat; Energy Metabolism; Fasting; Gene Expression; Glutamyl Aminopeptidase; Hypothalamus; Intra-Abdominal Fat; Leptin; Lipid Metabolism; Lipoprotein Lipase; Liver; Male; Mice; Mice, Inbred ICR; Muscle, Skeletal; Olive Oil; Real-Time Polymerase Chain Reaction; Renin-Angiotensin System; RNA, Messenger; Weight Gain

Stress has a major impact on the modulation of metabolism, as previously evidenced by hyperglycemia following chronic social defeat (CSD) stress in mice. Although CSD-triggered metabolic dysregulation might predispose to pre-diabetic conditions, insulin sensitivity remained intact, and obesity did not develop, when animals were fed with a standard diet (SD). Here, we investigated whether a nutritional challenge, a high-fat diet (HFD), aggravates the metabolic phenotype and whether there are particularly sensitive time windows for the negative consequences of HFD exposure. Chronically stressed male mice and controls (CTRL) were kept under (i) SD-conditions, (ii) with HFD commencing post-CSD, or (iii) provided with HFD lasting throughout and after CSD. Under SD conditions, stress increased glucose levels early post-CSD. Both HFD regimens increased glucose levels in non-stressed mice but not in stressed mice. Nonetheless, when HFD was provided after CSD, stressed mice did not differ from controls in long-term body weight gain, fat tissue mass and plasma insulin, and leptin levels. In contrast, when HFD was continuously available, stressed mice displayed reduced body weight gain, lowered plasma levels of insulin and leptin, and reduced white adipose tissue weights as compared to their HFD-treated non-stressed controls. Interestingly, stress-induced adrenal hyperplasia and hypercortisolemia were observed in mice treated with SD and with HFD after CSD but not in stressed mice exposed to a continuous HFD treatment. The present work demonstrates that CSD can reduce HFD-induced metabolic dysregulation. Hence, HFD during stress may act beneficially, as comfort food, by decreasing stress-induced metabolic demands.

Topics: Animals; Blood Group Antigens; Diet, High-Fat; Energy Intake; Glucose Tolerance Test; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Social Defeat; Stress, Psychological; Weight Gain

The current study examined the role of sex differences in the development of risk factors associated with obesity and its comorbidities using models that differ in their susceptibility to develop obesity, obesity-resistant S5B/Pl (S5B) and obesity-prone Osborne-Mendel (OM) rats. Male and female rats were fed a low fat or high fat diet (HFD) and markers of metabolic syndrome (MetSyn) and expression of inflammatory cytokines/chemokines in visceral and subcutaneous adipose depots were measured. We hypothesized that male and female OM and S5B rats would exhibit differential responses to the consumption of HFD and that females, regardless of susceptibility to develop obesity, would display decreased obesity-related risk factors. Results suggested that consumption of HFD increased adiposity and fasting glucose levels in male OM and S5B rats, decreased circulating adiponectin levels in male S5B rats, and increased body weight and triglyceride levels in male OM rats. The consumption of HFD increased body weight and adiposity in female OM rats, not female S5B rats. Overall, female rats did not meet criteria for MetSyn, while male rats consuming HFD met criteria for MetSyn. Visceral and subcutaneous adipose tissue inflammation was higher in male rats. In visceral adipose tissue, HFD consumption differentially altered expression of cytokines in male and female S5B and OM rats. These findings suggest that resistance to obesity in males may be overridden by chronic consumption of HFD and lead to increased risk for development of obesity-related comorbidities, while female rats appear to be protected from the adverse effects of HFD consumption.

Topics: Adipose Tissue; Animals; Biomarkers; Body Weight; Diet, High-Fat; Female; Inflammation; Leptin; Male; Metabolic Syndrome; Obesity; Rats; Sex Factors; Weight Gain

Since alterations of the gut microbiota have been shown to play a major role in obesity, probiotics have attracted attention. Our aim was to identify probiotic candidates for the management of obesity using a combination of in vitro and in vivo approaches. We evaluated in vitro the ability of 23 strains to limit lipid accumulation in adipocytes and to enhance the secretion of satiety-promoting gut peptide in enteroendocrine cells. Following the in vitro screening, selected strains were further investigated in vivo, single, or as mixtures, using a murine model of diet-induced obesity. Strain

Topics: Adipocytes; Animals; Bile Acids and Salts; Diet; Disease Models, Animal; Enteroendocrine Cells; Gastrointestinal Hormones; Gastrointestinal Microbiome; Hypothalamus; Leptin; Mice; Obesity; Obesity Management; Probiotics; Receptors, Leptin; Weight Gain

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.

Topics: Animals; Anti-Obesity Agents; Blood Glucose; Body Weight; Cyclopentane Monoterpenes; Diet, High-Fat; Energy Intake; Ghrelin; Glucosides; Hypothalamus; Insulin; Leptin; Male; Mice; Pro-Opiomelanocortin; Pyrans; Taste Perception; Weight Gain

Di-(2-ethylhexyl) phthalate has been reported to interfere with the development and function of animal reproductive systems. However, hardly any studies provide methods to minimize or prevent the adverse effects of DEHP on reproduction. The energy balance state of mammals is closely related to reproductive activities, and the reproductive axis can regulate reproductive activities according to changes in the body's energy balance state. In this study, the effects of every other day fasting (EODF), as a way of intermittent fasting, on preventing the precocious puberty induced by DEHP in female rats was studied. EODF significantly improved the advancement of vaginal opening age (as the markers of puberty onset) and elevated serum levels of luteinizing hormone and estradiol (detected by ELISA) induced by 5 mg kg

Topics: Animals; Diethylhexyl Phthalate; Estradiol; Fasting; Female; Follicle Stimulating Hormone; Hypothalamo-Hypophyseal System; Leptin; Luteinizing Hormone; Ovary; Pituitary Gland; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sexual Maturation; Time Factors; Vagina; Weight Gain

This study evaluated the effect of green banana flour (GBF) consumption on obesity-related conditions in mice fed high-fat diets. GBF was prepared using stage 1 green banana pulp, which was dehydrated and milled. Mice were fed a control diet (

Topics: Adiposity; Animals; Diet, High-Fat; Disease Models, Animal; Food, Fortified; Gastrointestinal Microbiome; Inflammation; Interleukin-6; Leptin; Male; Mice, Inbred C57BL; Mice, Obese; Musa; Obesity; Tumor Necrosis Factor-alpha; Weight Gain

The leptin system plays a crucial role in the regulation of appetite and energy homeostasis in vertebrates. While the phenotype of morbid obesity due to leptin (Lep) or leptin receptor (LEPR) loss of function is well established in mammals, evidence in fish is controversial, questioning the role of leptin as the vertebrate adipostat. Here we report on three (Lepr) loss of function (LOF) and one leptin loss of function alleles in zebrafish. In order to demonstrate that the Lepr LOF alleles cannot transduce a leptin signal, we measured socs3a transcription after i.p. leptin which is abolished by Lepr LOF. None of the Lepr/Lepa LOF alleles leads to obesity/a body growth phenotype. We explore possible reasons leading to the difference in published results and find that even slight changes in background genetics such as inbreeding siblings and cousins can lead to significant variance in growth.

Topics: Adiposity; Animals; Female; Leptin; Loss of Function Mutation; Male; Obesity; Receptors, Leptin; Weight Gain; Zebrafish

Anorexia nervosa (AN) is a severe eating disorder where caloric restriction, excessive physical activity and metabolic alterations lead to life-threatening situations. Despite weight restoration after treatment, a significant part of patients experience relapses. In this translational study, we combined clinical and preclinical approaches. We describe preliminary data about the effect of weight gain on the symptomatology of patients suffering from acute AN (

Topics: Adolescent; Adult; Animals; Anorexia Nervosa; Body Mass Index; Body Weight; Exercise; Feeding Behavior; Female; Ghrelin; Heart Rate; Humans; Hypothalamus; Leptin; Mice; Mice, Inbred C57BL; Models, Animal; Neuropeptides; Recurrence; RNA, Messenger; Weight Gain; Young Adult

Hypoxia and hyperoxia are disparate stressors which can have destructive influences on fish growth and physiology. It is yet to be determined if hypoxia and hyperoxia have a cumulative effect in aquatic ecosystems that affect biological parameters in fish, and to understand if this is associated with gene expression. Here we address whether growth performance and expressions of growth, immune system and stress related genes were affected by hypoxia and hyperoxia in fish. Rainbow trout was chosen as the study organism due to its excellent service as biomonitor. After an acclimatization period, fish were exposed to hypoxia (4.0 ± 0.5 ppm O

Topics: Animals; Fish Proteins; Gene Expression Regulation; Growth Hormone; HSP70 Heat-Shock Proteins; Hyperoxia; Hypoxia; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Leptin; Liver; Oncorhynchus mykiss; Oxygen; Stress, Physiological; Weight Gain

The AT1 receptor blocker telmisartan (TEL) prevents diet-induced obesity. Hypothalamic lipid metabolism is functionally important for energy homeostasis, as a surplus of lipids induces an inflammatory response in the hypothalamus, thus promoting the development of central leptin resistance. However, it is unclear as to whether TEL treatment affects the lipid status in the hypothalamus. C57BL/6N mice were fed with chow (CONchow) or high-fat diet (CONHFD). HFD-fed mice were gavaged with TEL (8 mg/kg/day, 12 weeks, TELHFD). Mice were phenotyped regarding weight gain, energy homeostasis, and glucose control. Hypothalamic lipid droplets were analyzed by fluorescence microscopy. Lipidomics were assessed by performing liquid chromatography-mass spectrometry in plasma and hypothalami. Adipokines were investigated using immunosorbent assays. Glial fibrillary acidic protein (GFAP) was determined by Western blotting and immunohistochemical imaging. We found that body weight, energy homeostasis, and glucose control of TEL-treated mice remained normal while CONHFD became obese. Hypothalamic ceramide and triglyceride levels as well as alkyne oleate distribution were normalized in TELHFD. The lipid droplet signal in the tanycyte layer was higher in CONHFD than in CONchow and returned to normal under TELHFD conditions. High hypothalamic levels of GFAP protein indicate astrogliosis of CONHFD mice while normalized GFAP, TNFα, and IL1α levels of TELHFD mice suggest that TEL prevents hypothalamic inflammation. In conclusion, TEL has anti-obese efficacy and prevented lipid accumulation and lipotoxicity, which is accompanied by an anti-inflammatory effect in the murine hypothalamus. Our findings support the notion that a brain-related mechanism is involved in TEL-induced weight loss.

Topics: Angiotensin II Type 1 Receptor Blockers; Animal Feed; Animals; Diet, High-Fat; Hypothalamus; Leptin; Lipid Droplets; Lipid Metabolism; Mice; Mice, Inbred C57BL; Obesity; Telmisartan; Weight Gain

The objective of this study was to investigate the role of palmitoylethanolamide (PEA) in the regulation of energy homeostasis in goldfish (Carassius auratus). We examined the effects of acute or chronic intraperitoneal treatment with PEA (20 μg·g

Topics: Amides; Animals; Body Weight; CLOCK Proteins; Eating; Energy Metabolism; Ethanolamines; Gene Expression Regulation; Goldfish; Homeostasis; Hypothalamus; Injections, Intraperitoneal; Leptin; Lipid Metabolism; Liver; Locomotion; Palmitic Acids; Peroxisome Proliferator-Activated Receptors; Weight Gain

Obesity is a worldwide health problem. Semaphorins are involved in axonal guidance; however, the role of secretory semaphorin 3G (SEMA3G) in regulating adipocyte differentiation remains unclear. Microarray analysis showed that the SEMA3G gene was upregulated in an in vitro model of adipogenesis. In this study, SEMA3G was highly expressed in the white adipose tissue and liver. Analysis of 3T3-L1 cell and primary mouse preadipocyte differentiation showed that SEMA3G mRNA and protein levels were increased during the middle stage of cell development. In vitro experiments also showed that adipocyte differentiation was promoted by SEMA3G; however, SEMA3G inhibition using a recombinant lentiviral vector expressing a specific shRNA showed the opposite results. Mice were fed a chow or high-fat diet (HFD); knockdown of SEMA3G was found to inhibit weight gain, reduce fat mass in the tissues, prevent lipogenesis in the liver tissue, reduce insulin resistance and ameliorate glucose tolerance in HFD mice. Additionally, the effect of SEMA3G on HFD-induced obesity was activated through PI3K/Akt/GSK3β signaling in the adipose tissue and the AMPK/SREBP-1c pathway in the liver. Moreover, the plasma concentrations of SEMA3G and leptin were measured in 20 obese and 20 non-obese human subjects. Both proteins were increased in obese subjects, who also exhibited a lower level of adiponectin and presented with insulin resistance. In summary, we demonstrated that SEMA3G is an adipokine essential for adipogenesis, lipogenesis, and insulin resistance and is associated with obesity. SEMA3G inhibition may, therefore, be useful for treating diet-induced obesity and its complications.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adult; Animals; Cell Differentiation; Diet, High-Fat; Disease Models, Animal; Female; Gene Knockdown Techniques; Humans; Insulin Resistance; Leptin; Lipogenesis; Male; Mice; Obesity; Semaphorins; Weight Gain

Topics: Brain; Humans; Janus Kinase 2; Leptin; Nitriles; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Signal Transduction; STAT3 Transcription Factor; Weight Gain

Topics: Animals; Blood Glucose; Diet, High-Fat; Drugs, Chinese Herbal; Humans; Insulin; Leptin; Lipids; Magnesium; Metabolic Syndrome; Oxidative Stress; Rats; Salvia miltiorrhiza; Weight Gain; Zinc

Topics: Brain; Humans; Janus Kinase 2; Leptin; Nitriles; Pyrazoles; Pyrimidines; STAT3 Transcription Factor; Weight Gain

Epidemiological evidence indicates that breastfeeding provides protection against development of overweight/obesity. Nonetheless, a small subgroup of infants undergo excessive weight gain during exclusive breastfeeding, a phenomenon that remains unexplained. Breast milk contains both gut-seeding microbes and substrates for microbial growth in the gut of infants, and a large body of evidence suggests a role for gut microbes in host metabolism. Based on the recently established SKOT III cohort, we investigated the role of the infant gut microbiota in excessive infant weight gain during breastfeeding, including 30 exclusively breastfed infants, 13 of which exhibited excessive weight gain and 17 controls which exhibited normal weight gain during infancy. Infants undergoing excessive weight gain during breastfeeding had a reduced abundance of gut Enterococcus as compared with that observed in the controls. Within the complete cohort, Enterococcus abundance correlated inversely with age/gender-adjusted body-weight, body-mass index and waist circumference, body fat and levels of plasma leptin. The reduced abundance of Enterococcus in infants with excessive weight gain was coupled to a lower content of Enterococcus in breast milk samples of their mothers than seen for mothers in the control group. Together, this suggests that lack of breast milk-derived gut-seeding Enterococci may contribute to excessive weight gain in breastfed infants.

Topics: Breast Feeding; Enterococcus; Female; Humans; Infant; Leptin; Milk, Human; Obesity; Weight Gain

Diet-induced obesity (DIO) has been shown to increase DNA methyltransferases (DNMTs) expression and DNMTs binding at obesity-associated genes. Natural compounds have the potential to reverse obesity-associated gene expression via the regulation of DNA methylation. The objective of this study was to determine the effect of health promoting compounds of flaxseed on DNMTs and obesity-associated gene expression and weight gain. Sixty C57BL/6J male mice were randomly assigned into one of the following diet groups and fed for eight weeks: 45% kcal fat; 45% kcal fat+10% whole flaxseed; 45% kcal fat+6% defatted flaxseed; 45% kcal fat+4% flaxseed oil; and 16% kcal fat. DNMT1, DNMT3a, DNMT3b, leptin, and peroxisome proliferator-activated receptor (PPAR)-α expressions in adipose and muscle tissues were determined by real-time PCR. The health promoting compounds of flaxseed affected selected gene expression and attenuated weight gain. Further research is needed to identify the specific mechanisms modulating leptin or PPAR-α expression during DIO development.

Topics: Adipose Tissue; Animals; Diet, High-Fat; Flax; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Weight Gain

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

Liver kinase B1 (LKB1) is a serine/threonine kinase. Although many biological functions of LKB1 have been identified, the role of hypothalamic LKB1 in the regulation of central energy metabolism and susceptibility to obesity is unknown. Therefore, we constructed POMC neuron-specific LKB1 knockout mice (PomcLkb1 KO) and studied it at the physiological, morphological, and molecular biology levels.. Eight-week-old male PomcLkb1 KO mice and their littermates were fed a standard chow fat diet (CFD) or a high-fat diet (HFD) for 3 months. Body weight and food intake were monitored. Dual-energy X-ray absorptiometry was used to measure the fat mass and lean mass. Glucose and insulin tolerance tests and serum biochemical markers were evaluated in the experimental mice. In addition, the levels of peripheral lipogenesis genes and central energy metabolism were measured.. PomcLkb1 KO mice did not exhibit impairments under normal physiological conditions. After HFD intervention, the metabolic phenotype of the PomcLkb1 KO mice changed, manifesting as increased food intake and an enhanced obesity phenotype. More seriously, PomcLkb1 KO mice showed increased leptin resistance, worsened hypothalamic inflammation and reduced POMC neuronal expression.. We provide evidence that LKB1 in POMC neurons plays a significant role in regulating energy homeostasis. LKB1 in POMC neurons emerges as a target for therapeutic intervention against HFD-induced obesity and metabolic diseases.

Topics: Adipose Tissue; AMP-Activated Protein Kinases; Animals; Diet, High-Fat; Epididymis; Feeding Behavior; Gene Deletion; Gene Expression Regulation; Glucose; Hypothalamus; Inflammation; Leptin; Liver; Male; Mice, Inbred C57BL; Mice, Knockout; Neurons; NF-kappa B; Obesity; Pro-Opiomelanocortin; Protein Serine-Threonine Kinases; Weight Gain

Maintaining energy homeostasis requires coordinating physiology and behavior both on an acute timescale to adapt to rapid fluctuations in caloric intake and on a chronic timescale to regulate body composition. Hypothalamic agouti-related peptide (AgRP)-expressing neurons are acutely activated by caloric need, and this acute activation promotes increased food intake and decreased energy expenditure. On a longer timescale, AgRP neurons exhibit chronic hyperactivity under conditions of obesity and high dietary fat consumption, likely due to leptin resistance; however, the behavioral and metabolic effects of chronic AgRP neuronal hyperactivity remain unexplored. Here, we use chemogenetics to manipulate G

Topics: Adiposity; Agouti-Related Protein; Animals; Body Weight; Caloric Restriction; Eating; Energy Intake; Energy Metabolism; Female; GTP-Binding Protein alpha Subunits, Gq-G11; Homeostasis; Hypothalamus; Leptin; Male; Mice; Mice, Inbred C57BL; Neurons; Obesity; Signal Transduction; Weight Gain

Overfeeding and rapid weight gain during early life are risk factors for the development of obesity in adulthood. This metabolic malprogramming may be mediated by endocrine disturbances during critical periods of development. Cholecystokinin (CCK) acts on the central nervous system by elevating thermogenesis and the activity of anorectic neurons, modulating overall energy balance. Therefore, we tested the hypothesis that postnatal overfeeding impaired CCK effects. Pups were raised in either a litter of three (neonatal overnutrition/small litter group) or 12 (controls/normal litter group) pups per dam to study the effects of postnatal overfeeding on the central and peripheral CCK systems in adulthood. Rats raised in small litters became overweight during lactation and remained overweight as adults, with increased adiposity and plasma levels of lipids, glucose, insulin, and leptin. Neonatally over-nourished rats showed attenuation of gastric emptying and anorexigenic response to CCK, suggesting that offspring from the SL group may present CCK resistance as adult male rats. Consistent with this idea, overweight rats displayed impaired central response in c-Fos immunoreactivity on the nucleus tractus solitarius, area postrema, paraventricular nucleus, central amygdala, arcuate nucleus, and dorsomedial hypothalamus in response to peripheral CCK at adulthood. The small litter group of adult male rats also exhibited reduced norepinephrine- and CCK-stimulated thermogenesis. Unresponsiveness to the effects of CCK may contribute to overweight and metabolic dysfunctions observed in postnatally over-nourished adult rats. Thus, the involvement of an impaired CCK system, among other neurohormonal failures, may contribute to the development of obesity.

Topics: Adipose Tissue; Adiposity; Animals; Animals, Newborn; Brain Mapping; Central Nervous System; Cholecystokinin; Endocrine System; Energy Metabolism; Female; Gastric Emptying; Glucose; Homeostasis; Hypothalamus; Leptin; Lipids; Male; Obesity; Overnutrition; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Thermogenesis; Weight Gain

The prevalence of adolescent obesity has increased dramatically, becoming a serious public health concern. While previous evidence suggests that in utero- and early postnatal overnutrition increases adult-onset obesity risk, the neurobiological mechanisms underlying this outcome are not well understood. Non-neuronal cells play an underestimated role in the physiological responses to metabolic/nutrient signals. Hypothalamic glial-mediated inflammation is now considered a contributing factor in the development and perpetuation of obesity; however, attention on the role of gliosis and microglia activation in other nuclei is still needed.. Here, we demonstrate that early life consumption of high-fat/sucrose diet (HFSD) is sufficient to increase offspring body weight, hyperleptinemia and potentially maladaptive cytoarchitectural changes in the brainstem dorsal-vagal-complex (DVC), an essential energy balance processing hub, across postnatal development. Our data demonstrate that pre- and postnatal consumption of HFSD result in increased body weight, hyperleptinemia and dramatically affects the non-neuronal landscape, and therefore the plasticity of the DVC in the developing offspring.. Current findings are very provocative, considering the importance of the DVC in appetite regulation, suggesting that HFSD-consumption during early life may contribute to subsequent obesity risk via DVC cytoarchitectural changes.

Topics: Animals; Body Weight; Brain Stem; Diet, High-Fat; Dietary Sucrose; Female; Glucagon-Like Peptide 1; Insulin; Leptin; Male; Maternal Nutritional Physiological Phenomena; Neuronal Plasticity; Obesity; Overnutrition; Rats; Rats, Sprague-Dawley; Weight Gain

Social contact deficit is considered a stressful circumstance associated with various neural, hormonal, genetic, immune, and behavioral effects. A growing body of clinical and basic science evidence suggests that social isolation is linked to a higher risk of various neurological, cardiovascular, and metabolic diseases, including hypertension, diabetes mellitus, and obesity. However, the impact of the deficit of social interaction on kidney function is not well established. The Dahl salt-sensitive (SS) rat is a classical model of salt-induced hypertension and associated kidney injury. In this study, we investigated the effect of 30 days of social isolation (SI) on blood and urine electrolytes and metabolic, physiological, and behavioral parameters in adolescent male Dahl SS rats fed a normal 0.4% NaCl diet. SI rats demonstrated increased behavioral excitability compared with rats kept in groups. We also observed increased food consumption and a decrease in plasma leptin levels in the SI group without differences in water intake and weight gain compared with grouped animals. No changes in the level of blood and urine electrolytes, 24-h urine output, creatinine clearance, and albumin/creatinine ratio were identified between the SI and grouped rats. These findings indicate that 30 days of social isolation of adolescent Dahl SS rats affects metabolic parameters but has no apparent influence on kidney function.

Topics: Age Factors; Animals; Behavior, Animal; Biomarkers; Eating; Energy Metabolism; Kidney; Leptin; Male; Rats, Inbred Dahl; Social Isolation; Sodium Chloride, Dietary; Time Factors; Weight Gain

What is the central question of this study? Studies reported the efficacy of metformin as a promising drug for preventing or treating of metabolic diseases. Nutrient stresses during neonatal life increase long-term risk for cardiometabolic diseases. Can early metformin treatment prevent the malprogramming effects of early overfeeding? What is the main finding and its importance? Neonatal metformin treatment prevented early overfeeding-induced metabolic dysfunction in adult rats. Inhibition of early hyperinsulinaemia and adult hyperphagia might be associated with decreased metabolic disease risk in these animals. Therefore, interventions during infant development offer a key area for future research to identify potential strategies to prevent the long-term metabolic diseases. We suggest that metformin is a potential tool for intervention.. Given the need for studies investigating the possible long-term effects of metformin use at crucial stages of development, and taking into account the concept of metabolic programming, the present work aimed to evaluate whether early metformin treatment might program rats to resist the development of adult metabolic dysfunctions caused by overnutrition during the neonatal suckling phase. Wistar rats raised in small litters (SLs, three pups per dam) and normal litters (NLs, nine pups per dam) were used as models of early overfeeding and normal feeding, respectively. During the first 12 days of suckling, animals from SL and NL groups received metformin, whereas the controls received saline injections. Food intake and body weight were monitored from weaning until 90 days of age, when biometric and biochemical parameters were assessed. The metformin treatment decreased insulin concentrations in pups from SL groups, and as adults, these animals showed improvements in glucose tolerance, insulin sensitivity, body weight gain, white fat pad stores and food intake. Low-glucose insulinotrophic effects were observed in pancreatic islets from both NL and SL groups. These results indicate that early postnatal treatment with metformin inhibits early overfeeding-induced metabolic dysfunctions in adult rats.

Topics: Adipose Tissue, White; Animals; Animals, Newborn; Blood Glucose; Body Composition; Body Weight; Female; Insulin; Insulin Resistance; Islets of Langerhans; Leptin; Male; Metabolic Diseases; Metformin; Obesity; Overnutrition; Rats; Rats, Wistar; Weight Gain

Gestational complications, including preeclampsia and gestational diabetes, have long-term adverse consequences for offspring's metabolic and cardiovascular health. A low-grade systemic inflammatory response is likely mediating this. Here, we examine the consequences of LPS-induced gestational inflammation on offspring's health in adulthood. LPS was administered to pregnant C57Bl/6J mice on gestational day 10.5. Maternal plasma metabolomics showed oxidative stress, remaining for at least 5 days after LPS administration, likely mediating the consequences for the offspring. From weaning on, all offspring was fed a control diet; from 12 to 24 weeks of age, half of the offspring received a western-style diet (WSD). The combination of LPS-exposure and WSD resulted in hyperphagia and increased body weight and body fat mass in the female offspring. This was accompanied by changes in glucose tolerance, leptin and insulin levels and gene expression in liver and adipose tissue. In the hypothalamus, expression of genes involved in food intake regulation was slightly changed. We speculate that altered food intake behaviour is a result of dysregulation of hypothalamic signalling. Our results add to understanding of how maternal inflammation can mediate long-term health consequences for the offspring. This is relevant to many gestational complications with a pro-inflammatory reaction in place.

Topics: Adipose Tissue; Animals; Appetite Regulation; Diet, High-Fat; Female; Hyperphagia; Hypothalamus; Insulin; Leptin; Lipopolysaccharides; Liver; Maternal-Fetal Exchange; Mice, Inbred C57BL; Oxidative Stress; Pregnancy; Sex Characteristics; Weight Gain

Topics: Animals; Diet; Diet, High-Fat; Dietary Supplements; Dose-Response Relationship, Drug; Eating; Energy Metabolism; Female; Folic Acid; Gene Expression; Hypothalamus; Insulin Resistance; Lactation; Leptin; Parturition; Phenotype; Pregnancy; Rats; Rats, Wistar; Tetrahydrofolates; Weaning; Weight Gain

Obesity and weight gain in bipolar disorder (BD) have multifactorial underlying causes such as medication side effects, atypical depressive symptomatology, genetic variants, and disturbances in the neuro-endocrinal system. Therefore, we aim to explore the associations between food craving (FC), clinical parameters, psychotropic medication, and appetite-related hormones. In this cross-sectional investigation, 139 individuals with BD and 93 healthy controls (HC) completed the food craving inventory (FCI). In addition, blood samples (including leptin and acylated ghrelin) were analyzed and sociodemographic and anthropometric data were collected. Individuals with BD reported higher frequencies of total FC as well as craving for fat and fast food than HC. Additionally, we found a significant negative correlation between FC and ghrelin levels in BD. Smokers with BD reported significantly more craving for high fat foods than non-smokers. Age was significantly associated with FC independent of group. Individuals with BD taking olanzapine and quetiapine reported higher frequencies of craving for sweet food, while patients currently taking lithium reported less total FC compared to those without lithium therapy. Likewise, patients currently taking valproate reported less total FC and less craving for sweets than those not taking valproate. FC appears to be of clinical relevance in individuals with BD. Contrary to previous data, this does not seem to be a female phenomenon only and might encompass more than the specific craving for carbohydrates. Although due to the cross sectional design, causality cannot be determined, the association between depressive symptomatology and fast food craving warrants further research.

Topics: Acylation; Adult; Anthropometry; Appetite; Bipolar Disorder; Craving; Cross-Sectional Studies; Fast Foods; Female; Ghrelin; Hormones; Humans; Leptin; Male; Middle Aged; Non-Smokers; Obesity; Smokers; Valproic Acid; Weight Gain; Young Adult

Perturbations in postnatal leptin signaling have been associated with altered susceptibility to diet-induced obesity (DIO) under high-fat-diet (HFD), albeit with contradicting evidence. Previous studies have shown that alpha murine urokinase-type plasminogen activator (αMUPA) mice have a higher and longer postnatal leptin surge compared with their wild types (WTs) as well as lower body weight and food intake under regular diet (RD). Here we explored αMUPA's propensity for DIO and the effect of attenuating postnatal leptin signaling with leptin antagonist (LA) on energy homeostasis under both RD and HFD. Four-day-old αMUPA pups were treated on alternate days until postnatal day 18 with either vehicle or LA (10 or 20 mg·day

Topics: Animals; Animals, Newborn; Body Weight; Diet, High-Fat; Disease Susceptibility; Eating; Energy Metabolism; Female; Hyperinsulinism; Leptin; Mice; Obesity; Pregnancy; Receptors, Urokinase Plasminogen Activator; Signal Transduction; Species Specificity; Weight Gain

Obesity and associated metabolic comorbidities represent a growing public health problem. In this study, we demonstrate the use of a newly created fusion gene of exendin-4 and α1-antitrypsin to control obesity and obesity-associated metabolic disorders including insulin resistance, fatty liver and hyperglycemia. The fusion gene encodes a protein with exendin-4 peptide placed at the N-terminus of human α-1 antitrypsin, and is named EAT. Hydrodynamic transfer of the EAT gene to mice prevents high-fat diet-induced obesity, insulin resistance and fatty liver development. In diet-induced obese mice, expression of EAT gene induces weight loss, improves glucose homeostasis, and attenuates hepatic steatosis. In ob/ob mice, EAT gene transfer suppresses body weight gain, maintains metabolic homeostasis, and completely blocks fatty liver development. Six-month overexpression of the EAT fusion gene in healthy mice does not lead to any detectable toxicity. Mechanistic study reveals that the resulting metabolic benefits are achieved by a reduced food take and down-regulation of transcription of pivotal genes responsible for lipogenesis and lipid droplet formation in the liver and chronic inflammation in visceral fat. These results validate the feasibility of gene therapy in preventing and restoring metabolic homeostasis under diverse pathologic conditions, and provide evidence in support of a new strategy to control obesity and related metabolic diseases.

Topics: Adiposity; alpha 1-Antitrypsin; Animals; Anti-Obesity Agents; Diet, High-Fat; Exenatide; Gene Expression Regulation; Genetic Vectors; Glucose; Insulin Resistance; Leptin; Male; Mice, Inbred C57BL; Mice, Obese; Non-alcoholic Fatty Liver Disease; Obesity; Protein Engineering; Recombinant Fusion Proteins; Weight Gain

Dietary factors have significant effects on the brain, modulating mood, anxiety, motivation and cognition. To date, no attention has been paid to the consequences that the combination of ethanol (EtOH) and a high-fat diet (HFD) have on learning and mood disorders during adolescence. The aim of the present work was to evaluate the biochemical and behavioral consequences of ethanol binge drinking and an HFD consumption in adolescent mice.. Animals received either a standard diet or an HFD (ad libitum vs. binge pattern) in combination with ethanol binge drinking and were evaluated in anxiety and memory. The metabolic profile and gene expression of leptin receptors and clock genes were also evaluated.. Excessive white adipose tissue and an increase in plasma insulin and leptin levels were mainly observed in ad libitum HFD + EtOH mice. An upregulation of the Lepr gene expression in the prefrontal cortex and the hippocampus was also observed in ad libitum HFD groups. EtOH-induced impairment on spatial memory retrieval was absent in mice exposed to an HFD, although the aversive memory deficits persisted. Mice bingeing on an HFD only showed an anxiolytic profile, without other alterations. We also observed a mismatch between. Our results confirm the bidirectional influence that occurs between the composition and intake pattern of a HFD and ethanol consumption during adolescence, even when the metabolic, behavioral and chronobiological effects of this interaction are dissociated.

Topics: Adiposity; Animals; ARNTL Transcription Factors; Bulimia; CLOCK Proteins; Diet, High-Fat; Ethanol; Hippocampus; Learning; Leptin; Male; Mice; Mood Disorders; Prefrontal Cortex; Receptors, Leptin; Weight Gain

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipose Tissue; Allium; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation; Diet, High-Fat; Leptin; Lipogenesis; Lipolysis; Lipoprotein Lipase; Liver; Mice; Mice, Obese; Obesity; Phytotherapy; Plant Extracts; Sterol Esterase; Weight Gain

Early infant weight development influences metabolic regulation later in life. For the prevention of obesity and metabolic diseases, it is important to understand the underlying mechanisms in detail.. This study aims to examine the effects of maternal anthropometric, sociodemographic, and lifestyle factors on maternal and cord blood leptin levels at birth and on the development of body mass index (BMI) standard deviation scores (SDS) in offspring up to 1 year of age.. Seventy-six mother-child pairs were enrolled in this follow-up analysis in a cross-sectional design. Standardized questionnaires were used to collect information regarding maternal anthropometrics, lifestyle habits, and sociodemographic conditions, and newborn weight, or, rather, BMI-SDS, development during the first year of life.. Cord blood leptin (β = -0.222, p = 0.074), maternal leptin (β = 0.414, p = 0.001), and female sex of the offspring (β = 0.385, p = 0.003) explained 29.0% of the variance in BMI-SDS changes in the first year of life. Cord blood leptin was influenced by newborn sex (male; β = -0.220, p = 0.025) and maternal moderate-intensity physical activity in the third trimester (β = 0.265, p = 0.007, corr. R2 = 9.2%); maternal leptin was influenced by maternal prepregnancy BMI (β = 0.602, p < 0.001) and weight gain during pregnancy (β = 0.247, p = 0.004, corr. R2 = 35.5%).. Higher maternal and lower cord blood leptin levels are associated with a higher BMI-SDS increase during the first year of life. Maternal leptin is influenced by maternal BMI and weight gain during pregnancy, and cord blood leptin is influenced by maternal physical activity; therefore, it can be suggested that an active and healthy maternal lifestyle may play a pivotal and beneficial role in the offspring's weight development.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; Body Weight; Child Development; Cross-Sectional Studies; Female; Fetal Blood; Follow-Up Studies; Humans; Infant; Infant, Newborn; Leptin; Life Style; Male; Mothers; Obesity; Pregnancy; Reference Standards; Research Design; Weight Gain

This study was to investigate the degree of susceptibility to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), between the two mice inbred lines C57BL/6N (6N) and C57BL/6J (6J).. Four-week old male mice of 6N and 6J substrains (n = 8) were randomized to standard diet (SD) group or high fat (HF) diet group. At the age of 13-week, all two groups of mice were subjected to either air or IH (IH30; thirty hypoxic events per hour) for one week.. All mice fed with HF diet exhibited obesity with more body weight and fat mass (percentage to body weight) gain. IH reduced serum LDL, HDL and total cholesterol levels in lean 6J mice. In obese mice, IH lowered obesity-induced serum total cholesterol level in 6J substrain but raised further in 6N substrain. Furthermore, IH caused elevation of serum FFA and MDA levels, and pro-inflammatory cytokines MCP-1 and IL-6 levels in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of lean 6J but not lean 6N mice. There was reduced number of adipocytes and elevation of macrophages in SAT and VAT of HF-induced obese mice of both substrains. IH led to increased number of adipocytes and macrophages in SAT of lean 6J mice.. The genetic difference between 6N and 6J mice may have direct impact on metabolic and inflammatory responses after IH. Therefore, attention must be given for the selection of C57BL mice substrains in the experimental IH-exposed mouse model.

Topics: Adiponectin; Animals; Biomarkers; Blood Glucose; Diet, High-Fat; Disease Models, Animal; Hypoxia; Inflammation; Inflammation Mediators; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Thinness; Weight Gain

Neonatal anoxia may cause neurological injuries, behavioral alterations and changes in somatic growth. Somatic developmental changes suggest a possible effect of anoxia on energy metabolism and/or feeding behavior. Short-term effects of oxygen deficit on energy homeostasis have been described. In contrast, just a few studies report long-term effects. This study investigated the effects of neonatal anoxia on energy metabolism and somatic development at adulthood of males and females Wistar rats.. Male (m) and female (f) rats were exposed, on postnatal day 2 (P2), to either 25-min of Anoxia or Control treatment. At P34 part of the subjects of each group was fasted for 18 h, refeed for 1 h and then perfused 30 min later, at P35; the remaining subjects were submitted to these treatments at P94 and perfused at P95. Therefore, there were 8 groups: AmP35, AmP95, AfP35, AfP95, CmP35, CmP95, CfP35 and CfP95. For subjects perfused at P95, body weight and food intake were recorded up to P90. For subjects perfused at P35 and P95, glycemia, leptin and insulin were assessed after fasting and refeed. After perfusion the encephalon and pancreas were collected for Fos immunohistochemistry and Hematoxylin-Eosin stain analyses.. Even though neonatal anoxia did not interfere with regular food intake, it reduced body weight gain along growing in both male and female subjects as compared to the corresponding controls. At P35 neonatal anoxia decreased post-prandial glycemia and increased insulin. While at P95 neonatal anoxia altered the pancreatic histomorphology and increased post-fasting weight loss, decreasing leptin, insulin and glycemia secretion, as well Fos immunoreactivity (IR) in ARC.. Neonatal anoxia impairs long-term energy metabolism and somatic development in Wistar rats, with differences related to sex and age.

Topics: Animals; Animals, Newborn; Blood Glucose; Energy Metabolism; Fasting; Female; Hypoxia; Insulin; Leptin; Male; Rats; Rats, Wistar; Weight Gain

Topics: Adipose Tissue; Animals; Brain; Diet; Disease Models, Animal; Eating; Endoplasmic Reticulum Stress; Inflammation; Leptin; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Obese; NF-kappa B; Obesity; Phaeophyceae; Phloroglucinol; Pyrogallol; RAW 264.7 Cells; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Toll-Like Receptor 4; Weight Gain

Estrogens protect against diet-induced obesity in women and female rodents. For example, a lack of estrogens in postmenopausal women is associated with an increased risk of weight gain, cardiovascular diseases, low-grade inflammation, and cancer. Estrogens act with leptin to regulate energy homeostasis in females. Leptin-deficient mice (ob/ob) exhibit morbid obesity and insulin resistance. The gut microbiome is also critical in regulating metabolism. The present study investigates whether estrogens and leptin modulate gut microbiota in ovariectomized ob/ob (obese) or heterozygote (lean) mice fed high-fat diet (HFD) that received either 17β-Estradiol (E2) or vehicle implants. E2 attenuated weight gain in both genotypes. Moreover, both obesity (ob/ob mice) and E2 were associated with reduced gut microbial diversity. ob/ob mice exhibited lower species richness than control mice, while E2-treated mice had reduced evenness compared with vehicle mice. Regarding taxa, E2 was associated with an increased abundance of the S24-7 family, while leptin was associated with increases in Coriobacteriaceae, Clostridium and Lactobacillus. Some taxa were affected by both E2 and leptin, suggesting these hormones alter gut microbiota of HFD-fed female mice. Understanding the role of E2 and leptin in regulating gut microbiota will provide important insights into hormone-dependent metabolic disorders in women.

Topics: Animals; Diet, High-Fat; Estradiol; Feeding Behavior; Female; Gastrointestinal Microbiome; Insulin Resistance; Leptin; Mice; Mice, Obese; Weight Gain

Adiponectin and leptin are involved in appetite control and body weight regulation. We aimed to evaluate the relationship between breast milk adipokine levels and short-term growth of preterm and term infants. Thirty-one preterm (median=35.3 weeks) and 34 term (median=38.7 weeks) infants were enrolled. Enzyme-linked immunosorbent assay was used to detect adipokines in mature milk. Infant growth was followed during the first 3 months. Although weight gain in the first month was insufficient, positive linear growth was observed in the following months for preterm infants, while term infants had positive steady linear growth. The median level of adipokines was found to be higher in preterm infants (P>0.05). Adiponectin showed significant negative correlations with some anthropometric measurements of term infants. However, in preterm infants, adiponectin was negatively correlated with length increment and positively correlated with body mass index (BMI) increment in the second-third month. In addition, leptin was negatively associated with the head circumference at birth in preterm infants and the triceps skinfold thickness increment in the first-second month term infants (P<0.05). In linear regression models, while gestational age, adiponectin and leptin were not related, maternal age and pre-pregnancy BMI had effects on body weight increment in 0-1 months (P<0.05). In conclusion, adiponectin may affect short-term growth, while leptin has no important effect. It would be beneficial to carry out longitudinal studies to evaluate the effects of these adipokines on the growth of infants.

Topics: Adiponectin; Adolescent; Adult; Body Mass Index; Body Weight; Breast Feeding; Female; Follow-Up Studies; Gestational Age; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Leptin; Linear Models; Maternal Age; Milk, Human; Models, Biological; Pregnancy; Weight Gain; Young Adult

Obesity has reached global epidemic proportions and is associated with serious medical comorbidities and economic consequences. In this preclinical study, we characterized how the palatable diet changed food intake pattern, caloric intake, metabolic profile and hormone levels. We also evaluated the expression of dopamine D2 receptors in the rat striatum.. Male Wistar rats were fed with either high-fat or high-sucrose diet for 5 weeks according to different feeding regimes: ad libitum access or scheduled for a 2-h period each day without caloric restriction during the remainder of the day.. Both diets resulted in an enhancement in caloric intake and total body weight. Post-meal data showed that high-fat diet increased cholesterol, triglycerides and glucose concentrations. Animals fed on high sucrose diet were only hyperglycemic. High-fat diet schedules resulted in the enhancement of leptin concentrations, while increases in blood levels of ghrelin were noted after intermitted high-fat or continuous high-sucrose diet. Finally, we report that only ad libitum high-sucrose evoked a significant enhancement of the dopamine D2 receptor protein level and a reduction in the D2 mRNA and receptor affinity in the rat striatum. Independently of the diet type, a similar reduction in dopamine D2 receptor affinity (decrease in KD value) was found in the striatum of rats with intermittent food access.. The findings provide a better understanding of eating disorders and indicate that diet composition leading to obesity induces distinct changes in dopamine D2 receptor signaling in the striatum.

Topics: Animal Nutritional Physiological Phenomena; Animals; Biomarkers; Blood Glucose; Cholesterol; Corpus Striatum; Diet, High-Fat; Dietary Sucrose; Disease Models, Animal; Energy Intake; Energy Metabolism; Feeding Behavior; Ghrelin; Hormones; Leptin; Male; Nutritional Status; Obesity; Rats, Wistar; Receptors, Dopamine D2; Signal Transduction; Time Factors; Triglycerides; Weight Gain

To determine the efficacy of Corchorus olitorius (C. olitorius) leaf extract in the prevention of metabolic syndrome induced in rats by high-fat diet (HFD) and compare it with that of orlistat.. Phytochemical analysis was performed. Effect of orlistat and C. olitorius extract on lipase activity and acute food intake were investigated. Body weight, biochemical parameters and histopathological examination were demonstrated.. Corchorus olitorius extract inhibited the pancreatic lipase activity, but orlistat was more potent. Cumulative food intake has not changed by the tested agents. In obese rats, C. olitorius or orlistat significantly decreased weight gain and visceral white adipose tissue. They exhibited a significant reduction in serum glucose, total cholesterol, triglycerides, low density lipoprotein cholesterol, free fatty acids, IL-1β, tumour necrosis factor-α (TNF-α), insulin and leptin levels of obese rat groups while high density lipoprotein cholesterol and adiponectin levels were significantly increased by them. Histopathological examination of the liver revealed that C. olitorius was more effective than orlistat in the alleviating of steatosis and adipocyte hypertrophy shown in obese control rats.. Corchorus olitorius is effective as orlistat in preventing obesity, hyperlipidaemia, steatosis and insulin resistance. These actions may be mediated by inhibiting of lipase activity, TNF-α, IL-1β and leptin resistance along with increasing of adiponectin.

Topics: Adiponectin; Animals; Anti-Obesity Agents; Corchorus; Cytokines; Diet, High-Fat; Hyperlipidemias; Insulin; Insulin Resistance; Leptin; Lipase; Male; Metabolic Syndrome; Obesity; Orlistat; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Weight Gain

A large part of the daily intake of children in the U.S. consists of snacks, with the average child consuming three snacks per day. Despite this, little research has been conducted to determine the metabolic and behavioral effects of snacking. Using a developing female rat model, our studies aimed to determine the effects of snacking during development before the protective effects of estrogen on weight gain would be relevant. Additionally, to determine if snack composition is important, we created one healthy and one unhealthy snacking group provided with chow and three snacks each in addition to a chow-only group. We found that both snacking groups experienced increased weight gain, elevated abdominal fat pad mass, prolonged leptin resistance into adulthood, and insulin insensitivity that was not observed in their non-snacking counterparts. These physiological differences were measured despite both snacking groups having a similar caloric intake as the chow-only group throughout the study. In addition to physiological changes, both snacking groups showed a preference for snacks over chow and ate more often during the inactive light phase than typical for rats, with the unhealthy snacking group presenting this behavioral change earlier than the healthy snacking group. Our results suggest that constant access to palatable snacks, which is often the case for children in western countries, alters feeding behaviors in relation to food choice and time of day when eating occurs. Snacking during development seemed to promote signs of metabolic syndrome in adulthood even when excess caloric intake was not observed. Our work further suggests that development is a vulnerable time for palatable snack presentation when prepubertal females lack the protective effects of estrogen and exhibit reduced leptin feedback on food intake. Thus snacking from weaning onward could be a contributor to the current childhood obesity crisis.

Topics: Abdominal Fat; Animals; Body Composition; Eating; Estrogens; Feeding Behavior; Female; Food Preferences; Glucose Tolerance Test; Insulin Resistance; Leptin; Rats; Rats, Long-Evans; Snacks; Weight Gain

L-Lysine (Lys) is a popular additive in foods, but the physiological effects of excess Lys supplementation are poorly understood and upper limits of safe intake have not been established. The objectives of this study were to examine the effects of dietary supplementation with increasing amounts of Lys on body weight (BW), food intake, and various blood hematological and biochemical parameters in rats. Male Sprague-Dawley rats at 10 weeks of age were assigned to ten diet groups (eight rats/group) and fed diets containing either 7% or 20% casein and supplemented with either 0% (Control), 1.5%, 3%, 6% Lys, or 6% Lys + 3% arginine for 1 week. Rats fed 7% casein with ≥ 1.5% Lys supplementation had lower serum albumin and leptin and higher LDL cholesterol (LDLC), ratios of total cholesterol (TC):HDL cholesterol (HDLC) and LDLC:HDLC than those fed 7% casein Control diet (P < 0.05). Rats fed 7% casein diet supplemented with 3% Lys diet had lower BW gain, food intake, serum alkaline phosphatase activity, and increased mean corpuscular hemoglobin concentration, blood urea nitrogen and serum pancreatic polypeptide compared to rats fed the Control diet (P < 0.05). Addition of 6% Lys in 7% casein caused significant BW loss (P < 0.001) and altered additional parameters. Addition of 6% Lys in a 20% casein diet reduced BW gain and food intake and altered numerous parameters. Arg supplementation normalized many of the endpoints changed by Lys. Collectively, these results show that Lys supplementation affects BW, food intake and a number of hematological and biochemical parameters. These effects of Lys supplementation were confined primarily in diets with lower levels of dietary protein. In the context of a low protein diet (7% casein), levels of Lys supplementation ≥ 1.5% may exert adverse health effects in rats.

Topics: Animal Feed; Animals; Body Composition; Body Weight; Caseins; Cholesterol, HDL; Cholesterol, LDL; Diet; Dietary Supplements; Eating; Leptin; Lysine; Male; Rats; Rats, Sprague-Dawley; Serum Albumin; Weight Gain

Ethanolic extract of leaves of Morus alba L. (M. alba), known as white mulberry, was orally administered (100 mg/kg b.wt) for 8 weeks to female Wistar rats that were fed a high-cholesterol diet (HCD), to investigate the potential of M. alba leaves in attenuation of obesity, dyslipidemia, insulin resistance, and deficits in mood, cognitive as well as motor activity that are linked to the adipokines secretions of visceral adipose tissue. Results showed that M. alba diminished body weight gain, hypercholesterolemia, hypertriglyceridemia, atherogenic (AI) & coronary artery indices (CRI), and ameliorated glucose level and insulin resistance index in rats on HCD, compared with untreated HCD rats. Moreover, M. alba administration significantly decreased serum leptin and resistin contents as well as their mRNA expression in visceral adipose tissue, but significantly increased serum adiponectin level, and its mRNA expression in visceral adipose tissue in rats fed on HCD, compared to those in untreated HCD group. Regarding behavioral alterations, M. alba attenuated motor deficit, declined memory, depression and anxiety-like behavior, as well in rats on HCD, compared to that noticed in untreated HCD rats. The current data showed that serum leptin and resistin showed a positive correlation with and body weight gain, triglycerides (TG), AI as well as CRI, but showed a negative correlation with exploration, declined memory, depression- and anxiety-like behavior. Conversely, serum adiponectin showed a negative correlation with and body weight gain, TG, AI as well as CRI, but showed a positive correlation with locomotor activity, exploration, declined memory, and depression- and anxiety-like behavior. In conclusion, M. alba leaves supplementation could attenuate adiposity, insulin resistance behavioral deficits via down-regulation of regulation of gene expression of leptin, resistin, but up-regulation of adiponectin gene expression in the visceral adipose tissue of rats fed a high-cholesterol diet.

Topics: Adiponectin; Adiposity; Animals; Behavior, Animal; Blood Glucose; Cholesterol, Dietary; Female; Gene Expression; Hyperlipidemias; Insulin Resistance; Leptin; Morus; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Resistin; Weight Gain

Weight gain is a common adverse effect of lithium augmentation. Previous studies indicate an impact of genetic variants at the leptin gene on weight gain as a consequence of psychopharmacological treatment. The primary aim of our study was to identify variants at the leptin locus that might predict lithium-induced weight gain. The secondary aim was to investigate if these variants modulate leptin levels. In 180 patients with acute major depressive disorder, body mass index was measured before and after 4 weeks of lithium augmentation, in a subsample also after 4 and/or 7 months. In a subsample of 89 patients, leptin serum concentrations were measured before and during lithium augmentation. We used linear mixed model analyzes to investigate the effects of 2 polymorphisms at the leptin locus (rs4731426 and rs7799039, employing the respective proxy SNPs rs2278815 and rs10487506) on changes in body mass index and leptin levels. For both polymorphisms, which are in high linkage disequilibrium, body mass index was significantly lower in homozygous A-allele carriers than in carriers of other genotypes at baseline. Over the follow-up period, body mass index increased less in homozygous A-allele carriers of rs4731426 than in carriers of other genotypes. This was not the case for rs7799039. Neither polymorphism modulated leptin protein expression. Our study strongly supports the hypothesis that genetic variability at the leptin locus is involved in lithium augmentation-associated weight gain in major depressive disorder. Furthermore, Genotype-Tissue Expression data provide strong evidence that rs4731426 influences the expression of leptin messenger ribonucleic acid in fibroblasts.

Topics: Adult; Depressive Disorder, Major; Female; Genotype; Humans; Ideal Body Weight; Leptin; Lithium; Male; Middle Aged; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Retrospective Studies; Weight Gain

Ectopic fat deposition is associated with increased tissue production of ceramides. Recent genetic mouse studies suggest that specific sphingolipid C16:0 ceramide produced by ceramide synthase 6 (CerS6) plays an important role in the development of insulin resistance. However, the therapeutic potential of CerS6 inhibition not been demonstrated. Therefore, we pharmacologically investigated the selective ablation of CerS6 using antisense oligonucleotides (ASO) in obese insulin resistance animal models.. We utilized ASO as therapeutic modality, CerS6 ASO molecules designed and synthesized were initially screened for in-vitro knock-down (KD) potency and cytotoxicity. ASOs with >85% inhibition of CerS6 mRNA were selected for further investigations. Most promising ASOs verified for in-vivo KD efficacy in healthy mice. CerS6 ASO (AAGATGAGCCGCACC) was found most active with hepatic reduction of CerS6 mRNA expression. Prior to longitudinal metabolic studies, we performed a dose titration target engagement analysis with CerS6 ASO in healthy mice to select the optimal dose. Next, we utilized leptin deficiency ob/ob and high fat diet (HFD) induced obese mouse models for pharmacological efficacy study.. CerS6 expression were significantly elevated in the liver and brown adipose, this was correlated with significantly elevated C16:0 ceramide concentrations in plasma and liver. Treatment with CerS6 ASO selectively reduced CerS6 expression by ∼90% predominantly in the liver and this CerS6 KD resulted in a significant reduction of C16:0 ceramide by about 50% in both liver and plasma. CerS6 KD resulted in lower body weight gain and accompanied by a significant reduction in whole body fat and fed/fasted blood glucose levels (1% reduction in HbA1c). Moreover, ASO-mediated CerS6 KD significantly improved oral glucose tolerance (during oGTT) and mice displayed improved insulin sensitivity. Thus, CerS6 appear to play an important role in the development of obesity and insulin resistance.. Our investigations identified specific and selective therapeutic valid ASO for CerS6 ablation in in-vivo. CerS6 should specifically be targeted for the reduction of C16:0 ceramides, that results in amelioration of insulin resistance, hyperglycemia and obesity. CerS6 mediated C16:0 ceramide reduction could be a potentially attractive target for the treatment of insulin resistance, obesity and type 2 diabetes.

Topics: Adipose Tissue, Brown; Animals; Blood Glucose; Ceramides; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Gene Knockdown Techniques; Hep G2 Cells; Humans; Insulin Resistance; Leptin; Liver; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Oligonucleotides, Antisense; Sphingosine N-Acyltransferase; Thionucleotides; Weight Gain

Stabilin-1 (STAB1) is a scavenger receptor expressed on alternatively activated macrophages and sinusoidal endothelial cells. Its ligands include oxidized low-density lipoprotein (LDL) and the extracellular matrix glycoprotein SPARC and it is present in both human and murine atherosclerotic lesions. We aimed to investigate the effect of specific deletion of STAB1 in bone marrow-derived cells, including macrophages on atherosclerotic lesion formation in mice.. Lethally irradiated hypercholesterolemic LDL receptor knockout mice received either wildtype (WT) or STAB1 knockout (STAB1 KO) bone marrow. Bone marrow transplanted mice were fed a Western-type diet for 9 weeks to induce atherosclerotic lesion formation.. Interestingly, LDL receptor knockout mice reconstituted with STAB1 KO bone marrow showed increased body weight gain (two-way ANOVA: p < 0.001) and larger white adipocyte cell sizes (43% increase in cell area; p < 0.05) as compared to WT bone marrow transplanted mice, which correlated positively (r = 0.82; p < 0.001). This was paralleled by a significant increase in white adipose tissue relative mRNA expression levels of the adipokine leptin (+94% p < 0.05). Despite these changes, no differences in serum lipid levels, the extent of in vivo macrophage foam cell formation or circulating leukocyte concentrations were observed. Moreover, the size and composition of atherosclerotic lesions was not different between the two experimental groups.. Bone marrow-specific Stabilin-1 deletion does not affect the susceptibility for atherosclerosis in mice. However, the increased body weight gain and adipocyte cell size highlight a potential role for leukocyte STAB1 in the development of metabolic disorders.

Topics: Adipocytes, White; Adipose Tissue, White; Animals; Aortic Diseases; Atherosclerosis; Cell Adhesion Molecules, Neuronal; Diet, Western; Disease Models, Animal; Foam Cells; Hypercholesterolemia; Leptin; Male; Mice, Inbred C57BL; Mice, Knockout; Plaque, Atherosclerotic; Receptors, LDL; Weight Gain

Antidepressants are among the most-prescribed class of drugs in the world and though weight gain is a common outcome of antidepressant treatment, that effect is not well understood. We employed an animal model comprised of 2 weeks of chronic restraint stress with antidepressant treatment, followed by diet-induced obesity. We showed that short-term antidepressant treatment had long-lasting effects, not only leading to weight gain, but also enhancing trabecular and cortical bone features in rats; therefore, weight gain in this model was different from that of the classic diet-induced obesity. Late in the post-restraint recovery period, antidepressant-treated animals were significantly heavier and had better bone features than saline-treated controls, when assessed in the distal femoral metaphysis. The propensity to gain weight might have influenced the rate of catch-up growth and bone allometry, as heavier animals treated with fluoxetine also had enhanced bone features when compared to non-stressed animals. Therefore, short-term antidepressant treatment ameliorated the long-term effects of stress on body growth and bone. Growth and bone structural features were associated with leptin levels, and the interaction between leptin levels and antidepressant was significant for bone mineral content, suggesting that short-term antidepressants in the context of long-term diet-induced obesity modified the role of leptin in bone formation. To our knowledge this is the first study reporting that short-term antidepressant treatment has long-lasting effects in restoring the effects of chronic stress in body weight and bone formation. Our findings may be relevant to the understanding and treatment of osteoporosis, a condition of increasing prevalence due to the aging population.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Bone Density; Disease Models, Animal; Fluoxetine; Leptin; Male; Obesity; Rats; Rats, Sprague-Dawley; Stress, Psychological; Weight Gain

Obese children grow faster than their normal-weight peers. Insulin resistance and hyperinsulinemia have been associated with obesity-related growth acceleration. To determine whether obesity-associated hyperinsulinemia promotes bone growth by activating the insulin receptor in the growth plate, we generated

Topics: 3-Hydroxybutyric Acid; Animals; Apoptosis; Bone Development; Cell Differentiation; Cell Proliferation; Cells, Cultured; Chondrocytes; Diet, High-Fat; Gene Deletion; Growth Plate; Hormones; Insulin; Insulin-Like Growth Factor I; Leptin; Metabolome; Mice, Knockout; Organ Specificity; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptor, Insulin; Signal Transduction; Tibia; Weight Gain

Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal%; carbohydrate, 52 kcal%; fat, 32 kcal%) that provided methionine at control (Con; 0.86% methionine) or low levels (0.17%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet-induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits

Topics: Adiponectin; Adipose Tissue; Animal Feed; Animals; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Diet; Fibroblast Growth Factors; Humans; Hyperglycemia; Insulin; Leptin; Liver; Male; Methionine; Mice; Mice, Obese; Vegans; Weight Gain

Resistin promotes hypothalamic neuroinflammation and insulin resistance through Toll like receptor 4 (TLR4), this hormone is thought to be a link between obesity and insulin-resistance. Indeed, resistin plasma levels are higher in obese and insulin resistant subjects. However, the impact of maternal resistin on the predisposition of offspring to hypothalamic neuroinflammation is unknown. Here, female mice were treated with resistin during gestation/lactation periods, then hypothalamic neuroinflammation was investigated in male offspring at p28 and p90. At p28, resistin increased the expression of inflammation markers (IL6, TNFα and NFκB) and TLR4 in the hypothalamus and decreased both hypothalamic insulin and leptin receptors' expression. The hypothalamic up-regulation IL6, TNFα and TLR4 was sustained until p90 promoting most likely hypothalamic inflammation. Maternal resistin also increased IL6 and TNFα in the adipose tissue of offspring at p90 associated with a higher body weight gain. In contrast, liver and muscle were not affected. These findings reveal that the augmentation of maternal resistin during gestation and lactation promotes hypothalamic and adipose tissue inflammation of offspring as evidenced by sustained increase of inflammation markers from weaning to adulthood. Thus, maternal resistin programs offspring hypothalamic and adipose tissue inflammation predisposing then offspring to body weight gain.

Topics: Animals; Animals, Newborn; Body Weight; Female; Glucose Intolerance; Hypothalamus; Inflammation; Inflammation Mediators; Insulin Resistance; Insulinoma; Lactation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Mice; Pregnancy; Resistin; Weaning; Weight Gain

Obesity is becoming a global epidemic and is a risk factor for breast cancer. Environmental enrichment (EE), a model recapitulating an active lifestyle, leads to leanness, resistance to diet-induced obesity (DIO) and cancer. One mechanism is the activation of the hypothalamic-sympathoneural-adipocyte (HSA) axis. This results in the release of norepinephrine onto adipose tissue inducing a drop of leptin. This study aimed to test the effects of EE on breast cancer onset and progression while considering the effect of leptin by utilizing the transgenic MMTV-PyMT model as well as several models of varied leptin signaling. EE was highly effective at reducing weight gain, regardless of the presence of leptin. However, the effects of EE on tumor progression were dependent on leptin signaling. EE decreased leptin and reduced mammary tumor growth rate in MMTV-PyMT spontaneous and DIO transplantation models; in contrast, the absence of leptin in ob/ob mice resulted in increased tumor growth likely due to elevated norepinephrine levels. Our results suggest that the microenvironment is critical in breast tumorigenesis and that the drop in leptin is an important peripheral mediator of the EE anti-breast cancer effects, offsetting the potential pro-tumorigenic effects of norepinephrine responding to a complex environment.

Topics: Animals; Diet, High-Fat; Disease Progression; Female; Humans; Leptin; Mammary Neoplasms, Experimental; Mammary Tumor Virus, Mouse; Mice, Inbred C57BL; Mice, Obese; Mice, Transgenic; Obesity; Signal Transduction; Tumor Microenvironment; Weight Gain

Major Depressive Disorder (MDD) involves changes in appetite and weight, with a subset of individuals at an increased risk of weight gain. Pathways to weight gain may include appetite disturbances, excess eating, and dysregulation of appetite hormones. However, little research has simultaneously examined relationships between hormones, eating behaviours and MDD symptoms. Plasma ghrelin and leptin, biometrics, eating behaviours and psychopathology were compared between depressed (n = 60) and control (n = 60) participants. Depressed participants were subcategorised into those with increased or decreased appetite/weight for comparison by subtype. The Dutch Eating Behaviours Questionnaire and Yale Food Addiction Scale measured eating behaviours. Disordered eating was higher in MDD than controls, in females than males, and in depressed individuals with increased, compared to decreased, appetite/weight. Leptin levels were higher in females only. Leptin levels correlated positively, and ghrelin negatively, with disordered eating. The results provide further evidence for high levels of disordered eating in MDD, particularly in females. The correlations suggest that excessive eating in MDD is significantly linked to appetite hormones, indicating that it involves physiological, rather than purely psychological, factors. Further, longitudinal, research is needed to better understand whether hormonal factors play a causal role in excessive eating in MDD.

Topics: Adolescent; Adult; Appetite; Biomarkers; Cross-Sectional Studies; Depressive Disorder, Major; Feeding and Eating Disorders; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Surveys and Questionnaires; Weight Gain; Young Adult

Over the past few years, the effects of a high-fat diet (HFD) on cognitive functions have been broadly studied as a model of obesity, although no studies have evaluated whether these effects are maintained after the cessation of this diet. In addition, the behavioral effects of having a limited access to an HFD (binge-eating pattern) are mostly unknown, although they dramatically increase the vulnerability to drug use in contrast to having continuous access. Thus, the aim of the present study was to compare the effects of an intermittent versus a continuous exposure to an HFD during adolescence on cognition and anxiety-like behaviors, as well as to study the changes observed after the interruption of this diet. Adolescent male mice received for 40 days a standard diet, an HFD with continuous access or an HFD with sporadic limited access (2 h, three days a week). Two additional groups were fed with intermittent or continuous access to the HFD and withdrawn from this diet 15 days before the behavioral tests. Only the animals with a continuous access to the HFD showed higher circulating leptin levels, increased bodyweight, marked memory and spatial learning deficits, symptoms that disappeared after 15 days of HFD abstinence. Mice that binged on fat only showed hyperlocomotion, which normalized after 15 days of HFD cessation. However, discontinuation of fat, either in a binge or a continuous pattern, led to an increase in anxiety-like behavior. These results highlight that exposure to a high-fat diet during adolescence induces alterations in brain functions, although the way in which this diet is ingested determines the extent of these behavioral changes.

Topics: Age Factors; Animals; Anxiety; Behavior, Animal; Body Weight; Bulimia; Cognition; Diet, High-Fat; Feeding Behavior; Learning; Leptin; Male; Memory; Mice; Obesity; Weight Gain

Sirtuin 1 (Sirt1) is an NAD-dependent class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, evidence suggests that SIRT1 in neurons plays a role in the central regulation of energy balance and reproduction, but no studies have addressed the contribution of astrocytes. We show here that overexpression of SIRT1 in astrocytes causes markedly increased food intake, body weight gain, and glucose intolerance, but expression of a deacetylase-deficient SIRT1 mutant decreases food intake and body weight and improves glucose tolerance, particularly in female mice. Paradoxically, the effect of these SIRT1 mutants on insulin tolerance was reversed, with overexpression showing greater insulin sensitivity. The mice overexpressing SIRT1 were more active, generated more heat, and had elevated oxygen consumption, possibly in compensation for the increased food intake. The female overexpressing mice were also more sensitive to diet-induced obesity. Reproductively, the mice expressing the deacetylase-deficient SIRT1 mutant had impaired estrous cycles, decreased LH surges, and fewer corpora lutea, indicating decreased ovulation. The GnRH neurons were responsive to kisspeptin stimulation, but hypothalamic expression of Kiss1 was reduced in the mutant mice. Our results showed that SIRT1 signaling in astrocytes can contribute to metabolic and reproductive regulation independent of SIRT1 effects in neurons.

Topics: Animals; Astrocytes; Eating; Estrous Cycle; Female; Follicle Stimulating Hormone; Glucose; Glucose Intolerance; Gonadotropin-Releasing Hormone; Hypothalamus; Insulin Resistance; Leptin; Luteinizing Hormone; Male; Mice; Neurons; Sirtuin 1; Testis; Weight Gain

Topics: Adult; Age Factors; Breast Feeding; Child Development; CpG Islands; DNA (Cytosine-5-)-Methyltransferase 1; DNA Methylation; Epigenome; Gene Expression Regulation, Developmental; Humans; Infant; Insulin-Like Growth Factor II; Leptin; Metabolome; Pediatric Obesity; Prospective Studies; Retinoid X Receptor alpha; Risk Factors; Time Factors; Weight Gain; Young Adult

Studies on the effects of high fructose corn syrup (HFCS) on the metabolism are scarce and their results are inconsistent.. The aim of this research was to examine in an animal model the effect of replacing sucrose with HFCS-55 on the levels of glucose, insulin and leptin, and on the consumption of feed, body weight gain and fat storage.. The experiment was carried out on 30 Wistar male rats aged 5 months, fed 3 different diets, containing whole grains (group I), 10% sucrose (group II) and 10% HFCS (group III).. It was found that the amount of daily energy intake was similar for all the groups of animals. There was no difference in fasting glucose and insulin level and homeostatic model assessment for insulin resistance (HOMA-IR) index. The higher leptin level was determined in blood plasma of the animal fed a feed with sucrose (group 2) compared to group 1 and group 3 (360 ng/mL vs 263 and 230 ng/mL, respectively). Despite the similar amounts of consumed energy, the animals fed with modified feeds achieved higher weight gain and the effect of HFCS-55 was similar to the effect of sucrose.. The obtained results indicate similar metabolic effects of HFCS-55 and sucrose in feed, at the level of 11% dietary energy value, on the energy intake, body weight gain and periorgan adipose tissue accumulation in rats. The results suggest that accusations against HFCS as the major dietary contributor to overweight and obesity are unfounded, and the total elimination of HFCS from the diet seems to be unnecessary. The modified feeds (containing both sucrose and HFCS) produced greater absolute weight gain and weight gain per kilojoule consumed compared to standard feeds. This may indicate not just a basic thermodynamic consequence of consuming more energy, but a change in the metabolic efficiency when consuming a diet with simple sugars and refined carbohydrates.

Topics: Animals; Body Weight; Energy Metabolism; High Fructose Corn Syrup; Insulin; Leptin; Male; Obesity; Rats; Rats, Wistar; Weight Gain

Despite benefits, atypical antipsychotics produce troublesome metabolic adverse effects particularly hyperphagia, weight gain, dyslipidemia, hyperglycemia and insulin resistance which further develop metabolic and cardiac complications. The animal models studied for antipsychotic-induced weight gain only focused on metabolic alteration in antipsychotics treated animals but none has considered psychosis as a predisposing factor which mimics the clinical condition. The present study was aimed to rule out the impact of pharmacologically induced psychosis-like phenotype on metabolic alterations induced by antipsychotics. Female BALB/c mice (weighing 18-23 g) exhibiting schizophrenia-like behavior after 5 days of MK-801 treatment (0.1 mg/kg, i.p.) were administered olanzapine (3 and 6 mg/kg, per oral) and risperidone (2 and 4 mg/kg, per oral) for six weeks. Acute as well as chronic treatment with olanzapine and risperidone treatment significantly reduced locomotion, increased feed intake and body weight in a time-dependent manner, which confirms the face validity of the animal model. Olanzapine (6 mg/kg) treatment significantly altered glucose and lipid homeostasis which was further accompanied by elevated levels of proinflammatory cytokines, ghrelin and leptin. These metabolic and biochemical alterations have demonstrated construct validity. Further, no significant difference was observed in the metabolic parameters in control and schizophrenic mice treated with olanzapine which confers that antipsychotic-induced metabolic alterations are independent of psychosis. Our study concluded that six-week olanzapine (6 mg/kg) treatment in control mice induced most of the clinically relevant physiological, biochemical and metabolic alterations (clinically relevant), that is independent of pharmacologically-induced psychosis.

Topics: Animals; Antipsychotic Agents; Body Weight; Female; Ghrelin; Hyperglycemia; Leptin; Mice; Mice, Inbred BALB C; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Weight Gain

Selenium, an essential trace element known mainly for its antioxidant properties, is critical for proper brain function and regulation of energy metabolism. Whole-body knockout of the selenium recycling enzyme, selenocysteine lyase (Scly), increases susceptibility to metabolic syndrome and diet-induced obesity in mice. Scly knockout mice also have decreased selenoprotein expression levels in the hypothalamus, a key regulator of energy homeostasis. This study investigated the role of selenium in whole-body metabolism regulation using a mouse model with hypothalamic knockout of Scly. Agouti-related peptide (Agrp) promoter-driven Scly knockout resulted in reduced weight gain and adiposity while on a high-fat diet (HFD). Scly-Agrp knockout mice had reduced Agrp expression in the hypothalamus, as measured by Western blot and immunohistochemistry (IHC). IHC also revealed that while control mice developed HFD-induced leptin resistance in the arcuate nucleus, Scly-Agrp knockout mice maintained leptin sensitivity. Brown adipose tissue from Scly-Agrp knockout mice had reduced lipid deposition and increased expression of the thermogenic marker uncoupled protein-1. This study sheds light on the important role of selenium utilization in energy homeostasis, provides new information on the interplay between the central nervous system and whole-body metabolism, and may help identify key targets of interest for therapeutic treatment of metabolic disorders.

Topics: Adipose Tissue, Brown; Adiposity; Agouti-Related Protein; Animals; Diet, High-Fat; Disease Models, Animal; Female; Gene Knockout Techniques; Hypothalamus; Leptin; Lyases; Male; Mice, Inbred C57BL; Mice, Knockout; Neurons; Obesity; Signal Transduction; Uncoupling Protein 1; Weight Gain

Fatty acid-induced hypothalamic inflammation (HI) is a potential cause of the obesity epidemic. It is unclear whether saturated or n-6 polyunsaturated fat is the primary driver of these effects. Premenopausal women are protected, in part, from obesity and associated comorbidities by circulating 17β-estradiol (E2). It is unknown how HI interacts with E2, because most studies of HI do not examine females despite the involvement of E2 in hypothalamic energy homeostasis. Our objective is to determine the effects of high-fat diets with varying levels of linoleic acid (LA) and saturated fat on the energy and glucose homeostasis in female mice with and without E2. Female C57BL/6J mice were fed either a control diet or a 45% kilocalories from fat diet with varying levels of LA (1, 15, or 22.5% kilocalories from LA) with or without E2 (300 μg/kg/day orally). After 8 weeks, the oil-treated high-fat groups gained more weight than control groups regardless of fat type. E2 reduced body fat accumulation in all high-fat groups. Glucose clearance from glucose challenge was impaired by LA. Nighttime O

Topics: Adiposity; Animals; Blood Glucose; Body Composition; Body Weight; Diet; Diet, High-Fat; Dietary Fats; Estradiol; Fatty Acids; Female; Homeostasis; Hypothalamus; Interleukin-6; Leptin; Linoleic Acid; Mice; Mice, Inbred C57BL; Obesity; Oxygen Consumption; Weight Gain

Exercise during pregnancy has beneficial effects on maternal and offspring's health in humans and mice. The underlying mechanisms remain unclear. This comparative study aimed to determine the long-term effects of an exercise program on metabolism, weight gain, body composition and changes in hormones [insulin, leptin, brain-derived neurotrophic factor (BDNF)]. Pregnant women (n=34) and mouse dams (n=44) were subjected to an exercise program compared with matched controls (period I). Follow-up in the offspring was performed over 6 months in humans, corresponding to postnatal day (P) 21 in mice (period II). Half of the mouse offspring was challenged with a high-fat diet (HFD) for 6 weeks between P70 and P112 (period III). In period I, exercise during pregnancy led to 6% lower fat content, 40% lower leptin levels and an increase of 50% BDNF levels in humans compared with controls, which was not observed in mice. After period II in humans and mice, offspring body weight did not differ from that of the controls. Further differences were observed in period III. Offspring of exercising mouse dams had significantly lower fat mass and leptin levels compared with controls. In addition, at P112, BDNF levels in offspring were significantly higher from exercising mothers while this effect was completely blunted by HFD feeding. In this study, we found comparable effects on maternal and offspring's weight gain in humans and mice but different effects in insulin, leptin and BDNF. The long-term potential protective effects of exercise on biomarkers should be examined in human studies.

Topics: Adiposity; Adult; Animals; Biomarkers; Brain-Derived Neurotrophic Factor; Diet, High-Fat; Disease Models, Animal; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Insulin; Leptin; Mice; Mice, Inbred C57BL; Mothers; Obesity; Physical Conditioning, Animal; Physical Conditioning, Human; Physical Fitness; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Weight Gain

Obesity, besides being a problem of metabolic dysfunction, constitutes a risk factor for psychological disorders. Experimental models of diet-induced obesity have revealed that obese animals are prone to anxious and depressive-like behaviors. The present study aimed to evaluate whether Bifidobacterium pseudocatenulatum CECT 7765 could reverse the neurobehavioral consequences of obesity in a high-fat diet (HFD) fed mouse model via regulation of the gut-brain axis. Adult male wild-type C57BL-6 mice were fed a standard diet or HFD, supplemented with either placebo or the bifidobacterial strain for 13 weeks. Behavioral tests were performed, and immune and neuroendocrine parameters were analyzed including leptin and corticosterone and their receptors, Toll-like receptor 2 (TLR2) and neurotransmitters. We found that obese mice showed anhedonia (p < 0.050) indicative of a depressive-like behavior and an exaggerated hypothalamic-pituitary axis (HPA)-mediated stress response to acute physical (p < 0.001) and social stress (p < 0.050), but these alterations were ameliorated by B. pseudocatenulatum CECT 7765 (p < 0.050). These behavioral effects were parallel to reductions of the obesity-associated hyperleptinemia (p < 0.001) and restoration of leptin signaling (p < 0.050), along with fat mass loss (p < 0.010). B. pseudocatenulatum CECT 7765 administration also led to restoration of the obesity-induced reductions in adrenaline in the hypothalamus (p < 0.010), involved in the hypothalamic control of energy balance. Furthermore, the bifidobacterial strain reduced the obesity-induced upregulation of TLR2 protein or gene expression in the intestine (p < 0.010) and the hippocampus (p < 0.050) and restored the alterations of 5-HT levels in the hippocampus (p < 0.050), which could contribute to attenuating the obesity-associated depressive-like behavior (p < 0.050). In summary, the results indicate that B. pseudocatenulatum CECT 7765 could play a role in depressive behavior comorbid with obesity via regulation of endocrine and immune mediators of the gut-brain axis.

Topics: Adiposity; Anhedonia; Animals; Anxiety; Behavior, Animal; Bifidobacterium; Catecholamines; Corticosterone; Depression; Feces; Leptin; Male; Mice, Inbred C57BL; Mice, Obese; Motor Activity; Neurosecretory Systems; Receptors, Glucocorticoid; Receptors, Leptin; Serotonin; Stress, Physiological; Toll-Like Receptor 2; Weight Gain

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

Chrysanthemum indicum (CI) is widely distributed in China and many parts of the tropical world, and has been reported to have antibacterial, antiviral, anti-oxidant and immunomodulatory effects, but no information is available on its effects on high fat diet (HFD)-induced obesity. This was undertaken to investigate the mechanism responsible for the effect of ethyl acetate fraction of CI (CIEA) on adipogenesis, in vitro and in vivo models of obesity. In the in vitro study, differentiating 3T3-L1 cells were treated with media to initiate differentiation (MDI) in the presence or absence of CIEA with different concentrations, and in the in vivo study, C57BL/6 mice were fed with HFD and administered CIEA daily for six weeks. Garcinia cambogia (GC) was used as the positive control, and was administered in the same manner as CIEA. Results showed CIEA reduced HFD-induced body weight gain, epididymal white adipose tissue (eWAT), and liver weight. In addition, CIEA significantly decreased serum lipid profiles, including total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDLc) and increased high density lipoprotein cholesterol (HDLc) levels. Furthermore, CIEA also reduced leptin levels and increased adiponectin levels in serum, and significantly decreased peroxisome proliferator-activated receptor [Formula: see text] (PPAR[Formula: see text]) and CCAAT/enhancer-binding protein (C/EPBs) levels, but increased PPAR[Formula: see text] level and the phosphorylation of AMP-activated protein kinase (AMPK) in eWATs and in the liver tissues of HFD fed obese mice. Taken together, these results indicate CIEA might be beneficial for preventing obesity.

Topics: 3T3-L1 Cells; Adipogenesis; Adiponectin; Adipose Tissue; AMP-Activated Protein Kinases; Animals; Chrysanthemum; Diet, High-Fat; Dose-Response Relationship, Drug; Leptin; Lipid Metabolism; Liver; Mice; Mice, Inbred C57BL; Obesity; Organ Size; Phytotherapy; Plant Extracts; PPAR gamma; Signal Transduction; Weight Gain

The aim of this study was to evaluate the association of dietary patterns (DP) with maternal adiposity indicators, leptin, adiponectin and insulin concentrations during pregnancy. A prospective cohort of pregnant women followed up at the 5th-13th, 20th -26th and 30th-36th gestational weeks and 30-40 d postpartum was conducted in Rio de Janeiro. A FFQ was administered in the third trimester (30th-36th gestational weeks). The reduced rank regression procedure was used to identify DP that explain response variables (dietary fibre and total fat) related to indicators of maternal adiposity (postpartum weight retention and gestational weight gain (GWG) adequacy), and plasma leptin, adiponectin and insulin concentrations. The associations between tertiles of DP and the outcomes were determined using logistic regression or longitudinal linear mixed-effect regression models. The mean daily energy intake during pregnancy was 10 104 (sd 3234) kJ (2415 (sd 773) kcal), and GWG was 11·9 (sd 4·2) kg. In all, 40 % of women presented pre-gestational overweight/obesity. Excessive GWG occurred in 34·7 % of pregnant women and 56·6 % were overweight/obese at postpartum. The 'common-Brazilian' DP (characterised by higher intake of beans, rice and lower intake of fast food/snacks, candies/table sugar and processed meats/bacon) was positively associated with adiponectin (β=1·07; 95 % CI 0·17, 1·98). The 'Western' DP (characterised by higher intake of fast food/snacks and processed meat/bacon and lower intake of noodles/pasta/roots/tubers and sodas) was negatively associated with adiponectin (β=-1·11; 95 % CI -2·00, -0·22) and positively associated with leptin concentrations (β=64·9; 95 % CI 22·8, 107·0) throughout pregnancy. It may be suggested that the 'common-Brazilian' is a healthy DP and beneficial for serum concentrations of adiponectin and leptin.

Topics: Adiponectin; Adiposity; Adult; Brazil; Cohort Studies; Diet; Diet, Healthy; Dietary Fats; Dietary Fiber; Energy Intake; Female; Gestational Age; Humans; Insulin; Leptin; Maternal Nutritional Physiological Phenomena; Obesity; Overweight; Pregnancy; Prospective Studies; Weight Gain

Topics: Adipose Tissue, White; Animals; Antidepressive Agents; Body Weight; Brain-Derived Neurotrophic Factor; Energy Metabolism; Fluoxetine; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Receptor, trkB; Weight Gain

Youth exposed to antipsychotics may experience several metabolic consequences that often limit the effectiveness of this class of drugs.. The aim of this study was to compare several metabolic markers between subjects who experienced antipsychotic-induced weight gain and untreated obese patients.. Nineteen non-diabetic youth (mean age 159 months, mean body mass index z-score 1.81) experiencing antipsychotic-induced weight gain and an age-, sex-, and body mass index-matched group of non-diabetic obese patients with no record of treatment (n = 19, mean age 147 months, mean body mass index z-score 2) were compared for a wide range of metabolic factors using a Bioplex Multiplex system.. C-peptide, glucose-dependent insulinotropic polypeptide, and adipsin were significantly higher in the antipsychotic-induced weight gain group, whereas visfatin was significantly higher in the untreated obese patients. When age, sex, pubertal status, and body mass index were controlled, C-peptide, glucose-dependent insulinotropic polypeptide, and visfatin remained significant, whereas adipsin fell slightly below the threshold of statistical significance. No other statistically significant difference emerged.. Antipsychotic-induced weight gain and untreated obesity showed some similarities, confirming that levels of some hormones, such as leptin and ghrelin, are related to body mass index rather than to antipsychotic exposure. Some differences were also noted; for example, the antipsychotic-induced weight gain group displayed higher C-peptide, glucose-dependent insulinotropic polypeptide, and adipsin, which may reflect β-cell stress and may suggest susceptibility to insulin resistance and lower visfatin, possibly indicating a lower inflammatory status.

Topics: Adolescent; Antipsychotic Agents; Body Mass Index; Child; Female; Ghrelin; Humans; Insulin Resistance; Leptin; Male; Obesity; Weight Gain

Cord blood adiponectin and leptin concentrations are associated with birth weight and adiposity. Birth size and rate of infant weight gain are associated with future obesity risk. However, it is unclear whether biomarkers reflecting the intrauterine environment are predictive of infant prospective body composition change.. To examine whether cord blood adiponectin and leptin are predictive of neonatal adiposity and fat mass (FM) accrual to 3 months of age.. Participants (n = 36) were healthy African American infants. Leptin and adiponectin concentrations were measured in umbilical cord blood. At 2 weeks and 3 months, infant body composition was assessed via air displacement plethysmography. Weight-for-length z-scores (WLZ) were calculated using World Health Organization standards. Multiple linear regression was used to examine associations of cord blood adiponectin and leptin with birth WLZ; WLZ, FM and fat-free mass at 2 weeks, and the conditional change in these variables from 2 weeks to 3 months (body composition at 3 months adjusted for body composition at 2 weeks).. Adiponectin was positively associated with FM at 2 weeks (r = 0.45, P < 0.01), but inversely associated with conditional FM change from 2 weeks to 3 months of age (r = -0.38, P < 0.05). Leptin was not significantly associated with infant body composition.. Adiponectin may be a marker for FM accrual in African American infants, a relatively understudied population with a high long-term obesity risk. Mechanistic studies are needed to determine whether adiponectin directly influences infant growth or is simply a maker reflective of other ongoing biological changes after birth.

Topics: Adiponectin; Adipose Tissue; Adiposity; Biomarkers; Birth Weight; Black or African American; Body Composition; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Leptin; Male; Plethysmography; Weight Gain

The hypothalamus is involved in the regulation of food intake and energy homeostasis. The arcuate nucleus (ARC) and median eminence (ME) are the primary hypothalamic sites that sense leptin and nutrients in the blood, thereby mediating food intake. Recently, studies demonstrating a role for non-neuronal cell types, including astrocytes and tanycytes, in these regulatory processes have begun to emerge. However, the molecular mechanisms involved in these activities remain largely unknown. In this study, we examined in detail the localization of fatty acid-binding protein 7 (FABP7) in the hypothalamic ARC and sought to determine its role in the hypothalamus. We performed a phenotypic analysis of diet-induced FABP7 knockout (KO) obese mice and of FABP7 KO mice treated with a single leptin injection. Immunohistochemistry revealed that FABP7

Topics: Animals; Arcuate Nucleus of Hypothalamus; Astrocytes; Cells, Cultured; Diet, High-Fat; Eating; Fatty Acid-Binding Protein 7; Leptin; Male; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins; Neuroglia; Neurons; Oligodendroglia; Phosphorylation; STAT3 Transcription Factor; Stem Cells; Weight Gain

Although some drugs used in the treatment of epilepsy are known to affect body weight, the hormonal factors responsible have not been sufficiently described. The purpose of this study was to compare insulin, leptin, neuropeptide Y and ghrelin levels in children with epilepsy receiving monotherapy with topiramate (TPM) and valproic acid (VPA), the drugs whose effects on body weight have been most discussed, with those of a control group.. 48 patients (25 VPA, 23 TPM) aged between 6 and 15.5 years, presenting to the Karadeniz Technical University Medical Faculty Pediatric Neurology Clinic, diagnosed with idiopathic epilepsy or location-related idiopathic epilepsy, and receiving VPA or TPM monotherapy for at least 6 months were included in the study. Twenty-five healthy subjects with similar demographic characteristics were enrolled as the control group. Blood samples were collected from the patient and control groups after fasting for at least 10-12 h and again 1 and 2 h postprandially. Body mass index (BMI) values were calculated for all cases. VPA levels, glucose, insulin, leptin, neuropeptide Y and ghrelin were investigated in all three separate blood samples.. Age, height, weight and BMI were similar between the patient and control groups. Significant weight gain was observed throughout treatment in the VPA group compared to the TPM group. High fasting and postprandial insulin levels were observed in the VPA group. VPA group leptin and neuropeptide Y (NPY) levels were also higher than in the TPM and control groups. No significant difference was determined in ghrelin levels in the patient groups compared to the controls.. Low blood sugar not being observed, even though insulin levels are high, after fasting and in the postprandial period in epileptic children receiving VPA is indicative of insulin resistance. The elevation in leptin and neuropeptide Y levels observed in the VPA group also suggest this.

Topics: Adolescent; Anticonvulsants; Biomarkers; Blood Glucose; Body Mass Index; Child; Epilepsy; Fructose; Ghrelin; Humans; Insulin; Leptin; Neuropeptide Y; Topiramate; Treatment Outcome; Valproic Acid; Weight Gain

In birds little is known about the hormonal signals that communicate nutritional state to the brain and regulate appetitive behaviours. In mammals, the peptide hormones ghrelin and leptin elevate and inhibit consumption and food hoarding, respectively. But in birds, administration of both ghrelin and leptin inhibit food consumption. The role of these hormones in the regulation of food hoarding in avian species has not been examined. To investigate this, we injected wild caught coal tits (

Topics: Animals; Appetitive Behavior; Dose-Response Relationship, Drug; Eating; Feeding Behavior; Ghrelin; Injections, Intramuscular; Leptin; Pectoralis Muscles; Songbirds; Weight Gain

The aim of this study was to examine the effects of 2 postweaning feeding management approaches (FEED: 0.8 [HIGH] vs 0.6 [MOD] kg/d target ADG) on the performance of heifers of 2 beef breeds (BREED: Parda de Montaña [PA] vs Pirenaica) calving at 2 yr. Twenty-five heifers previously creep fed before weaning (6 mo) were assigned to 2 planes of nutrition from 6 to 15 mo of age. At 15 mo, they were inseminated, and then received similar diets until weaning of their first calf (4 mo postcalving). Several parameters were measured to analyze growth and development (BW; ADG; size measures at 6 mo, 15 mo, calving, and weaning), performance at puberty and first breeding, and dam and calf performance in the first lactation (calving traits, ADG, milk yield). Metabolic (glucose, cholesterol, NEFA, β-hydroxybutyrate, and urea) and endocrine status (IGF-I and leptin) were assessed in plasma samples collected every 3 mo from 6 mo to calving and monthly during lactation. No interaction between BREED and FEED was observed. Heifers from the HIGH feeding treatment had higher postweaning ADG than those on the LOW diet. At 15 mo, they had greater BW, heart girth, and external pelvic area, but they did not differ thereafter. All heifers reached puberty at similar BW (55% mature BW) but different ages. Heifers from the HIGH treatment tended (P < 0.09) to be pubertal earlier, and PA heifers were 1.6 mo younger than Pirenaica heifers (P < 0.05) at puberty. At the time of conception (452 ± 59 kg) and calving (471 ± 51 kg), BW was above common recommendations in all groups. Calving traits and performance in lactation did not differ between feeding treatments. BREED only influenced birth weight; PA calves being heavier (P < 0.05), which resulted in a larger calf/cow BW ratio, but no effect on calving difficulty or subsequent performance. Metabolic substrates and hormones depended mostly on sampling date, which was related to current energy and protein intake. Glucose (P < 0.001), cholesterol (P < 0.001), and IGF-I (P < 0.05) were greater during the postweaning phase in heifers on the HIGH diet, and persistent physiological effects were observed during lactation. Age at puberty was negatively related with IGF-I (r = -0.43, P < 0.001), but not with leptin concentrations. In conclusion, regardless of breed, a moderate growth rate ensured adequate heifer development and performance until the first lactation, whereas no advantage was gained from enhanced postweaning gains.

Topics: 3-Hydroxybutyric Acid; Animal Nutritional Physiological Phenomena; Animals; Blood Glucose; Breeding; Cattle; Cholesterol; Diet; Fatty Acids, Nonesterified; Feeding Methods; Female; Insulin-Like Growth Factor I; Lactation; Leptin; Male; Red Meat; Sexual Maturation; Urea; Weaning; Weight Gain

Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a high-fat diet (HFD). After the eight-week administration of COSCs on obese rats, the body weight gain, fat/body ratio, and related biochemical indices were measured. The hepatic expressions of the leptin signal pathway (JAK2-STAT3) and gene expressions of adipogenesis-related targets were also determined. Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment.

Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Anti-Obesity Agents; Body Weight; Capsules; Chitosan; Diet, High-Fat; Janus Kinase 2; Leptin; Lipids; Liver; Male; Obesity; Oligosaccharides; Rats; Rats, Sprague-Dawley; Signal Transduction; STAT3 Transcription Factor; Weight Gain

Schizophrenia is among the top half of the 25 leading causes of disabilities worldwide with a 10-20 year decrease in life expectancy. Ineffective pharmacotherapy in the management of cognitive deficits and weight gain are known to be significant contributors; therefore interventions that may mitigate one, or both, of these parameters would be highly beneficial. Manipulation of the gut microbiome using dietary supplements such as prebiotics may be one such intervention. Preclinical studies have shown that a 2-4 week dietary supplementation with a prebiotic has beneficial effects on learning and memory, and prevents pro-inflammatory signals that are detrimental to cognitive processes. Furthermore, prebiotics influence metabolism, and in obesity they increase the expression of anorexigenic gut hormones such as peptide tyrosine tyrosine, glucagon-like peptide 1 and leptin, as well as decrease levels of orexigenic hormones such as ghrelin. Despite compelling evidence for the pro-cognitive and neuroprotective effects of prebiotics in rodents, their ability to alleviate cognitive deficits or enhance cognition needs to be evaluated in humans. Here we suggest that important symptoms associated with schizophrenia, such as cognitive impairment and weight gain, may benefit from concurrent prebiotic therapy.

Topics: Cognition; Dietary Supplements; Gastrointestinal Microbiome; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Obesity; Peptide YY; Prebiotics; Schizophrenia; Weight Gain

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

Lavatera critica, a leafy green herb, is reported to have many pharmacological activities; but, the improvement of insulin sensitivity against the high gram-fat diet (HGFD)-caused insulin resistance (IR) has not yet been studied.. This study evaluated the role of Lavatera critica leaf extract (LCE) in systemic insulin resistance through the alleviation of adipose tissue inflammation and oxidative damage in HGFD fed mice.. The mice were fed with HGFD for 10 weeks and the diet was supplemented with LCE each day for the next five weeks. Body weight, food intake, leptin, blood glucose, insulin, insulin resistance, and pro- and anti-inflammatory genes expression were assessed on day 106.. The HGFD control mice displayed markedly elevated adipose tissue inflammation, oxidative stress, insulin inactivity, and hyperglycemia. Administration of LCE in the HGFD mice, especially a dose of 100 mg/kg, lowered the body weight, food intake, plasma leptin, plasma glucose, plasma insulin, insulin resistance, and increased the food efficacy ratio when compared with the HGFD control mice. The oral glucose tolerance test (OGTT) revealed that LCE prevented further increase in the circulating levels after the glucose load. LCE-treated mice demonstrated a marked suppression of pro-inflammatory cytokines mRNA expression. On the other hand, the mice showed a higher anti-inflammatory genes mRNA expression in the adipose tissue. In addition, LCE treatment improved the oxidative damage as evidenced by the reduced levels of lipid hydroperoxides and thiobarbituric acid reactive substances coupled with the increased antioxidants (superoxide dismutase, total glutathione, glutathione/glutathione disulfide ratio and glutathione peroxidase) in the adipose tissue, plasma and erythrocytes. Gas chromatography-mass spectrometry analysis of the bioactive compounds revealed the presence of 9, 12, 15-octadecatrienoic acid, vitamin E, phytol, hexadecanoic acid, benzenepropanoic acid, and stigmasterol.. These findings prove that LCE improves the insulin-sensitizing activity in the mouse model of HGFD-caused IR, probably due to the amelioration of adipose tissue inflammation and oxidative damage. Hence, the LCE could serve as a useful anti-diabetic agent.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Blood Glucose; Diabetes Mellitus, Experimental; Eating; Gas Chromatography-Mass Spectrometry; Gene Expression Regulation; Glucose Tolerance Test; Hypoglycemic Agents; Inflammation Mediators; Insulin; Insulin Resistance; Leptin; Male; Malvaceae; Mice, Inbred C57BL; Oxidative Stress; Panniculitis; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Time Factors; Weight Gain

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

RF-amide-related peptide-3 (RFRP-3), the mammalian ortholog of gonadotropin-inhibiting hormone, operates as inhibitory signal for the reproductive axis. Recently, RFRP-3 has been also suggested to stimulate feeding, and therefore might contribute to the control of body weight and its alterations. Yet, characterization of the metabolic actions of RFRP-3 has been so far superficial and mostly pharmacological. Here, we aim to investigate the physiological roles of RFRP-3 signaling in the control of feeding and metabolic homeostasis using a novel mouse model of genetic ablation of its canonical receptor, NPFF1R.. Food intake, body weight gain and composition, and key metabolic parameters, including glucose tolerance and insulin sensitivity, were monitored in mice with constitutive inactivation of NPFF1R.. Congenital elimination of NPFF1R in male mice resulted in changes in feeding patterns, with a decrease in spontaneous food intake and altered responses to leptin and ghrelin: leptin-induced feeding suppression was exaggerated in NPFF1R null mice, whereas orexigenic responses to ghrelin were partially blunted. Concordant with this pro-anorectic phenotype, hypothalamic expression of Pomc was increased in NPFF1R null mice. In contrast, spontaneous feeding and neuropeptide expression remained unaltered in NPFF1R KO female mice. Despite propensity for reduced feeding, ablation of NPFF1R signaling in male mice did not cause overt alterations in body weight (BW) gain or composition, neither it affected BW responses to high fat diet (HFD), total energy expenditure or RQ ratios. Yet, NPFF1R KO males showed a decrease in locomotor activity. Conversely, NPFF1R null female mice tended to be heavier and displayed exaggerated BW increases in response to obesogenic insults, such as HFD or ovariectomy. These were associated to increased fat mass, decreased total energy expenditure in HFD, and unaltered RQ ratios or spontaneous locomotor activity. Finally, lack of NPFF1R signaling worsened the metabolic impact of HFD on glycemic homeostasis in males, as revealed by impaired glucose tolerance and insulin sensitivity, while female mice remained unaffected.. Our data support a discernible orexigenic role of NPFF1R signaling selectively in males, which might modulate the effects of leptin and ghrelin on food intake. In addition, our study is the first to disclose the sex-biased, deleterious impact of the lack of NPFF1R signaling on body weight and fat composition, energy expenditure, locomotor activity and glucose balance, which exaggerates some of the metabolic consequences of concurrent obesogenic insults, such as HFD, in a sexually dimorphic manner.. Our data are the first to document the nature and magnitude of the regulatory actions of RFRP-3/NPFF1R signaling in the control of feeding and metabolic homeostasis in a physiological setting. Our results not only suggest an orexigenic action of endogenous RFRP-3, specifically in males, but reveal also the detrimental impact of ablation of NPFF1R signaling on body composition, energy expenditure, locomotor activity or glucose balance, especially when concurrent with other obesogenic insults, as HFD, thereby providing the first evidence for additional metabolic effects of RFRP-3, other that the mere control of feeding. Interestingly, alterations of such key metabolic parameters occurred in a sex-biased manner, with males being more sensitive to deregulation of locomotor activity and glycemic control, while females displayed clearer obesogenic responses and deregulated energy expenditure. While our study cannot discard the possibility of RFRP-3 actions via alternative pathways, such as NPFF2R, our data pave the way for future analyses addressing the eventual contribution of altered RFRP-3/NPFF1R signaling in the development of metabolic alterations (including obesity and its comorbidities), especially in conditions associated to reproductive dysfunction.

Topics: Animals; Body Composition; Diet, High-Fat; Eating; Energy Metabolism; Ghrelin; Glucose Intolerance; Homeostasis; Hypothalamus; Insulin Resistance; Leptin; Male; Mice; Mice, Knockout; Neuropeptides; Receptors, Neuropeptide; Sex Characteristics; Weight Gain

The blood levels of Adiponectin, anti-inflammatory and anti-arteriosclerotic adipocytokine, decrease due to smoking and obesity. Cigarette smokers are generally known to gain weight after smoking cessation (SC). Nevertheless, precise changes in serum adiponectin levels after SC and specific effects of abdominal obesity on those changes remain unknown. The objective of this study was to elucidate the changes in serum adiponectin levels after SC and the effects of abdominal obesity on those changes.. In 86 patients (56 males and 30 females) who had successfully quit smoking, serum adiponectin levels were measured using an enzyme-linked immunosorbent assay at baseline and 1 year after beginning SC.. Body mass index and waist circumference (WC) were significantly increased 1 year after beginning SC. Adiponectin levels, however, did not change after SC. Using the median ΔWC (+2.8%) as the cutoff point, patients were then divided into two groups. The percent change in adiponectin levels from baseline to 1 year was significantly greater in the ΔWC < median group (-1.1%) than in the ΔWC ≥ median group (+8.1%) (p = 0.011).. Despite weight gain and increased abdominal obesity, serum adiponectin levels did not decrease after SC. Therefore, the beneficial effect of SC may eliminate the adverse effects of subsequent weight gain. Conversely, patients with less abdominal obesity had increased adiponectin levels 1 year after SC. Therefore, in such patients, the beneficial effect of SC on adiponectin levels is apparent.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Body Mass Index; Female; Humans; Leptin; Male; Middle Aged; Obesity, Abdominal; Prospective Studies; Smoking; Smoking Cessation; Waist Circumference; Weight Gain

Dietary interventions in rodents can induce an excess of adipose tissue and metabolic disorders that resemble human obesity. Nevertheless, these approaches are not standardized, and the phenotypes may vary distinctly among studies. The aim of this study was to investigate the effects of different dietary interventions on nutritional, metabolic, biochemical, hormonal, and cardiovascular profiles, as well as to add to development and characterization of an experimental model of obesity.. Male Wistar rats were randomized into four groups: control diet (C), high-sugar (HS), high-fat (HF), or high-sugar and high-fat (HFHS). Weekly measurements of body weight, adiposity, area under the curve (AUC) for glucose, blood pressure (BP) and serum triglycerides, total cholesterol level, and leptin were performed.. HF and HFHS models were led to obesity by increases in adipose tissue deposition and the adiposity index. All hypercaloric diets presented systolic BP increases. In addition, the AUC for glucose was greater in HF and HFHS than in C, and only the HF group presented hyperleptinemia.. HF and HFHS diet approaches promote obesity and comorbidities, and thus represent a useful tool for studying human obesity-related disorders. By contrast, the HS model did not prove to be a good model of obesity.

Topics: Adiposity; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Biomarkers; Blood Glucose; Blood Pressure; Cholesterol; Dietary Fats; Dietary Sugars; Disease Models, Animal; Energy Intake; Health Status; Leptin; Male; Nutritive Value; Obesity; Rats, Wistar; Time Factors; Triglycerides; Weight Gain

Obesity and related morbidities pose a major health threat. Obesity is associated with increased blood concentrations of the anorexigenic hormone leptin; however, obese individuals are resistant to its anorexigenic effects. We examined the phenomenon of reduced leptin signaling in a high-fat diet-induced obesity model in mice. Obesity promoted matrix metalloproteinase-2 (Mmp-2) activation in the hypothalamus, which cleaved the leptin receptor's extracellular domain and impaired leptin-mediated signaling. Deletion of Mmp-2 restored leptin receptor expression and reduced circulating leptin concentrations in obese mice. Lentiviral delivery of short hairpin RNA to silence

Topics: Animals; Brain; Diet, High-Fat; Enzyme Activation; Hypothalamus; Leptin; Male; Matrix Metalloproteinase 2; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B; Obesity; Rats, Wistar; Receptors, Leptin; Signal Transduction; Weight Gain

BACKGROUND Obesity during pregnancy is a potential threat to the health and neurodevelopment of the offspring. This study investigated the effect of maternal diet-induced obesity (DIO) on the cognitive abilities of the offspring in rats. MATERIAL AND METHODS Female Sprague-Dawley rats were fed a high-fat diet to induce obesity, and the leptin levels in dams and offspring were evaluated using ELISA. The effect of DIO on the learning and memory in offspring was measured using electrophysiology and the Morris water maze test. In addition, the expression of molecules related to synaptic plasticity was investigated. Furthermore, the effect of leptin on neuronal cells was investigated, and the influence of leptin on the regulation of calcium current activity was evaluated in vitro. RESULTS Results showed that DIO dams had increased leptin levels during gestation, and offspring had drastically decreased leptin levels after delivery. The cognitive ability of offspring with maternal DIO was mildly impaired after delivery. Furthermore, long-term potentiation in DIO neonatal offspring was lower than in the control group at 2-3 weeks old; decreased expression of the leptin receptor was accompanied by N-methyl-D-aspartate receptor (NMDAR) downregulation during neonatal development. In addition, it was demonstrated that leptin enhanced NMDAR activity and promoted calcium current activity in a concentration-dependent manner. CONCLUSIONS The results indicated that the neonatal offspring of DIO dams showed cognitive impairment during neonatal development, which may be attributed to leptin withdrawal.

Topics: Animals; Body Weight; Cognition; Cognitive Dysfunction; Diet, High-Fat; Female; Glucose Tolerance Test; Leptin; Male; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Receptors, Leptin; Weight Gain

Some infants experience excessive weight gain (EWG) during exclusive breastfeeding, but causes and consequences are unknown. The objective was to identify factors associated with early EWG. Infants with EWG (HW-group) were examined at 5, 9 and 18 mo and compared to a breastfed group with normal weight gain (NW-group). Anthropometry, body composition, milk and blood samples, and milk intake were measured. Mean body-mass-index-for-age

Topics: Adiposity; Age Factors; Appetite Regulation; Breast Feeding; Child Development; Feeding Behavior; Female; Humans; Infant; Infant Behavior; Infant Nutritional Physiological Phenomena; Leptin; Male; Nutritional Status; Prospective Studies; Weight Gain

Rumination about body weight/figure as well as food is common in patients with Anorexia Nervosa (AN) and may be a maintenance factor of the disorder. While rumination can generally be considered as a cognitive-affective process, food-related rumination may be driven primarily by a physiological response to undernutrition. In the current longitudinal study, we integrate ecological momentary assessment of rumination and affect and, as a biological marker of undernutrition, plasma leptin levels collected from 33 AN patients. At the very acute stage and again after short-term weight-restoration patients answered short questionnaires six times per day over two weeks. Analyses via hierarchical linear modelling confirmed that rumination is closely linked to affect in AN before and after weight-restoration. Rumination about food decreased during weight-restoration and was correlated with leptin levels. In contrast, rumination about body weight/figure was not linked to leptin, persisted after weight gain, and showed stronger connections with affect. This suggests that rumination about body weight/figure seems to be a cognitive-affective aspect of the disorder, but food-related rumination may need to be considered from a physiological perspective. It is possible that food-related ruminative thoughts reflect a physiological symptom induced by undernutrition, similar to well-described leptin-associated changes in physical activity.

Topics: Adolescent; Affect; Anorexia Nervosa; Biomarkers; Body Image; Child; Ecological Momentary Assessment; Female; Food; Humans; Leptin; Longitudinal Studies; Rumination, Cognitive; Weight Gain

Topics: Adipose Tissue; Animals; Antioxidants; Diet; Dose-Response Relationship, Drug; Gene Expression Regulation; Hypertriglyceridemia; Leptin; Male; Rats; Rats, Wistar; Resveratrol; Signal Transduction; STAT3 Transcription Factor; Weight Gain

Atypical antipsychotics are associated with adverse metabolic effects including weight gain, increased adiposity, dyslipidaemia, alterations in glucose metabolism and insulin resistance. Increasing evidence suggests that metabolic dysregulation precedes weight gain development. The aim of this study was to evaluate alterations in adipokines, hormones and basic serum biochemical parameters induced by chronic treatment with depot risperidone at two doses (20 and 40 mg/kg) in female Sprague-Dawley rats. Dose-dependent metabolic alterations induced by risperidone after 6 weeks of treatment were revealed. Concomitant to weight gain and increased liver weight, an adverse lipid profile with an elevated triglyceride level was observed in the high exposure group, administered a 40 mg/kg dose repeatedly, while the low dose exposure group, administered a 20 mg/kg dose, developed weight gain without alterations in the lipid profile and adipokine levels. An initial peak in leptin serum level after the higher dose was observed in the absence of weight gain. This finding may indicate that the metabolic alterations observed in this study are not consequent to body weight gain. Taken together, these data may support the primary effects of atypical antipsychotics on peripheral tissues.

Topics: Adipokines; Animals; Antipsychotic Agents; Female; Leptin; Lipids; Rats; Rats, Sprague-Dawley; Risperidone; Weight Gain

To examine whether baseline chronic stress, morning cortisol, and other appetite-related hormones (leptin, ghrelin, and insulin) predict future weight gain and food cravings in a naturalistic, longitudinal, 6-month follow-up study.. A prospective community cohort of 339 adults (age 29.1 ± 9.0 years; BMI = 26.7 ± 5.4 kg/m. Over the 6-month period, 49.9% of the sample gained weight. Food cravings and chronic stress decreased over 6 months (Ps < 0.05). However, after adjusting for covariates, individuals with higher baseline total ghrelin had significantly higher food cravings at 6 months (P = 0.04). Furthermore, higher cortisol, insulin, and chronic stress were each predictive of greater future weight gain (Ps < 0.05).. These results suggest that ghrelin plays a role in increased food cravings and reward-driven eating behaviors. Studies are needed that examine the utility of stress reduction methods for normalizing disrupted cortisol responses and preventing future weight gain.

Topics: Adult; Appetite; Body Mass Index; Body Weight; Craving; Fasting; Feeding Behavior; Female; Follow-Up Studies; Ghrelin; Heat-Shock Proteins; Humans; Hydrocortisone; Insulin; Leptin; Linear Models; Longitudinal Studies; Male; Predictive Value of Tests; Prospective Studies; Weight Gain; Young Adult

This study aimed to investigate leptin immuno-staining of the porcine ovary in different reproductive stages. Ovaries from 21 gilts were collected from slaughterhouses. The ovarian tissue sections were incubated with a polyclonal anti-leptin as a primary antibody. The immuno-staining in ovarian tissue compartments was calculated using imaging software. Leptin immuno-staining was found in primordial, primary, preantral and antral follicles. Leptin immuno-staining was expressed in the oocyte and granulosa and theca interna layers in both preantral and antral follicles. In the corpora lutea, leptin immuno-staining was found in the cytoplasm of the luteal cells. The leptin immuno-staining in the granulosa cell layer of preantral follicles did not differ compared to antral follicles (90.7 and 91.3%, respectively, P > 0.05). However, the leptin immuno-staining in the theca interna layer of preantral follicles was lower than antral follicles (49.4 and 74.3%, respectively, P < 0.001). There was no difference in leptin immuno-staining in the granulosa cell layer between follicular and luteal phases (92.4 and 89.7%, respectively, P > 0.05). However, the leptin immuno-staining in the theca interna layer of follicular phase was greater than that in the luteal phase (72.7 and 51.0%, respectively, P < 0.001). These findings indicated that leptin exists in different compartments of the porcine ovary, including the oocyte, granulosa cells, theca interna cells, corpus luteum, blood vessel and smooth muscles. Therefore, this morphological study confirmed a close relationship between leptin and ovarian function in the pig.

Topics: Angiogenic Proteins; Animals; Body Weight; Corpus Luteum; Female; Follicular Phase; Granulosa Cells; Image Processing, Computer-Assisted; Immunohistochemistry; Leptin; Luteal Phase; Oocytes; Ovarian Follicle; Ovary; Swine; Theca Cells; Weight Gain

Sleep fragmentation (SF) is highly prevalent and has emerged as an important contributing factor to obesity and metabolic syndrome. We hypothesized that SF-induced increases in protein tyrosine phosphatase-1B (PTP-1B) expression and activity underlie increased food intake, inflammation, and leptin and insulin resistance.. Wild-type (WT) and ObR-PTP-1b-/- mice (Tg) were exposed to SF and control sleep (SC), and food intake was monitored. WT mice received a PTP-1B inhibitor (RO-7d; Tx) or vehicle (Veh). Upon completion of exposures, systemic insulin and leptin sensitivity tests were performed as well as assessment of visceral white adipose tissue (vWAT) insulin receptor sensitivity and macrophages (ATM) polarity.. SF increased food intake in either untreated or Veh-treated WT mice. Leptin-induced hypothalamic STAT3 phosphorylation was decreased, PTP-1B activity was increased, and reduced insulin sensitivity emerged both systemic and in vWAT, with the latter displaying proinflammatory ATM polarity changes. All of the SF-induced effects were abrogated following PTP-1B inhibitor treatment and in Tg mice.. SF induces increased food intake, reduced leptin signaling in hypothalamus, systemic insulin resistance, and reduced vWAT insulin sensitivity and inflammation that are mediated by increased PTP-1B activity. Thus, PTP-1B may represent a viable therapeutic target in the context of SF-induced weight gain and metabolic dysfunction.

Topics: Adipose Tissue, White; Animals; Eating; Hypothalamus; Inflammation; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Macrophages; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Receptor, Insulin; Signal Transduction; Sleep Deprivation; STAT3 Transcription Factor; Tyrosine; Weight Gain

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

Using a previously established model for nutritional acceleration of puberty, beef heifers ( = 48; 1/2 Angus × 1/4 Hereford × 1/4 Brahman) were used in a replicated 2 × 2 factorial design to examine the effects of diet type (high forage [HF] vs. high concentrate [HC]) and rate of BW gain (low gain [LG], 0.45 kg/d, vs. high gain [HG], 0.91 kg/d) on key metabolic hormones and age at puberty. After weaning at 14 ± 1 wk of age, heifers were assigned randomly to be fed HC-HG, HC-LG, HF-HG, or HF-LG ( = 12/group) beginning at 4 mo of age for 14 wk. Heifers were then switched to a common growth diet until puberty. Average daily gain was greater ( < 0.04) during the dietary treatment phase in HG heifers (0.81 ± 0.06 kg/d) than in LG heifers (0.43 ± 0.06 kg/d), and there was no diet type × rate of gain interaction. Puberty was achieved at a younger age (54.5 ± 1.8 wk) in both HG groups than in LG groups (60.2 ± 1.9 wk; < 0.04), but dietary energy source (HC vs. HF) did not influence this variable. Moreover, mean BW at puberty did not differ by diet type or rate of gain during the dietary treatment phase. Nonetheless, heifers fed HC-HG exhibited a striking increase ( < 0.0001) in serum leptin beginning at 26 ± 1 wk of age and remained elevated ( < 0.01) throughout the remainder of the experimental feeding phase compared to all other treatments. However, serum leptin in HC-HG dropped precipitously when heifers were switched to the common growth diet and did not differ from that of other groups thereafter. Overall mean concentrations of serum glucose were greater ( < 0.006) in HG heifers than in LG during the dietary treatment phase, with serum insulin also greater ( < 0.04) in HG than in LG only during weeks 20, 22, and 30. Mean serum IGF-1 was not affected by dietary type or rate of BW gain. We speculate that failure of the marked increase in serum leptin observed in HC-HG heifers during the dietary treatment phase to further accelerate puberty compared to HF-HG occurred because of its abrupt decline at the onset of the common growth phase, thus attenuating the temporal cue for activation of the reproductive neuroendocrine system.

Topics: Animal Feed; Animal Husbandry; Animal Nutritional Physiological Phenomena; Animals; Cattle; Diet; Energy Metabolism; Female; Insulin-Like Growth Factor I; Leptin; Reproduction; Sexual Maturation; Weaning; Weight Gain

High fat-high sucrose (HF-HS) diet, known as the western diet, has been shown to induce the onset of obesity via increasing metabolic inflammation, insulin resistance and adipose tissue dysfunction. Hyperleptinemia, hyperglycemia and dyslipidemia are also the primary observations of obesogenic diet induced obesity. We have previously reported anti-adipogenic and insulin sensitizing effects of blue mussels (BM) using 3T3-L1 cells. BM is a rich source of omega-3 polyunsaturated fatty acids, phytosterols and other micronutrients that has been shown to elicit benefits under obese conditions using in-vitro cell culture models. However, no studies to date have established the anti-obesity effects, safety and efficacy of BM in an in-vivo animal model. In the present study, we fed a HF-HS diet supplemented with different concentrations of BM freeze-dried powder (1.25, 2.5 and 5% w/w) to C57BL/6 mice for 12weeks. A HF-HS diet caused rapid weight gain, hyperglycemia, dyslipidemia, hyperleptinemia, and increased plasma levels of inflammatory cytokines; interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Incorporating 2.5% BM in the HF-HS diet prevented weight gain, dyslipidemia, hyperglycemia and reduced the levels of inflammatory cytokines and leptin mRNA expression. Furthermore, plasma from 2.5% BM increased cholesterol efflux capacity of J774 macrophage cells, compared to plasma from HF-HS diet. There was no effect of 1.25% BM on any tested parameters, while 5% BM was not palatable after four weeks. In conclusion, our findings have established the efficacy and safety of BM using C57BL/6 mice, demonstrating that BM has the potential to target obesity and related complications.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Biomarkers; Cholesterol; Cytokines; Diet, High-Fat; Diet, Western; Dietary Sucrose; Dietary Supplements; Dyslipidemias; Hyperglycemia; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Macrophages; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Models, Animal; Mytilus edulis; Obesity; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Gain

The contribution of leptin-induced modulation of dopamine neurons to feeding behavior and energy homeostasis remains unclear. Midbrain dopamine neurons regulate the reward value of food, and direct leptin administration to the midbrain reduces food intake. However, selective deletion of leptin receptors (Leprs) from dopamine neurons has no effect on body weight, food intake, or hedonic responses, suggesting that leptin acts indirectly or demonstrating that sufficient compensation occurs to mask any direct leptin-dopamine effects. To further explore the role of direct Lepr-dopamine neuron signaling in the control of feeding behavior and energy homeostasis, we generated mice in which Leprs were expressed exclusively in dopamine transporter (DAT)-expressing neurons (LeprDAT). We then assessed weekly body weight, daily food intake, hyperphagic feeding, and leptin-induced suppression of feeding in the LeprDAT mice compared with their Lepr-deficient (LeprNULL) and wild-type control (LeprCON) littermates. We also used metabolic cages to characterize running wheel activity, home-cage activity, and total energy expenditure. As expected, LeprNULL mice exhibited increased body weight and food intake compared with LeprCON mice. LeprDAT male mice exhibited acute leptin-induced suppression of food intake and reduced hedonic feeding but also exhibited significantly increased postweaning body weight gain compared with the LeprNULL mice. This was associated with significantly reduced home-cage activity counts, although no differences in food intake were observed between the LeprDAT and LeprNULL mice. These data demonstrate that restoring Lepr signaling exclusively in dopamine neurons reduces some aspects of food reward and activity but does not ameliorate the obesity phenotype of Lepr-deficient mice.

Topics: Animals; Dopamine Plasma Membrane Transport Proteins; Dopaminergic Neurons; Eating; Feeding Behavior; Female; Hyperphagia; Leptin; Male; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Obesity; Receptors, Leptin; Reward; Signal Transduction; Weight Gain

The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (SHR), long-term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin-angiotensin system.. In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks-YMSHR) and old (21-22 months-OMSHR) male SHR that increased serum testosterone by 2-fold in young males and by 4-fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in YMSHR but had no effect in OMSHR. Mean arterial pressure (MAP) was significantly higher in OMSHR than in YMSHR and testosterone supplements decreased MAP in OMSHR, but significantly increased MAP in YMSHR. Enalapril, the angiotensin-converting enzyme inhibitor, reduced MAP in both control and testosterone-supplemented YMSHR, but had a greater effect on MAP in testosterone-treated rats, suggesting the mechanism responsible for the increase in MAP in YMSHR is mediated at least in part by activation of the renin-angiotensin system.. Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long-term or short-term.

Topics: Adiposity; Age Factors; Aging; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Arterial Pressure; Disease Models, Animal; Enalapril; Estradiol; Hormone Replacement Therapy; Hypertension; Leptin; Male; Rats, Inbred SHR; Renin-Angiotensin System; Risk Factors; Testosterone; Weight Gain

The aim of this study was to investigate the effect of a high fat diet with experimental oil consisting of 60% MUFAs (monounsaturated fatty acids) with a P/S ratio of 5 on fat deposition and lipid metabolism in obese hamsters. Hamsters were randomly assigned to a control group and a diet-induced obesity group for nine weeks. Then an additional eight-week experimental period began, during which obese hamsters were randomly divided into three groups and fed different amounts of the experimental oil mixture in their diets as follows: 5%, 15%, and 20% w/w (OB-M5, OB-M15, and OB-M20 groups, respectively). The results showed that the OB-M15 and OB-M20 groups had significantly lower blood cholesterol and higher insulin levels. Compared to the control group, the three obese groups exhibited higher hepatic fatty acid synthase activity; however, the acyl-CoA oxidase activities were also enhanced. Although dietary fat content differed, there were no differences in energy intake, final body weights, and epididymal fat weights among the four groups. These results suggest that regardless of whether the specimens had a high fat intake or not, dietary fat containing high MUFAs with a high P/S ratio had beneficial effects on maintaining blood lipid profiles and may not result in body fat accumulation in obese hamsters, possibly by promoting lipolytic enzyme activities.

Topics: Adiponectin; Adiposity; Animals; Blood Glucose; Body Weight; Cholesterol; Cricetinae; Diet, High-Fat; Dietary Fats; Fatty Acid Synthases; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Insulin; Leptin; Lipid Metabolism; Lipoprotein Lipase; Liver; Male; Obesity; PPAR gamma; RNA, Messenger; Sterol Esterase; Triglycerides; Weight Gain

Body weight (BW) cycling, the yo-yo effect, is generally thought to have adverse effects on human metabolic health. However, human and animal experiments are limited in number and do not provide clear answers, partly due to large variations in experimental design, parameters measured, and definitions of BW cycling. Here, we examined the effect of repetitive BW cycling versus single- and non-cycling control groups, without alterations in diet composition, on steady state BW and metabolic parameters.. We induced well-defined BW cycles on a semi-purified high fat diet in C57BL/6J mice, a well-described animal model for diet-induced obesity, and measured energy expenditure and relevant metabolic parameters.. Our setup indeed resulted in the intended BW changes and always reached a stage of energy balance. A history of weight cycling did not result in increased BW or fat mass compared with the control group, nor in deteriorated serum concentrations of glucose, adipokines and serum triglyceride and free fatty acid (FFA) concentrations. If anything, BW tended to be reduced, presumably because of a reduced overall energy intake in BW cycling animals.. Repeated cycling in BW without changes in diet composition does not lead to impaired metabolic health nor increased BW (gain).

Topics: Adiponectin; Adiposity; Animals; Blood Glucose; Body Weight; Diet, High-Fat; Endpoint Determination; Energy Metabolism; Fatty Acids, Nonesterified; Leptin; Male; Mice; Mice, Inbred C57BL; Triglycerides; Weight Gain

Context Emblica officinalis Gaertn. (family-Phyllanthaceae) fruits, known commonly as amla, is extensively used in Indian traditional system of medicine for the treatment of various disorders. The ethanolic E. officinalis extract is reported to have various activity such as antidiabetic, antihyperlipidemic and antioxidant activity in experimental animals. Objective To evaluate anti-obesity effect of aqueous E. officinalis extract in murine model of high fat diet (HFD)-induced obesity. Materials and methods Male Wistar rats fed with HFD (20 g/day/rat, p.o) for a period of 42 days were used to induce obesity. Aqueous E. officinalis extract (20 mg/kg bw) administered orally to HFD-fed rats from day 8 to 50 days for a period of 42 days. Body weight gain, serum lipids, insulin and leptin parameters were measured. Results Oral feeding of the aqueous E. officinalis extract (20 mg/kg) to HFD-induced obese rats for a period of 42 days resulted in significant reduction in body weight gain, insulin, leptin, lipids as compared to rats fed HFD alone. Further, the extract also showed significant increase in high density lipoprotein (HDL-C) levels. Discussion and conclusions These results show that aqueous E. officinalis extract possess significant anti-obesity potential.

Topics: Animals; Anti-Obesity Agents; Cholesterol, HDL; Diet, High-Fat; Insulin; Leptin; Lipids; Male; Obesity; Phyllanthus emblica; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Weight Gain

Breast milk is known to contain many bioactive hormones and peptides, which can influence infant growth and development. In this context, the purpose of this study was to evaluate the influence of different clinical pregnancy conditions on hormone concentrations in colostrum and mature breast milk.. An observational study was performed with mother-newborn pairs divided into five groups according to maternal clinical background: diabetes (12), hypertension (5), smoking (19), intrauterine growth restriction of unknown causes with small-for-gestational-age newborns at delivery (12), and controls (21). Socioeconomic data, anthropometric measurements and breast milk samples were collected between the first 24 and 48 h and 30 days postpartum. Leptin, adiponectin, and insulin levels in breast milk were measured by immunoassays.. A significant decrease in leptin (p = 0.050) and insulin (p = 0.012) levels from colostrum to mature breast milk in mothers of small-for-gestational-age infants was observed. Maternal body mass index was correlated with both leptin and insulin, but not with adiponectin. Insulin levels were negatively correlated to infant weight gain from birth to one month (p = 0.050). In addition, catch-up growth was verified for small-for-gestational-age infants throughout the first month of life.. This study suggests that a remarkable decrease in leptin and insulin levels in mature milk of mothers of small-for-gestational-age newborns may be involved in the rapid weight gain of these newborns. The physiological and external mechanisms by which these significant decreases and rapid weight gains occur in this group remain to be elucidated.

Topics: Adiponectin; Breast Feeding; Colostrum; Female; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Small for Gestational Age; Insulin; Leptin; Milk, Human; Postpartum Period; Pregnancy; Prospective Studies; Weight Gain

Topics: Adult; Alleles; Body Mass Index; Brazil; Female; Follow-Up Studies; Gene Frequency; Humans; Leptin; Obesity; Overweight; Polymorphism, Single Nucleotide; Pregnancy; Prospective Studies; Receptors, Leptin; Risk Factors; Socioeconomic Factors; Weight Gain; Young Adult

The effect of obesity on testicular activity in prepubertal and pubertal rats was investigated in the present study. Obesity was induced in adult females by feeding a high-calorie diet (HCD). These females were mated with normal males and were fed an HCD during pregnancy and lactation. The male offspring born to obese mothers and fed an HCD after weaning were found to be obese. Seminiferous tubules of offspring from control mothers (OCM) and offspring from HCD-fed mothers (OHCDM) had the same set of germ cells at different age intervals, namely spermatogonia, leptotene spermatocytes, zygotene spermatocytes, pachytene spermatocytes and round and elongated spermatids on postnatal days (PND) 7, 13, 17, 24 and 36, and on the day of preputial separation, respectively. However, there was a significant decrease in round and elongated spermatids and the epididymal sperm count, coupled with a significant decrease in testosterone and an increase in leptin serum concentrations in OHCDM compared with OCM. These results show that obesity in prepubertal rats does not affect the age-dependent appearance of germ cells according to developmental hierarchy, but it does interfere with spermatid formation, resulting in a reduced sperm count, which may be due to a deficiency of testosterone mediated by hyperleptinaemia.

Topics: Animals; Diet, High-Fat; Female; Lactation; Leptin; Male; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Spermatic Cord; Spermatogenesis; Testosterone; Weight Gain

Our aim was to characterize the effect of an unfamiliar high-fat diet (HFD) on circadian feeding behaviour, plasma parameters, body weight (BW), and gene expression in the prefrontal cortex (PFC) of adolescent male mice. To this end, mice were allowed to consume a HFD during 48 h, but one group was allowed a free choice of HFD or normal chow (FC-HFD), while the other was restricted to a non-optional unfamiliar HFD feeding (NOP-HFD).. Energy intake was monitored at 6-h intervals during 48 h. Mice cohorts were killed at 6-h intervals after 48-h dietary treatment, and PFC samples dissected for RT-PCR analysis.. Mice on the FC-HFD protocol avoided eating the standard chow, showed lower energy intake and lower BW increase than NOP-HFD mice. All animals with access to HFD exhibited nocturnal overeating, but diurnal hyperphagia was more prominent in the FC-HFD cohort. A robust increase in tyrosine hydroxylase (Th) gene expression was detected specifically during the light period of the circadian cycle in FC-HFD mice. In contrast, both protocols similarly up-regulated the expression of cytosolic malic enzyme (Me1), which is very sensitive to HFD.. Our data show that the PFC participates in driving motivational feeding during HFD-evoked hyperphagia and also suggest that sensory neural pathways might be relevant for the onset of eating disorders and overweight. Moreover, we have observed that animals that had the possibility of choosing between standard chow and HFD were more hyperphagic and specifically displayed an overexpression of the tyrosine hydroxylase gene.

Topics: Animals; Blood Glucose; Body Weight; Choice Behavior; Circadian Rhythm; Diet, High-Fat; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Gene Expression Regulation; Hyperphagia; Insulin; Leptin; Malate Dehydrogenase; Male; Mice; Mice, Inbred C57BL; Overweight; Prefrontal Cortex; Receptors, Leptin; Tyrosine 3-Monooxygenase; Weight Gain

To analyze weight gain, metabolic hormones, and homocysteine (Hcys) levels in children and adolescents on antipsychotics (AP) during a year-long follow-up. 117 patients, AP-naïve or quasi-naïve (less than 30 days on AP), were included. Weight, body mass index (BMI), BMI z-score (z-BMI), and levels of leptin, insulin, insulin resistance (HOMA-IR), adiponectin, ghrelin, thyroid stimulating hormone (TSH), free thyroxine (FT4), and Hcys were measured at baseline, and at 3, 6, and 12 months, while patients remained on the same AP. Patients (mean age: 14.4 ± 3 years; 64.1 % male) were on risperidone (N = 84), olanzapine (N = 20) or quetiapine (N = 13) from baseline up to 1-year follow-up and significantly increased weight (5.8 ± 4.3 kg at 3-month, 8.1 ± 6.1 kg at 6-month, and 11.6 ± 7.0 kg at 1 year), BMI, and z-BMI. Leptin levels significantly increased from baseline to 3 and 6 months, as did TSH levels from baseline to 3 months, while FT4 levels decreased from baseline to 3 and 6 months. Patients with BMI >85th percentile at baseline (N = 16) significantly increased weight, BMI, and z-BMI, more than patients with normal BMI over time. Higher baseline levels of insulin, HOMA-IR, and leptin were associated with increased weight/BMI during follow-up, while higher baseline levels of FT4, adiponectin, and ghrelin were associated with lower weight/BMI during follow-up. All AP were associated with increased weight and BMI/z-BMI in all of the assessments; however, at 1-year assessment, this increase was significantly higher for patients on quetiapine. Both higher baseline levels of insulin, HOMA-IR, and leptin, as well as being overweight/obese at baseline were associated with increased weight/BMI during 1-year follow-up in children and adolescents on AP. Awareness of weight-related parameters in this population may help inform decisions regarding AP prescriptions.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Body Weight; Child; Child, Preschool; Female; Follow-Up Studies; Ghrelin; Homocysteine; Humans; Insulin; Leptin; Male; Obesity; Olanzapine; Prospective Studies; Risperidone; Time Factors; Treatment Outcome; Weight Gain

This study aimed to investigate the relationship between skinfold thickness and serum leptin, ghrelin, adiponectin, and resistin levels in infants of diabetic mothers. Biochemical parameters were also similar for the two groups (infants of diabetic mothers and controls) (p > 0.05). We confirmed that there was a negative correlation between birth weight and serum ghrelin level (p < 0.05) in the two groups. When it was evaluated for control newborns, a positive correlation between abdominal circumference and serum resistin level was found in the controls (p < 0.05). Our results indicate that gestational diabetes by appropriate diet or insulin treatment may be effective in the protection of fetuses of diabetic mothers from the negative effects of gestational diabetes. Ghrelin alone was negatively correlated with birth weight. This negative correlation could be potentially advantageous to infants, because a reduction in appetite might prevent excessive food intake and postnatal weight gain.

Topics: Adiponectin; Adipose Tissue; Anthropometry; Birth Weight; Case-Control Studies; Diabetes, Gestational; Feeding Behavior; Female; Gestational Age; Ghrelin; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Infant, Newborn; Leptin; Male; Pregnancy; Resistin; Skinfold Thickness; Weight Gain

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

The pacu Piaractus mesopotamicus is an omnivorous fish considered a promising species for aquaculture. Little is known about the endocrine regulation of feeding in this species. In this study, transcripts for orexin, cocaine and amphetamine regulated transcript (CART), cholecystokinin (CCK) and leptin were isolated in pacu. Orexin, CCK and leptin have widespread mRNA distributions in brain and periphery, CART is limited to the brain. To examine the role of these peptides in the regulation of feeding and energy status, mRNA expression levels were compared between fed and fasted fish and around feeding time. Both orexin and CART brain expressions were affected by fasting and displayed periprandial changes, suggesting a role in both short- and long-term regulation of feeding. CCK intestinal expression decreased in fasted fish and displayed periprandial changes, suggesting CCK acts as a peripheral satiety factor. Leptin was not affected by fasting but displayed periprandial changes, suggesting a role as a short-term regulator. To examine if these peptides are affected by diet, brain and gut expressions were assessed in fish fed with different diets containing soy protein concentrate. Food intake, weight gain and expressions of orexin, CART, CCK and leptin were little affected by replacement of fish protein with soy protein, suggesting that pacu is able to tolerate and grow well with a diet rich in plant material. Overall, our results suggest that orexin, CART, CCK and leptin are involved in the physiology of feeding of pacu and that their expressions are little affected by plant-based diets.

Topics: Animal Feed; Animals; Appetite Regulation; Aquaculture; Brain; Cholecystokinin; Diet; Energy Intake; Fish Proteins; Fishes; Gene Expression Regulation, Developmental; Intestinal Mucosa; Leptin; Nerve Tissue Proteins; Neurons; Orexins; Organ Specificity; Random Allocation; Soybean Proteins; Weight Gain

The phosphoinositide phosphatase, myotubularin-related protein 14 (MTMR14), has been reported to play an important role in the regulation of muscle performance, autophagy, and aging in mice. We previously showed that MTMR14-knockout (KO) mice gain weight earlier than their wild-type (WT) littermates even on a normal chow diet (NCD), suggesting that this gene might also be involved in regulating metabolism. In the present study, we evaluated the effect of MTMR14 deficiency on high-fat diet (HFD)-induced obesity, lipid accumulation, metabolic disorders, and inflammation in WT and MTMR14-KO mice fed with NCD or HFD. To this end, MTMR14-KO mice fed with HFD showed significantly increased body weight, blood glucose levels, serum triglyceride (TG) levels, and total cholesterol (TC) levels as compared to their age-matched WT control. Additionally, lipid accumulation also increased in the KO mice. Simultaneously, the expression of metabolism-associated genes (Glut4, adiponectin, and leptin) was different in the liver, muscle, and fatty tissue of MTMR14-KO mice fed with HFD. More importantly, the expression of several inflammation-associated genes (TNF-α, IL-6, IL-1β, and MCP-1) dramatically increased in the liver, muscle, and fatty tissue of MTMR14-KO mice relative to control. Taken together, these results suggest that MTMR14 deficiency accelerates HFD-induced metabolic dysfunction and inflammation. Furthermore, the results showed that exacerbated metabolic dysfunction and inflammation may be regulated via the PI3K/Akt and ERK signaling pathways.

Topics: Adiponectin; Adipose Tissue; Animals; Cytokines; Diet, High-Fat; Gene Expression Regulation; Glucose Transporter Type 4; Hyperglycemia; Hyperlipidemias; Leptin; Lipid Metabolism; Liver; Male; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Obesity; Phosphoric Monoester Hydrolases; Random Allocation; Weight Gain

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

Research indicates that breast milk contains bioactive components that influence metabolism in infancy and may play a role in the prevention of obesity in early childhood. In our initial study, 147 breastfeeding mother/child pairs were followed from birth to 2 years of age to examine the relationship between breast milk leptin and total adiponectin (collected at 6 weeks and 4 months postpartum) and infant body composition. Higher breast milk total adiponectin was related to greater fat mass and weight gain in children at 1 and 2 years of age, whereas leptin showed no association.. In this follow-up, we examined the relationship between both adipokines and children's body weight, body mass index percentiles, sum of four skin-folds, percentage of body fat, fat mass and lean body mass at 3, 4 and 5 years of age.. Breast milk adipokines were largely unrelated to child anthropometric measures.. Our results do not provide significant evidence that breast milk adipokines can predict adiposity in preschool children.

Topics: Adiponectin; Adiposity; Anthropometry; Body Composition; Breast Feeding; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Leptin; Milk, Human; Weight Gain

A significant change in the Western diet, concurrent with the obesity epidemic, was a substitution of saturated fatty acids with polyunsaturated, specifically linoleic acid (LA). Despite increasing investigation on type as well as amount of fat, it is unclear which fatty acids are most obesogenic. The objective of this study was to determine the obesogenic potency of LA vs. saturated fatty acids and the involvement of hypothalamic inflammation. Forty-eight mice were divided into four groups: low-fat or three high-fat diets (HFDs, 45% kcals from fat) with LA comprising 1%, 15% and 22.5% of kilocalories, the balance being saturated fatty acids. Over 12 weeks, bodyweight, body composition, food intake, calorimetry, and glycemia assays were performed. Arcuate nucleus and blood were collected for mRNA and protein analysis. All HFD-fed mice were heavier and less glucose tolerant than control. The diet with 22.5% LA caused greater bodyweight gain, decreased activity, and insulin resistance compared to control and 1% LA. All HFDs elevated leptin and decreased ghrelin in plasma. Neuropeptides gene expression was higher in 22.5% HFD. The inflammatory gene Ikk was suppressed in 1% and 22.5% LA. No consistent pattern of inflammatory gene expression was observed, with suppression and augmentation of genes by one or all of the HFDs relative to control. These data indicate that, in male mice, LA induces obesity and insulin resistance and reduces activity more than saturated fat, supporting the hypothesis that increased LA intake may be a contributor to the obesity epidemic.

Topics: Animals; Carbon Dioxide; Chemokine CX3CL1; Diet, Fat-Restricted; Encephalitis; Fatty Acids; Ghrelin; Glucose; Hypothalamus; Leptin; Linoleic Acid; Male; Mice, Inbred C57BL; Weight Gain

Cell proliferation and neuroinflammation in the adult hypothalamus may contribute to the pathogenesis of obesity. We tested whether the intertwining of these two processes plays a role in the metabolic changes caused by 3 weeks of a high-saturated fat diet (HFD) consumption. Compared with chow-fed mice, HFD-fed mice had a rapid increase in body weight and fat mass and specifically showed an increased number of microglia in the arcuate nucleus (ARC) of the hypothalamus. Microglia expansion required the adequate presence of fats and carbohydrates in the diet because feeding mice a very high-fat, very low-carbohydrate diet did not affect cell proliferation. Blocking HFD-induced cell proliferation by central delivery of the antimitotic drug arabinofuranosyl cytidine (AraC) blunted food intake, body weight gain, and adiposity. AraC treatment completely prevented the increase in number of activated microglia in the ARC, the expression of the proinflammatory cytokine tumor necrosis factor-α in microglia, and the recruitment of the nuclear factor-κB pathway while restoring hypothalamic leptin sensitivity. Central blockade of cell proliferation also normalized circulating levels of the cytokines leptin and interleukin 1β and decreased peritoneal proinflammatory CD86 immunoreactive macrophage number. These findings suggest that inhibition of diet-dependent microglia expansion hinders body weight gain while preventing central and peripheral inflammatory responses due to caloric overload.

Topics: Adiposity; Animals; Antimitotic Agents; Arabinonucleosides; Arcuate Nucleus of Hypothalamus; Body Weight; Cell Proliferation; Cytarabine; Cytidine; Diet, High-Fat; Eating; Hypothalamus; Inflammation; Interleukin-1beta; Leptin; Macrophages, Peritoneal; Male; Mice; Microglia; NF-kappa B; Obesity; Tumor Necrosis Factor-alpha; Weight Gain

Topics: 3T3-L1 Cells; Adipose Tissue; Animals; Cell Cycle Proteins; Energy Metabolism; Genetic Predisposition to Disease; Growth Differentiation Factor 15; Homeostasis; Insulin Resistance; Leptin; Lipolysis; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Mitochondria, Liver; Mitochondria, Muscle; Muscle, Skeletal; Obesity; Oxidation-Reduction; Oxidative Phosphorylation; Phenotype; Recombinant Proteins; RNA Interference; Signal Transduction; Time Factors; Transcription Factor CHOP; Transfection; Unfolded Protein Response; Weight Gain

Effectors of the phosphoinositide 3-kinase (PI3K) signal transduction pathway contribute to the hypothalamic regulation of energy and glucose homeostasis in divergent ways. Here we show that central nervous system (CNS) action of the PI3K signaling intermediate atypical protein kinase C (aPKC) constrains food intake, weight gain, and glucose intolerance in both rats and mice. Pharmacological inhibition of CNS aPKC activity acutely increases food intake and worsens glucose tolerance in chow-fed rodents and causes excess weight gain during high-fat diet (HFD) feeding. Similarly, selective deletion of the aPKC isoform

Topics: Animals; Diet, High-Fat; Eating; Energy Metabolism; Glucose; Glucose Intolerance; Hypothalamus; Insulin Resistance; Isoenzymes; Leptin; Male; Melanocortins; Mice; Neurons; Obesity; Paraventricular Hypothalamic Nucleus; Phosphatidylinositol 3-Kinases; Pro-Opiomelanocortin; Protein Kinase C; Rats; Signal Transduction; Weight Gain

Preterm, very-low-birth-weight (PT-VLBW) neonates are at-risk for metabolic syndrome later in life. At 1-3 y, they exhibit excessive weight-for-length z-scores (Wt-L. This was a cross-sectional cohort study of PT-VLBW infants at 1, 2, and 3 y of age (40/cohort). We measured SBP, abdominal circumference (AC) and anthropometrics; calculated age/gender-specific z-scores for Wt, L, Wt-L and subscapular skin fold (SS. Serum leptin was unaffected by chronologic age and gender, but was positively correlated with weight, Wt-L. Although serum leptin was unrelated to advancing age, gender, and SBP in PT-VLBW infants, levels correlated with measures of adiposity at 1 and 3 y, females > males, suggesting leptin resistance may occur in early infancy.

Topics: Adiponectin; Adiposity; Age Factors; Biomarkers; Blood Pressure; Child Development; Child, Preschool; Cross-Sectional Studies; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Leptin; Male; Metabolic Syndrome; Resistin; Risk Factors; Sex Factors; Skinfold Thickness; Waist Circumference; Weight Gain

Previous longitudinal studies have shown inconsistent results regarding the influence of adipokines on changes in weight and body fat. We aimed to determine the predictive value of serum leptin, adiponectin, and their ratio on subsequent changes in obesity measures in children.. Two hundred forty-six obese and 532 nonobese children aged 6-11 years were remeasured for BMI and waist circumference after 6.4 ± 0.2 years. Z-score of BMI was used to standardize for age and sex. Obesity was defined using the international BMI cutoffs. Waist-to-height ratio (WHtR) was calculated to define central obesity using a boundary value of 0.5. Fasting serum leptin and adiponectin levels were measured at baseline.. Newly identified obese children had significantly higher levels of leptin and leptin-to-adiponectin ratio than nonobese children. There were lower adiponectin levels in boys with persistent obesity versus those with transient obesity. After adjusting for age, Tanner stage, and corresponding adiposity measures at baseline, leptin levels and leptin-to-adiponectin ratio were positively associated with BMI Z-score gain in girls and WHtR gain in boys. An inverse association between leptin and BMI Z-score gain was detected in boys. Stratified analyses revealed significant associations only in the nonobese and prepubertal group. There were no significant associations between adiponectin and changes in obesity measures.. High leptin levels and leptin-to-adiponectin ratio are sex-specific predictors of obesity measures gain in nonobese and prepubertal children. Body composition measurement is necessary to assess fat mass growth and distribution during childhood and adolescence.

Topics: Adiponectin; Adiposity; Body Height; Body Mass Index; Body Weight; Child; China; Fasting; Female; Humans; Leptin; Male; Pediatric Obesity; Prospective Studies; Sex Factors; Waist Circumference; Weight Gain

Gestational weight gain (GWG) is an important modifiable factor known to influence fetal outcomes including birth weight and adiposity. Unlike behaviors such as smoking and alcohol consumption, the effect of GWG throughout pregnancy on fetal development and other outcomes has not been extensively studied. The aim of this study was to investigate the relationship of GWG with endocrine factors such as adiponectin, leptin, and C-reactive protein which may be associated with inflammatory response, fetal growth, and adiposity later in life. Data were obtained from the Ulm Birth Cohort Study (UBCS) and the Ulm SPATZ Health Study, two methodologically similar birth cohort studies including newborns and their mothers recruited from 11/2000-11/2001 and 04/2012-05/2013. In the two included birth cohorts we consistently observed statistically significant positive associations between GWG beginning as early as the second trimester with fetal cord blood leptin and stronger association beginning as early as the first trimester with post-delivery maternal serum leptin. Total weight gain exceeding commonly accepted recommended guidelines was consistently associated with higher leptin levels in both cord blood and post-delivery maternal serum. These results suggest a potential pathomechanistic link between fetal environment and surrogate markers of long-term health.

Topics: Adiponectin; Adiposity; Adult; Biomarkers; Birth Weight; C-Reactive Protein; Case-Control Studies; Female; Fetal Weight; Humans; Infant, Newborn; Leptin; Male; Pregnancy; Pregnancy Complications; Weight Gain

Patients with central precocious puberty (CPP) may have increased serum leptin levels; however, it is not well known whether this increase differs between patients with and without obesity. Our objectives were to describe the changes in serum leptin in girls with CPP in the first 12 months after diagnosis based on body mass index (BMI) and to explore whether serum leptin level at CPP diagnosis is related to BMI z-score (BMIz) after a 1-year follow-up.. A prospective cohort study was performed. We included 42 girls with idiopathic CPP in Tanner stages II and III. Anthropometric measurements were performed, and serum leptin was measured at study initiation and after 12 months. Patients were stratified according to BMI category (30 with a BMI in the <94th percentile and 12 with a BMI in the >95th percentile). Study variables were compared. Correlations among leptin, BMIz, and body fat were assessed.. Leptin increased gradually during the first year of treatment. In girls with a BMI in the <94th percentile at diagnosis, body fat percentage increased gradually during the first year of follow-up.. Girls with a BMI in the <94th percentile have a greater risk of weight increase. Leptin level >10.5 ng/dL at diagnosis is a risk factor for weight gain after 1 year.. BMI = body mass index BMIz = BMI z-score CPP = central precocious puberty GnRHa = gonadotropin-releasing hormone analogue.

Topics: Body Mass Index; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Leptin; Pediatric Obesity; Puberty, Precocious; Weight Gain

We investigated the relationship between early antibiotic exposure before 6 months age and risk for obesity at 2 years in a high-risk, low-income, urban Latino cohort (n = 97), with the hypothesis that antibiotic exposure would increase risk for obesity by 2 years. Data were collected through maternal report of infant 24-hour dietary intake at 4-6 weeks, 6 months, 1, and 2 years; and food frequency questionnaires at 4-6 weeks, 6 months, 1, and 2 years. Antibiotic use data, including type and frequency, were collected through maternal self-report at 6 months and 1 year. Cord blood levels of leptin and insulin were measured at birth. Chi-squared tests were used to assess the relationship between obesity and dichotomous predictors and Student's t-tests for continuous predictors. Multivariable logistic models were used to ascertain independent predictors of obesity at age 2. We found that early antibiotic exposure before 6 months was independently associated with increased risk for rapid infant weight gain [odds ratio (OR) 6.42, 95% confidence interval (CI, defined as the range in which sample will fall with 95% confidence: 1.17-35.06)] and obesity at age 2 [OR 6.15, 95% CI (1.03-36.70)]. These findings provide evidence promoting antibiotic stewardship in pediatric practices to minimize exposure in the first 6 months of life.

Topics: Anti-Bacterial Agents; Child, Preschool; Diet; Female; Fetal Blood; Hispanic or Latino; Humans; Infant; Insulin; Leptin; Logistic Models; Male; Odds Ratio; Pediatric Obesity; Poverty; Pregnancy; Risk Factors; Surveys and Questionnaires; Weight Gain

A total of 2,948 steers (mean initial BW = 568.9 ± 49.4 kg) were used to evaluate the effect of the LEP R25C SNP genotype on feed intake, growth performance, and carcass characteristics over time. Steers were grouped into 5 blocks, each consisting of 10 pens initially, and then at approximately 24 d prior to the assigned slaughter date, cattle in each pen were randomly selected either to remain in the pen they were in (group A) or to be assigned to a new pen (group B). Steers were allocated to 5 blocks and 6 harvest weeks (-3, -2, 0, 2, 3, and 4 wk) relative to the projected end point. Steers were weighed and ultrasound scanned at 60 and 1 d prior to harvest. Leptin genotype affected ( ≤ 0.011) 12th-rib fat and i.m. fat percentage (IMF) for each slaughter group at both 60 and 1 d prior to slaughter, although rib eye area (REA) was not affected ( = 0.773) by leptin genotype 60 d prior to slaughter in any group. Time affected ( < 0.001) live BW as well as 12th-rib fat, REA, and IMF measured 60 and 1 d prior to each slaughter time. Dry matter intake was also higher ( = 0.003) for cattle of the animals homozygous for the T allele (TT) genotype compared to those with the animals homozygous for the C allele (CC) genotype (9.59 vs. 9.29 ± 0.075 kg). The LEP R25C genotype affected key traits related to carcass fatness; specifically, compared to cattle of the CC genotype, cattle of the TT genotype had a higher ( = 0.016) calculated empty body fat (29.1 vs. 28.8 ± 0.133%) and higher ( = 0.020 calculated yield grade (2.62 vs. 2.52 ± 0.035). Additionally, like for live measures, TT cattle tended ( = 0.093) to have a higher 12th-rib fat (13.2 vs. 12.8 ± 0.26 mm). However, the LEP R25C genotype did not affect KPH ( = 0.854) or marbling score ( = 0.240), nor did it affect any USDA quality measure ( ≥ 0.350). The leptin genotype also affected ( = 0.048) HCW, which was highest for steers of the TT genotype (400.9 vs. 403.5 ± 3.41kg). Results indicate that the leptin R25C genotype and time impacted most traits associated with fatness.

Topics: Adipose Tissue; Animal Feed; Animals; Body Composition; Cattle; Gene Expression Regulation; Genotype; Leptin; Male; Phenotype; Polymorphism, Single Nucleotide; Weight Gain

High-fat (HF) diets result in weight gain, hyperphagia, and reduced dopamine D2 signaling; however, these findings have been obtained only under free-feeding conditions. This study tested the extent to which HF diet affects effort-dependent food procurement and the extent to which dopamine signaling is involved. Male Sprague-Dawley rats consumed either a HF (n=20) or a standard-chow (n=20) diet. We assessed the sensitivity to effort-based reinforcement in 10 rats from each group by measuring consumption across a series of fixed-ratio schedules (FR 5-FR 300) under a closed economy and quantified performance using the exponential-demand equation. For each FR, acute injections of 0 or 0.1 mg/kg of haloperidol, a D2 antagonist, were administered to assess dopamine-related changes in consumption. Rats fed a HF diet consumed more calories and weighed significantly more than rats fed standard-chow. Food consumption decreased in both groups in an effort-dependent manner, but there were no group differences. Haloperidol reduced responding in an FR-dependent manner for both groups. Animals exposed to a HF diet showed an altered sensitivity to haloperidol relative to rats fed a standard diet, suggesting that HF diet alters sensitivity to DA signaling underlying effort-based food procurement.

Topics: Animals; Body Weight; Diet, High-Fat; Dietary Fats; Dopamine; Energy Intake; Feeding Behavior; Haloperidol; Hyperphagia; Leptin; Male; Obesity; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; Weight Gain

Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM%) was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI), weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin (

Topics: Adiponectin; Adiposity; Body Composition; Body Mass Index; Brazil; Cross-Sectional Studies; Female; Fetal Development; Humans; Infant, Newborn; Leptin; Linear Models; Male; Pediatric Obesity; Plethysmography; Pregnancy; Socioeconomic Factors; Weight Gain

Perinatal high-fat diet is associated with obesity and metabolic diseases in adult offspring. Resveratrol has been shown to exert antioxidant and anti-obesity actions. However, the effects of resveratrol on leptinemia and leptin signaling are still unknown as well as whether resveratrol treatment can improve metabolic outcomes programmed by maternal high-fat diet. We hypothesize that resveratrol treatment in male rats programmed by high-fat diet would decrease body weight and food intake, and leptinemia with changes in central leptin signaling.. Female Wistar rats were divided into two groups: control group (C), which received a standard diet containing 9 % of the calories as fat, and high-fat group (HF), which received a diet containing 28 % of the calories as fat. Dams were fed in C or HF diet during 8 weeks before mating and throughout gestation and lactation. C and HF male offspring received standard diet throughout life. From 150 until 180 days of age, offspring received resveratrol (30 mg/Kg body weight/day) or vehicle (carboxymethylcellulose).. HF offspring had increased body weight, hyperphagia and increased subcutaneous and visceral fat mass compared to controls, and resveratrol treatment decreased adiposity. HF offspring had increased leptinemia as well as increased SOCS3 in the arcuate nucleus of the hypothalamus, which suggest central leptin resistance. Resveratrol treatment rescued leptinemia and increased p-STAT3 content in the hypothalamus with no changes in SOCS3, suggesting improvement in leptin signaling.. Collectively, our data suggest that resveratrol could reverse hyperleptinemia and improve central leptin action in adult offspring from HF mothers attenuating obesity.

Topics: Adipose Tissue; Animals; Body Composition; Diet, High-Fat; Female; Hyperphagia; Hypothalamus; Janus Kinase 2; Leptin; Male; Maternal Nutritional Physiological Phenomena; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Resveratrol; Signal Transduction; STAT3 Transcription Factor; Stilbenes; Suppressor of Cytokine Signaling 3 Protein; Weight Gain

Overnutrition during early development has been linked to metabolic disease and obesity in adulthood. Interventions to ameliorate this metabolic malprogramming are needed. Our objective was to determine whether prebiotic fibre would reduce weight gain and improve satiety hormone profiles in rats overnourished during the suckling period.. Male Sprague-Dawley rats reared in small litter (SL 3 pups) or normal litter (NL 12 pups) were randomized at weaning to AIN-93 (control) or a 10 % oligofructose (OFS) diet for 16 weeks. Body composition, an oral glucose tolerance test for glucose and gut hormones, and gut microbiota were assessed.. At weaning, body weight was higher in SL than in NL rats (P < 0.03). At 19 weeks, body weight was lower with OFS than control (P < 0.04). There was a diet × litter size interaction wherein OFS in SL rats reduced body fat (%) to levels seen in NL rats (P < 0.05). OFS attenuated the glucose response in SL but not in NL rats (P < 0.015). Independent of litter size, OFS decreased total AUC for glucose-dependent insulinotropic polypeptide (P < 0.002) and increased total AUC for peptide YY (P < 0.01) and glucagon-like peptide-1 (P < 0.04) when compared to control. OFS, not litter size, played the predominant role in altering gut microbiota which included increased bifidobacteria and Akkermansia muciniphila with OFS.. Postnatal consumption of OFS by rats raised in SL was able to attenuate body fat and glycaemia to levels seen in NL rats. OFS appears to influence satiety hormone and gut microbiota response similarly in overnourished and control rats.

Topics: Animals; Blood Glucose; Body Composition; Dietary Fiber; Energy Intake; Fatty Acids, Volatile; Gastric Inhibitory Polypeptide; Gastrointestinal Microbiome; Ghrelin; Glucagon-Like Peptide 1; Glucose Tolerance Test; Insulin; Islet Amyloid Polypeptide; Leptin; Male; Oligosaccharides; Organ Size; Overnutrition; Peptide YY; Prebiotics; Rats; Rats, Sprague-Dawley; Weight Gain

The Roux-en-Y gastric bypass (RYGB) is the gold standard bariatric operation. However, a major concern in late follow-up is the substantial weight regain. Understanding the role of gastrointestinal hormone secretion in this situation is relevant.. The aim of the present study was to evaluate the influence of gastrointestinal hormones comparing postprandial secretion of ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and leptin between patients with weight regain and those with favorable weight control. Twenty-four patients with follow-up from 27 to 59 months were divided into two groups according to sustained weight loss: group A (14 patients) had sustained weight losses, and group B (10 patients) had significant weight regain. Basal serum levels of ghrelin, GIP, GLP-1, and leptin after fasting and 30, 60, 90, and 120 min after a standard meal were measured.. There was no difference in the ghrelin secretion. There was a difference in the GIP secretion, with a higher percentage increase in 30 min in group A (330% × 192.2%; p = 0.01). There were also differences in the GLP-1 secretion, with higher increases in absolute (p = 0.03) and percentage values after 30 min in group A (124% × 46.5%; p = 0.01). There was also a difference between baseline leptin values, with higher levels in group B (p = 0.02).. The secretion of gut hormones in patients with weight regain after RYGB is different from that in patients with satisfactory weight outcome. After meal stimulation, reduced levels of GIP and GLP-1 may indicate the influence of gut hormones in the process of weight regain.

Topics: Adult; Bendamustine Hydrochloride; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Middle Aged; Obesity, Morbid; Postprandial Period; Weight Gain

Although the effect of genetic background on obesity-related phenotypes is well established, the main objective of this study is to determine the phenotypic responses to cafeteria diet (CAF) of two genetically distinct inbred rat strains and give insight into the molecular mechanisms that might be underlying. Lewis (LEW) and Wistar-Kyoto (WKY) rats were fed with either a standard or a CAF diet. The effects of the diet and the strain in the body weight gain, food intake, respiratory quotient, biochemical parameters in plasma as well as in the expression of genes that regulate leptin signalling were determined. Whereas CAF diet promoted weight gain in LEW and WKY rats, as consequence of increased energy intake, metabolic management of this energy surplus was significantly affected by genetic background. LEW and WKY showed a different metabolic profile, LEW rats showed hyperglycaemia, hypertriglyceridemia and high FFA levels, ketogenesis, high adiposity index and inflammation, but WKY did not. Leptin signalling, and specifically the LepRb-mediated regulation of STAT3 activation and Socs3 gene expression in the hypothalamus were inversely modulated by the CAF diet in LEW (upregulated) and WKY rats (downregulated). In the present study, we show evidence of gene-environment interactions in obesity exerted by differential phenotypic responses to CAF diet between LEW and WKY rats. Specifically, we found the leptin-signalling pathway as a divergent point between the strain-specific adaptations to diet.

Topics: Adiposity; Animals; Diet; Eating; Energy Metabolism; Fast Foods; Gene-Environment Interaction; Genotype; Leptin; Male; Obesity; Organ Size; Rats, Inbred Lew; Rats, Inbred WKY; Signal Transduction; Weight Gain

In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats.

Topics: Animals; Blood Glucose; Drinking Water; Energy Intake; Fasting; Glucose Transporter Type 2; Insulin; Insulin Resistance; Leptin; Male; Peptide YY; Rats; Saccharin; Taste; Weight Gain; Yogurt

The aim of the study was to define the prevalence and degree of advanced bone age (ABA) in normal vs. excessive weight children, and identify variables affecting ABA.. We studied 167 children (3-18 years) with normal weight (28 F, 28 M), overweight (8 F, 12 M), and obesity (OB) (63 F, 28 M) at AI duPont Hospital for Children. We assessed bone age (BA), insulin, leptin, estradiol (E2), DHEAS, and IGF-1 levels.. Almost 25% of OB children have ABA>2 SDS, 33% >2 years (range 2-6.5 years advanced). ABA correlated with leptin, DHEAS and BMI z-score in girls, and with IGF-1 z-score and BMI z-score in boys (p<0.01). Girls with ABA had higher BMI z-score (p<0.001), insulin levels (p=0.02), and rates of weight gain (p=0.03). Boys with ABA had greater BMI z-score (p<0.001), but rate of weight gain did not differ. The greatest degree of ABA was found combining variables by tertiles. The top tertile of BA/CA had the highest insulin and IGF-1 z-scores. The top combined tertiles of DHEAS and BMI z-score or DHEAS and leptin in girls had the highest BA/CA. In boys, the top tertiles of BMI z-score and IGF-1 z-score produced the highest BA/CA. The lowest combined tertiles of any variables related to the lowest BA/CA.. Multiple factors influence skeletal maturation. Almost 25% of children with OB have ABA, associated with BMI z-score, and one or more of the following: insulin, leptin, DHEAS, IGF-1, and rate of weight gain. This report delineates the prevalence and degree of ABA by sex, in children with normal versus excessive weight.

Topics: Adolescent; Age Determination by Skeleton; Body Mass Index; Body Weight; Bone Development; Bone Regeneration; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Obesity; Puberty; Sex Factors; Weight Gain

To evaluate the effect of leptin and other selected variables on gestational weight gain (GWG) according to pre-gestational body mass index (BMI).. Prospective cohort.. Public Health Center, Rio de Janeiro, Brazil.. Two hundred and twenty-eight pregnant women.. Women were followed at the 5-13, 20-26 and 30-36th gestational weeks. The effects of independent variables on GWG in normal weight (BMI 18.5-24.9 kg/m(2) ), overweight (BMI 25.0-29.9 kg/m(2) ) and obese (BMI ≥ 30.0 kg/m(2) ) women were assessed using longitudinal linear mixed-effects models.. Maternal body weight (kg) throughout pregnancy.. Leptin concentrations were associated with GWG in normal weight (β = 0.048, P < 0.001) and overweight (β = 0.023, P = 0.048) women, but not in obese ones (β = 0.011, P = 0.308). Additionally, the number of hours slept per night decreased the effect of leptin on GWG in OW women (β = -0.013, P = 0.002). The effect of other maternal characteristics on GWG was different depending on the BMI category.. Leptin concentrations were positively associated with GWG in normal weight and overweight women, but not in obese ones. Maternal height was associated with GWG in all BMI categories, but other variables such as sleep duration, QUICKI values, HDL-c, smoking habit and marital status presented differential effects according to BMI. We encourage further studies to investigate the association between leptin and gestational weight gain, taking into account the pre-pregnancy weight and sleep duration, in order to compare and confirm our results.. Leptin is associated with weight gain in normal weight and overweight pregnant women, but not in obese ones.

Topics: Adult; Body Mass Index; Brazil; Female; Humans; Ideal Body Weight; Leptin; Linear Models; Longitudinal Studies; Obesity; Overweight; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Prospective Studies; Weight Gain

Di(2-ethylhexyl) phthalate (DEHP) is reported to cause obesity and hypothyroidism in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of obesity and hypothyroidism and to discover the relationship between them.. Male C3H/He mice were treated with DEHP for 5 weeks, and the body weight, food intake, and body temperature were recorded during the exposure. After exposure, key organs and serum were analyzed by Q-PCR, Western blot, and ELISA.. DEHP induced significant body weight gain and adipogenesis in all exposure groups except for 0.05 mg/kg. Marked hyperphagia and daytime hypothermia were also observed, which were accompanied by disturbed hypothalamic neuropeptide expression and reduced BAT UCP1 expression. In addition, WAT lipid metabolism was significantly deceased at low dose (0.5 mg/kg) and increased at high dose (50 and 200 mg/kg). DEHP also induced hypothyroidism, which was probably attributed to the combined effects of hepatic CAR activation and hypothalamic TRH inhibition induced by hypothalamic leptin resistance.. Chronic DEHP exposure could induce obesity by interrupting energy homeostasis, which is probably due to the synergistic effects of hypothyroidism and hypothalamic leptin resistance.

Topics: Adipogenesis; Animals; Body Weight; Diethylhexyl Phthalate; Hypothalamus; Hypothyroidism; Leptin; Male; Mice; Mice, Inbred C3H; Obesity; Plasticizers; Real-Time Polymerase Chain Reaction; Weight Gain

Amylin enhances arcuate (ARC) and ventromedial (VMN) hypothalamic nuclei leptin signaling and synergistically reduces food intake and body weight in selectively bred diet-induced obese (DIO) rats. Since DIO (125)I-amylin dorsomedial nucleus-dorsomedial VMN binding was reduced, we postulated that this contributed to DIO ventromedial hypothalamus (VMH) leptin resistance, and that impairing VMH (ARC + VMN) calcitonin receptor (CTR)-mediated signaling by injecting adeno-associated virus (AAV) expressing a short hairpin portion of the CTR mRNA would predispose diet-resistant (DR) rats to obesity on high-fat (45%) diet (HFD). Depleting VMH CTR by 80-90% in 4-wk-old male DR rats reduced their ARC and VMN (125)I-labeled leptin binding by 57 and 51%, respectively, and VMN leptin-induced phospho-signal transducer and activator of transcription 3-positive neurons by 59% vs. AAV control rats. After 6 wk on chow, VMH CTR-depleted DR rats ate and gained the equivalent amount of food and weight but had 18% heavier fat pads (relative to carcass weight), 144% higher leptin levels, and were insulin resistant compared with control AAV DR rats. After 6 wk more on HFD, VMH CTR-depleted DR rats ate the same amount but gained 28% more weight, had 60% more carcass fat, 254% higher leptin levels, and 132% higher insulin areas under the curve during an oral glucose tolerance test than control DR rats. Therefore, impairing endogenous VMH CTR-mediated signaling reduced leptin signaling and caused DR rats to become more obese and insulin resistant, both on chow and HFD. These results suggest that endogenous VMH amylin signaling is required for full leptin signaling and protection from HFD-induced obesity.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Diet, High-Fat; Eating; Glucose Intolerance; Insulin Resistance; Iodine Radioisotopes; Islet Amyloid Polypeptide; Leptin; Male; Obesity; Radionuclide Imaging; Rats; Receptors, Calcitonin; RNA, Small Interfering; STAT3 Transcription Factor; Ventromedial Hypothalamic Nucleus; Weight Gain

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

Elevated serum leptin levels following rapid therapeutically induced weight gain in anorexia nervosa (AN) patients are discussed as a potential biomarker for renewed weight loss as a result of leptin-related suppression of appetite and increased energy expenditure. This study aims to analyze the predictive value of leptin levels at discharge as well as the average rate of weight gain during inpatient or day patient treatment for body weight at 1-year follow-up. 121 patients were recruited from the longitudinal Anorexia Nervosa Day patient versus Inpatient (ANDI) trial. Serum leptin levels were analyzed at referral and discharge. A multiple linear regression analysis to predict age-adjusted body mass index (BMI-SDS) at 1-year follow-up was performed. Leptin levels, the average rate of weight gain, premorbid BMI-SDS, BMI-SDS at referral, age and illness duration were included as independent variables. Neither leptin levels at discharge nor rate of weight gain significantly predicted BMI-SDS at 1-year follow-up explaining only 1.8 and 0.4 % of the variance, respectively. According to our results, leptin levels at discharge and average rate of weight gain did not exhibit any value in predicting weight at 1-year follow-up in our longitudinal observation study of adolescent patients with AN. Thus, research should focus on other potential factors to predict weight at follow-up. As elevated leptin levels and average rate of weight gain did not pose a risk for reduced weight, we found no evidence for the beneficial effect of slow refeeding in patients with acute AN.

Topics: Adolescent; Anorexia Nervosa; Biomarkers; Body Mass Index; Body Weight; Child; Female; Humans; Inpatients; Leptin; Patient Discharge; Predictive Value of Tests; Treatment Outcome; Weight Gain

The objective of this experiment was to determine the association of circulating plasma leptin concentrations with production and body composition measures of finishing beef steers and heifers and to determine if multiple sampling time points improve the associations of plasma leptin concentrations with production and body composition traits. Individual dry matter intake (DMI) and ADG were determined for 84 d using steers and heifers (n = 127 steers and n = 109 heifers). Blood was collected on day 0, day 42, and day 83 for determination of plasma leptin concentrations. Leptin concentrations were greater in heifers than those in steers on day 0 (P < 0.001 for sex by day interaction), and leptin concentrations increased in both sexes but were not different from each other on day 83. Leptin concentrations at all 3 time points and the mean were shown to be positively associated with DMI (P ≤ 0.006), whereas the mean leptin concentration explaining 8.3% of the variance of DMI. Concentrations of leptin at day 42, day 83, and the mean of all 3 time points were positively associated with ADG (P ≤ 0.011). Mean leptin concentration was negatively associated with gain:feed ratio and positively associated with residual feed intake (RFI), indicating that more efficient cattle had lower leptin concentrations. However, leptin concentrations explained very little of the variation in residual feed intake (≤ 3.2% of the variance). Leptin concentrations were positively associated with body fat measured by ultrasonography at the 12th rib and over the rump (P < 0.001), with the mean leptin concentration explaining 21.9% and 12.7% of the variance in 12th rib and rump fat thickness, respectively. The same trend was observed with carcass composition where leptin concentrations were positively associated with 12th rib fat thickness, USDA-calculated yield grade (YG), and marbling score (P ≤ 0.006) and mean leptin concentration explained 16.8, 18.2, and 4.6% of the variance for 12th rib fat thickness, yield grade, and marbling score, respectively. Given these and previous results, it appears that leptin physiology could be a candidate for mechanisms that contribute to feed intake and feed efficiency variation in beef cattle.

Topics: Animal Feed; Animals; Body Composition; Cattle; Eating; Energy Metabolism; Female; Leptin; Male; Sex Factors; Weight Gain

Leptin triggers signaling events with significant transcriptional responses that are essential to metabolic processes affecting obesity and glucose disposal. We asked whether hexamethylene bis-acetamide inducible-1 (Hexim1), an inhibitor of RNA II polymerase-dependent transcription elongation, regulates leptin-Janus kinase 2 signaling axis in the hypothalamus. We subjected C57BL6 Hexim1 heterozygous (HT) mice to high-fat diet and when compared with wild type, HT mice were resistant to high-fat diet-induced weight gain and remain insulin sensitive. HT mice exhibited increased leptin-pY(705)Stat3 signaling in the hypothalamus, with normal adipocyte size, increased type I oxidative muscle fiber density, and enhanced glucose transporter 4 expression. We also observed that normal Hexim1 protein level is required to facilitate the expression of CCAAT/enhancer-binding proteins (C/EBPs) required for adipogenesis and inducible suppressor of cytokine signaling 3 (SOCS) expression. Further support on the role of Hexim1 regulating C/EBPs during adipocyte differentiation was shown when HT 3T3L1 fibroblasts failed to undergo adipogenesis. Hexim1 selectively modulates leptin-mediated signal transduction pathways in the hypothalamus, the expression of C/EBPs and peroxisome proliferator-activated receptor-γ (PPAR γ) in skeletal muscle and adipose tissue during the adaptation to metabolic stress. We postulate that Hexim1 might be a novel factor involved in maintaining whole-body energy balance.

Topics: 3T3 Cells; Adipogenesis; Animals; Arcuate Nucleus of Hypothalamus; Diet, High-Fat; Glucose; Glucose Transporter Type 4; Haploinsufficiency; HEK293 Cells; Heterozygote; Humans; Janus Kinase 2; Leptin; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Obesity; Phosphotyrosine; RNA-Binding Proteins; Signal Transduction; STAT3 Transcription Factor; Transcription Factors; Weight Gain

The aim of this study was to explore the effects of different amounts of dietary fatty acids on body weight, fat accumulation, and lipid metabolism of hamsters.. Sixty male golden Syrian hamsters were randomly divided into six groups. Three of the groups (the S groups) were fed experimental diets containing 5%, 15%, and 20% (w/w) fat of soybean oil (S5, S15, and S20, respectively), and the other three groups (the M groups) were fed the same proportions of an experimental oil mixture (M5, M15, and M20, respectively). The experimental oil mixture consisted of 60% monounsaturated fatty acids (MUFAs) and a polyunsaturated-to-saturated fatty acid ratio of 5 with a mixture of soybean and canola oils. Food consumption was measured daily, and body weights were measured weekly. Serum insulin and leptin concentrations were measured and hepatic fatty acid metabolic enzymes and adipose differentiation markers were determined using an enzyme activity analysis and quantitative polymerase chain reaction.. Results showed that the weight and weight gain of the S20 group were significantly greater than those of the other five groups. When the total fat consumption increased, the body weight, weight gain, and adipose tissue weight of the S groups significantly increased, but there were no significant differences in these parameters among the M groups. Serum low-density lipoprotein cholesterol concentrations were significantly lower in the M15 and S15 groups. The S20 group had significantly higher leptin and insulin concentrations and lipoprotein lipase was promoted, but the acetyl-coenzyme A oxidase and carnitine palmitoyltransferase-1, were significantly lower.. The study demonstrated that a special experimental oil mixture (with 60% MUFAs and a ratio of 5) with high fat can prevent body weight gain and body fat accumulation by lowering insulin concentrations and increasing hepatic lipolytic enzyme activities.

Topics: Adipogenesis; Adiposity; Animals; Biomarkers; Cholesterol, LDL; Diet, High-Fat; Dietary Fats; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Gene Expression Regulation, Enzymologic; Insulin; Leptin; Lipid Metabolism; Liver; Male; Mesocricetus; Overweight; Random Allocation; Rapeseed Oil; Soybean Oil; Weight Gain

Olanzapine (OLZ) treatment is associated with a high risk of weight gain, and may cause abnormalities in glycolipid metabolism. Therefore, the underlying mechanism of OLZ-related weight gain is needed to clarify but not yet been adequately determined. In recent years, adipocytokines such as leptin, adiponectin, and tumor necrosis factor (TNF)-α, which play important roles in energy homeostasis, have been suggested as biomarkers of weight gain. Here, we determined if baseline plasma concentrations of leptin, adiponectin, and TNF-α predict weight gain following OLZ treatment.. We recruited 31 schizophrenia outpatients (12 men and 19 women, 28.8 ± 10.2 years old) that were unmedicated or on another antipsychotic monotherapy medication. Baseline body mass index (BMI) and plasma levels of leptin, adiponectin, and TNF-α were obtained. All patients started or were switched to OLZ monotherapy for a maximum of 1 year. BMI was also obtained at the endpoint.. Mean BMI change following OLZ treatment was 2.1 ± 2.7 kg/m2. BMI change from baseline to endpoint negatively-correlated with baseline leptin levels in female patients (r = -0.514, P = 0.024), but not male patients. Baseline adiponectin or TNF-α levels were not correlated with BMI change.. Baseline plasma leptin can have an effect on subsequent weight gain following OLZ treatment in female patients with schizophrenia.

Topics: Adiponectin; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Female; Humans; Leptin; Male; Olanzapine; Schizophrenia; Tumor Necrosis Factor-alpha; Weight Gain; Young Adult

Exercise plays a critical role in regulating glucose homeostasis and body weight. However, the mechanism of exercise on metabolic functions associated with the CNS has not been fully understood. C57BL6 male mice (n=45) were divided into three groups: normal chow diet, high-fat diet (HFD) treatment, and HFD along with voluntary running wheel exercise training for 12 weeks. Metabolic function was examined by the Comprehensive Lab Animal Monitoring System and magnetic resonance imaging; phenotypic analysis included measurements of body weight, food intake, glucose and insulin tolerance tests, as well as insulin and leptin sensitivity studies. By immunohistochemistry, the amount changes in the phosphorylation of signal transducer and activator of transcription 3, neuronal proliferative maker Ki67, apoptosis positive cells as well as pro-opiomelanocortin (POMC)-expressing neurons in the arcuate area of the hypothalamus was identified. We found that 12 weeks of voluntary exercise training partially reduced body weight gain and adiposity induced by an HFD. Insulin and leptin sensitivity were enhanced in the exercise training group verses the HFD group. Furthermore, the HFD-impaired POMC-expressing neuron is remarkably restored in the exercise training group. The restoration of POMC neuron number may be due to neuroprotective effects of exercise on POMC neurons, as evidenced by altered proliferation and apoptosis. In conclusion, our data suggest that voluntary exercise training improves metabolic symptoms induced by HFD, in part through protected POMC-expressing neuron from HFD and enhanced leptin signaling in the hypothalamus that regulates whole-body energy homeostasis.

Topics: Adiposity; Animals; Cell Proliferation; Diet, High-Fat; Energy Metabolism; Hypothalamus; Insulin Resistance; Leptin; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Neurons; Obesity; Physical Conditioning, Animal; Physical Exertion; Pro-Opiomelanocortin; Signal Transduction; Weight Gain

AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the "multiple hit hypothesis" of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-α, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis.

Topics: Adipose Tissue; Animals; Diet, High-Fat; Fatty Liver; Glycation End Products, Advanced; Humans; Inflammation; Interleukin-6; Leptin; Liver; Mice; Non-alcoholic Fatty Liver Disease; Obesity; Oxidation-Reduction; Peroxidase; Tumor Necrosis Factor-alpha; Weight Gain

To examine associations of birth size and weight gain during 4 early-life age intervals with midchildhood adiposity and metabolic profile and to evaluate for an interaction between birth size and early-life weight gain.. Using data from 963 participants of Project Viva, a US prebirth cohort, we used multivariable linear regression to examine relations of birth size (tertiles of birthweight-for-gestational-age z-score) and weight gain (body mass index z-score [BMIZ] change) during 4 age intervals (birth-6 months, 6 months-1 year, 1-2 years, 2-3 years) with body composition and metabolic biomarkers during midchildhood (6.6-10.7 years).. After accounting for confounders and previous growth, greater BMIZ change during all 4 age intervals corresponded with higher midchildhood adiposity, with larger effect sizes for later (1-2 years and 2-3 years) vs earlier (birth-6 months and 6 months-1 year) time frames. We observed effect modification by birth size for the birth-6 months and 6 months-1 year intervals. Greater birth-6 months BMIZ change was associated with higher overall adiposity (0.40 [95% CI 0.29, 0.51] kg dual x-ray absorptiometry total fat mass per z-score) among children in the highest birth size tertile. Similar associations were observed for central adiposity. Each increment in 6 months-1 year BMIZ change corresponded with 0.55 (0.05, 1.05) units higher homeostatic model assessment of insulin resistance and 2.68 (0.96, 4.40) ng/mL higher leptin among the smallest infants.. BMIZ gain after 1 year is associated with greater midchildhood adiposity regardless of birth size, whereas the long-term influence of weight gain during the first postnatal year may depend on size at birth. Future studies are warranted to validate findings and examine relations with conventional birth size cut-offs.

Topics: Absorptiometry, Photon; Adiposity; Biomarkers; Birth Weight; Body Composition; Body Mass Index; Child; Child, Preschool; Cohort Studies; Humans; Infant; Infant, Newborn; Insulin Resistance; Leptin; Multivariate Analysis; Weight Gain

Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. In non-pregnant populations, low leptin levels stimulate positive energy balance. In pregnancy, both the placenta and adipose tissue contribute to circulating leptin levels. We tested whether maternal leptin levels are associated with subsequent GWG and whether this association varies depending on stage of pregnancy and on maternal body mass index (BMI).. This prospective cohort study included 675 pregnant women followed from 1(st) trimester until delivery. We collected anthropometric measurements, blood samples at 1(st) and 2(nd) trimester, and clinical data until delivery. Maternal leptin was measured by ELISA (Luminex technology). We classified women by BMI measured at 1(st) trimester: BMI < 25 kg/m(2) = normal weight; 25 ≤ BMI < 30 kg/m(2) = overweight; and BMI ≥ 30 kg/m(2) = obese.. Women gained a mean of 6.7 ± 3.0 kg between 1(st) and 2(nd) trimester (mid pregnancy GWG) and 5.6 ± 2.5 kg between 2(nd) and the end of 3(rd) trimester (late pregnancy GWG). Higher 1(st) trimester leptin levels were associated with lower mid pregnancy GWG, but the association was no longer significant after adjusting for % body fat (%BF; β = 0.38 kg per log-leptin; SE = 0.52; P = 0.46). Higher 2(nd) trimester leptin levels were associated with greater late pregnancy GWG and this association remained significant after adjustment for BMI (β = 2.35; SE = 0.41; P < 0.0001) or %BF (β = 2.01; SE = 0.42; P < 0.0001). In BMI stratified analyses, higher 2(nd) trimester leptin levels were associated with greater late pregnancy GWG in normal weight women (β = 1.33; SE = 0.42; P =0.002), and this association was stronger in overweight women (β = 2.85; SE = 0.94; P = 0.003--P for interaction = 0.05).. Our results suggest that leptin may regulate weight gain differentially at 1(st) versus 2(nd) trimester of pregnancy: at 2(nd) trimester, higher leptin levels were associated with greater subsequent weight gain--the opposite of its physiologic regulation in non-pregnancy--and this association was stronger in overweight women. We suspect the existence of a feed-forward signal from leptin in second half of pregnancy, stimulating a positive energy balance and leading to greater weight gain.

Topics: Adult; Body Mass Index; Female; Humans; Leptin; Overweight; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Pregnancy Trimester, Second; Prospective Studies; Risk Factors; Weight Gain

The aim of this work was to determine the effect of a fructose rich diet (FRD) consumed by the pregnant mother on the endocrine-metabolic and in vivo and in vitro adipose tissue (AT) functions of the male offspring in adulthood. At 60 days of age, rats born to FRD-fed mothers (F) showed impaired glucose tolerance after glucose overload and high circulating levels of leptin (LEP). Despite the diminished mass of retroperitoneal AT, this tissue was characterized by enhanced LEP gene expression, and hypertrophic adipocytes secreting in vitro larger amounts of LEP. Analyses of stromal vascular fraction composition by flow cytometry revealed a reduced number of adipocyte precursor cells. Additionally, 60 day-old control (C) and F male rats were subjected to control diet (CC and FC animals) or FRD (CF and FF rats) for three weeks. FF animals were heavier and consumed more calories. Their metabolic-endocrine parameters were aggravated; they developed severe hyperglycemia, hypertriglyceridemia, hyperleptinemia and augmented AT mass with hypertrophic adipocytes. Our study highlights that manipulation of maternal diet induced an offspring phenotype mainly imprinted with a severely unhealthy adipogenic process with undesirable endocrine-metabolic consequences, putting them at high risk for developing a diabetic state.

Topics: Adipose Tissue; Adiposity; Age Factors; Animal Nutritional Physiological Phenomena; Animals; Biomarkers; Blood Glucose; Dietary Carbohydrates; Energy Intake; Female; Fructose; Leptin; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Sex Factors; Weight Gain

Dietary fiber and proteins are individually known to decrease feeding, but could result greater weight management benefit when both are combined. We hypothesized that supplementing the diet with fermented barley, being rich in both dietary fiber and proteins, could lower energy intake by modulating the mRNA expression level of hypothalamic genes associated with the regulation of feeding behavior and satiety; thereby decreasing body weight gain. To test our hypothesis, four groups of Sprague Dawley rats were arranged in a 2 × 2 factorial design (n = 6), low-fat diet with either guar gum (LFD-G) or fermented barley (LFD-FB) and high-fat diet with either guar gum (HFD-G) or fermented barley (HFD-FB). Using oral gavage, fermented barley was given at a dosage of 1500 mg/kg body weight and guar gum was supplemented in an equivalent quantity to that of the fiber in the fermented barley. After 19 weeks, the fermented barley-supplemented groups showed a significant reduction in energy intake, triglyceride, body weight gain, and serum leptin, compared to the guar gum-supplemented groups in both the low- and high-fat diet groups. Likewise, the anorexigenic gene proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) mRNA level were significantly higher in the fermented barley-supplemented groups compared to the guar gum-supplemented groups in rats fed on both high- and low-fat diets. In conclusion, fermented barley supplementation upregulated hypothalamic POMC/CART, decreased energy intake in both low- and high-fat diet groups, and prevented excessive weight gain in rats.

Topics: Animals; Body Weight; Dietary Fiber; Dietary Supplements; Energy Intake; Fermentation; Hordeum; Humans; Hypothalamus; Leptin; Male; Nerve Tissue Proteins; Obesity; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Weight Gain

Most adipose tissue programming is realized in early life. Also, the postnatal three months, rather than the later phases of infancy, may be more relevant in the development of an adverse cardiometabolic risk profile. The adipokines phenotype, as a predictor of early-life weight gain, has been recently explored in cord blood. To determine whether in addition to leptin levels in cord samples, adiponectin, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor alpha (TNF-α) levels improve weight gain prediction during the first three months of life.. Adiponectin, IL-6, MCP-1, leptin, resistin, PAI-1, and TNF-α were measured by multiplex immunoassay in a subsample of 86 healthy term newborns.. Leptin levels significantly predicted weight gain at 3 months of follow-up (r2=0.09, p=0.006). In the multivariate analysis, including additional adipokines in the model, stepwise or all at once, did not increase the prediction of weight gain after the first three months of life.. Adding adiponectin, IL-6, MCP-1, resistin, PAI-1, and TNF-α to the prediction model of weight gain in healthy newborns did not prove to be useful. It is probable that their relative contribution to weight gain is not important. Only leptin was relevant as a predictor of weight gain at the 3-month endpoint.

Topics: Adipokines; Adiponectin; Adipose Tissue; Birth Weight; Chemokine CCL2; Fetal Blood; Follow-Up Studies; Humans; Immunoassay; Infant; Infant, Newborn; Interleukin-6; Leptin; Multivariate Analysis; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Resistin; Tumor Necrosis Factor-alpha; Weight Gain

The current prevalence of diet-induced overweight and obesity in adolescents and adults is continuously growing. Although the detrimental biochemical and metabolic consequences of obesity are widely studied, its impact on stress-coping behavior and its interaction with specific exercise doses (in terms of intensity, duration and frequency) need further investigation. To this aim, we fed adolescent rats either an obesogenic diet (cafeteria diet, CAF) or standard chow (ST). Each group was subdivided into four subgroups according to the type of treadmill intervention as follows: a sedentary group receiving no manipulation; a control group exposed to a stationary treadmill; a low-intensity treadmill group trained at 12 m/min; and a higher intensity treadmill group trained at 17 m/min. Both the diet and treadmill interventions started at weaning and lasted for 8 weeks. Subjects were tested for anxiety-like behavior in the open field test and for coping strategies in the two-way active avoidance paradigm at week 7 and were sacrificed at week 8 for biometric and metabolic characterization. CAF feeding increased the weight gain, relative retroperitoneal white adipose tissue (RWAT %), and plasma levels of glucose, insulin, triglycerides and leptin and decreased the insulin sensitivity. Treadmill intervention partially reversed the RWAT% and triglyceride alterations; at higher intensity, it decreased the leptin levels of CAF-fed animals. CAF feeding decreased the motor activity and impaired the performance in a two-way active avoidance assessment. Treadmill intervention reduced defecation in the shuttle box, suggesting diminished anxiety. CAF feeding combined with treadmill training at 17 m/min increased the time spent in the center of the open field and more importantly, partially reversed the two-way active avoidance deficit. In conclusion, this study demonstrates that at doses that decreased anxiety-like behavior, treadmill exercise partially improved the coping strategy in terms of active avoidance behavior in the CAF-fed animals. This effect was not observed at lower doses of treadmill training.

Topics: Adipose Tissue, White; Animals; Blood Glucose; Diet; Dietary Fats; Exercise Test; Female; Hyperinsulinism; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Obesity; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Stress, Physiological; Triglycerides; Weight Gain

Energy reserve, estimated as body condition score (BCS), is the major determinant of the re-initiation of ovarian activity in postpartum cows. Leptin, IGF-I and insulin are positively related to BCS and are putative mediators between BCS and reproductive function. However, when BCS and body composition dissociates, concentrations of these metabolic hormones are altered. We hypothesized that increasing lean muscle tissue, but not fat tissue, would diminish the reproductive response to oestrus induction treatments. Thirty lactating beef cows with BCS of 3.10±1.21 and 75.94±12 days postpartum were divided in two groups. Control cows (n=15) were supplemented with 10.20 kg of concentrate daily for 60 days. Treated cows (n=15) were supplemented equally, and received a β-adrenergic receptor agonist (β-AA; 0.15 mg/kg BW) to achieve accretion of lean tissue mass and not fat tissue mass. Twelve days after ending concentrate supplementation/β-AA treatment, cows received a progestin implant to induce oestrus. Cows displaying oestrus were inseminated during the following 60 days, and maintained with a fertile bull for a further 21 days. Cows in both groups gained weight during the supplementation period (Daily weight gain: Control=0.75 kg v. β-AA=0.89 kg). Cows treated with β-AA had a larger increase in BCS (i.e. change in BCS: control=1 point (score 4.13) v. β-AA=2 points (score 5.06; P0.05) did not differ between groups. However, the number of cows displaying oestrus (control 13/15 v. β-AA 8/15; P<0.05) and the percentage cycling (control 6/8 v. β-AA 3/10; P=0.07) after progestin treatment and the pregnancy percentage at the end of the breeding period (control 13/15 v. β-AA 8/15; P<0.05) were lower in β-AA than control cows. In summary, the increase BCS through muscle tissue accretion, but not through fat tissue accretion, resulted in a lower response to oestrus induction, lower percentage of cycling animals and lower pregnancy percentage after progestin treatment; which was associated with a decrease in serum concentrations of leptin and IGF-I.

Topics: Adipose Tissue; Adrenergic beta-Agonists; Animals; Body Composition; Cattle; Diet; Dietary Supplements; Estrus; Female; Insulin-Like Growth Factor I; Lactation; Leptin; Muscles; Postpartum Period; Pregnancy; Random Allocation; Red Meat; Reproduction; Weight Gain

Pre-adipocytes and adipocytes are responsive to the acute phase protein serum amyloid A (SAA). The combined effects triggered by SAA encompass an increase in pre-adipocyte proliferation, an induction of TNF-α and IL-6 release and a decrease in glucose uptake in mature adipocytes, strongly supporting a role for SAA in obesity and related comorbidities. This study addressed whether SAA depletion modulates weight gain and insulin resistance induced by a high-fat diet (HFD).. Male Swiss Webster mice were fed an HFD for 10 weeks under an SAA-targeted antisense oligonucleotide (ASOSAA) treatment in order to evaluate the role of SAA in weight gain.. With ASOSAA treatment, mice receiving an HFD did not differ in energy intake when compared with their controls, but were prevented from gaining weight and developing insulin resistance. The phenotype was characterised by a lack of adipose tissue expansion, with low accumulation of epididymal, retroperitoneal and subcutaneous fat content and decreased inflammatory markers, such as SAA3 and toll-like receptor (TLR)-4 expression, as well as macrophage infiltration into the adipose tissue. Furthermore, a metabolic status similar to chow-fed mice counterparts could be observed, with equivalent levels of leptin, adiponectin, IGF-I, SAA, fasting glucose and insulin, and remarkable improvement in glucose and insulin tolerance test profiles. Surprisingly, the expected HFD-induced metabolic endotoxaemia was also prevented by the ASOSAA treatment.. This study provides further evidence of the role of SAA in weight gain and insulin resistance. Moreover, we also suggest that beyond its proliferative and inflammatory effects, SAA is part of the lipopolysaccharide signalling pathway that links inflammation to obesity and insulin resistance.

Topics: Adiponectin; Animals; Diet, High-Fat; Endotoxemia; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Male; Mice; Obesity; Real-Time Polymerase Chain Reaction; Serum Amyloid A Protein; Weight Gain

During pregnancy, metabolic interactions must be adapted, though neuroendocrine mechanisms for increased food intake are poorly understood. The objective of this study was to characterize differences in insulin, leptin, and agouti-related protein (AgRP) levels in serum and cerebrospinal fluid (CSF) in pregnant women with normal weight (NW) and pregnant women with overweight (OW) or obesity (OB). Placenta as a source for increased peripheral AgRP levels during pregnancy was also investigated.. Women were recruited at admission for elective cesarean section. Insulin, AgRP, and leptin were measured in serum and CSF from 30 NW, 25 OW, and 21 OB at term. Serum during pregnancy and placenta at term were collected for further AgRP analysis.. Immunohistology showed placental production of AgRP and serum AgRP levels increased throughout pregnancy. CSF AgRP, leptin, and insulin levels were higher in OW and OB than NW. Serum leptin and insulin levels were higher and AgRP lower in OB than NW.. High serum AgRP levels might protect from the suppressive effects of leptin during pregnancy. Pregnant women with OB and OW might further be protected from the suppressive effect of leptin by high CSF AgRP levels. Evidence was found, for the first time, of human placental AgRP production mirrored by levels in the circulation.

Topics: Adult; Agouti-Related Protein; Body Mass Index; Energy Intake; Female; Humans; Insulin; Leptin; Obesity; Overweight; Placenta; Pregnancy; Prospective Studies; Weight Gain

Sulforaphane (SFN), a dietary phase-2 enzyme inducer that mitigates cellular oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2) activation, is known to exhibit beneficial effects in the vessel wall. For instance, it inhibits vascular smooth muscle cell (VSMC) proliferation, a major event in atherosclerosis and restenosis after angioplasty. In particular, SFN attenuates the mitogenic and pro-inflammatory actions of platelet-derived growth factor (PDGF) and tumor necrosis factor-α (TNFα), respectively, in VSMCs. Nevertheless, the vasoprotective role of SFN has not been examined in the setting of obesity characterized by hyperleptinemia and insulin resistance. Using the mouse model of western diet-induced obesity, the present study demonstrates for the first time that subcutaneous delivery of SFN (0.5mg/Kg/day) for~3weeks significantly attenuates neointima formation in the injured femoral artery [↓ (decrease) neointima/media ratio by~60%; n=5-8]. This was associated with significant improvements in metabolic parameters, including ↓ weight gain by~52%, ↓ plasma leptin by~42%, ↓ plasma insulin by~63%, insulin resistance [↓ homeostasis model assessment of insulin resistance (HOMA-IR) index by~73%], glucose tolerance (↓ AUCGTT by~24%), and plasma lipid profile (e.g., ↓ triglycerides). Under in vitro conditions, SFN significantly decreased leptin-induced VSMC proliferation by~23% (n=5) with associated diminutions in leptin-induced cyclin D1 expression and the phosphorylation of p70S6kinase and ribosomal S6 protein (n=3-4). The present findings reveal that, in addition to improving systemic metabolic parameters, SFN inhibits leptin-induced VSMC proliferative signaling that may contribute in part to the suppression of injury-induced neointima formation in diet-induced obesity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Obesity Agents; Anticarcinogenic Agents; Antioxidants; Aorta; Cell Proliferation; Cells, Cultured; Diet, Western; Femoral Artery; Humans; Injections, Subcutaneous; Insulin Resistance; Isothiocyanates; Leptin; Male; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Neointima; Obesity; Oxidative Stress; Sulfoxides; Weight Gain

While leptin is a well-known regulator of body fat mass, it remains unclear how circulating leptin is sensed centrally to maintain energy homeostasis. Here we show that genetic and pharmacological ablation of adult NG2-glia (also known as oligodendrocyte precursors), but not microglia, leads to primary leptin resistance and obesity in mice. We reveal that NG2-glia contact the dendritic processes of arcuate nucleus leptin receptor (LepR) neurons in the median eminence (ME) and that these processes degenerate upon NG2-glia elimination, which explains the consequential attenuation of these neurons' molecular and electrical responses to leptin. Our data therefore indicate that LepR dendrites in the ME represent the principal conduits of leptin's anorexigenic action and that NG2-glia are essential for their maintenance. Given that ME-directed X-irradiation confirmed the pharmacological and genetically mediated ablation effects on body weight, our findings provide a rationale for the known obesity risk associated with cranial radiation therapy.

Topics: Aging; Animals; Anorexia; Arcuate Nucleus of Hypothalamus; Body Weight; Cell Proliferation; Cytarabine; Dendrites; Electrophysiological Phenomena; Female; Gene Deletion; Leptin; Male; Median Eminence; Mice; Microglia; Mitosis; Neuroglia; Obesity; Phenotype; Receptors, Leptin; Signal Transduction; Weight Gain

BACKGROUND Obesity causes several health complications along with disruption of the reproductive system. The aim of the current study was to determine how long-term intake of very high fat diet (VHFD) changes the hormonal milieu, affecting the cellular morphology and reproductive cycle in female mice. MATERIAL AND METHODS Mice were fed on normal diet (ND) and VHFD for 2 weeks, 12 weeks, and 25-27 weeks. We assessed changes in body weight, food consumption, energy intake, cellular and tissue morphology, hormonal levels (leptin, insulin, and estradiol), and vaginal smears were performed at various time points to determine the length and cellularity at each stage of the estrous cycle. RESULTS Mice fed on VHFD showed a significant increase in weight gain, reduction in food intake, and increase in energy intake compared to animals fed on ND, indicating that the caloric density of the diet is responsible for the differences in weight gain. Hormonal analysis showed hyperleptinemia, hyperinsulinemia, and increases in estrogen levels, along with increases in size of the islet of Langerhans and adipocytes. After 25-27 weeks, all animals fed on VHFD showed complete acyclicity; elongation of phases (e.g., diestrous), skipping of phases (e.g., metestrous), or a combination of both, indicating disruption in the reproductive cycle. Quantitative analysis showed that in the diestrous phase there was a 70% increase in cell count in VHFD compared to animals fed on ND. CONCLUSIONS The above results show that morphological and hormonal changes caused by VHFD probably act via negative feedback to the hypothalamic-pituitary axis to shut down reproduction, which has a direct effect on the estrous cycle, causing acyclicity in mice.

Topics: Adipocytes; Animals; Body Weight; Diet, High-Fat; Eating; Energy Intake; Estradiol; Estrous Cycle; Female; Hormones; Insulin; Leptin; Mice; Mice, Inbred C57BL; Obesity; Weight Gain

Peroxisome proliferator-activated receptor-γ (PPARγ), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARγ in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARγ in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARγ and the tdTomato reporter. Inducible expression of both forms of PPARγ was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NES(Cre)/PPARγ-P467L) or selectively in POMC neurons (POMC(Cre)/PPARγ-P467L). Whereas POMC(Cre)/PPARγ-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMC(Cre)/PPARγ-P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMC(Cre)/PPARγ-WT mice and controls in response to 60% high-fat diet. However, POMC(Cre)/PPARγ-WT, but not POMC(Cre)/PPARγ-P467L, mice increased body weight in response to rosiglitazone, a PPARγ agonist. These observations support the concept that alterations in PPARγ-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions.

Topics: 3T3 Cells; Adipogenesis; Animals; Body Weight; Brain; Cell Line; Diet, High-Fat; Energy Metabolism; Female; HEK293 Cells; Homeostasis; Humans; Leptin; Male; Mice; Neurons; Obesity; PPAR gamma; Pro-Opiomelanocortin; Rosiglitazone; Thiazolidinediones; Weight Gain

This study tested whether the maternal transport of dexamethasone (DEXA) may affect the development of the neuroendocrine system. DEXA (0.2mg/kg b.w., subcutaneous injection) was administered to pregnant rats from gestation day (GD) 1-20. In the DEXA-treated group, a decrease in maternal serum thyroxine (T4), triiodothyronine (T3), and increase in thyrotropin (TSH) levels (hypothyroid status) were observed at GDs 15 & 20 with respect to control group. The reverse pattern (hyperthyroid status) was observed in their fetuses at embryonic days (EDs) 15 & 20. Although the maternal body weight was diminished, the weight of the thyroid gland was increased at studied GDs as compared to the control group. The fetal growth retardation, hyperleptinemia, hyperinsulinism, and cytokines distortions (transforming growth factor-beta; TGF-β, tumor necrosis factor-alpha; TNF-α, and interferon-γ; IFN-γ) were noticed at examined EDs if compared to the control group. Alternatively, the maternofetal thyroid dysfunctions due to the maternal DEXA administration attenuated the levels of fetal cerebral norepinephrine (NE) and epinephrine (E), and elevated the levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) at considered days. These alterations were age-dependent and might damage the nerve transmission. Finally, maternal DEXA might act as neuroendocrine disruptor causing dyshormonogenesis and fetal cerebral dysfunction.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Dexamethasone; Endocrine Disruptors; Female; Fetal Development; Fetal Growth Retardation; Hyperinsulinism; Hypothyroidism; Injections, Subcutaneous; Leptin; Maternal-Fetal Exchange; Neurosecretory Systems; Organ Size; Pregnancy; Rats, Wistar; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine; Weight Gain

The differentiation of adipocytes is tightly regulated by a variety of intrinsic molecules and also by extrinsic molecules produced by adjacent cells. Dysfunction of adipocyte differentiation causes lipodystrophy, which impairs glucose and lipid homeostasis. Although dysfunction of immunoproteasomes causes partial lipodystrophy, the detailed molecular mechanisms remain to be determined. Here, we demonstrate that Psmb8, a catalytic subunit for immunoproteasomes, directly regulates the differentiation of preadipocytes and additionally the differentiation of preadipocytes to mature adipocytes. Psmb8(-/-) mice exhibited slower weight gain than wild-type mice, and this was accompanied by reduced adipose tissue volume and smaller size of mature adipocytes compared with controls. Blockade of Psmb8 activity in 3T3-L1 cells disturbed the differentiation to mature adipocytes. Psmb8(-/-) mice had fewer preadipocyte precursors, fewer preadipocytes and a reduced ability to differentiate preadipocytes toward mature adipocytes. Our data demonstrate that Psmb8-mediated immunoproteasome activity is a direct regulator of the differentiation of preadipocytes and their ultimate maturation.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipose Tissue; Animals; Cells, Cultured; Cysteine Proteinase Inhibitors; Diet, High-Fat; Insulin; Leptin; Leupeptins; Lipids; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligopeptides; Organ Size; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Weight Gain

Meta-analytical data show lithium augmentation (LA) as an effective treatment strategy in major depression. Weight-gain is a common side effect of LA. The proteohormone leptin is discussed to be involved in the pathophysiology of weight gain induced by psychopharmacological treatment. The purpose of our study was to investigate the association of leptin and body mass index (BMI) during LA in a prospective cohort study.. Leptin serum concentrations and body mass index (BMI) were measured in a total of 89 acute depressive patients before and then after four weeks of LA.. In a linear mixed model analysis the following variables had a significant positive effect on BMI: time (equal with "treatment effect of LA"; F1.83=6.05; p=0.016) and leptin (F1.111=13.83; p=0.0003) as well as the covariates male gender (F1.89=5.08; p=0.027) and adiposity (F1.85=105.13; p<0.0001).. If the reported effect of leptin on BMI is specific to LA remains unclear without a control group.. Leptin signalling might be involved in lithium-induced weight-gain.

Topics: Adult; Aged; Body Mass Index; Body Weight; Cohort Studies; Depressive Disorder, Major; Female; Humans; Leptin; Lithium; Male; Middle Aged; Obesity; Prospective Studies; Weight Gain

Recent studies have demonstrated that epigenetic changes resulting from malnutrition might play important roles in transgenerational links with metabolic diseases. Previously, we observed that exposure to a high-fat diet (HFD) in utero caused a metabolic syndrome-like phenomenon through epigenetic modifications of the adiponectin and leptin genes that persisted for multiple generations. Recent etiological studies indicated that paternal BMI had effects on offspring BMI that were independent of but additive to maternal BMI effects. Thus, we examined whether paternal HFD-induced obesity affected the metabolic status of offspring through epigenetic changes in the adiponectin and leptin genes. Additionally, we investigated whether a normal diet during subsequent generations abolished the epigenetic changes associated with paternal HFD exposure before conception. We observed the effects of paternal HFD exposure before conception over multiple generations on offspring metabolic traits, including weight and fat gain, glucose intolerance, hypertriglyceridemia, abnormal adipocytokine levels, hypertension, and adiponectin and leptin gene expression and epigenetic changes. Normal diet consumption by male offspring during the subsequent generation following paternal HFD exposure diminished whereas consumption for two generations completely abolished the effect of paternal HFD exposure on metabolic traits and adipocytokine promoter epigenetic changes in the offspring. The effects of paternal HFD exposure on offspring were relatively weaker than those following HFD exposure in utero. However, paternal HFD exposure had an additive metabolic effect for two generations, suggesting that both paternal and maternal nutrition might affect offspring metabolism through epigenetic modifications of adipocytokine genes for multiple generations.

Topics: Adipokines; Adiponectin; Animals; Chromatin Immunoprecipitation; Diet, High-Fat; Epigenesis, Genetic; Female; Gene Expression; Glucose Intolerance; Hypertension; Hypertriglyceridemia; Leptin; Male; Metabolic Syndrome; Mice; Obesity; Paternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Promoter Regions, Genetic; Real-Time Polymerase Chain Reaction; RNA, Messenger; Weight Gain

Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype.. The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model.. Female heterozygous endothelial nitric oxide synthase(-/+) mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol-treated vs metabolic-like syndrome-nontreated mice and obese-myoinositol/D-chiroinositol-treated vs obese nontreated mice.. Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo (P = .04), whereas there was no difference in systolic blood pressure between treated and placebo-treated obese pregnant mice. Pregnant metabolic-like syndrome mice treated with myoinositol/D-chiroinositol showed lower glucose values during the glucose tolerance test and in the area under the curve (myoinositol/D-chiroinositol: 17512.5 ± 3984.4 vs placebo: 29687.14 ± 8258.7; P = .003), but no differences were seen in the obese pregnant mice. Leptin serum levels were lower in the metabolic-like syndrome-myoinositol/D-chiroinositol-treated mice compared with the placebo group (myoinositol/D-chiroinositol: 16985 ± 976.4 pg/dL vs placebo: 24181.9 ± 3128.2 pg/dL, P = .045). No other differences were seen in any of the remaining serum metabolic biomarkers studied in metabolic-like syndrome and in obese pregnant mice. Maternal weight gain was not different in the pregnant metabolic-like syndrome dams, whereas it was lower in the obese myoinositol/D-chiroinositol-treated dams compared with the placebo group (myoinositol/D-chiroinositol: 10.9 ± 0.5 g vs 12.6 ± 0.6 g, P = .04). Fetal and placental weights did not differ between myoinositol/D-chiroinositol-treated and nontreated pregnant dams with metabolic-like syndrome and obesity.. Combined inositol treatment during pregnancy improves blood pressure, glucose levels at the glucose tolerance test, and leptin levels in pregnant dams with metabolic-like syndrome phenotype but not in obese pregnant dams. In addition, inositol treatment was associated with lower gestational weight gain in the obese but not in the metabolic-like syndrome pregnant dams.

Topics: Animals; Biomarkers; Blood Glucose; Dietary Supplements; Disease Models, Animal; Female; Gastric Inhibitory Polypeptide; Gestational Age; Ghrelin; Glucose Tolerance Test; Inositol; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase Type III; Obesity; Pregnancy; Pregnancy Complications; Weight Gain

Topics: Administration, Oral; Agouti-Related Protein; Animals; Benzodiazepines; Dopamine Antagonists; Eating; Gene Expression; Hypothalamus; Leptin; Male; Nerve Tissue Proteins; Neuropeptide Y; Olanzapine; Pro-Opiomelanocortin; Random Allocation; Rats, Wistar; RNA, Messenger; Serotonin Antagonists; Weight Gain

Obesity is a worldwide threat to public health in modern society, which may result from leptin resistance and disorder of thermogenesis. The present study investigated whether astragaloside IV (ASI) could prevent obesity in high-fat diet (HFD)-fed and db/db mice. In HFD-fed mice, ASI prevented body weight gain, lowered serum triglyceride and total cholesterol levels, mitigated liver lipid accumulation, reduced fat tissues and decreased the enlargement of adipose cells. In metabolic chambers, ASI lessened appetite of the mice, decreased their respiratory exchange ratio and elevated VCO2 and VO2 without altering circadian motor activity. Moreover, ASI modulated thermogenesis associated gene expressions in liver and brawn fat tissues, as well as leptin resistance evidenced by altered expressions of leptin, leptin receptor (ObR) or appetite associated genes. In SH-SY5Y cells, ASI enhanced leptin signaling transduction. However, in db/db mice, ASI did not change body weight gain and appetite associated genes. But it decreased serum triglyceride and total cholesterol levels as well as liver triglyceride. Meanwhile, it significantly modulated gene expressions of PPARα, PGC1-α, UCP2, ACC, SCD1, LPL, AP2, CD36 and SREBP-1c. Collectively, our study suggested that ASI could efficiently improve lipid metabolism in obese mice probably through enhancing leptin sensitivity and modulating thermogenic network.

Topics: Adipose Tissue; Animals; Body Weight; Cell Line; Diet, High-Fat; Gene Expression; Leptin; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Receptors, Leptin; Saponins; Thermogenesis; Triglycerides; Triterpenes; Weight Gain

Weight regain frequently follows interventions that reduce body weight, leading to a failure in long-term obesity treatment. Inhibitory proteins of the leptin signaling pathway, such as the suppressor of cytokine signaling 3 (SOCS3), have been studied in conditions that predispose animals to obesity. However, whether SOCS3 modulates postrestriction hyperphagia and weight regain remains unknown. Mice lacking SOCS3 protein specifically in leptin receptor (LepR)-expressing cells (LepR SOCS3 knockout [KO]) were generated and studied in fasting and refeeding conditions. LepR SOCS3 KO mice exhibited increased leptin sensitivity in the hypothalamus. Notably, LepR SOCS3 KO males and females showed attenuated food intake and weight regain after 48 hours of fasting. Postrestriction hyperleptinemia was also prevented in LepR SOCS3 KO mice. Next, we studied possible mechanisms and neural circuits involved in the SOCS3 effects. SOCS3 deletion did not prevent fasting- or refeeding-induced c-Fos expression in the arcuate nucleus of the hypothalamus (ARH) nor fasting-induced increased excitability of ARH LepR-expressing cells. On the other hand, SOCS3 ablation reduced the mRNA levels of hypothalamic orexigenic neuropeptides during fasting (neuropeptide Y, agouti-related protein, orexin, and melanin-concentrating hormone). In summary, our findings suggest that increased leptin sensitivity contributes to the maintenance of a reduced body weight after food deprivation. In addition, the attenuated postrestriction food intake observed in mutant mice was not explained by fasting-induced changes in the activity of ARH neurons but exclusively by a lower transcription of orexigenic neuropeptides during fasting. These results indicate a partial dissociation between the regulation of neuronal activity and gene expression in ARH LepR-expressing cells.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Fasting; Female; Hyperphagia; Leptin; Male; Mice, Inbred C57BL; Mice, Knockout; Neurons; Proto-Oncogene Proteins c-fos; Receptors, Leptin; Suppressor of Cytokine Signaling 3 Protein; Weight Gain

Metabolic adverse effects of atypical antipsychotics (AAP) contribute significantly to increased risk of cardiovascular morbidity and mortality in patients suffering from schizophrenia. Extensive preclinical research has addressed this issue over the past years, though mechanisms underlying these adverse effects of AAP are still not understood completely. Recently, attention is drawn towards the role of adipose tissue metabolism and neurohormonal regulations.. The aim of this study was to evaluate the time-dependent effects of olanzapine depot administration at clinically relevant dosing on the regulation of energy homeostasis, glucose and lipid metabolism, gastrointestinal and adipose tissue-derived hormones involved in energy balance regulations in female Sprague-Dawley rats. The study lasted 8 weeks and the markers were assayed at day 8, 15, 29, 43 and 57.. The results indicate that in the absence of hyperphagia, olanzapine chronic exposure induced weight gain from the beginning of the study. In the later time-point, increased adiposity was also observed. In the initial phase of the study, lipid profile was altered by an early increase in triglyceride level and highly elevated leptin level was observed. Clear bi-phasic time-dependent effect of olanzapine on leptin serum concentration was demonstrated. Olanzapine treatment did not lead to changes in serum levels of ghrelin, FGF-21 and pro-inflammatory markers IL-1a, IL-6 and TNF-α at any time-point of the study.. This study provides data suggesting early alteration in adipose tissue endocrine function as a factor involved in mechanisms underlying metabolic adverse effects of antipsychotics.

Topics: Adipose Tissue; Animals; Antipsychotic Agents; Benzodiazepines; Drug-Related Side Effects and Adverse Reactions; Female; Leptin; Olanzapine; Rats; Rats, Sprague-Dawley; Triglycerides; Weight Gain

Previous studies reported that the co-injection of leptin and cannabinoid CB1 receptor antagonists reduces food intake and body weight in rats, and this effect is more profound than that induced by these compounds individually. Additionally, serotonin mediates the effects of numerous anorectic drugs. To investigate whether serotonin interacts with leptin and endocannabinoids to affect food intake and body weight, we administered 5-hydroxytryptamine(HT)1B and 5-hydroxytryptamine(HT)2C serotonin receptor antagonists (3 mg/kg GR 127935 and 0.5 mg/kg SB 242084, respectively) to male Wistar rats treated simultaneously with leptin (100 μg/kg) and the CB1 receptor inverse agonist AM 251 (1 mg/kg) for 3 days. In accordance with previous findings, the co-injection of leptin and AM 251, but not the individual injection of each drug, resulted in a significant decrease in food intake and body weight gain. Blockade of the 5-HT1B and 5-HT2C receptors completely abolished the leptin- and AM 251-induced anorectic and body-weight-reducing effects. These results suggest that serotonin mediates the leptin- and AM 251-dependent regulation of feeding behavior in rats via the 5-HT1B and 5-HT2C receptors.

Topics: Aminopyridines; Animals; Cannabinoid Receptor Agonists; Drug Synergism; Eating; Indoles; Leptin; Male; Oxadiazoles; Piperazines; Piperidines; Pyrazoles; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Serotonin, 5-HT1B; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT1 Receptor Antagonists; Serotonin 5-HT2 Receptor Antagonists; Weight Gain

Low early-life leptin concentrations may promote faster weight gain in infancy. We aimed to examine the associations between cord blood leptin concentrations and changes in weight and body composition during infancy.. Serum leptin was measured at 15 weeks gestation, in umbilical cord blood collected at delivery and at 2 years in 334 children from the Cork Baseline Birth Cohort Study. Body composition was measured at 2 days and 2 months using air displacement plethysmography. Conditional change in weight standard deviation scores over a number of age intervals in the first 2 years and conditional change in fat mass index (FMI) and fat-free mass index (FFMI) (kg/(length)m(2)) between birth and 2 months were calculated and associations with cord blood leptin were examined using linear regression.. At birth, cord blood leptin was positively correlated with FMI (r = 0.48, P < 0.001) and showed a weaker correlation with FFMI (r = 0.12, P = 0.05). After adjustment for confounders, higher cord blood leptin (per ng/mL) was associated with slower conditional weight gain between birth and 2 months (β (95% CI): -0.024 (-0.035, -0.013), P < 0.001) but not over subsequent age intervals. Cord blood leptin was also inversely associated with conditional change in FMI (-0.021 (-0.034, -0.007, P = 0.003) but not FFMI between birth and 2 months.. These are the first data to show that associations between higher cord blood leptin and slower weight gain during infancy are driven by lower increases in adiposity, at least in early infancy.

Topics: Adipose Tissue; Birth Weight; Body Composition; Body Mass Index; Body Weight; Female; Fetal Blood; Gestational Age; Humans; Infant; Infant, Newborn; Leptin; Male; Plethysmography; Weight Gain

Experimental and epidemiological evidence demonstrate that ancestral diet might contribute towards offspring health. This suggests that nutrition may be able to modify genetic or epigenetic information carried by germ cells (GCs). To examine if a parental high fat diet (HFD) influences metabolic health in two generations of offspring, GC-eGFP Sprague Dawley rats were weaned onto HFD (45% fat) or Control Diet (CD; 10% fat). At 19 weeks, founders (F0) were bred with controls, establishing the F1 generation. HFD resulted in 9.7% and 14.7% increased weight gain in male and female F0 respectively. F1 offspring of HFD mothers and F1 daughters of HFD-fed fathers had increased weight gain compared to controls. F1 rats were bred with controls at 19 weeks to generate F2 offspring. F2 male offspring derived from HFD-fed maternal grandfathers exhibited increased adiposity, plasma leptin and luteinising hormone to testosterone ratio. Despite transmission via the founding male germline, we did not find significant changes in the F0 intra-testicular GC transcriptome. Thus, HFD consumption by maternal grandfathers results in a disrupted metabolic and reproductive hormone phenotype in grandsons in the absence of detectable changes in the intra-testicular GC transcriptome.

Topics: Adiposity; Animals; Diet, High-Fat; Female; Gene Expression Profiling; Leptin; Luteinizing Hormone; Male; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Sex Factors; Testis; Testosterone; Weaning; Weight Gain

We previously reported that offspring heterozygous mice partially lacking endothelial nitric oxide synthase (eNOS) gene, and born to hypertensive eNOS-/- Knockout mother, are hypertensive. We hypothesized that those offspring when placed on high-fat diet (HFD) will undergo altered metabolic programming increasing their risk for developing metabolic syndrome.. eNOS-/-KO and wild-type mice (eNOS+/+WT) were cross-bred to produce heterozygous offspring: maternal heterozygous (Mat, eNOS-/+), born from hypertensive eNOS-/-KO mothers; and paternal heterozygous (Pat, eNOS-/+), born from normotensive WT mothers. Mat, eNOS-/+ and Pat, eNOS-/+ female were allocated to HFD or control diet (CD) until 8 weeks of age. Then a metabolic profile was obtained: weight, glucose/insulin tolerance test (GTT, ITT), systolic blood pressure (SBP), serum fasting levels of insulin, adiponectin, leptin, and a lipid panel.. Weight was not different between all offspring within each diet. GTT curve was higher in Mat, eNOS-/+ vs. Pat, eNOS-/+ offspring on both diet (P < 0.001). In ITT, glucose level at 15 minutes was higher in Mat, eNOS-/+ on HFD. Insulin level was increased in Mat, eNOS-/+ vs. Pat, eNOS-/+ on either diet. SBP was elevated in Mat, eNOS-/+ vs. Pat, eNOS-/+ on CD and was further raised in Mat, eNOS-/+ offspring on HFD (P < 0.001). No other differences were seen except for lower high-density lipoprotein levels in Mat, eNOS-/+ fed HFD (P < 0.003).. Mat, eNOS-/+ offspring exposed in utero to maternal hypertension and fed HFD postnatally have increased susceptibility for metabolic abnormalities. Thus, maternal HTN is a risk factor for altered fetal metabolic programming.

Topics: Adiponectin; Animals; Biomarkers; Blood Glucose; Blood Pressure; Diet, High-Fat; Disease Models, Animal; Female; Genetic Predisposition to Disease; Heterozygote; Hypertension; Insulin; Leptin; Lipids; Metabolic Syndrome; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase Type III; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Time Factors; Weight Gain

The neonatal leptin surge, occurring from postnatal day (PND) 5 to 13 and peaking at PND9 in rodents, is important for the development of neuroendocrine circuits involved in metabolic control and reproductive function. We previously demonstrated that treatment with a leptin antagonist from PND 5 to 9, coincident with peak leptin levels in the neonatal surge, modified trophic factors and markers of cell turnover and neuronal maturation in the hypothalamus of peri-pubertal rats. The kisspeptin system and metabolic neuropeptide and hormone levels were also modified. Here our aim was to investigate if the timing of pubertal onset is altered by neonatal leptin antagonism and if the previously observed peripubertal modifications in hormones and neuropeptides persist into adulthood and affect male sexual behavior. To this end, male Wistar rats were treated with a pegylated super leptin antagonist (5mg/kg, s.c.) from PND 5 to 9 and killed at PND102-103. The appearance of external signs of pubertal onset was delayed. Hypothalamic kiss1 mRNA levels were decreased in adult animals, but sexual behavior was not significantly modified. Although there was no effect on body weight or food intake, circulating leptin, insulin and triglyceride levels were increased, while hypothalamic leptin receptor, POMC and AgRP mRNA levels were decreased. In conclusion, alteration of the neonatal leptin surge can modify the timing of pubertal onset and have long-term effects on hypothalamic expression of reproductive and metabolic neuropeptides.

Topics: Animals; Animals, Newborn; Gene Expression; Hypothalamus; Kisspeptins; Leptin; Male; Nerve Tissue Proteins; Neuropeptide Y; Pro-Opiomelanocortin; Rats, Wistar; Receptors, Leptin; Sexual Behavior, Animal; Sexual Maturation; Signal Transduction; Weight Gain

We have reported a correlation between hypothalamic expression of Creb-binding protein (Cbp) and lifespan, and that inhibition of Cbp prevents protective effects of dietary restriction during aging, suggesting that hypothalamic Cbp plays a role in responses to nutritional status and energy balance. Recent GWAS and network analyses have also implicated Cbp as the most connected gene in protein-protein interactions in human Type 2 diabetes. The present studies address mechanisms mediating the role of Cbp in diabetes by inhibiting hypothalamic Cbp using a Cre-lox strategy. Inhibition of hypothalamic Cbp results in profound obesity and impaired glucose homeostasis, increased food intake, and decreased body temperature. In addition, these changes are accompanied by molecular evidence in the hypothalamus for impaired leptin and insulin signaling, a shift from glucose to lipid metabolism, and decreased Pomc mRNA, with no effect on locomotion. Further assessment of the significance of the metabolic switch demonstrated that enhanced expression of hypothalamic Cpt1a, which promotes lipid metabolism, similarly resulted in increased body weight and reduced Pomc mRNA.

Topics: Animals; Body Temperature; Brain-Derived Neurotrophic Factor; Carnitine O-Palmitoyltransferase; CREB-Binding Protein; Diabetes Mellitus, Type 2; Down-Regulation; Eating; Energy Metabolism; Female; Gene Expression Regulation; Glucose; Humans; Hypothalamus; Insulin; Leptin; Lipid Metabolism; Male; Mice; Obesity; Pro-Opiomelanocortin; Signal Transduction; Weight Gain

Postmenopausal diabetes is exacerbated by estrogen deficiency. Ovariectomized (OVX) animal models can be used to develop strategies for preventing or treating postmenopausal symptoms. We previously found that a diet containing kudzu (Pueraria lobata) vine ethanol extract (PVEE) suppressed weight gain in OVX mice. Therefore, this study further elucidated how PVEE affected OVX mice. Ten-week-old OVX or sham-operated mice were fed diets containing either no PVEE (control) or 20 mg•kg

Topics: Adiponectin; Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Disease Models, Animal; Female; Hypoglycemic Agents; Insulin; Isoflavones; Leptin; Mice; Organ Size; Ovariectomy; Phytotherapy; Plant Extracts; Postmenopause; Pueraria; Triglycerides; Uterus; Weight Gain

Exclusively breastfed infants born to obese mothers have previously been shown to gain less weight by 1-month postpartum than infants of normal-weight mothers. Our hypothesis is that human milk composition and volume may differ between obese and normal-weight mothers.. To compare human milk leptin, macronutrient concentration, and volume in obese and normal-weight mothers. Mother and infant characteristics were studied as secondary aims.. This cross-sectional observational study compared 50 obese mothers matched for age, parity, ethnic origin, and educational level with 50 normal-weight mothers. Leptin, macronutrient human milk concentration, and milk volume were determined at 1 month in exclusively breastfed infants. Mother characteristics and infant growth were recorded.. Human milk leptin concentration was higher in obese mothers than normal-weight mothers (4.8±2.7 vs. 2.5±1.5 ng.mL-1, p<0.001). No difference was observed between obese and normal-weight mothers in protein, lipid, carbohydrate content, and volume, nor in infant weight gain.. Leptin concentration was higher in the milk of obese mothers than that of normal-weight mothers, but macronutrient concentration was not. It remains to be established whether the higher leptin content impacts on infant growth beyond the 1-month of the study period.

Topics: Adult; Body Weight; Breast Feeding; Carbohydrates; Case-Control Studies; Child Development; Cross-Sectional Studies; Female; Humans; Infant; Infant, Newborn; Leptin; Lipids; Male; Milk, Human; Mothers; Obesity; Postpartum Period; Pregnancy; Proteins; Weight Gain

Obesity is a multifactorial disease with genetic, social, and environmental influences. This study aims at analyzing the effects of the combination of a refined carbohydrate diet and exposure to hyperoxia on the pulmonary oxidative and inflammatory response in mice. Twenty-four mice were divided into four groups: control group (CG), hyperoxia group (HG), refined carbohydrate diet group (RCDG), and refined carbohydrate diet + hyperoxia group (RCDHG). The experimental diet was composed of 10% sugar, 45% standard diet, and 45% sweet condensed milk. For 24 hours, the HG and RCDHG were exposed to hyperoxia and the CG and RCDG to ambient air. After the exposures were completed, the animals were euthanized, and blood, bronchoalveolar lavage fluid, and lungs were collected for analyses. The HG showed higher levels of interferon-

Topics: Adipocytes; Adiposity; Animals; Antioxidants; Biomarkers; Blood Glucose; Bronchoalveolar Lavage Fluid; Cell Count; Cholesterol; Dietary Carbohydrates; Epididymis; Feeding Behavior; Hyperoxia; Immunoassay; Inflammation; Leptin; Lung; Male; Mice, Inbred BALB C; Oxidation-Reduction; Oxidative Stress; Weight Gain

Adipokines in breast milk have been associated with infant growth trajectories.. We aimed to explore the relationship of leptin and adiponectin in breast milk with infant weight gain and body composition up to the age of 2 years.. Breast milk samples were collected from exclusively or partially breastfeeding mothers at 6 weeks (n = 152) and 4 months (n = 120) post-partum. Leptin and adiponectin were determined in skim breast milk and related to infant growth and fat mass assessed by skin-fold thickness measurements. A total of 118 infants were examined at 2 years.. The levels of both milk adipokines were slightly lower at 4 months compared with 6 weeks post-partum. Breast milk leptin was largely unrelated to infant anthropometric measures up to 2 years. Milk adiponectin tended to be inversely related to early infant anthropometry up to 4 months, but beyond was positively associated with weight gain and the sum of skin-folds up to 2 years.. Our results suggest that higher adiponectin levels in breast milk might be associated with greater weight gain and higher fat mass in the offspring up to 2 years.

Topics: Adiponectin; Body Composition; Breast Feeding; Child, Preschool; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Leptin; Longitudinal Studies; Male; Maternal Nutritional Physiological Phenomena; Milk, Human; Randomized Controlled Trials as Topic; Skinfold Thickness; Weight Gain

Manilkara zapota is a tropical evergreen tree belonging to the Sapotaceae family; its parts are used in alternative medicine to treat coughs and colds and possess diuretic, antidiarrheal, antibiotic, antihyperglycemic, and hypocholesterolemic effects. There are no studies on metabolic profile after using the fruit, and this study aimed at evaluating the effects of the leaf and pulp of M. zapota fruit on the metabolic profile of Wistar rats. Male rats were treated for 50 days with M. zapota leaf juice or fruit juice, after which their biochemical and body composition profiles were analyzed (glycemia, triglycerides, high-density lipoprotein cholesterol (HDL-c), insulin, leptin, aspartate transaminase, alanine aminotransferase, Lee Index, and body mass index). Our results indicate significantly lower levels of glycemia, insulin, leptin, cholesterol, and triglycerides and augmented levels of HDL-c in animals treated with the leaves or fruit of this plant. The percentage of weight gain also declined in animals treated with M. zapota fruit pulp. The use of the M. zapota may be helpful in the prevention of obesity, diabetes, dyslipidemia, and their complications.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Dyslipidemias; Fruit; Hyperglycemia; Hypoglycemic Agents; Hypolipidemic Agents; Insulin; Leptin; Lipids; Male; Manilkara; Metabolome; Obesity; Phytotherapy; Plant Extracts; Plant Leaves; Rats, Wistar; Weight Gain

Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment.

Topics: Adiponectin; Adult; Antipsychotic Agents; Biomarkers; C-Reactive Protein; Clozapine; Complement Factor D; Cross-Sectional Studies; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-6; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT2C; Retrospective Studies; Schizophrenia; Weight Gain

In addition to the amount of ingested calories, both timing of food intake and meal composition are determinants of body weight gain. However, at present, it is unknown if the inappropriate timing of diet components is responsible for body weight gain. In the present study, we therefore studied a time-dependent effect of the diet composition on energy homeostasis. Male Wistar rats were subjected to chow ad libitum (chow group) or a choice diet with saturated fat, a 30% sugar solution, chow and tap water. The choice diet was provided either with all components ad libitum (AL), with ad libitum access to chow, tap water and a 30% sugar solution, but with access to saturated fat only during the light period (LF), or with ad libitum access to chow, tap water and saturated fat, but access to a 30% sugar solution only during the light period (LS). Caloric intake and body weight gain were monitored during 31 days. Energy expenditure was measured in the third week in calorimetric cages. All rats on a choice diet showed hyperphagia and gained more body weight compared to the chow group. Within the choice diet groups, rats on the LS diet were most food efficient (i.e. gained most body weight per ingested calorie) and showed a lower respiratory exchange ratio (RER) with an anti-phasic pattern, whereas no differences in locomotor activity or heat production were found. Collectively these data indicate that the timing of the diet composition affects food efficiency, most likely due to a shifted oxidation pattern, which can predispose for obesity. Further studies are underway to assess putative mechanisms involved in this dysregulation.

Topics: Animals; Body Composition; Body Weight; Calorimetry; Circadian Rhythm; Diabetes Mellitus, Type 2; Diet; Dietary Fats; Dietary Sucrose; Disease Models, Animal; Eating; Energy Intake; Feeding Behavior; Homeostasis; Leptin; Light; Male; Obesity; Oxygen; Rats; Rats, Wistar; Time Factors; Weight Gain

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

Reduced GH levels have been associated with improved glucose metabolism and increased longevity despite obesity in multiple mouse lines. However, one mouse line, the GH receptor antagonist (GHA) transgenic mouse, defies this trend because it has reduced GH action and increased adiposity, but glucose metabolism and life span are similar to controls. Slight differences in glucose metabolism and adiposity profiles can become exaggerated on a high-fat (HF) diet. Thus, in this study, male and female GHA and wild-type (WT) mice in a C57BL/6 background were placed on HF and low-fat (LF) diets for 11 weeks, starting at 10 weeks of age, to assess how GHA mice respond to additional metabolic stress of HF feeding. On a HF diet, all mice showed significant weight gain, although GHA gained weight more dramatically than WT mice, with males gaining more than females. Most of this weight gain was due to an increase in fat mass with WT mice increasing primarily in the white adipose tissue perigonadal depots, whereas GHA mice gained in both the sc and perigonadal white adipose tissue regions. Notably, GHA mice were somewhat protected from detrimental glucose metabolism changes on a HF diet because they had only modest increases in serum glucose levels, remained glucose tolerant, and did not develop hyperinsulinemia. Sex differences were observed in many measures with males reacting more dramatically to both a reduction in GH action and HF diet. In conclusion, our findings show that GHA mice, which are already obese, are susceptible to further adipose tissue expansion with HF feeding while remaining resilient to alterations in glucose homeostasis.

Topics: Adipocytes; Adiposity; Animals; Body Weight; Cattle; Diet, High-Fat; Disease Models, Animal; Eating; Female; Glucose; Glucose Intolerance; Hyperinsulinism; Insulin; Leptin; Liver; Male; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Receptors, Somatotropin; Triglycerides; Weight Gain

Chronic intermittent hypoxia during sleep (IH), as occurs in sleep apnea, promotes systemic insulin resistance. Resveratrol (Resv) has been reported to ameliorate high-fat diet-induced obesity, inflammation, and insulin resistance. To examine the effect of Resv on IH-induced metabolic dysfunction, male mice were subjected to IH or room air conditions for 8 weeks and treated with either Resv or vehicle (Veh). Fasting plasma levels of glucose, insulin, and leptin were obtained, homeostatic model assessment of insulin resistance index levels were calculated, and insulin sensitivity tests (phosphorylated AKT [also known as protein kinase B]/total AKT) were performed in 2 visceral white adipose tissue (VWAT) depots (epididymal [Epi] and mesenteric [Mes]) along with flow cytometry assessments for VWAT macrophages and phenotypes (M1 and M2). IH-Veh and IH-Resv mice showed initial reductions in food intake with later recovery, with resultant lower body weights after 8 weeks but with IH-Resv showing better increases in body weight vs IH-Veh. IH-Veh and IH-Resv mice exhibited lower fasting glucose levels, but only IH-Veh had increased homeostatic model assessment of insulin resistance index vs all 3 other groups. Leptin levels were preserved in IH-Veh but were significantly lower in IH-Resv. Reduced VWAT phosphorylated-AKT/AKT responses to insulin emerged in both Mes and Epi in IH-Veh but normalized in IH-Resv. Increases total macrophage counts and in M1 to M2 ratios occurred in IH-Veh Mes and Epi compared all other 3 groups. Thus, Resv ameliorates food intake and weight gain during IH exposures and markedly attenuates VWAT inflammation and insulin resistance, thereby providing a potentially useful adjunctive therapy for metabolic morbidity in the context of sleep apnea.

Topics: Animals; Anti-Obesity Agents; Drug Evaluation, Preclinical; Eating; Hypoxia; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Macrophages; Male; Mice, Inbred C57BL; Random Allocation; Resveratrol; Stilbenes; Weight Gain

The present study investigated the anti-obesity effects of pomegranate (Punica granatum) juices from the two Saudi Arabian, Taif red, Taif white, and Egyptian pomegranates in high-fat diet (HFD)-induced obese rats. Administrating any of the used juices decreased the body weight gain, food consumption, and serum levels of lipid, leptin, and glucose, while it increased serum insulin level. Histologically, all types of juices decreased the number and size of lipid droplets in hepatocytes compared to the obese, non-treated animals. All juices types upregulated the hepatic mRNA expression of hormone-sensitive lipase, pyruvate kinase, and adiponectin in obese rats; the genes were all suppressed by HFD feeding. Additionally, the expression of fatty acid synthase, sterol regulatory element-binding protein-1c, and acetyl-CoA carboxylase1 was also upregulated by all types of juices. Conversely, ghrelin mRNA expression was downregulated by all used juices' types. These findings demonstrate that all types of tested juices protect against the HFD-induced obesity in rats.

Topics: Acetyl-CoA Carboxylase; Adiponectin; Animals; Beverages; Blood Glucose; Diet, High-Fat; Dietary Fats; Eating; Fatty Acid Synthases; Gene Expression; Ghrelin; Insulin; Leptin; Lipid Droplets; Lythraceae; Male; Obesity; Pyruvate Kinase; Rats; Rats, Wistar; Sterol Esterase; Sterol Regulatory Element Binding Protein 1; Triglycerides; Weight Gain

Bacterially derived factors are implicated in the causation and persistence of obesity. Ingestion of a high fat diet in rodents and obesity in human subjects is associated with chronic elevation of low plasma levels of lipopolysaccharide (LPS), a breakdown product of Gram-negative bacteria. The terminals of vagal afferent neurons are positioned within the gut mucosa to convey information from the gut to the brain to regulate food intake and are responsive to LPS. We hypothesized that chronic elevation of LPS could alter vagal afferent signaling. We surgically implanted osmotic mini-pumps that delivered a constant, low-dose of LPS into the intraperitoneal cavity of rats (12.5 μg/kg/hr for 6 weeks). LPS-treated rats developed hyperphagia and showed marked changes in vagal afferent neuron function. Chronic LPS treatment reduced vagal afferent leptin signaling, characterized by a decrease in leptin-induced STAT3 phosphorylation. In addition, LPS treatment decreased cholecystokinin-induced satiety. There was no alteration in leptin signaling in the hypothalamus. These findings offer a mechanism by which a change in gut microflora can promote hyperphagia, possibly leading to obesity.

Topics: Animals; Blotting, Western; Eating; Hyperphagia; Immunohistochemistry; Leptin; Lipopolysaccharides; Male; Neurons, Afferent; Nodose Ganglion; Peroxidase; Rats, Wistar; Satiation; Sincalide; Weight Gain

Although adipokines and insulin resistance are known to be correlated with body fatness, it is unclear whether they are independently related to weight gain experience. We examined the associations of serum adipokines and marker of insulin resistance with past weight gain during adulthood by taking the degree of attained body mass index (BMI) level into consideration.. Subjects were 399 Japanese municipal employees, aged ⩾ 30 years, who participated in a health survey. Serum adipokines were measured using a Luminex suspension bead-based multiplexed array. Weight change during adulthood was calculated as the difference between measured current weight and recalled weight at the age of 20 years. Multiple regression was performed to calculate mean adipokine levels and homeostasis model assessment of insulin resistance (HOMA-IR) according to weight gain (< 5 kg, 5-9.9 kg, or ⩾ 10 kg) with adjustment for current BMI.. Weight gain from the age of 20 years was significantly and positively associated with leptin levels even after adjustment for current BMI (P for trend < 0.001), whereas it was significantly and inversely associated with adiponectin levels in a BMI-adjusted model among subjects aged ⩾ 40 years (P for trend=0.03). Weight gain was associated with HOMA-IR in a BMI-unadjusted model (P for trend < 0.001), but this association was largely attenuated after adjustment for BMI. Resistin, plasminogen activator inhibitor-1 and visfatin were not associated with past weight gain.. Results suggest that a large weight gain during adulthood is associated with higher leptin and lower adiponectin levels independently of the degree of attained BMI level.

Topics: Adiponectin; Adipose Tissue; Adult; Asian People; Biomarkers; Body Mass Index; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Life Style; Linear Models; Male; Nicotinamide Phosphoribosyltransferase; Plasminogen Activator Inhibitor 1; Resistin; Weight Gain; Young Adult

Increased body weight (BW) gain during the juvenile period leads to early maturation of the reproductive neuroendocrine system. We investigated whether a nutritional regimen that advances the onset of puberty leads to alterations in the hypothalamic neuropeptide Y (NPY) circuitry that are permissive for enhanced gonadotropin-releasing hormone (GnRH) secretion. It was hypothesized that NPY mRNA and NPY projections to GnRH and kisspeptin neurons are reduced in heifers that gain BW at an accelerated rate, compared with a lower one, during the juvenile period. Heifers were weaned at approximately 4 mo of age and fed diets to promote relatively low (0.5 kg/day; low gain [LG]) or high (1.0 kg/day; high gain [HG]) rates of BW gain until 8.5 mo of age. Heifers that gained BW at a higher rate exhibited greater circulating concentrations of leptin and reduced overall NPY expression in the arcuate nucleus. The proportion of GnRH neurons in close apposition to NPY fibers and the magnitude of NPY projections to GnRH neurons located in the mediobasal hypothalamus were reduced in HG heifers. However, no differences in NPY projections to kisspeptin neurons in the arcuate nucleus were detected between HG and LG heifers. Results indicate that a reduction in NPY innervation of GnRH neurons, particularly at the level of the mediobasal hypothalamus, occurs in response to elevated BW gain during the juvenile period. This functional plasticity may facilitate early onset of puberty in heifers.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Cattle; Female; Gonadotropin-Releasing Hormone; Kisspeptins; Leptin; Neurons; Neuropeptide Y; Sexual Maturation; Weight Gain

Foods that are rich in fat and or sodium chloride promote obesity and associated diseases, whereas intake of dietary fiber averts obesity development. Salicornia herbacea (SH) is a rich source of dietary fiber and high in sodium chloride; therefore, we investigated whether replacing common salt with SH in a high-fat diet could prevent obesity development.. Mice were divided into five groups: group ND was fed a normal diet, group HD was fed a high-fat diet, group HD-NaCl was fed a high fat diet with sodium chloride 10 g kg(-1) , group HD-CL was fed a high-fat diet with cellulose 30 g kg(-1) and group HD-SH was fed a high-fat diet with SH powder 50 g kg(-1) . The amount of sodium chloride and cellulose added in the respective diet was equivalent to their amount in SH. Data from our study showed that, SH supplementation significantly decreased body weight gain, liver weight, hepatic triglyceride, serum leptin and insulin, along with the mRNA level of key lipid anabolic genes such as SREBP-1c, PPARγ and FAS compared to the HD group.. The results of this study demonstrated that SH is a potential natural anti-obesity agent that can be used in place of sodium chloride.

Topics: Animals; Anti-Obesity Agents; Chenopodiaceae; Diet, High-Fat; Dietary Fats; Dietary Fiber; Dietary Supplements; Insulin; Leptin; Lipid Metabolism; Liver; Male; Mice, Inbred ICR; Mice, Obese; Obesity; Phytotherapy; Plant Extracts; RNA, Messenger; Sodium Chloride, Dietary; Triglycerides; Weight Gain

Regulation of body composition during childhood is complex. Numerous hormones are potentially involved. Leptin has been proposed to restrain weight gain, but results are inconsistent.. We examined whether baseline fasting levels of ghrelin, adiponectin, leptin, insulin, IGF-I, osteocalcin, and intact parathyroid hormone (iPTH) were associated with body composition cross sectionally and longitudinally in 633 8-11-year-olds.. Data on hormones and body composition by dual-energy x-ray absorptiometry from the OPUS School Meal Study were used. We looked at baseline hormones as predictors of baseline fat mass index (FMI) or fat-free mass index (FFMI), and also subsequent changes (3 and 6 months) in FMI or FFMI using models with hormones individually or combined.. Cross-sectionally, baseline leptin was positively associated with FMI in girls (0.211 kg/m(2) pr. μg/mL; 97.5% confidence interval [CI],0.186-0.236; P < .001) and boys (0.231 kg/m(2) pr. μg/mL; 97.5% CI, 0.200-0.261; P < .001). IGF-I in both sexes and iPTH in boys were positively associated with FMI. An inverse association between adiponectin and FFMI in boys and a positive association between IGF-I and FFMI were found in girls. In longitudinal models, baseline leptin was inversely associated with subsequent changes in FMI (-0.018 kg/m(2) pr. μg/mL; 97.5% CI, -0.034 - -0.002; P = .028) and FFMI (-0.014 kg/m(2) pr. μg/mL; 97.5% CI, -0.024 - -0.003; P = .006) in girls.. Cross-sectional findings support that leptin is produced in proportion to body fat mass, but the longitudinal observations support that leptin inhibits gains in FMI and FFMI in girls, a finding that may reflect preserved leptin sensitivity in this predominantly normal weight population.

Topics: Adipose Tissue; Appetite Regulation; Body Composition; Bone and Bones; Child; Cross-Sectional Studies; Female; Hormones; Humans; Leptin; Longitudinal Studies; Male; Osteogenesis; Weight Gain

Environmental endocrine disruptors are implicated as putative contributors to the burgeoning metabolic disease epidemic. Tolylfluanid (TF) is a commonly detected fungicide in Europe, and previous in vitro and ex vivo work has identified it as a potent endocrine disruptor with the capacity to promote adipocyte differentiation and induce adipocytic insulin resistance, effects likely resulting from activation of glucocorticoid receptor signaling. The present study extends these findings to an in vivo mouse model of dietary TF exposure. After 12 weeks of consumption of a normal chow diet supplemented with 100 parts per million TF, mice exhibited increased body weight gain and an increase in total fat mass, with a specific augmentation in visceral adipose depots. This increased adipose accumulation is proposed to occur through a reduction in lipolytic and fatty acid oxidation gene expression. Dietary TF exposure induced glucose intolerance, insulin resistance, and metabolic inflexibility, while also disrupting diurnal rhythms of energy expenditure and food consumption. Adipose tissue endocrine function was also impaired with a reduction in serum adiponectin levels. Moreover, adipocytes from TF-exposed mice exhibited reduced insulin sensitivity, an effect likely mediated through a specific down-regulation of insulin receptor substrate-1 expression, mirroring effects of ex vivo TF exposure. Finally, gene set enrichment analysis revealed an increase in adipose glucocorticoid receptor signaling with TF treatment. Taken together, these findings identify TF as a novel in vivo endocrine disruptor and obesogen in mice, with dietary exposure leading to alterations in energy homeostasis that recapitulate many features of the metabolic syndrome.

Topics: Adiponectin; Adiposity; Animals; Circadian Rhythm; Eating; Endocrine Disruptors; Energy Metabolism; Gene Expression Regulation; Glucose Tolerance Test; Insulin; Insulin Resistance; Leptin; Male; Metabolic Diseases; Mice; Oligonucleotide Array Sequence Analysis; RNA; Sulfonamides; Toluidines; Weight Gain

The purpose of this study was to investigate the association of trimester-specific gestational weight gain with offspring fetal growth, obesity risk, and cardiometabolic health outcomes from birth to 4 years of age.. We conducted the present study with 977 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. We measured birthweight, body mass index from 6 months to 4 years of age, waist circumference, skinfold thickness, blood pressure, and blood levels of lipids, C-reactive protein, and adipose tissue hormones at 4 years of age. We used multiple linear and log Poisson regression models to examine the association of exposure with continuous or binary outcomes, respectively.. Greater rate of gestational weight gain in the first trimester of pregnancy (per 200 g/wk) was associated with increased risk of overweight/obesity from 2 years (relative risk [RR], 1.25; 95% confidence interval [CI], 1.09-1.42) to 4 years of age (RR, 1.15; 95% CI, 1.05-1.25), but not with birth size. Each 200 g/wk of weight gain in the first trimester of pregnancy was also associated with greater risk of high waist circumference (RR, 1.13; 95% CI, 1.04-1.23), high sum of skinfold thickness (RR, 1.15; 95% CI, 1.02-1.29), and higher diastolic blood pressure at 4 years of age (β, 0.43 mm Hg; 95% CI, 0.00-0.86). Greater rate of gestational weight gain during the second and third trimesters of pregnancy (per 200 g/wk) was associated with greater risk of large-for-gestational-age neonates (RR, 1.22; 95% CI, 1.02, 1.45) and higher levels of cord blood leptin (ratio of geometric means, 1.08; 95% CI, 1.00-1.17), but not with child anthropometry at later ages.. Timing of gestational weight gain may influence childhood cardiometabolic outcomes differentially.

Topics: Biomarkers; Blood Pressure; Body Mass Index; Child, Preschool; Female; Fetal Development; Follow-Up Studies; Humans; Infant, Newborn; Leptin; Lipids; Male; Models, Statistical; Pediatric Obesity; Pregnancy; Pregnancy Trimesters; Prenatal Exposure Delayed Effects; Prospective Studies; Risk Factors; Skinfold Thickness; Waist Circumference; Weight Gain

Studies in vitro have highlighted the potential involvement of neuregulin 1 (NRG1) in the regulation of energy metabolism. This effect has also been suggested in vivo, as intracerebroventricular injection of NRG1 reduces food intakes and weight gain in rodents. Thus, it was hypothesised that NRG1 might affect serum leptin levels in mice.. Weight, food intakes, energy expenditure, spontaneous physical activity and serum leptin levels were evaluated in normal-weight C57BL/6JRJ mice following intraperitoneal administration of NRG1 (50 μg/kg, three times/week) or saline for 8 weeks. Based on the results of this first experiment, leptin-resistant obese db/db mice were then given NRG1 for 8 weeks.. Leptin serum concentrations were six times higher in C57BL/6JRJ mice treated with NRG1 than in the animals given saline. NRG1 treatment also reduced weight gain by 10% and food intakes by 15% compared with saline treatment, while energy expenditure remained unchanged. In db/db mice, serum leptin concentrations, weight gain, food intakes, energy expenditure and spontaneous physical activity were not altered by NRG1 treatment.. The decrease in food intakes and weight gain associated with NRG1 treatment in C57BL/6JRJ mice may be partly explained by increased leptin levels, whereas db/db mice were not affected by the treatment, suggesting resistance to NRG1 in this pathological state.

Topics: Animals; Diabetes Mellitus, Type 2; Eating; Energy Metabolism; Insulin; Leptin; Mice; Mice, Obese; Neuregulin-1; Weight Gain

Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo.. C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1β, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed.. Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Body Composition; Cholesterol; Diabetes Mellitus, Type 2; Diet, High-Fat; Fatty Liver; Gluconeogenesis; Glucose-6-Phosphatase; Hypoglycemic Agents; Insulin; Insulin Resistance; Interleukin-1beta; Isothiocyanates; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Moringa oleifera; Obesity; Plant Extracts; Resistin; Tumor Necrosis Factor-alpha; Weight Gain

Whole grain consumption reduces the risk of major chronic diseases. It is not clear how whole grains exert their beneficial effects.. The aim was to compare the physiologic effects of whole grain oat (WGO) flour with low bran oat (LBO) flour.. Two AIN-93G-based diets were formulated with either WGO or LBO flour. Five-week-old male C57BL/6J mice were fed LBO (n = 11) and WGO (n = 13) diets for 8 wk. Cecal microbiota was profiled by pyrosequencing of the 16S ribosomal RNA gene. Data are reported as means ± SEMs or antilogs of the mean (mean - SEM, mean + SEM).. The weight gain was 14.6% less in the WGO group during week 7 (P = 0.04). WGO improved insulin sensitivity as reflected by significantly lower plasma insulin [1500 (1370, 1650) ng/L vs. 2340 (2090, 2620) ng/L; P = 0.006], C-peptide (3980 ± 548 ng/L vs. 7340 ± 1050 ng/L; P = 0.007), and homeostasis model assessment-estimated insulin resistance (21.4 ± 2.3 vs. 34.7 ± 4.9; P = 0.03). Plasma total cholesterol was 9.9% less and non-HDL cholesterol was 11% less in the WGO group. A comparison of relative abundance indicated Prevotellaceae, Lactobacillaceae, and Alcaligenaceae families were 175.5% (P = 0.03), 184.5% (P = 0.01), and 150.0% (P = 0.004), respectively, greater in the WGO group and Clostridiaceae and Lachnospiraceae families were 527% (P = 0.004) and 62.6% (P = 0.01), respectively, greater in the LBO group. Cecal microbiota composition predicts 63.9% variation in plasma insulin and 88.9% variation in plasma non-HDL cholesterol.. In mice, WGOs improved insulin sensitivity and plasma cholesterol profile compared with LBOs, and the effects were associated with the changes in cecal microbiota composition. Increasing WGO consumption may help improve insulin sensitivity and dyslipidemia in chronic diseases.

Topics: Alcaligenaceae; Animals; Avena; Bacteroidetes; Cecum; Cholesterol; Dietary Fiber; Feces; Flour; Glucose Tolerance Test; Insulin; Insulin Resistance; Lactobacillaceae; Leptin; Male; Mice; Mice, Inbred C57BL; Microbiota; Organ Size; Resistin; RNA, Ribosomal, 16S; Weight Gain

Excessive relative interdialytic weight gain (RIDWG, %) is an important risk factor for long-term adverse cardiovascular outcomes in chronic hemodialysis (HD) patients. On the other hand, it may also be an index of good appetite and nutritional status. We aimed to assess the relationship between RIDWG and appetite, nutrition, inflammation parameters of chronic HD patients.. 100 chronic anuric HD patients were enrolled in this prospective study between January 2013 and January 2014. Patients with hospitalization, major surgery, obvious infectious/inflammatory disease, end-stage liver disease, malignancies, and malabsorption syndromes were excluded. Patients were divided into 3 groups according to their RIDWG levels; group 1 = RIDWG < 3%, group 2 = RIDWG: 3 - 5%, and group 3 = RIDWG > 5%.. Group 3 patients were younger (p = 0.011) and had a lower body mass index (BMI) (p = 0.014). Nutrition and inflammation parameters including malnutrition inflammation score (MIS), serum albumin, prealbumin, triceps skinfold thickness, hs-CRP, and TNF-α ere not significantly different between the groups. Leptin and leptin/BMI ratio were significantly lower in group 3 (p = 0.001). RIDWG was negatively correlated with age (p = 0.001, r = -0.371), BMI (p = 0.001, r = -0.372), leptin (p = 0.001, r = -0.369), leptin/BMI (p = 0.001, r = -0.369). After adjustment for BMI in linear regression analyis, leptin/BMI remained significantly correlated with RIDWG (p = 0.024).. This study revealed that RIDWG was associated with younger age, lower BMI and dry weight, and lower serum leptin levels. More detailed studies are needed to validate and dissect the mechanisms of these findings.

Topics: Adult; Aged; Body Mass Index; Female; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Prospective Studies; Renal Dialysis; Serum Albumin; Weight Gain

The impacts of high-fat diets (HFDs) on the onset of metabolic endotoxemia and low-grade inflammation are well established in rodent models. However, the dose-effect of dietary lipid intakes on these parameters is not known. We hypothesized that increasing dietary lipid amounts could be linked to parallel increases of endotoxemia, low-grade inflammation, and metabolic and intestinal alterations. Six-week-old male C57BL/6J mice were fed a low-fat diet (LFD, 2.6 wt% of lipids), a moderate HFD (mHFD, 22 wt% of lipids), or a very HFD (vHFD, 45 wt% of lipids) formulated mainly using chow ingredients and milk fat. After 12 weeks, white adipose tissues, liver, intestine, distal colon contents, and plasma were collected. Only vHFD mice significantly increased body weight and fat mass vs LFD mice. This was associated with increases of plasma concentrations of triglycerides, leptin and adiponectin, and liver lipids. No such differences were observed between LFD and mHFD mice. However, mHFD developed metabolic endotoxemia and inflammation, unlike vHFD mice. In turn, vHFD mice showed more goblet cells in all intestine segments vs both other groups and a decrease of Bacteroides-Prevotella in their microbiota vs LFD mice. Finally, mHFD mice colon exhibited a decrease in lactobacilli and in the levels of occludin phosphorylation. Altogether, using complex HFD, no associations were observed between dietary lipid amounts and the magnitude of endotoxemia, inflammation, and physiological alterations developed. These results reveal the impact of the diet composition on intestinal goblet cells and mucus coat, bringing new insights about further consequences on HFD-induced metabolic disorders.

Topics: Adiponectin; Adipose Tissue, White; Animals; Colon; Diet, Fat-Restricted; Diet, High-Fat; Dietary Fats; Endotoxemia; Goblet Cells; Inflammation; Interleukin-6; Intestinal Mucosa; Intestines; Leptin; Lipopolysaccharides; Liver; Male; Mice; Mice, Inbred C57BL; Occludin; Triglycerides; Weight Gain; Zonula Occludens-1 Protein

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

Helicobacter pylori, is an invariably commensal resident of the gut microbiome associated with gastric ulcer in adults. In addition, these patients also suffered from a low grade inflammation that activates the immune system and thus increased shunting of energy to host defense mechanisms. To assess whether a H. pylori infection could affect growth in early life, we determined the expression levels of selected metabolic gut hormones in germ free (GF) and specific pathogen-free (SPF) mice with and without the presence of H. pylori. Despite H. pylori-infected (SPFH) mice display alteration in host metabolism (elevated levels of leptin, insulin and peptide YY) compared to non-infected SPF mice, their growth curves remained the same. SPFH mice also displayed increased level of eotaxin-1. Interestingly, GF mice infected with H. pylori (GFH) also displayed increased levels of ghrelin and PYY. However, in contrast to SPFH mice, GFH showed reduced weight gain and malnutrition. These preliminary findings show that exposure to H. pylori alters host metabolism early in life; but the commensal microbiota in SPF mice can attenuate the growth retarding effect from H. pylori observed in GF mice. Further investigations of possible additional side effects of H. pylori are highly warranted.

Topics: Animals; Body Mass Index; Chemokine CCL11; Energy Metabolism; Ghrelin; Helicobacter Infections; Helicobacter pylori; Host-Pathogen Interactions; Humans; Insulin; Intestine, Large; Leptin; Mice, Inbred C57BL; Microbiota; Models, Biological; Peptide Hormones; Peptide YY; Specific Pathogen-Free Organisms; Weight Gain

To clarify the anti-obesity effect of Allomyrina dichotoma larvae (ADL), we previously reported that ADL block adipocyte differentiation on 3T3-L1 cell lines through downregulation of transcription factors, such as peroxisome proliferator-activated receptor-γ (PPARG) and CCAAT/enhancer binding protein-α (CEBPA). In this study, we tested whether ADL prevent obesity in mice fed a high-fat diet (HFD) and further investigated the mechanism underlying the effects of ADL. All mice were maintained on a normal-fat diet (NFD) for 1 week and then assigned to one of five treatment groups: (1) NFD; (2) HFD; (3) HFD and 100 mg·kg(-1)·day(-1) ADL; (4) HFD and 3000 mg·kg(-1)·day(-1) ADL; or (5) HFD and 3000 mg·kg(-1)·day(-1) yerba mate (Ilex paraguariensis, positive control). ADL and yerba mate were administered orally daily. Mice were fed experimental diets and body weight was monitored weekly for 6 weeks. Our results indicated that ADL reduced body weight gain, organ weight and adipose tissue volume in a dose-dependent manner. Body weight gain was approximately 22.4% lower compared to mice fed only HFD, but the difference did not reach the level of statistical significance. Real-time polymerase chain reaction (PCR) analysis revealed that gene expression levels of PPARG, CEBPA and lipoprotein lipase (LPL) in the epididymal fat tissue of HFD-fed mice receiving 3000 mg·kg(-1)·day(-1) ADL were reduced by 12.4-, 25.7-, and 12.3-fold, respectively, compared to mice fed HFD only. Moreover, mice administered ADL had lower serum levels of triglycerides and leptin than HFD-fed mice that did not receive ADL. Taken together our results suggest that ADL and its constituent bioactive compounds hold potential for the treatment and prevention of obesity.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Arthropods; Biological Products; CCAAT-Enhancer-Binding Proteins; Diet, High-Fat; Gene Expression; Larva; Leptin; Lipoprotein Lipase; Male; Mice, Inbred BALB C; Obesity; PPAR gamma; Triglycerides; Weight Gain

The role of hyperleptinemia in cardiovascular diseases is well known; however, in the renal tissue, the exact site of leptin's action has not been established. This study was conducted to assess the effect of leptin treatment for 7 and 28 days on renal function and morphology and the participation of angiotensin II (Ang II), through its AT1 receptor. Rats were divided into four groups: sham, losartan (10 mg/kg/day, s.c.), leptin (0.5 mg/kg/day for the 7 days group and 0.25 mg/kg/day for the 28 days group) and leptin plus losartan. Plasma leptin, Ang II and endothelin 1 (ET-1) levels were measured using an enzymatic immuno assay. The systolic blood pressure (SBP) was evaluated using the tail-cuff method. The renal plasma flow (RPF) and the glomerular filtration rate (GFR) were determined by p-aminohippuric acid and inulin clearance, respectively. Urinary Na+ and K+ levels were also analyzed. Renal morphological analyses, desmin and ED-1 immunostaining were performed. Proteinuria was analyzed by silver staining. mRNA expression of renin-angiotensin system (RAS) components, TNF-α and collagen type III was analyzed by quantitative PCR. Our results showed that leptin treatment increased Ang II plasma levels and progressively increased the SBP, achieving a pre-hypertension state. Rats treated with leptin 7 days showed a normal RPF and GFR, but increased filtration fraction (FF) and natriuresis. However, rats treated with leptin for 28 showed a decrease in the RPF, an increase in the FF and no changes in the GFR or tubular function. Leptin treatment-induced renal injury was demonstrated by: glomerular hypertrophy, increased desmin staining, macrophage infiltration in the renal tissue, TNF-α and collagen type III mRNA expression and proteinuria. In conclusion, our study demonstrated the progressive renal morphological changes in experimental hyperleptinemia and the interaction between leptin and the RAS on these effects.

Topics: Albuminuria; Angiotensin II; Animals; Blood Pressure; Feeding Behavior; Hemodynamics; Immunohistochemistry; Kidney; Kidney Tubules; Leptin; Male; Peptides; Polymerase Chain Reaction; Rats, Wistar; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; RNA, Messenger; Systole; Time Factors; Weight Gain

Polyphenols from fruits have been implied in the prevention of risk factors for cardiometabolic disorders and cardiovascular disease. The purpose of this study was to investigate if the consumption of peach and plum juice has a protective effect against obesity and metabolic disorders that promote the development of cardiovascular diseases. Obese Zucker and lean rats were fed with peach, plum juice ad libitum or placebo. Body weight gain, biochemical markers and molecular markers for inflammation and cardiovascular disease in heart tissue were quantified. Results show that peach and plum juice consumption protected against a combination of obesity-induced metabolic disorders including hyperglycemia, insulin and leptin resistance, dyslipidemia and low-density lipoprotein oxidation. This was accompanied by a decreased expression of pro-atherogenic and pro-inflammatory biomarkers in plasma and heart tissues including intercellular cell adhesion molecule-1, monocyte chemotactic protein-1, NF-κB and foam cell adherence to aortic arches. In addition, peach and plum juice consumption decreased the levels of angiotensin II in plasma and its receptor Agtr1 in heart tissues, suggesting a role of peach and plum polyphenols as peroxisome proliferator-activated receptor-γ agonists. Furthermore, only plum juice significantly prevented body weight gain and increased the ratio high-density lipoprotein cholesterol/total cholesterol in plasma. This effect is most likely attributed to the plum's higher content of polyphenols (three times that of peach). Altogether, these results imply that cardioprotective effects can be achieved by replacing drinks high in sugar content with fruit juice rich in polyphenols in a diet.

Topics: Angiotensin II; Animals; Biomarkers; Cardiovascular Diseases; Chemokine CCL2; Fruit and Vegetable Juices; Insulin; Intercellular Adhesion Molecule-1; Leptin; Male; Metabolic Syndrome; NF-kappa B; Obesity; Polyphenols; PPAR gamma; Prunus domestica; Prunus persica; Rats; Rats, Zucker; Receptor, Angiotensin, Type 1; Risk Factors; RNA, Messenger; Weight Gain

Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased β3-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. Taken together our results demonstrate that BAT transplantation may reduce obesity and its related diseases by activating endogenous BAT.

Topics: Adiponectin; Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Energy Metabolism; Fatty Acids; Fatty Liver; Gene Expression; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Male; Mice; Mice, Obese; Obesity; Oxygen Consumption; RNA, Messenger; Thermogenesis; Thyroxine; Triiodothyronine; Weight Gain

To characterize mechanisms responsible for fat accumulation we used a selectively bred obesity-prone (OP) and obesity-resistant (OR) rat model where the rats were fed a Western diet for 76 days. Body composition was assessed by magnetic resonance imaging scans, and as expected, the OP rats developed a higher degree of fat accumulation compared with OR rats. Indirect calorimetry showed that the OP rats had higher respiratory exchange ratio (RER) compared with OR rats, indicating an impaired ability to oxidize fat. The OP rats had lower expression of carnitine palmitoyltransferase 1b in intra-abdominal fat, and higher expression of stearoyl-CoA desaturase 1 in subcutaneous fat compared with OR rats, which could explain the higher fat accumulation and RER values. Basal metabolic parameters were also examined in juvenile OP and OR rats before and during the introduction of the Western diet. Juvenile OP rats likewise had higher RER values, indicating that this trait may be a primary and contributing factor to their obese phenotype. When the adult obese rats were exposed to the orexigenic and adipogenic hormone ghrelin, we observed increased RER values in both OP and OR rats, while OR rats were more sensitive to the orexigenic effects of ghrelin as well as ghrelin-induced attenuation of activity and energy expenditure. Thus increased fat accumulation characterizing obesity may be caused by impaired oxidative capacity due to decreased carnitine palmitoyltransferase 1b levels in the white adipose tissue, whereas ghrelin sensitivity did not seem to be a contributing factor.

Topics: Adiposity; Animals; Calorimetry, Indirect; Carnitine O-Palmitoyltransferase; Diet, High-Fat; Disease Models, Animal; Down-Regulation; Eating; Energy Metabolism; Gene Expression Regulation; Ghrelin; Hypothalamus; Insulin; Intra-Abdominal Fat; Leptin; Magnetic Resonance Imaging; Male; Muscle, Skeletal; Obesity; Oxidation-Reduction; Rats; Subcutaneous Fat; Time Factors; Weight Gain

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

Prader-Willi syndrome (PWS) is a multigene disorder associated with neonatal failure to thrive, developmental delay and endocrine abnormalities suggestive of hypothalamic dysfunction. Children with PWS typically develop overt hyperphagia and obesity ∼8 years of age, later than children with other genetic forms of obesity. This suggests a postnatal developmental or degenerative component to PWS-associated obesity. De novo inactivating mutations in one PWS candidate gene, MAGEL2, have been identified in children with features of PWS. Adult mice lacking Magel2 are insensitive to the anorexic effect of leptin treatment, and their hypothalamic pro-opiomelanocortin (POMC) neurons fail to depolarize in response to leptin. However, it is unclear whether this leptin insensitivity is congenital, or whether normal leptin sensitivity in neonatal Magel2-null mice is lost postnatally. We used in vitro cytosolic calcium imaging to follow the postnatal development of leptin responses in POMC neurons in these mice. Leptin caused an activation of POMC neurons in wild-type acute hypothalamic slice preparations at all ages, reflecting their normal leptin-invoked depolarization. Normal leptin responses were found in Magel2-null mice up to 4 weeks of age, but the proportion of leptin-responsive POMC neurons was reduced in 6-week-old Magel2-null mice. The number of α-melanocyte-stimulating hormone immunoreactive fibers in the paraventricular hypothalamic nucleus was also reduced in mutant mice at 6 weeks of age. A similar progressive loss of leptin sensitivity caused by loss of MAGEL2 in children with PWS could explain the delayed onset of increased appetite and weight gain in this complex disorder.

Topics: Animals; Antigens, Neoplasm; Arcuate Nucleus of Hypothalamus; Disease Models, Animal; Humans; Hypothalamus; Leptin; Mice; Neurons; Prader-Willi Syndrome; Pro-Opiomelanocortin; Proteins; Weight Gain

Obesity susceptibility in humans and in rodent strains varies in response to the consumption of high-energy density (HED) diets. However, the exact mechanism(s) involved in this susceptibility remain(s) unresolved. The aim of the present study was to gain greater insight into this susceptibility by using C57BL/6J (B6) mice that were separated into obesity-prone (diet-induced obese (DIO)) and obesity-resistant (diet-induced resistant (DR)) groups following an HED diet for 6 weeks. Physiological, biochemical and gene expression assessments of energy balance were performed in the DIO and DR mice on an HED diet and chow-fed mice. The increased weight gain of the DIO mice as compared to the DR mice was associated with increased energy intake and higher plasma leptin and adiponectin levels but not with reduced physical activity or resting energy expenditure. Hypothalamic Pomc gene expression was elevated, but there were no changes in Npy or Agrp expression. Adipose tissue leptin and adiponectin gene expression were significantly reduced in the DIO group as compared to the DR group. Interestingly, ileum expression of G protein-coupled receptor (Gpr) 40 (Gpr40) was significantly increased, whereas Gpr120, Gpr119, Gpr41, and glucagon-like peptide 1 (Glp1) were reduced. Contrastingly, the lower weight gain of the DR group was associated with elevated adipose tissue leptin and adiponectin gene expression, but there were no differences in plasma hormone or hypothalamic gene expression levels as compared to chow-fed mice. Therefore, the present data demonstrate that susceptibility and resistance to diet-induced weight gain in B6 mice appears to be predominantly driven by peripheral rather than hypothalamic modifications, and changes in gut-specific receptors are a potentially important contributor to this variation.

Topics: Adiponectin; Adipose Tissue, White; Adiposity; Animals; Arcuate Nucleus of Hypothalamus; Disease Resistance; Energy Intake; Female; Gene Expression Profiling; Gene Expression Regulation; Ileum; Leptin; Mice, Inbred C57BL; Nerve Tissue Proteins; Neurons; Obesity; Pro-Opiomelanocortin; Receptors, G-Protein-Coupled; Up-Regulation; Weight Gain

Maternal obesity increases adult offspring risk for cardiovascular disease; however, the role of offspring adiposity in mediating this association remains poorly characterized.. To investigate the associations of maternal pre-pregnant body mass index (maternal BMI) and gestational weight gain (GWG) with neonatal cardiometabolic markers independent of fetal growth and neonatal adiposity.. A total of 753 maternal-infant pairs from the Healthy Start study, a large multiethnic pre-birth observational cohort were used. Neonatal cardiometabolic markers included cord blood glucose, insulin, glucose-to-insulin ratio (Glu/Ins), total and high-density lipoprotein cholesterol (HDL-c), triglycerides, free fatty acids and leptin. Maternal BMI was abstracted from medical records or self-reported. GWG was calculated as the difference between the first pre-pregnant weight and the last weight measurement before delivery. Neonatal adiposity (percent fat mass) was measured within 72 h of delivery using whole-body air-displacement plethysmography.. In covariate adjusted models, maternal BMI was positively associated with cord blood insulin (P=0.01) and leptin (P<0.001) levels, and inversely associated with cord blood HDL-c (P=0.05) and Glu/Ins (P=0.003). Adjustment for fetal growth or neonatal adiposity attenuated the effect of maternal BMI on neonatal insulin, rendering the association nonsignificant. However, maternal BMI remained associated with higher leptin (P<0.0011), lower HDL-c (P=0.02) and Glu/Ins (P=0.05), independent of neonatal adiposity. GWG was positively associated with neonatal insulin (P=0.02), glucose (P=0.03) and leptin levels (P<0.001) and negatively associated with Glu/Ins (P=0.006). After adjusting for neonatal adiposity, GWG remained associated with higher neonatal glucose (P=0.02) and leptin levels (P=0.02) and lower Glu/Ins (P=0.048).. Maternal weight prior and/or during pregnancy is associated with neonatal cardiometabolic makers including leptin, glucose and HDL-c at delivery, independent of neonatal adiposity. Our results suggest that intrauterine exposure to maternal obesity influences metabolic processes beyond fetal growth and fat accretion.

Topics: Adiposity; Adult; Birth Weight; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Colorado; Female; Fetal Development; Humans; Infant, Newborn; Insulin; Leptin; Lipoproteins, HDL; Longitudinal Studies; Obesity; Plethysmography; Pregnancy; Risk Factors; Triglycerides; Weight Gain

The leptin (LEP) gene encodes a protein that greatly affects the regulation of body weight, energy balance, and food intake in mammals. The objective of the present work was to identify genetic variants of the caprine LEP gene in 411 individuals from five Chinese goat breeds. Six novel single nucleotide polymorphisms (SNPs) (g.117T > C, g.1642G > A, g.2883G > A, g.3053T > C, g.3190G > A, and g.3314T > C) were detected using DNA sequencing. A chi-squared (χ(2)) test showed that all of the LEP SNPs were in Hardy-Weinberg equilibrium in the studied population (P > 0.05). Six common haplotypes were identified in the five goat populations, with frequencies ranging from 0.083 to 0.244. The r(2) linkage disequilibrium plot of the LEP SNPs indicated linkage disequilibrium only in the cultured breeds (NJ and JY). Statistical analysis revealed that all of the six SNPs of the LEP gene were associated with growth traits. The individuals with the GG genotype at g.1642G>A and g.3190G > A loci showed higher birth weight (2.38 ± 0.03, 2.43 ± 0.05) and weight at 2 months of age (10.59 ± 0.16, 10.71 ± 0.26) than the A-bearing genotypes (AA or GA, P < 0.05). Our findings indicate that polymorphisms of the caprine LEP gene might be important genetic factors influencing growth traits, and these genetic markers may be useful for future marker-assisted selection programs in goat breeding and production.

Topics: Animals; Animals, Newborn; Base Sequence; Birth Weight; China; DNA; Female; Genetic Association Studies; Genetic Markers; Goats; Haplotypes; Leptin; Linkage Disequilibrium; Male; Polymorphism, Single Nucleotide; Quantitative Trait, Heritable; Selective Breeding; Weight Gain

To identify possible mechanisms linking obesity in pregnancy to increased fetal adiposity and growth, a unique mouse model of maternal obesity associated with fetal overgrowth was developed, and the hypothesis that maternal obesity causes up-regulation of placental nutrient transporter expression and activity was tested.. C57BL/6J female mice were fed a control (C) or a high-fat/high-sugar (HF/HS) pelleted diet supplemented by ad libitum access to sucrose (20%) solution, mated, and studied at embryonic day 18.5.. HF/HS diet increased maternal fat mass by 2.2-fold (P < 0.01) and resulted in glucose intolerance with normal fasting glucose. Maternal circulating insulin, leptin, and cholesterol were increased (P < 0.05) whereas total and high-molecular-weight adiponectin was decreased (P < 0.05). HF/HS diet increased fetal weight (+18%, P = 0.0005). In trophoblast plasma membranes (TPM) isolated from placentas of HF/HS-fed animals, protein expression of glucose transporter (GLUT) 1 and 3, sodium-coupled neutral amino acid transporter (SNAT) 2, and large neutral amino acid transporter 1 (LAT1) was increased. TPM System A and L amino acid transporter activity was increased in the HF/HS group.. Up-regulation of specific placental nutrient transporter isoforms may constitute a mechanism underlying fetal overgrowth in maternal obesity.

Topics: Animals; Disease Models, Animal; Female; Fetal Weight; Insulin; Leptin; Mice; Mice, Inbred C57BL; Mothers; Obesity; Pregnancy; Up-Regulation; Weight Gain

Diabesity-associated metabolic stresses modulate the development of Alzheimer's disease (AD). For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity. We characterized APPswe/PS1dE9 transgenic mice treated with a combination of high-fat diet with streptozotocin (HFSTZ) in the early stage of AD. HFSTZ-treated APPswe/PS1dE9 transgenic mice exhibited worse metabolic stresses related to diabesity, while serum β-amyloid levels were elevated and hepatic steatosis became apparent. Importantly, two-way analysis of variance shows a significant interaction between HFSTZ and genetic background of AD, indicating that APPswe/PS1dE9 transgenic mice are more vulnerable to HFSTZ treatment. In addition, body weight gain, high hepatic triglyceride, and hyperglycemia were positively associated with serum β-amyloid, as validated by Pearson's correlation analysis. Our data suggests that the interplay between genetic background of AD and HFSTZ-induced metabolic stresses contributes to the development of obesity and hepatic steatosis. Alleviating metabolic stresses including dysglycemia, obesity, and hepatic steatosis could be critical to prevent peripheral β-amyloid accumulation at the early stage of AD.

Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Analysis of Variance; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Disease Models, Animal; Fatty Acids, Nonesterified; Fatty Liver; Humans; Leptin; Lipids; Liver; Male; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Peptide Fragments; Presenilin-1; Stress, Physiological; Triglycerides; Weight Gain

Obesity impairs cognition, and the leptin-induced increase of brain-derived neurotrophic factor (BDNF) and neurogenesis. Tea consumption improves cognition and increases brain activation in the prefrontal cortex.. This study examined whether teasaponin, an active ingredient in tea, could improve memory and central leptin effects on neurogenesis in the prefrontal cortex of obese mice, and in vitro in cultured prefrontal cortical neurons. Teasaponin (10 mg/kg, intraperitoneal) for 21 days improved downstream leptin signaling (JAK2 and STAT3), and leptin's effect on BDNF, in the prefrontal cortex of high-fat diet (HFD) fed mice. Prefrontal cortical neurons were cultured with teasaponin and palmitic acid (the most abundant dietary saturated fatty acid) to examine their effects on neurogenesis and BDNF expression in response to leptin. Palmitic acid decreased leptin's effect on neurite outgrowth, postsynaptic density protein 95, and BDNF expression in cultured cortical neurons, which was reversed by teasaponin.. Teasaponin improved the leptin sensitivity of prefrontal cortical neurons in obese mice or when treated by palmitic acid. This in turn increased BDNF expression and neurite growth. Therefore, teasaponin supplementation may be used to prevent obesity-associated neurodegeneration and improve cognitive function.

Topics: Animals; Brain-Derived Neurotrophic Factor; Cells, Cultured; Diet, High-Fat; Hyperinsulinism; Insulin; Leptin; Male; Mice, Inbred C57BL; Mice, Obese; Neurons; Obesity; Palmitic Acid; Prefrontal Cortex; Saponins; STAT3 Transcription Factor; Tea; Weight Gain

In this study, the effects of agavins (branched fructans) along with a diet shift on metabolic parameters, short chain fatty acid (SCFA) production and gastrointestinal hormones in overweight mice were established. Male C57BL/6 mice were fed with a standard (ST) or high fat (HF) diet over the course of 5 weeks, with the objective to induce overweightness in the animals, followed by a diet shift (HF_ST) and a diet shift with agavins (HF_ST + A) or inulin (HF_ST + O) for 5 additional weeks. After the first 5 weeks, the HF group showed a 30% body weight gain and an increase in glucose, triglyceride and cholesterol concentrations of 9%, 79% and 38% respectively when compared to the ST group (P < 0.05). Only the overweight mice that received agavins or inulin in their diets reversed the metabolic disorders induced by consumption of the HF diet, reaching the values very close to those of the ST group (P < 0.05). Furthermore, the consumption of agavins or inulin led to higher SCFA concentrations in the gut and modulated hormones such as GLP-1 and leptin involved in food intake regulation (P < 0.05). These findings demonstrate that a change of diet and fructan consumption such as agavins is a good alternative to increase weight loss and to improve the metabolic disorders associated with being overweight.

Topics: Animals; Blood Glucose; Cholesterol; Diet, High-Fat; Energy Intake; Fatty Acids, Volatile; Fructans; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Hydrogen-Ion Concentration; Inulin; Leptin; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Overweight; Principal Component Analysis; Triglycerides; Weight Gain

Traditional Asian diet rich in soy isoflavones (ISOs) is discussed to be linked to a lower obesity prevalence. In lifelong and short-term exposure scenarios we investigated effects of an ISO-rich diet on the body composition and development of obesity in female rats.. Female Wistar rats grew up on ISO-free or ISO-rich control diet (CON ISO: 467 mg/kg diet). Starting postnatal day 83, ovariectomized and intact animals received high calorie Western diet (WD) in the absence or presence of ISO (WD ISO: 431 mg/kg diet) for 12 weeks to induce obesity or maintained on respective control diet (CON). One group starting ISO exposure after ovariectomy mimics short-term ISO exposure in postmenopausal Western women. Lifelong but not short-term ISO exposure resulted in reduced body weight, visceral fat mass, serum leptin, and smaller adipocytes. ISO decreased hepatic SREBP-1c, ACC, FAS, and PPARγ mRNA expression in nonobese animals. Moreover, ovariectomy reduced skeletal muscle weight, which was antagonized by both short-term and lifelong ISO exposure.. Our results indicate that in female rats lifelong but not short-term ISO intake reduces the risk to develop obesity. Furthermore, lifelong and short-term ISO exposure may antagonize loss of skeletal muscle mass induced by ovariectomy.

Topics: Adipocytes; Animals; Body Composition; Dietary Supplements; Energy Intake; fas Receptor; Female; Glycine max; Insulin-Like Growth Factor I; Isoflavones; Leptin; Obesity; Ovariectomy; PPAR alpha; PPAR gamma; Rats, Wistar; Sterol Regulatory Element Binding Protein 1; Weight Gain

Maternal stress exerts long-lasting postnatal growth on offspring, which persist into adulthood. However, the effect of maternal stress on appetizing system has not been widely reported. In this study, we found that maternal immobilization stress (IS) during lactation resulted in low body weight and food intake. Immunohistochemistry showed an increase in stomach ghrelin protein expression. The central regulation of body weight and food intake occurs in the hypothalamus, which contains multiple neuronal systems that play important roles in the regulation of energy homeostasis. These systems including multiple neuropeptides involve in the ghrelin pathway of appetite regulation. Therefore, real time reverse transcription polymerase chain reaction (RT-PCR) was used to measure the change of mRNA expression of ghrelin pathway related hormones in order to explore the mechanisms involved in the appetite regulation. Expression levels of the hypothalamic 5-hydroxytryptamine 2c receptor (5-HT2cR) and 5-HT2bR, which are essential for the development and function of ghrelin and leptin, were decreased, as well as those of corticotrophin releasing factor (CRF) and pro-opiomelanocortin (POMC). While the expression of growth hormone secretagogue receptor (GHSR), neuropeptide-Y (NPY) and agouti-related protein (AgRP) showed an increase with significant difference. These results suggest that stress in a postpartum mother has persistent effects on the body weight of their offspring. Increased ghrelin and decreased leptin expression in the stomach may play a role in these effects.

Topics: Agouti Signaling Protein; Animals; Appetite Regulation; Corticotropin-Releasing Hormone; Disease Models, Animal; Eating; Feeding Behavior; Female; Gastric Mucosa; Ghrelin; Hypothalamus; Lactation; Leptin; Maternal Exposure; Mice, Inbred ICR; Neuropeptide Y; Postpartum Period; Pro-Opiomelanocortin; Receptor, Serotonin, 5-HT2B; Receptor, Serotonin, 5-HT2C; Receptors, Ghrelin; Restraint, Physical; Stress, Psychological; Time Factors; Weight Gain

Clinical practice shows that thiazolidinediones (TZDs) induce weight gain in patients with type-II diabetes mellitus during treatment, which restrains its application and generalization clinically. It has been demonstrated that acupuncture therapy is useful in easing obesity in clinical trials. In the present paper, we summarize the underlying mechanism of weight gain induced by TZDs through food intake-related targets in the central nervous system and analyze the possible effects of acupuncture therapy. Acupuncture therapy is expected to reduce weight gain side effect of TZDs through 1) lowering permeability of blood brain barrier to reduce TZDs concentration in the brain, 2) upregulating the expression of hypothalamic leptin and inhibiting hypothalamic neuropiptide Y expression, and 3) down-regulating activities of peroxisome proliferator-activated receptor to reduce energy intake and fat syntheses.

Topics: Acupuncture Therapy; Animals; Central Nervous System; Diabetes Mellitus, Type 2; Eating; Humans; Hypoglycemic Agents; Leptin; Peroxisome Proliferator-Activated Receptors; Thiazolidinediones; Weight Gain

We conducted this investigation in order to examine the anti-obesity and hypolipidaemic effects of Nelumbo nucifera seed ethanol extract (NSEE) in vitro and in vivo.. To study the anti-obesity effect of NSEE in vitro and in vivo, human pre-adipocytes were treated with NSEE, and male Sprague-Dawley rats were fed with a normal diet and a high-fat diet with or without NSEE, respectively.. In vitro treatment with NSEE resulted in inhibition of lipid accumulation and decreased expression of peroxisome proliferator-activated receptor gamma (PPARγ), glucose transporter 4 (GLUT4), and leptin in cultured human adipocytes, indicating that it inhibited the differentiation of pre-adipocytes into adipocytes. Administration of NSEE resulted in significantly reduced body weight gain and adipose tissue weights in rats. Serum triglyceride and leptin level of the high-fat diet + NSEE group was significantly lower, compared to the high-fat group.. These results demonstrate an inhibitory effect of NSEE on adipogenesis. In addition, NSEE had a beneficial effect, reducing adipose tissue weights, ameliorating blood lipid profile, and modulating serum leptin level in rats fed a high-fat diet. Therefore, we suggest that lotus seed has a potential to be developed as an effective agent against obesity-related diseases.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipose Tissue; Animals; Anti-Obesity Agents; Diet, High-Fat; Glucose Transporter Type 4; Hyperlipidemias; Hypolipidemic Agents; Leptin; Male; Mice; Nelumbo; Obesity; Phytotherapy; Plant Extracts; PPAR gamma; Rats; Rats, Sprague-Dawley; Seeds; Triglycerides; Weight Gain

Both insufficiency and resistance to the actions of the adipocyte-derived hormone leptin promote hunger, increased food intake and greater body weight. Some studies suggest that adults reporting binge eating have increased serum leptin compared with those without binge eating, even after adjusting for the greater adiposity that characterizes binge eaters. Pediatric binge or loss of control (LOC) eating are prospective risk factors for excessive weight gain and may predict development of metabolic abnormalities, but whether LOC eating is associated with higher leptin among children is unknown. We therefore examined leptin and LOC eating in a pediatric cohort.. A convenience sample of 506 lean and obese youth (7-18 years) was recruited from Washington, DC and its suburbs. Serum leptin was collected after an overnight fast. Adiposity was measured by dual-energy X-ray absorptiometry or air displacement plethysmography. LOC eating was assessed by interview methodology.. Leptin was strongly associated with fat mass (r=0.79, P<0.001). However, even after adjusting for adiposity and other relevant covariates, youth with LOC eating had higher serum leptin compared with those without LOC episodes (15.42±1.05 vs 12.36±1.04 ng ml(-1), P<0.001). Neither reported amount of food consumed during a recent LOC episode nor number of LOC episodes in the previous month accounted for differences in leptin (P>0.05). The relationship between LOC eating and leptin appeared to be significant for females only (P=0.002).. Reports of LOC eating were associated with higher fasting leptin in youth, beyond the contributions of body weight. Prospective studies are required to elucidate whether LOC eating promotes greater leptin or whether greater leptin resistance may promote LOC eating.

Topics: Absorptiometry, Photon; Adolescent; Adolescent Behavior; Affect; Bulimia; Child; Child Behavior; Cross-Sectional Studies; District of Columbia; Energy Intake; Feeding Behavior; Female; Humans; Hunger; Internal-External Control; Leptin; Male; Prospective Studies; Sampling Studies; Satiation; Weight Gain

Obese leptin deficient (ob/ob) mice are a model of adiposity that displays increased levels of fat, glucose, and liver lipids. Our hypothesis is that HO-1 overexpression ameliorates fatty liver development.. Obese mice were administered cobalt protoporphyrin (CoPP) and stannic mesoporphyrin (SnMP) for 6 weeks. Heme, HO-1, HO activity, PGC1α, FGF21, glycogen content, and lipogenesis were assessed.. CoPP administration increased hepatic HO-1 protein levels and HO activity, decreased hepatic heme, body weight gain, glucose levels, and resulted in decreased steatosis. Increased levels of HO-1 produced a decrease in lipid droplet size, Fatty acid synthase (FAS) levels involving recruitment of FGF21, PPARα, and Glut 1. These beneficial effects were reversed by inhibition of HO activity.. Increased levels of HO-1 and HO activity reduced the levels of obesity by reducing hepatic heme and lipid accumulation. These changes were manifested by decreases in cellular heme, increases in FGF21, glycogen content, and fatty liver. The beneficial effect of HO-1 induction results from an increase in PPARα and FGF21 levels and a decrease in PGC1α, levels they were reversed by SnMP. Low levels of HO-1 and HO activity are responsible for fatty liver.

Topics: Adiposity; Animals; Fatty Liver; Fibroblast Growth Factors; Glucose Transporter Type 1; Glycogen; Heme; Heme Oxygenase-1; Leptin; Liver; Male; Membrane Proteins; Mesoporphyrins; Mice; Mice, Obese; Obesity; PPAR alpha; Protoporphyrins; Tin Compounds; Transcription Factors; Weight Gain

Gastric vagal afferents convey satiety signals in response to mechanical stimuli. The sensitivity of these afferents is decreased in diet-induced obesity. Leptin, secreted from gastric epithelial cells, potentiates the response of vagal afferents to mechanical stimuli in lean mice, but has an inhibitory effect in high-fat diet (HFD)-induced obese mice. We sought to determine whether changes in vagal afferent function and response to leptin in obesity were reversible by returning obese mice consuming a HFD to standard laboratory chow diet (SLD).. Eight-week-old female C57BL/6 mice were either fed a SLD (N=20) or HFD (N=20) for 24 weeks. A third group was fed a HFD for 12 weeks and then a SLD for a further 12 weeks (RFD, N=18). An in vitro gastro-oesophageal vagal afferent preparation was used to determine the mechanosensitivity of gastric vagal afferents and the modulatory effect of leptin (0.1-10 nM) was examined. Retrograde tracing and quantitative RT-PCR were used to determine the expression of leptin receptor (LepR) messenger RNA (mRNA) in whole nodose and specific cell bodies traced from the stomach.. After 24 weeks, both the HFD and RFD mice had increased body weight, gonadal fat mass, plasma leptin, plasma insulin and daily energy consumption compared with the SLD mice. The HFD and RFD mice had reduced tension receptor mechanosensitivity and leptin further inhibited responses to tension in HFD, RFD but not SLD mice. Mucosal receptors from both the SLD and RFD mice were potentiated by leptin, an effect not seen in HFD mice. LepR expression was unchanged in the whole nodose, but was reduced in the mucosal afferents of the HFD and RFD mice.. Disruption of gastric vagal afferent function by HFD-induced obesity is only partially reversible by dietary change, which provides a potential mechanism preventing maintenance of weight loss.

Topics: Afferent Pathways; Animals; Body Weight; Diet, High-Fat; Energy Intake; Feeding Behavior; Female; Gastric Mucosa; Immunohistochemistry; Leptin; Mice; Mice, Inbred C57BL; Obesity; Real-Time Polymerase Chain Reaction; Receptors, Leptin; Thinness; Vagus Nerve; Weight Gain

Short sleep confers a higher risk of obesity in humans. Restricted sleep increases appetite, promotes higher calorie intake from fat and carbohydrate sources, and induces insulin resistance. However, the effects of fragmented sleep (SF), such as occurs in sleep apnea, on body weight, metabolic rates, and adipose tissue distribution are unknown.. C57BL/6 mice were exposed to SF for 8 weeks. Their body weight, food consumption, and metabolic expenditure were monitored over time, and their plasma leptin levels measured after exposure to SF for 1 day as well as for 2 weeks. In addition, adipose tissue distribution was assessed at the end of the SF exposure using MRI techniques.. Chronic SF-induced obesogenic behaviors and increased weight gain in mice by promoting increased caloric intake without changing caloric expenditure. Plasma leptin levels initially decreased and subsequently increased. Furthermore, increases in both visceral and subcutaneous adipose tissue volumes occurred.. These results suggest that SF, a frequent occurrence in many disorders and more specifically in sleep apnea, is a potent inducer of obesity via activation of obesogenic behaviors and possibly leptin resistance, in the absence of global changes in energy expenditure.

Topics: Animals; Body Fat Distribution; Calorimetry, Indirect; Disease Models, Animal; Energy Intake; Homeostasis; Intra-Abdominal Fat; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Sleep Deprivation; Subcutaneous Fat; Weight Gain

Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid precursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8 en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly increased ARA in phospholipids (ARA-PL), elevated 2-AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en% LNA. Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet.

Topics: Adipose Tissue; Analysis of Variance; Animals; Arachidonic Acids; Body Weight; Diet; Diet, Fat-Restricted; Endocannabinoids; Erythrocytes; Fatty Acids; Glycerides; Leptin; Linoleic Acid; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; Obesity; Phospholipids; Polyunsaturated Alkamides; Risk Factors; Weight Gain

We evaluated multiple effects of genetic variations of five candidate loci (LEP, LEPR, MC4R, PIK3C3 and VRTN) on four production traits (average daily weight gain (ADG); backfat thickness (BFT); loin eye muscle area (EMA); and intramuscular fat content (IMF)) in a closed nucleus herd of pure Duroc pigs. Polymorphisms in LEPR, MC4R and PIK3C3 had significant single gene effects on ADG and BFT. The additive genetic variance in ADG and BFT (16.99% and 22.51%, respectively) was explained by genetic effects of these three loci. No correlations were observed between the LEP genotype and production traits in this study. Although we detected marginally epistatic interactions between LEPR and PIK3C3 on the eye muscle area, there were no significant epistatic effects on any traits among all loci pairs. These results suggest that LEPR, MC4R, PIK3C3 and VRTN may independently influence growth rate and fat deposition. Furthermore, the statistical models for predicting the breeding values of each trait had the lowest Akaike's information criterion values when considering the effect of the MC4R, LEPR, PIK3C3 and VRTN genotype simultaneously. These results suggest that LEPR, MC4R, PIK3C3 and VRTN are useful markers for accurately predicting breeding values in Duroc pigs.

Topics: Adipose Tissue; Animals; Genetic Markers; Leptin; Muscle, Skeletal; Phosphatidylinositol 3-Kinases; Polymorphism, Genetic; Receptor, Melanocortin, Type 4; Receptors, Leptin; Swine; Weight Gain

Disruption of the circadian system can lead to metabolic dysfunction as a response to environmental alterations. This study assessed the effects of the association between obesity and chronic stress on the temporal pattern of serum levels of adipogenic markers and corticosterone in rats. We evaluated weekly weight, delta weight, Lee index, and weight fractions of adipose tissue (mesenteric, MAT; subcutaneous, SAT; and pericardial, PAT) to control for hypercaloric diet-induced obesity model efficacy. Wistar rats were divided into four groups: standard chow (C), hypercaloric diet (HD), stress plus standard chow (S), and stress plus hypercaloric diet (SHD), and analyzed at three time points: ZT0, ZT12, and ZT18. Stressed animals were subjected to chronic stress for 1h per day, 5 days per week, during 80 days. The chronic exposure to a hypercaloric diet was an effective model for the induction of obesity and metabolic syndrome, increasing delta weight, Lee index, weight fractions of adipose tissue, and triglycerides and leptin levels. We confirmed the presence of a temporal pattern in the release of triglycerides, corticosterone, leptin, and adiponectin in naïve animals. Chronic stress reduced delta weight, MAT weight, and levels of triglycerides, total cholesterol, and leptin. There were interactions between chronic stress and obesity and serum total cholesterol levels, between time points and obesity and adiponectin and corticosterone levels, and between time points and chronic stress and serum leptin levels. In conclusion, both parameters were able to desynchronize the temporal pattern of leptin and triglyceride release, which could contribute to the development of metabolic diseases such as obesity and metabolic syndrome.

Topics: Adiponectin; Adipose Tissue, White; Adiposity; Animals; Cholesterol; Chronic Disease; Circadian Rhythm; Corticosterone; Leptin; Male; Obesity; Rats; Rats, Wistar; Restraint, Physical; Stress, Psychological; Triglycerides; Weight Gain

Accelerated weight gain after (adeno)tonsillectomy has been reported in a number of studies. Whether (adeno)tonsillectomy is also a risk factor for development of overweight is unknown. We investigated serum leptin and plasma ghrelin levels before and 1 year after (adeno)tonsillectomy operation in children.. We studied 31 patients and 29 age- and sex-matched healthy control children. Auxologic evaluation and biochemical investigations were performed before surgery and 1 year later.. One year after surgery, height SDS (p = 0.001) and weight SDS (p = 0.004) were significantly increased in both groups. No changes in BMI SDS (p = 0.105) were observed. Preoperative leptin levels were significantly higher in patients than controls (p < 0.001). IGF-1, IGFBP-3, HOMA-IR and ghrelin values were not significantly different between the groups. One year after surgery, IGF-1 (p = 0.001) and IGFBP-3 (p = 0.001) were significantly increased, while ghrelin (p < 0.001) was significantly decreased. Postoperative leptin levels of patients were also significantly higher than preoperative values (p = 0.036).. Significantly higher leptin levels in patients compared to control both before and 1 year after an obstruction-relieving surgery suggested that higher levels might be due to leptin resistance in these patients. Based on our findings we recommend measurement of leptin levels longitudinally for at least 5 years after adenotonsillectomy.

Topics: Adenoidectomy; Case-Control Studies; Child; Child, Preschool; Female; Ghrelin; Humans; Leptin; Male; Overweight; Postoperative Complications; Risk Factors; Tonsillectomy; Weight Gain

Weight gain, insulin-like growth factor-I (IGF-I) levels, and excess exogenous steroid hormone use are putative cancer risk factors, yet their interconnected pathways have not been fully characterized. This cross-sectional study investigated the relationship between plasma IGF-I levels and weight gain according to body mass index (BMI), leptin levels, and exogenous estrogen use among postmenopausal women.. This study included 794 postmenopausal women who enrolled in an ancillary study of the Women's Health Initiative Observational Study between February 1995 and July 1998. The relationship between IGF-I levels and weight gain was analyzed using ordinal logistic regression. We used the molar ratio of IGF-I to IGF binding protein-3 (IGF-I/IGFBP-3) or circulating IGF-I levels adjusting for IGFBP-3 as a proxy of bioavailable IGF-I. The plasma concentrations were expressed as quartiles.. Among the obese group, women in the third quartile (Q3) of IGF-I and highest quartile of IGF-I/IGFBP-3 were less likely to gain weight (>3% from baseline) than were women in the first quartiles (Q1). Among the normal-weight group, women in Q2 and Q3 of IGF-I/IGFBP-3 were 70% less likely than those in Q1 to gain weight. Among current estrogen users, Q3 of IGF-I/IGFBP-3 had 0.5 times the odds of gaining weight than Q1.. Bioavailable IGF-I levels were inversely related to weight gain overall.. Although weight gain was not consistent with increases in IGF-I levels among postmenopausal women in this report, avoidance of weight gain as a strategy to reduce cancer risk may be recommended.

Topics: Aged; Body Mass Index; Cross-Sectional Studies; Estrogens; Female; Humans; Insulin-Like Growth Factor I; Leptin; Logistic Models; Middle Aged; Obesity; Postmenopause; Risk Factors; Treatment Outcome; Weight Gain

Obesity is associated with ageing and increased energy intake, while restriction of energy intake improves health and longevity in multiple organisms; the NAD(+)-dependent deacetylase sirtuin 1 (SIRT1) is implicated in this process. Pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons in the arcuate nucleus (ARC) of the hypothalamus are critical for energy balance regulation, and the level of SIRT1 protein decreases with age in the ARC. In the current study we tested whether conditional Sirt1 overexpression in mouse POMC or AgRP neurons prevents age-associated weight gain and diet-induced obesity.. We targeted Sirt1 cDNA sequence into the Rosa26 locus and generated conditional Sirt1 knock-in mice. These mice were crossed with mice harbouring either Pomc-Cre or Agrp-Cre and the metabolic variables, food intake, energy expenditure and sympathetic activity in adipose tissue of the resultant mice were analysed. We also used a hypothalamic cell line to investigate the molecular mechanism by which Sirt1 overexpression modulates leptin signalling.. Conditional Sirt1 overexpression in mouse POMC or AgRP neurons prevented age-associated weight gain; overexpression in POMC neurons stimulated energy expenditure via increased sympathetic activity in adipose tissue, whereas overexpression in AgRP neurons suppressed food intake. SIRT1 improved leptin sensitivity in hypothalamic neurons in vitro and in vivo by downregulating protein-tyrosine phosphatase 1B, T cell protein-tyrosine phosphatase and suppressor of cytokine signalling 3. However, these phenotypes were absent in mice consuming a high-fat, high-sucrose diet due to decreases in ARC SIRT1 protein and hypothalamic NAD(+) levels.. ARC SIRT1 is a negative regulator of energy balance, and decline in ARC SIRT1 function contributes to disruption of energy homeostasis by ageing and diet-induced obesity.

Topics: Animals; Calorimetry, Indirect; Genotype; Hypothalamus; Immunohistochemistry; Leptin; Male; Mice; Mice, Inbred C57BL; Polymerase Chain Reaction; Sirtuin 1; Weight Gain

Early in life, leptin plays a crucial role in hypothalamic neural organization. Leptin, most likely, controls neural gene expression conferring then specific phenotype regarding energy homeostasis. MicroRNAs are new regulators for several physiological functions, including the regulation of metabolism. However, the impact of leptin on hypothalamic microRNA patterns remains unknown. Here, we demonstrate that miR-200a, miR-200b and miR-429 are up-regulated in the hypothalamus of genetically obese and leptin deficient ob/ob mice. Leptin treatment down-regulates these miRNAs in ob/ob hypothalamus. The hypothalamic silencing of miR-200a increased the expression level of leptin receptor and insulin receptor substrate 2, reduced body weight gain, and restored liver insulin responsiveness. In addition, the overexpression of pre-miR-200a in a human neuroblastoma cell line impaired insulin and leptin signaling. These findings link the alteration of leptin and insulin signaling to the up-regulation of hypothalamic miR-200a which could be a new target for treatment of obesity.

Topics: Animals; Cell Line, Tumor; Feeding Behavior; Gene Expression Regulation; Humans; Hypothalamus; Insulin; Insulin Receptor Substrate Proteins; Leptin; Liver; Male; Mice; Mice, Obese; MicroRNAs; Neurons; Obesity; Receptors, Leptin; Signal Transduction; Weight Gain

It has been suggested a role of fatty acid ethanolamides in control of feeding behavior. Among these, palmitoylethanolamide (PEA) has not been directly implicated in appetite regulation and weight gain. The aim of this study was to investigate the effect of PEA on food intake and body weight and the interaction between PEA and hypothalamic leptin signaling in ovariectomized rats. Ovariectomy produced hyperphagia and increased weight gain, making it an useful model of mild obesity. Ovariectomized rats were treated with PEA (30 mg/kg sc) for 5 weeks. Then, blood was collected, and hypothalamus and adipose tissue were removed for histological, cellular, and molecular measurements. We showed that PEA caused a reduction of food intake, body weight, and fat mass. The mechanisms underlying PEA effects involved an improvement in hypothalamic leptin signaling, through a raise in signal transducer and activator of transcription 3 phosphorylation. We also reported that PEA reduced AMP-activated protein kinase-α phosphorylation and modulated transcription of anorectic and orexigenic neuropeptides in the hypothalamus. Moreover, PEA increased AMP-activated protein kinase-α phosphorylation and carnitine palmitoyltransferase 1 transcription in adipose tissue, suggesting an increase in ATP-producing catabolic pathway. PEA also polarized adipose tissue macrophages to M2 lean phenotype, associated to a reduction of inflammatory cytokines/adipokines. To demonstrate the direct effect of PEA on leptin sensitivity without interference of adiposity loss, we obtained consistent data in PEA-treated sham-operated animals and in vitro in SH-SY5Y neuroblastoma cell line. Therefore, our data provide a rationale for the therapeutic use of PEA in obese postmenopausal woman.

Topics: Adenosine Triphosphate; Adipokines; Amides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Cell Line, Tumor; Cytokines; Eating; Endocannabinoids; Ethanol; Ethanolamines; Fatty Acids; Feeding Behavior; Female; Glucose Tolerance Test; Humans; Leptin; Obesity; Ovariectomy; Palmitic Acids; Phosphorylation; Rats; Rats, Wistar; Signal Transduction; Weight Gain

Hyperleptinemia during postnatal life induces long-term effects on metabolism. However, these effects are controversial as both increased and decreased propensity towards obesity has been reported. To further analyze the effects of chronic neonatal hyperleptinemia on the subsequent metabolic profile, male Wistar rats proceeding from 18 different litters (8 pups/litter) received a daily subcutaneous injection of either saline (10 ml/kg, n=36) or leptin (3 μg/g, n=36) from postnatal day (PND) 2 to PND9. Rats were sacrificed at 10, 40, or 150 days of age. At 10 days of age, leptin treated rats had decreased body weight (p<0.001) and body fat (p<0.05). Leptin levels and glycemia were increased (p<0.01), whereas insulin, total lipids, triglycerides and glycerol levels were decreased (p<0.05). At PND40 rats receiving leptin had increased glycemia (p<0.01) and plasma HDL and LDL levels, but decreased total lipids (p<0.05). At PND150 neonatal leptin treatment induced different effects in rats raised in different litters. Rats from litter 1 had increased body weight (p<0.05), body fat (p<0.01), and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), total lipid (p<0.001), LDL (p<0.05), and glycerol (p<0.001) levels. In rats from litter 2 these parameters did not differ from controls. Rats from litter 3 had decreased body weight (p<0.05), visceral fat (p<0.01) and plasma leptin (p<0.001), cholesterol (p<0.001), triglyceride (p<0.001), glycerol (p<0.001), and HDL (p<0.001) levels. In conclusion, the metabolic response to postnatal leptin varies with age, with the response in adulthood being variable and most likely influenced by other factors, including the genetic make-up.

Topics: Aging; Animals; Animals, Newborn; Female; Hypothalamus; Leptin; Lipids; Litter Size; Male; Organ Size; Rats, Wistar; Receptors, Leptin; RNA, Messenger; Weight Gain

AT₁ receptor antagonists decrease body weight gain in models of murine obesity. However, fewer data are available concerning the anti-obesity effects of these antagonists, given as a treatment after obesity had been established.. In spontaneously hypertensive rats, obesity was established by cafeteria diet (CD) feeding for 19 weeks. Rats were then were treated with telmisartan (8 mg·kg⁻¹·d⁻¹) or amlodipine (10 mg·kg⁻¹·d⁻¹; serving as blood pressure control) or telmisartan + amlodipine (2 + 10 mg·kg⁻¹·d⁻¹; to control for dose-dependency) for 17 weeks. Rats receiving only chow (C(chow)) or CD-fed rats treated with vehicle (C(CD)) served as controls.. The CD feeding induced obesity, hyperphagia, hyperlipidaemia, and leptin and insulin resistance. Telmisartan reduced the CD-induced increase in body weight and abdominal fat mass. Whereas energy intake was higher rather than lower, the respiratory ratio was lower. After telmisartan, leptin-induced energy intake was reduced and respiratory ratio was increased compared with C(CD) rats. Telmisartan also decreased plasma levels of triglycerides, free fatty acids and low-density lipoprotein. Amlodipine alone or the combination telmisartan + amlodipine did not affect body weight and eating behaviour. Telmisartan, but not amlodipine and telmisartan + amlodipine, improved glucose utilization. The decrease in BP reduction was almost the same in all treatment groups.. Telmisartan exerted anti-obesity effects and restored leptin sensitivity, given as a treatment to rats with obesity. Such effects required high doses of telmisartan and were independent of the decrease in blood pressure.

Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Animals; Anti-Obesity Agents; Antihypertensive Agents; Behavior, Animal; Benzimidazoles; Benzoates; Diet, High-Fat; Dietary Sucrose; Drug Therapy, Combination; Energy Intake; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Random Allocation; Rats; Rats, Inbred SHR; Telmisartan; Weight Gain

Osteoporosis and overweight/obesity constitute major worldwide public health burdens that are associated with aging. A high proportion of women develop osteoporosis and increased intraabdominal adiposity after menopause. which leads to bone fractures and metabolic disorders. There is no efficient treatment without major side effects for these 2 diseases. We previously showed that the administration of oxytocin (OT) normalizes ovariectomy-induced osteopenia and bone marrow adiposity in mice. Ovariectomized mice, used as an animal model mimicking menopause, were treated with OT or vehicle. Trabecular bone parameters and fat mass were analyzed using micro-computed tomography. Herein, we show that this effect on trabecular bone parameters was mediated through the restoration of osteoblast/osteoclast cross talk via the receptor activator of nuclear factor-κB ligand /osteoprotegerin axis. Moreover, the daily administration of OT normalized body weight and intraabdominal fat depots in ovariectomized mice. Intraabdominal fat mass is more sensitive to OT that sc fat depots, and this inhibitory effect is mediated through inhibition of adipocyte precursor's differentiation with a tendency to lower adipocyte size. OT treatment did not affect food intake, locomotors activity, or energy expenditure, but it did promote a shift in fuel utilization favoring lipid oxidation. In addition, the decrease in fat mass resulted from the inhibition of the adipose precursor's differentiation. Thus, OT constitutes an effective strategy for targeting osteopenia, overweight, and fat mass redistribution without any detrimental effects in a mouse model mimicking the menopause.

Topics: Adipocytes; Adipose Tissue; Animals; Body Weight; Bone Diseases, Metabolic; Cell Culture Techniques; Coculture Techniques; Disease Models, Animal; Female; Leptin; Lipids; Menopause; Mice; Mice, Inbred C57BL; Osteoblasts; Osteoclasts; Osteoporosis; Ovariectomy; Oxygen; Oxytocin; Weight Gain; X-Ray Microtomography

Providing rats and mice with access to palatable high fat diets for a short period each day induces the consumption of substantial binge-like meals. Temporal food intake structure (assessed using the TSE PhenoMaster/LabMaster system) and metabolic outcomes (oral glucose tolerance tests [oGTTs], and dark phase glucose and insulin profiles) were examined in Sprague-Dawley rats given access to 60% high fat diet on one of 3 different feeding regimes: ad libitum access (HF), daily 2 h-scheduled access from 6 to 8 h into the dark phase (2 h-HF), and twice daily 1 h-scheduled access from both 1-2 h and 10-11 h into the dark phase (2×1 h-HF). Control diet remained available during the scheduled access period. HF rats had the highest caloric intake, body weight gain, body fat mass and plasma insulin. Both schedule-fed groups rapidly adapted their feeding behaviour to scheduled access, showing large meal/bingeing behaviour with 44% or 53% of daily calories consumed from high fat diet during the 2 h or 2×1 h scheduled feed(s), respectively. Both schedule-fed groups had an intermediate caloric intake and body fat mass compared to HF and control (CON) groups. Temporal analysis of food intake indicated that schedule-fed rats consumed large binge-type high fat meals without a habitual decrease in preceding intake on control diet, suggesting that a relative hypocaloric state was not responsible or required for driving the binge episode, and substantiating previous indications that binge eating may not be driven by hypothalamic energy balance neuropeptides. In an oGTT, both schedule-fed groups had impaired glucose tolerance with higher glucose and insulin area under the curve, similar to the response in ad libitum HF fed rats, suggesting that palatable feeding schedules represent a potential metabolic threat. Scheduled feeding on high fat diet produces similar metabolic phenotypes to mandatory (no choice) high fat feeding and may be a more realistic platform for mechanistic study of diet-induced obesity.

Topics: Animals; Blood Glucose; Bulimia; Dietary Fats; Eating; Fatty Acids, Nonesterified; Feeding Behavior; Ghrelin; Glucagon-Like Peptide 1; Insulin; Leptin; Male; Rats, Sprague-Dawley; Triglycerides; Weight Gain

This study investigated whether biochemical parameters add predictive information concerning risk for weight gain associated with treatment with atypical antipsychotics (AP) to that provided by baseline weight.. Weight changes were assessed in 25 patients with schizophrenia after 3-6 months of treatment. These patients were started on AP monotherapy owing to a first psychotic episode or resumed treatment after at least a 6-month period of abandonment. Anthropometric and biochemical data were collected and analyzed as predictors of early weight change.. The baseline biochemical and anthropometric data were not significantly higher in the patients than in the healthy participants. During follow up, the patients had significant increases in body mass index and total cholesterol and apolipoprotein B level. The baseline weight and leptin level were predictive of weight gain during follow up, with an inverse association in both cases.. Baseline weight and leptin level may help to assess the risk of early weight gain with AP.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Female; Humans; Leptin; Male; Middle Aged; Overweight; Schizophrenia; Weight Gain; Young Adult

Previous studies have demonstrated that early environmental interventions influence the consumption of palatable food and the abdominal fat deposition in female rats chronically exposed to a highly caloric diet in adulthood. In this study, we verified the metabolic effects of chronic exposure to a highly palatable diet, and determine the response to its withdrawal in adult neonatally handled and non-handled rats. Consumption of foods (standard lab chow and chocolate), body weight gain, abdominal fat deposition, plasma triglycerides, and leptin, as well as serum butyrylcholinesterase (BuChE), and cerebral acetylcholinesterase (AChE) activities were measured during chronic chocolate exposure and after deprivation of this palatable food in female rats exposed or not to neonatal handling (10 minutes/day, 10 first days of life). Handled rats increased rebound chocolate consumption in comparison to non-handled animals after 1 week of chocolate withdrawal; these animals also decreased body weight in the first 24 hours but this effect disappeared after 7 days of withdrawal. Chocolate increased abdominal fat in non-handled females, and this effect remained after 30 days of withdrawal; no differences in plasma leptin were seen after 7 days of withdrawal. Chocolate also increased serum BuChE activity in non-handled females, this effect was still evident after 7 days of withdrawal, but it disappeared after 30 days of withdrawal. Chocolate deprivation decreased cerebral AChE activity in both handled and non-handled animals. These findings suggest that neonatal handling modulates the preference for palatable food and induces a specific metabolic response that may be more adaptive in comparison to non-handled rats.

Topics: Abdominal Fat; Acetylcholinesterase; Adaptation, Psychological; Animals; Animals, Newborn; Behavior, Animal; Brain; Butyrylcholinesterase; Cacao; Diet; Energy Intake; Environment; Feeding Behavior; Female; Food Preferences; Handling, Psychological; Leptin; Obesity, Abdominal; Pregnancy; Rats; Rats, Wistar; Stress, Psychological; Substance Withdrawal Syndrome; Triglycerides; Weight Gain

To investigate associations of maternal gestational weight gain and body composition and their impact on offspring body composition and adipocytokine, glucose, and insulin concentrations at age 4 months.. This was a prospective study including 31 mother-infant pairs (N = 62). Maternal body composition was assessed using doubly labeled water. Infant body composition was assessed at 4 months using air displacement plethysmography, and venous blood was assayed for glucose, insulin, adiponectin, interleukin-6 (IL-6), and leptin concentrations.. Rate of gestational weight gain in midpregnancy was significantly associated with infant fat mass (r = 0.41, P = 0.03); rate of gestational weight in late pregnancy was significantly associated with infant fat-free mass (r = 0.37, P = 0.04). Infant birth weight was also strongly correlated with infant fat-free mass at 4 months (r = 0.63, P = 0.0002). Maternal BMI and maternal fat mass were strongly inversely associated with infant IL-6 concentrations (r = -0.60, P = 0.002 and r = -0.52, P = 0.01, respectively). Infant fat-free mass was inversely related to infant adiponectin concentrations (r = -0.48, P = 0.008) and positively correlated with infant blood glucose adjusted for insulin concentrations (r = 0.42, P = 0.04). No significant associations for leptin were observed.. Timing of maternal weight gain differentially impacts body composition of the 4-month-old infant, which in turn appears to affect the infant's glucose and adipokine concentrations.

Topics: Adipokines; Adiponectin; Adult; Birth Weight; Blood Glucose; Body Composition; Body Mass Index; Female; Humans; Infant; Insulin; Interleukin-6; Leptin; Maternal-Fetal Relations; Pregnancy; Prospective Studies; Weight Gain

Anorexia nervosa (AN) often presents with comorbid depressive symptoms and is characterized by low levels of neuroimmunomodulatory hormone - leptin. Treatment-induced weight gain tends to normalize those variables. The aim of the study was the longitudinal assessment of the relationship between leptin levels and depressive symptoms in patients with AN, since previous cross-sectional studies in different populations brought conflicting results.. Thirty AN inpatients were assessed twice - at admission and after mean body mass index (BMI) increase of 3.2 kg/m(2). Physical parameters were measured, blood samples for leptin levels drawn and depression evaluated with both clinician - (Hamilton Depression Rating Scale - HDRS) and self - (Beck Depression Inventory - BDI) rated scales at the same morning. Correlation coefficients between changes in assessed variables, and linear regression for changes in depression scores were calculated.. BMI and leptin levels showed significant increase after treatment, respectively 14.45±0.90 vs. 17.61±0.87 and 1.87±1.14 vs. 7.47±4.65, whereas severity of depressive symptoms measured with BDI and HDRS was significantly reduced: 18.69±12.65 vs. 11.62±11.59; 12.76±6.90 vs. 5.66±4.91, respectively. In linear regression analysis decrease of the clinician-rated depression score (HDRS) was directly associated with decrease in the self-assessed depressive symptoms (BDI) (standardized Beta=0.45; t=2.60; p<0.05) and inversely related to the increase in leptin level (standardized Beta=-0.33; t=-2.08; p<0.05).. These results may suggest, that increase in leptin levels during weight recovery in patients with AN is associated with objectively measured depressive symptoms. Longitudinal studies in other populations are warranted to establish whether this relationship is valid across the weight spectrum.

Topics: Adolescent; Anorexia Nervosa; Body Mass Index; Comorbidity; Depression; Humans; Leptin; Longitudinal Studies; Psychiatric Status Rating Scales; Severity of Illness Index; Weight Gain

This study sought to determine the role of white adipose tissue (WAT) metabolism in the prevention of insulin resistance (IR) by physical training (PT).. Male C57BL/6J mice were assigned into groups CHOW-SED (chow diet, sedentary; n=15), CHOW-TR (chow diet, trained; n=18), CAF-SED (cafeteria diet, sedentary; n=15) and CAF-TR (cafeteria diet, trained; n=18). PT consisted of running sessions of 60 min at 60% of maximal speed conducted five days per week for eight weeks.. PT prevented body weight and fat mass accretion in trained groups and prevented hyperglycemia, hyperinsulinemia, glucose intolerance and IR in the CAF-TR. The CAF-SED group presented higher leptin and free fatty acid and lower adiponectin serum levels compared with other groups. Lipolytic activity (in mmol/10(6) adipose cells) stimulated by isoproterenol increased in CHOW-TR (16347±3005), CAF-SED (18110±3788) and CAF-TR (15837±2845) compared with CHOW-SED (8377±2284). The CAF-SED group reduced FAS activity compared with CHOW-SED and CHOW-TR, reduced citrate synthase activity and increased DGAT2 content compared with other groups. Both trained groups reduced G6PDH activity and increased the expression of p-AMPK (Thr172) compared with sedentary groups. CAF-SED group had lower levels of AMPK, p-AMPK (Thr172), ACC and p-ACC (Ser79) compared with other groups.. The prevention of IR by PT is mediated by adaptations in WAT metabolism by improving lipolysis, preventing an increase in enzymes responsible for fatty acid esterification and by activating enzymes that improve fat oxidation instead of fat storage.

Topics: Adipocytes; Adiponectin; Adipose Tissue, White; Adiposity; Animals; Fatty Acids, Nonesterified; Glucose Intolerance; Hyperglycemia; Hyperinsulinism; Insulin Resistance; Isoproterenol; Leptin; Lipolysis; Male; Mice; Mice, Inbred C57BL; Oxidation-Reduction; Physical Conditioning, Animal; Physical Exertion; Weight Gain

Lotus (Nelumbo Nucifera) root, a well-known medicinal plant in Asia, is reported to have various therapeutic benefits, including anti-diabetes, anti-hypertension, and anti-hyperlipidaemia. We hypothesized that the ethanol extract of lotus root (ELR) would exhibit an anti-adipogenic effect in human pre-adipocytes as well as anti-obesity and anti-oxidant effects in rats fed a high-fat diet. Treatment with ELR in human pre-adipocytes resulted in inhibition of lipid accumulation and attenuated expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor gamma and adipocyte marker genes, such as glucose transporter 4 and leptin. Administration of ELR resulted in a significant decrease in relative weights of adipose tissues in rats fed a high-fat diet. Consumption of a high-fat diet resulted in an increase in serum total cholesterol (TC) and triglyceride (TG) levels; however, administration of ELR resulted in a decrease in the levels of TC and TG. Administration of ELR resulted in a decrease in the level of serum leptin and insulin. Administration of ELR in rats fed a high-fat diet resulted in a decrease in hepatic thiobarbituric acid reactive substance content, elevated by a high-fat diet and an increase in superoxide dismutase activity and hepatic glutathione content. These results suggest that lotus root exerts anti-oxidant and anti-obesity effects and could be used as a functional and nutraceutical ingredient in combatting obesity-related diseases.

Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Anti-Obesity Agents; Antioxidants; Cells, Cultured; Cholesterol, HDL; Cholesterol, LDL; Energy Intake; Flavonoids; Glutathione; Humans; Insulin; Leptin; Male; Nelumbo; Organ Size; Phenols; Plant Extracts; Plant Roots; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Triglycerides; Weight Gain

It has been reported that intrauterine undernutrition is closely associated with the pathogeneses of certain diseases in adulthood; i.e., insulin resistance and diabetes, and that leptin resistance plays a pivotal role in the pathology of such intrauterine growth restriction (IUGR)-related conditions. Therefore, examinations of IUGR-induced leptin resistance in early developmental period are important for protecting against future disease. In this study, the effects of prenatal undernutrition on the serum leptin levels and central leptin responses of rats during the neonatal and/or pre-pubertal period were examined. The 50% food-restricted undernourished dams' offspring (UNO) exhibited a significantly lower birth weight than the normal nutrition dams' offspring (NNO). However, the UNO grew rapidly, and their mean body weight had caught up with that of the NNO by postnatal day 8. Thus, there were no significant differences between the body weights of the two groups at postnatal day 12, 16, 20, or 28. The serum leptin levels of the UNO were significantly higher than those of the NNO at postnatal days 20 and 28. At postnatal day 28, no significant difference in the hypothalamic mRNA level of neuropeptide Y, which is the main target of leptin, or that of ObRb, which is the leptin receptor, was detected between the NNO and UNO. The chronic intracerebroventricular injection of leptin attenuated body weight gain in both the NNO and UNO; however, there were no significant differences between the body weights of the two groups at any of the examined postnatal time points, indicating that the UNO and NNO exhibited similar central sensitivity to leptin during the pre-pubertal period. These results suggest that prenatal undernutrition induces leptin resistance until the neonatal to pre-pubertal period and that these alterations might be caused by impaired transportation of leptin to central tissues.

Topics: Aging; Animals; Animals, Newborn; Birth Weight; Female; Fetal Growth Retardation; Humans; Infant Nutrition Disorders; Infant, Newborn; Injections, Intraventricular; Leptin; Male; Pregnancy; Pregnancy Complications; Puberty; Rats; Rats, Sprague-Dawley; Treatment Outcome; Weight Gain

Hyperprolactinemia occurs during gestation and lactation with marked hyperphagia associated with leptin resistance. Prolactin (PRL) induces the expression of orexigenic neuropeptide Y (NPY) in hypothalamic dorsomedial nucleus (DMH) leading to hyperphagia. Along this line prolactin receptor deficient (PRLR-/-) mice are resistant to obesity under high fat diet due to increased energy expenditure. As these mice have an altered food intake, our objective was to test whether leptin is responsible for these characteristics. PRLR-/- male mice and control littermates were injected subcutaneously every other day with 12 mg/kg pegylated superactive mouse leptin antagonist (PEG-SMLA) for 3 weeks. We tested the effect of PEG-SMLA on body weight, food intake and metabolic parameters. The antagonist led to a rapid increase in body weight (20%) but increased adipose mass in PEG-SMLA treated mice was less pronounced in PRLR-/- than in WT mice. Food intake of PEG-SMLA-injected animals increased during the first week period of the experiment but then declined to a similar level of the control animals during the second week. Interestingly, PRLR-/- mice were found to have the same bone volume than those of control mice although PEG-SMLA increased bone mass by 7% in both strains. In addition, PEG-SMLA led to insulin resistance and glucose intolerance as well as an altered lipid profile in treated mice. Altogether, these results suggest that PRLR-/- mice respond to leptin antagonist similarly to the control mice, indicating no interaction between the actions of the two hormones.

Topics: Adiposity; Animals; Bone and Bones; Glucose Intolerance; Glucose Tolerance Test; Insulin Resistance; Leptin; Male; Mice; Mice, Knockout; Polyethylene Glycols; Receptors, Prolactin; Trabecular Meshwork; Weight Gain

Estrogen is thought to aid maintenance of insulin sensitivity potentially through modulation of a counter-regulatory mechanism that interferes with the contribution of adaptive and innate immune systems to visceral fat deposition. We evaluated the impact of estrogen on long-term high fat diet (HFD) intake in B- and T-cell deficient and immunocompetent animals comparatively.. A total of 16 BALB and 16 SCID mice, 8 of each sex and strain, were randomized to receive low fat diet, 4.1% fat or HFD, 35% fat, such that there was a group of both each sex and each strain receiving each diet. Biweekly levels of adiponectin, leptin and insulin levels were assessed and a glucose tolerance test (GTT) was performed after 13 weeks.. Unlike their male counterparts, HFD-fed SCID females neither gained weight, nor became insulin resistant. Meanwhile, in the HFD-fed BALB groups both males and females gained weight similarly, but remarkable sexual dimorphism was nonetheless observed. The females had notable higher adiponectin levels as compared to males (10-60 μg/mL vs. 6-10 μg/mL respectively) causing the adiponectin-to-leptin (A/L) ratio to reach 80 one week after HFD initiation. The A/L dropped to 10, still higher than males, by week 13, but dropped to 2 by the end of the study in agreement with inverse insulin trends. None of the HFD-fed female groups developed insulin resistance (IR) by week 13, while all male counterparts had. Similar results were observed in the HFD-fed SCID groups whereby the females did not develop IR and had a higher A/L; however, adiponectin levels were comparable between groups (5-11 μg/mL).. The present study provides lacking evidence indicating that estrogen may be sufficient to prevent weight gain and development of glucose intolerance in high-fat fed B- and T-cell deficient mice.

Topics: Adiponectin; Animals; B-Lymphocytes; Diet, High-Fat; Disease Models, Animal; Female; Glucose Intolerance; Insulin; Insulin Resistance; Leptin; Male; Mice, Inbred BALB C; Mice, SCID; Random Allocation; Sex Factors; T-Lymphocytes; Time Factors; Weight Gain

We have recently demonstrated that C57BL/6NTac and C57BL/6JRj substrains are significantly different in their response to high-fat diet-induced obesity (DIO). The C57BL/6JRj substrain seems to be protected from DIO and genetic differences between C57BL/6J and C57BL/6N substrains at 11 single nucleotide polymorphism (SNP) loci have been identified. To define genetic variants as well as differences in parameters of glucose homeostasis and insulin sensitivity between C57BL/6NTac and C57BL/6JRj substrains that may explain the different response to DIO, we analyzed 208 first backcross (BC1) hybrids of C57BL/6NTac and C57BL/6JRj [(C57BL/6NTac × C57BL/6JRj)F1 × C57BL/6NTac] mice. Body weight, epigonadal and subcutaneous fat mass, circulating leptin, as well as parameters of glucose metabolism were measured after 10 wk of high-fat diet (HFD). Genetic profiling of BC1 hybrids were performed using TaqMan SNP genotyping assays. Furthermore, to assess whether SNP polymorphisms could affect mRNA level, we carried out gene expression analysis in murine liver samples. Human subcutaneous adipose tissue was used to verify murine data of SNAP29. We identified four sex-specific variants that are associated with the extent of HFD-induced weight gain and fat depot mass. BC1 hybrids carrying the combination of risk or beneficial alleles exhibit the phenotypical extremes of the parental strains. Murine and human SC expression analysis revealed Snap29 as strongest candidate. Our data indicate an important role of these loci in responsiveness to HFD-induced obesity and suggest genes of the synaptic vesicle release system such as Snap29 being involved in the regulation of high-fat DIO.

Topics: Adipose Tissue; Alleles; Animals; Body Weight; Diet, High-Fat; Female; Genetic Loci; Genotype; Glucose; Humans; Leptin; Male; Mice; Mice, Inbred C57BL; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Vesicular Transport Proteins; Weight Gain

Rats on different free-choice (fc) diets for 1 week of either chow, saturated fat and liquid sugar (fcHFHS), chow and saturated fat (fcHF), or chow and liquid sugar (fcHS) have differential levels of neuropeptide Y (NPY) mRNA in the arcuate nucleus. Because these differences were not explained by plasma leptin levels but did predict subsequent feeding behaviour, in the present study, we first examined whether leptin sensitivity could explain these differences. Second, we focused on the role of NPY on feeding behaviour, and measured NPY mRNA levels and sensitivity to NPY after 4 weeks on the different choice diets. To determine leptin sensitivity, we measured food intake after i.p. leptin or vehicle injections in male Wistar rats subjected to the fcHFHS, fcHS, fcHF or Chow diets for 7 days. Next, we measured levels of arcuate nucleus NPY mRNA with in situ hybridisation in rats subjected to the choice diets for 4 weeks. Finally, we studied NPY sensitivity in rats subjected to the fcHFHS, fcHS, fcHF or Chow diet for 4 weeks by measuring food intake after administration of NPY or vehicle in the lateral ventricle. Leptin decreased caloric intake in rats on Chow, fcHS and fcHF but not in rats on the fcHFHS diet. After 4 weeks, rats on the fcHFHS diet remained hyperphagic, whereas fcHS and fcHF rats decreased caloric intake to levels similar to rats on Chow. By contrast to 1 week, after 4 weeks, levels of NPY mRNA were not different between the diet groups. Lateral ventricle administration of NPY resulted in higher caloric intake in fcHFHS rats compared to rats on the other choice diets or rats on Chow. Our data show that consuming a combination of saturated fat and liquid sugar results in leptin resistance and increased NPY sensitivity that is associated with persistent hyperphagia.

Topics: Animals; Diet; Energy Intake; Energy Metabolism; Feeding Behavior; Injections, Intraventricular; Leptin; Male; Neuropeptide Y; Rats; Rats, Wistar; Weight Gain

Sex differences exist in the regulation of energy homeostasis in response to calorie scarcity or excess. Brain-derived neurotrophic factor (BDNF) is one of the anorexigenic neuropeptides regulating energy homeostasis. Expression of Bdnf mRNA in the ventromedial nucleus of the hypothalamus (VMH) is closely associated with energy and reproductive status. We hypothesized that Bdnf expression in the VMH was differentially regulated by altered energy balance in male and female rats. Using dietary intervention, including fasting-induced negative energy status and high-fat diet (HFD) feeding-induced positive energy status, along with low-fat diet (LFD) feeding and HFD pair-feeding (HFD-PF), effects of diets and changes in energy status on VMH Bdnf expression were compared between male and female rats. Fasted males but not females had lower VMH Bdnf expression than their fed counterparts following 24-hour fasting, suggesting that fasted males reduced Bdnf expression to drive hyperphagia and body weight gain. Male HFD obese and HFD-PF non-obese rats had similarly reduced expression of Bdnf compared with LFD males, indicating that dampened Bdnf expression was associated with feeding a diet high in fat instead of increased adiposity. Decreased BDNF signaling during HFD feeding would increase a drive to eat and may contribute to diet-induced obesity in males. In contrast, VMH Bdnf expression was stably maintained in females when energy homeostasis was disturbed. These results suggest sex-distinct regulation of central Bdnf expression by diet and energy status.

Topics: Adipose Tissue; Animals; Blood Glucose; Brain-Derived Neurotrophic Factor; Diet, Fat-Restricted; Diet, High-Fat; Eating; Estradiol; Fasting; Female; Gene Expression; Hyperphagia; Leptin; Male; Obesity; Rats, Long-Evans; RNA, Messenger; Sex Characteristics; Ventromedial Hypothalamic Nucleus; Weight Gain

A total of 2,958 steers (mean initial BW = 549.6 ± 3.88 kg) were used to test for the interactive effects, of leptin R25C genotypes (CC, CT, or TT) and feeding of ractopamine hydrochloride (RH) on growth performance and carcass traits. Before application of the drug, steers were blocked by arrival at the feed yard, genotyped for the leptin SNP, allotted to genotype-specific pens, and assigned randomly within genotype and block to 0 or 28 d of dietary RH. All pens within a block were slaughtered on the same day. Final BW of steers fed RH was 9.1 kg heavier (P < 0.001), and RH-fed steers had greater (P < 0.001) ADG and greater (P = 0.001) HCW than steers not fed RH. Feeding RH did not (P = 0.723) affect DMI but it did increase (P = 0.001) with increased frequency of the T allele (8.62, 8.70, and 8.82 kg/d for CC, CT, and TT, respectively). Consistent with the effect of leptin on DMI, increased frequency of the T allele also positively affected 12th rib fat (P = 0.001) and empty body fat (P = 0.001). Regardless of RH-feeding duration, TT steers produced a greater (P = 0.001) percentage of USDA yield grade (YG) 4 or higher carcasses (6.46 vs. 2.98%) and a lesser (P = 0.023) percentage of YG 1 carcasses (16.0 vs. 21.9%) than CC steers. In addition, RH-fed steers produced a lesser (P = 0.034) percentage of USDA YG 4 or higher carcasses (3.70 vs. 5.31%) and a lesser percentage (P = 0.019) of USDA Choice or higher carcasses (57.5 vs. 62.5%) than steers fed the control diet. Results indicated that leptin R25C genotype impacted most traits associated with fatness, whereas feeding RH for 28 d affected HCW and ADG positively but impacted marbling and USDA quality grades negatively.

Topics: Amino Acid Substitution; Animals; Body Composition; Cattle; Dietary Supplements; Genotype; Growth Substances; Leptin; Male; Phenethylamines; Polymorphism, Single Nucleotide; Weight Gain

The contraceptive skin patch (CSP) accepted by the U.S. FDA in 2001 includes ethinylestradiol and norelgestromine, whereas the subdermal contraceptive implant (SCI) has etonogestrel and is also approved by the FDA. In Mexico, both are now widely used for contraception but their effects on Mexican population are unknown. The objective of the study was to evaluate if these treatments induce metabolic changes in a sample of indigenous and mestizo Mexican women.. An observational, prospective, longitudinal, non-randomized study of women between 18 and 35 years of age assigned to CSP or SCI. We performed several laboratory tests: clinical chemistry, lipid profile, and liver and thyroid function tests. Also, serum levels of insulin, C-peptide, IGF-1, leptin, adiponectin, and C reactive protein were assayed.. Sixty-two women were enrolled, 25 used CSP (0 indigenous; 25 mestizos) and 37 used SCI (18 indigenous; 19 mestizos). Clinical symptoms were relatively more frequent in the SCI group. Thirty-four contraceptive users gained weight without other clinical significant changes. After 4 months of treatment, significant changes were found in some biochemical parameters in both treatment groups. Most were clinically irrelevant. Interestingly, the percentage of users with an abnormal atherogenic index diminished from 75% to 41.6% after follow-up.. The CSP slightly modified the metabolic variables. Most changes were nonsignificant, whereas for SCI users changes were more evident and perhaps beneficial. Results of this attempt to evaluate the effects of contraceptives in mestizo and native-American populations show that clinical symptoms are frequent in Mexican users of CSP and SCI. Although these medications may affect some metabolic variables, these changes seem clinically irrelevant. Induction of abnormalities in other physiological pathways cannot be ruled out.

Topics: Adiponectin; Adult; C-Peptide; C-Reactive Protein; Contraceptive Agents, Female; Desogestrel; Drug Combinations; Ethinyl Estradiol; Female; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Lipid Metabolism; Liver Function Tests; Longitudinal Studies; Mexico; Norgestrel; Oximes; Thyroid Function Tests; Transdermal Patch; Weight Gain

Secretin, a classical gastrointestinal hormone released from S cells in response to acid and dietary lipid, regulates pleiotropic physiological functions, such as exocrine pancreatic secretion and gastric motility. Subsequent to recently proposed revisit on secretin's metabolic effects, we have confirmed lipolytic actions of secretin during starvation and discovered a hormone-sensitive lipase-mediated mechanistic pathway behind. In this study, a 12 wk high-fat diet (HFD) feeding to secretin receptor-knockout (SCTR(-/-)) mice and their wild-type (SCTR(+/+)) littermates revealed that, despite similar food intake, SCTR(-/-) mice gained significantly less weight (SCTR(+/+): 49.6±0.9 g; SCTR(-/-): 44.7±1.4 g; P<0.05) and exhibited lower body fat content. These SCTR(-/-) mice have corresponding alleviated HFD-associated hyperleptinemia and improved glucose/insulin tolerance. Further analyses indicate that SCTR(-/-) have impaired intestinal fatty acid absorption while having similar energy expenditure and locomotor activity. Reduced fat absorption in the intestine is further supported by lowered postprandial triglyceride concentrations in circulation in SCTR(-/-) mice. In jejunal cells, transcript and protein levels of a key fat absorption regulator, cluster of differentiation 36 (CD36), was reduced in knockout mice, while transcript of Cd36 and fatty-acid uptake in isolated enterocytes was stimulated by secretin. Based on our findings, a novel positive feedback pathway involving secretin and CD36 to enhance intestinal lipid absorption is being proposed.

Topics: Adiposity; Animals; Carrier Proteins; CD36 Antigens; Diet, High-Fat; Dietary Fats; Energy Metabolism; Enterocytes; Feedback, Physiological; Female; Glucose Tolerance Test; Insulin Resistance; Intestinal Absorption; Jejunum; Leptin; Locomotion; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Receptors, G-Protein-Coupled; Receptors, Gastrointestinal Hormone; Secretin; Triglycerides; Weight Gain

Common polymorphisms in the first intron of FTO are associated with increased body weight in adults. Previous studies have suggested that a CUX1-regulatory element within the implicated FTO region controls expression of FTO and the nearby ciliary gene, RPGRIP1L. Given the role of ciliary genes in energy homeostasis, we hypothesized that mice hypomorphic for Rpgrip1l would display increased adiposity. We find that Rpgrip1l⁺/⁻ mice are hyperphagic and fatter, and display diminished suppression of food intake in response to leptin administration. In the hypothalamus of Rpgrip1l⁺/⁻ mice, and in human fibroblasts with hypomorphic mutations in RPGRIP1L, the number of AcIII-positive cilia is diminished, accompanied by impaired convening of the leptin receptor to the vicinity of the cilium, and diminished pStat3 in response to leptin. These findings suggest that RPGRIP1L may be partly or exclusively responsible for the obesity susceptibility signal at the FTO locus.

Topics: Adaptor Proteins, Signal Transducing; Adiposity; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Animals; Cells, Cultured; Cilia; Eating; Female; Fibroblasts; Humans; Hypothalamus; Introns; Leptin; Mice; Mice, Inbred C57BL; Polymorphism, Genetic; Proteins; Receptors, Leptin; STAT3 Transcription Factor; Weight Gain

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

It was hypothesized that metabolic programming of processes underlying puberty can be shifted temporally through the use of a stair-step compensatory growth model such that puberty is optimally timed to occur at 11 to 12 mo of age. Forty crossbred beef heifers were weaned at approximately 3.5 mo of age and, after a 2-wk acclimation period, were assigned randomly to 1 of 4 nutritional groups: 1) low control (LC), restricted feed intake of a forage-based diet to promote BW gain of 0.5 kg/d until 14 mo of age, 2) high control (HC), controlled feed intake of a high-concentrate diet to promote BW gain of 1 kg/d until 14 mo of age, 3) stair-step 1 (SS-1), ad libitum feed intake of a high-concentrate diet until 6.5 mo of age followed by restricted access to a high-forage diet to promote BW gain of 0.35 kg/d until 9 mo of age, ad libitum feed intake of a high-concentrate diet until 11.5 mo of age, and restricted intake of a high-forage diet to promote BW gain of 0.35 kg/d until 14 mo of age, and 4) stair-step 2 (SS-2), reverse sequence of SS-1, beginning with restricted access to a high-forage diet. Body weight (every 2 wk) and circulating concentrations of leptin (monthly) were determined throughout the experiment. Concentrations of progesterone in blood samples collected twice weekly beginning at 8 mo of age were used to determine pubertal status. Body weight gain followed a pattern similar to that proposed in our experimental design. Circulating concentrations of leptin increased following distinct elevations in BW but decreased abruptly after feed intake restriction. Survival analysis indicated that the percentage of pubertal heifers in the LC group was lower (P < 0.05) than all other groups throughout the experiment. Although heifers in SS-1 were nutritionally restricted between 6.5 and 9 mo of age, the proportion pubertal by 12 mo of age did not differ (P = 0.36) from that of the HC group, with 80% and 70% pubertal in SS-1 and HC, respectively. In contrast, the proportion of heifers pubertal by 12 mo of age in the SS-2 group (40%) was lower (P < 0.05) than both HC and SS-1. However, by 14 mo of age, 90% of heifers in the SS-2 group had also attained puberty compared to only 40% of the LC group. In summary, these data provide evidence that changes in the nutritional and metabolic status during the early juvenile period can program the onset of puberty that occurs months later, allowing optimal timing of sexual maturation in replacement beef heifers.

Topics: Age Factors; Animal Feed; Animal Husbandry; Animals; Cattle; Diet; Eating; Female; Leptin; Nutritional Physiological Phenomena; Sexual Maturation; Weight Gain

Suppression of body weight and symptom of anorexia are major symptoms of depression. Recently, we reported that chronic social defeat stress (CSDS) induced suppression of body weight gain and anorexic feeding behavior in rats. These abnormalities were the result of disrupted malonyl-coenzyme A (CoA) signaling pathway in the hypothalamus. However, the condition of peripheral leptin and its hypothalamic downstream signal molecules which regulate hypothalamic malonyl-CoA level in the CSDS-exposed rats (CSDS rats) is still unknown.. CSDS rats showed suppressed body weight gain and food intake. The weight of the CSDS rats' epididymal white adipose tissues was decreased when compared to the control rats. The plasma cholesterol concentration was decreased significantly in the CSDS rats compared to the control rats (P < 0.05). The plasma glucose concentration was slightly decreased in the CSDS rats compared to the control rats (P < 0.1). The expression of leptin mRNA in epididymal white adipose tissues and the plasma leptin concentration were decreased in CSDS rats. Furthermore, the phosphorylation of the hypothalamic downstream signals of leptin, including extracellular signal-regulated kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3), was decreased in CSDS rats.. Our results indicated that decreased peripheral leptin expression in CSDS rats could down-regulate the hypothalamic downstream signaling pathways of leptin while suppressed food intake. These data indicate that CSDS induces the down-regulation of hypothalamic AMPK following the elevation of hypothalamic malonyl-CoA levels and is independent of peripheral leptin and glucose.

Topics: Adaptation, Psychological; Animals; Anorexia; Chronic Disease; Depression; Eating; Hypothalamus; Leptin; Male; Rats; Rats, Wistar; Social Dominance; Stress, Psychological; Weight Gain

Early adiposity rebound (AR <5 years) has been consistently associated with increased obesity risk, but its relationship with metabolic markers is less clear; in addition, the biologic mechanisms involved in these associations have not been established.. The objective of this study was to assess the association between timing of AR and metabolic status at age 7 years, evaluating the potential role of adiposity, adipose functionality and skeletal maturation in this association.. We estimated the age of AR from the body mass index (BMI) trajectories from 0 to 7 years in 910 children from the Growth and Obesity Chilean Cohort Study (GOCS). At 7 years, we measured waist circumference (WC) and blood glucose, insulin, triglycerides and high-density lipoprotein-cholesterol levels and constructed a metabolic risk score. We also measured percent fat mass (adiposity), plasma concentrations of leptin and adiponectin (adipose functionality) and bone age using wrist ultrasound (skeletal maturation).. We found that 44% of the children had an AR <5 years. Earlier AR was associated with larger WC (β: 5.10 (95% confidence interval (CI): 4.29-5.91)), higher glucose (β: 1.02 (1.00-1.03)), insulin resistance (β Homeostatic Model Assessment: 1.06 (1.03-1.09)), triglycerides (β: 10.37 (4.01-6.73)) and adverse metabolic score (β: 0.30 (0.02-0.37)). Associations decreased significantly if adiposity was added to the models (i.e. β WC: 0.85 (0.33-1.38)) and, to a lesser extent, when adipokines (i.e. β WC: 0.73 (0.14-1.32)) and skeletal maturation (i.e. β WC: 0.65 (0.10-1.20)) were added.. In GOCS children, AR at a younger age predicts higher metabolic risk at 7 years; these associations are mostly explained by increased adiposity, but adipose dysfunction and accelerated skeletal maturation also have a role.

Topics: Adiponectin; Adiposity; Age Factors; Age of Onset; Biomarkers; Blood Glucose; Body Composition; Body Mass Index; Child; Child Development; Chile; Cholesterol, HDL; Cohort Studies; Female; Humans; Leptin; Lipoproteins, HDL; Male; Metabolic Syndrome; Pediatric Obesity; Risk Factors; Triglycerides; Waist Circumference; Weight Gain

Dynamics of body weight and food intake can be studied by temporally perturbing food availability. This perturbation can be obtained by modifying the amount of available food over time while keeping the overall food quantity constant. To describe food intake dynamics, we developed a mathematical model that describes body weight, fat mass, fat-free mass, energy expenditure and food intake dynamics in rats. In addition, the model considers regulation of food intake by leptin, ghrelin and glucose. We tested our model on rats experiencing temporally variable food availability. Our model is able to predict body weight and food intake variations by taking into account energy expenditure dynamics based on a memory of the previous food intake. This model allowed us to estimate this memory lag to approximately 8 days. It also explains how important variations in food availability during periods longer than these 8 days can induce body weight gains.

Topics: Animals; Body Weight; Caloric Restriction; Eating; Energy Intake; Energy Metabolism; Leptin; Memory; Models, Theoretical; Rats; Rats, Wistar; Weight Gain

The purpose of this study was to clarify, through a prospective study, the relationship between leptin and adiponectin levels, and subsequent weight change. The study subjects were 2,485 male office workers aged 35-64 employed by a company in Fukuoka Prefecture, Japan. Of these men, 1,936 (77.9%) received health check-ups both in 2005-2007 and 3 years later, in 2008-2010. Of the subjects who received both health check-ups, 352 were excluded duo to cancer, cardiac infarction, stroke or diabetes mellitus, leaving a total of 1,584. We divided them into tertiles according to baseline leptin and adiponectin levels, and compared the subsequent change in body mass index (BMI) over 3 years. The subjects with the lowest leptin levels showed a significantly greater increase in BMI (difference in change in BMI=0.178 kg/m2, 95% CI:0.025-0.331 kg/m2) over 3 years when those with the highest leptin levels were regarded as the reference even after adjusting for age, baseline BMI, smoking status, drinking status and exercise. The subjects with the highest adiponectin levels showed a greater increase in BMI (difference in change in BMI=0.099 kg/m2, 95% CI: -0.034-0.231 kg/m2) over 3 years when those with the lowest adiponectin levels were regarded as the reference, but this association was not statistically significant after adjusting for age, baseline BMI, smoking status, drinking status and exercise. Our findings suggest that higher leptin levels may suppress weight gain in Japanese male workers.

Topics: Adiponectin; Adult; Asian People; Body Mass Index; Body Weight; Humans; Japan; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Weight Gain

Free feeding (FF) with a high fat diet (HFD) causes excessive body weight gain, whereas restricted feeding (RF) with a HFD attenuates body weight gain. The effects of timing of feeding with a HFD (day vs. night) and feeding duration on energy homeostasis have not yet been investigated. In this study, we fed mice a HFD or a normal diet (ND) twice a day, during their active and inactive periods, on a schedule. The amount of food was regulated by feeding duration (2, 4 or 8 h). First, we investigated the effects of 4-h RF during active-inactive periods (ND-ND, HFD-HFD, ND-HFD or HFD-ND). Among all the 4-h RF groups, mice consumed almost the same amount of calories as those in the FF[ND] group, even those fed a HFD. Body weight and visceral fat in these three groups were lower than that in the FF[HFD] group. Second, we investigated the effects of RF duration. Body weight and visceral fat were higher in the 8-h groups than in the 4-h groups. Body weight and visceral fat were higher in the 2-h groups than in the 4-h groups even though the 2-h groups had less food. Third, we investigated the effects of eating a HFD during the inactive period, when RF duration was extended (2, 6 or 12 h). Mice were fed with a HFD during the inactive period for 2 h and fed with a ND during the active period for 2, 6 or 12 h. Body weight and visceral fat in these mice were comparable to those in the FF[ND] mice. The results of our first set of experiments suggest that 4-h RF was an adequate feeding duration to control the effect of a HFD on obesity. The results of our second set of experiments suggest 2-h RF (such as speed-eating) and 8-h RF, representative of eating disorders, are unhealthy feeding patterns related to obesity. The results of our third set of experiments suggest that eating a HFD for a short period during the night does not affect body weight and visceral fat. Taken together, these results indicate that consideration to feeding with a HFD during the inactive period and restricting eating habits relieve the risks of body weight gain and visceral fat accumulation.

Topics: Animals; Blood Glucose; Body Weight; Circadian Rhythm; Diet, High-Fat; Dietary Fats; Energy Intake; Feeding Behavior; Insulin; Intra-Abdominal Fat; Leptin; Liver; Male; Mice; Mice, Inbred ICR; Obesity; Time Factors; Weight Gain

Methyl CpG binding protein-2 (MECP2) is a chromatin-remodelling factor with a dual role in gene expression. Evidence from patients carrying MECP2 mutations and from transgenic mouse models demonstrates that this protein is involved in the control of body weight. However, the mechanism for this has not been fully elucidated. To address this, we used a previously characterized Mecp2-null mouse model and found that the increase in body weight is associated with an increased amount of adipose tissue and high leptin levels. Appropriate body weight control requires the proper expression of pro-opiomelanocortin (Pomc) and agouti-related peptide (Agrp), two neuropeptides essential for satiety and appetite signals, respectively. Our results show that in the absence of Mecp2, Pomc and Agrp mRNA expression are altered, and the mice are leptin resistant. To determine the mechanism underlying the defective leptin sensing, we evaluated the expression of genes and the post-translational modifications associated with leptin signalling, which are fundamental to Pomc and Agrp transcriptional control and proper leptin response. We found a decrease in the phosphorylation level of Akt and its target protein Foxo1, which indicate an alteration in leptin-induced signal transduction. Our results demonstrate that the absence of Mecp2 disrupted body weight balance by altering post-translational modifications in leptin-signalling components that regulate Pomc and Agrp expression.

Topics: Adiposity; Agouti-Related Protein; Animals; Forkhead Box Protein O1; Forkhead Transcription Factors; Gene Expression Regulation; Genotype; Hypothalamus; Leptin; Male; Methyl-CpG-Binding Protein 2; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Phosphorylation; Pro-Opiomelanocortin; Proto-Oncogene Proteins c-akt; RNA, Messenger; Signal Transduction; Transcription, Genetic; Weight Gain

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

Guggulsterone or guggulipid is a steroidal constituent present in the neutral fraction of gum resin of Commiphora mukul, commonly known as guggul. The traditional uses of guggul-resin extract are well documented in the Ayurveda-where it is prescribed to treat a variety of ailments including lipid-related disorders such as obesity and arteriosclerosis. The hypolipidemic activity of the extracts known since ancient times can be traced to the two closely related steroidal ketones, E-guggulsterone and Z-guggulsterone. In this study, we have investigated the dose dependent (100, 200, 400 mg/kg body weight) effect of guggulsterones on appetite regulating hormones [ghrelin, leptin, cholecystokinin (CCK)] and neurotransmitters (serotonin and dopamine), which play a major role in the energy homeostasis and thus influence obesity related factors. We have also studied its effect on food intake, body weight and plasma triglycerides and glucose in rats. Guggulsterones at the dose of 400 mg/kg body weight was able to significantly reduce food intake and limit body weight gain over a period of 15 days. It also significantly decreased the plasma ghrelin, glucose, triglyceride levels and increased plasma leptin, serotonin, dopamine levels, but did not show much effect on CCK levels.

Topics: Animals; Appetite; Blood Glucose; Cholecystokinin; Commiphora; Dopamine; Dose-Response Relationship, Drug; Eating; Energy Intake; Ghrelin; Leptin; Male; Obesity; Plant Extracts; Plant Gums; Pregnenediones; Rats, Wistar; Resins, Plant; Serotonin; Triglycerides; Weight Gain

Both sexes of mice were fed a high fat diet (HFD) for 10 weeks without and with polyphenolic-rich potato extracts (PRPE) of cultivars Onaway and Russet Burbank. PRPE attenuated weight gain in male and female mice by as much as 63.2%, which was associated mostly with a reduction in adiposity. Mice receiving PRPE showed enhanced capacity for blood glucose clearance. Sex differences regarding the impact of HFD and PRPE on plasma levels of insulin, ghrelin, leptin, gastric inhibitory peptide, and resistin were noted. PRPE may serve as part of a preventative dietary strategy against the development of obesity and type 2 diabetes.

Topics: Adiposity; Animals; Blood Glucose; Diet, High-Fat; Disease Models, Animal; Female; Gastric Inhibitory Polypeptide; Ghrelin; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Plant Extracts; Polyphenols; Resistin; Solanum tuberosum; Weight Gain

Undernutrition in early life has been reported to be closely associated with the development of non-communicable diseases in adulthood. Adequate treatment is important for reversing these effects. In the present study, we investigated the effects of undernutrition and anthropometric recovery on the weights and heights of children in relation to the concentrations of leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1). A total of 119 children (aged 6-16 years) from the slums of São Paulo were selected according to their nutritional status and divided into three groups as follows: control (healthy without intervention, n 38) with a height-for-age Z score (HAZ) and a BMI-for-age Z score (BAZ) > -1·6; undernourished (HAZ and/or BAZ < -1·6, n 54); recovered from undernutrition (after treatment in a rehabilitation centre; HAZ and BAZ > -1·6, n 27). Blood samples were collected to determine insulin, glucose, leptin, adiponectin and PAI-1 concentrations. Leptin concentrations in the undernourished group were lower than those in the control and recovered groups (mean 0·92 (95% CI 0·67, 1·25), 2·03 (95% CI 1·46, 2·82) and 1·66 (95% CI 1·15, 2·44) ng/ml, P=0·003), which had similar leptin concentrations. There were no differences in adiponectin and PAI-1 concentrations among the groups. A positive correlation between waist circumference and leptin concentrations was observed in all the girls and boys of the control group (control: r 0·729, P<0·01; undernourished: r 0·490, P<0·05; and recovered: r 0·829, P<0·01; r 0·673, P<0·05). Stronger correlations between leptin and insulin concentrations were observed in the recovered group. The results of the present study indicate that normal leptin concentrations are found when normal height and weight are achieved.

Topics: Adiponectin; Adolescent; Adolescent Development; Body Height; Bone Development; Brazil; Child; Child Development; Cross-Sectional Studies; Female; Growth Disorders; Humans; Insulin; Leptin; Male; Malnutrition; Plasminogen Activator Inhibitor 1; Poverty Areas; Waist Circumference; Weight Gain

The purpose of this study was to examine the antiobesity effects of Monascus pilosus-fermented black soybean (F-BS) in C57BL/6 mice with high-fat diet (HFD)-induced obesity. F-BS (oral, 0.5 and 1.0 g/kg per body weight, twice per day) ameliorated obesity by reducing body and liver weight increases, and regulating blood glucose and cholesterol levels in C57BL/6 mice fed a control or HFD with oral administration of F-BS for 12 weeks. F-BS suppressed the growth of epididymal, retroperitoneal, and perirenal fat pads by preventing increases in the adipocyte size. Moreover, the levels of blood glucose, total cholesterol, and leptin were significantly lowered by F-BS administration in a dose-dependent manner. These results indicated that F-BS is a beneficial food supplement for preventing obesity, controlling blood glucose, and lowering cholesterol. Future research strategies should address the mechanisms that selectively regulate obesity, including hyperglycemia and hypercholesterolemia.

Topics: Adipocytes; Adipose Tissue; Animals; Anti-Obesity Agents; Blood Glucose; Cholesterol; Diet, High-Fat; Dose-Response Relationship, Drug; Fermentation; Glycine max; Hypoglycemic Agents; Hypolipidemic Agents; Leptin; Liver; Male; Mice, Inbred C57BL; Monascus; Obesity; Plant Extracts; Soy Foods; Weight Gain

Chronic treatment with valproate (VPA) is commonly associated with weight gain, which potentially has important health implications, in particular increased central fat distribution. We utilized a VPA-discordant same-sex, twin and matched sibling pair study design to primarily examine for differences in fat distribution between patients with epilepsy treated with VPA compared to their matched twin or sibling control. Weight, blood pressure, and leptin levels were assessed.. Height, weight, waist and hip measurements, exercise, blood pressure (BP), and serum leptin levels were measured. Body composition was measured using dual-energy x-ray absorptiometry (DXA). Abdominal fat was expressed as a percentage of the abdominal region (AFat%); and of whole body fat (WBF); (AFat%WBF). Mean within-pair differences were assessed (VPA-user and nonuser). Restricted maximum likelihood (REML) linear mixed model analysis was fitted to examine associations of anthropometrics, zygosity, gender, menopausal status, VPA dose and duration, with weight and AFat%.. We studied 19 pairs of VPA-discordant, gender-matched (five male, 14 female) twins and siblings. Mean (standard deviation, SD) duration of therapy for VPA users was 11.0 (7.4) years. There were no statistically significant within-pair differences in age, height, weight, body mass index (BMI), BP, leptin level, WBF, AFat%, or AFat%WBF. For pairs in which VPA-user was treated for >11 years there were statistically significant mean within-pair differences in AFat%, (+7.1%, p = 0.03, n = 10 pairs), mean BP (+11.0 mm Hg, p = 0.006, n = 8 pairs); but not in AFat%WBF. VPA duration was positively associated with weight (estimate +0.98 kg/per year of VPA, p = 0.03); VPA treatment duration and dose were not significantly associated with AFat%.. This study demonstrated a relationship between long-term VPA use and abdominal adiposity (AFat%), which could have significant health implications. We recommend ongoing monitoring of weight, BMI, and blood pressure for patients taking VPA.

Topics: Abdominal Fat; Absorptiometry, Photon; Adult; Anticonvulsants; Blood Pressure; Body Composition; Body Fat Distribution; Diseases in Twins; Epilepsy; Female; Humans; Leptin; Male; Sex Factors; Siblings; Twins, Dizygotic; Twins, Monozygotic; Valproic Acid; Weight Gain

Several studies have shown that estrogens mimic leptin's effects on energy balance regulation. However, the findings regarding the consequences of reduced sex hormone levels on leptin sensitivity are divergent. In the present study, we employed different experimental paradigms to elucidate the interaction between estrogens, leptin, and energy balance regulation. We confirmed previous reports showing that ovariectomy caused a reduction in locomotor activity and energy expenditure leading mice to obesity and glucose intolerance. However, the acute and chronic anorexigenic effects of leptin were preserved in ovariectomized (OVX) mice despite their increased serum leptin levels. We studied hypothalamic gene expression at different time points after ovariectomy and observed that changes in the expression of genes involved in leptin resistance (suppressors of cytokine signaling and protein-tyrosine phosphatases) did not precede the early onset of obesity in OVX mice. On the contrary, reduced sex hormone levels caused an up-regulation of the long form of the leptin receptor (LepR), resulting in increased activation of leptin signaling pathways in OVX leptin-treated animals. The up-regulation of the LepR was observed in long-term OVX mice (30 d or 24 wk after ovariectomy) but not 7 days after the surgery. In addition, we observed a progressive decrease in the coexpression of LepR and estrogen receptor-α in the hypothalamus after the ovariectomy, resulting in a low percentage of dual-labeled cells in OVX mice. Taken together, our findings suggest that the weight gain caused by reduced sex hormone levels is not primarily caused by induction of a leptin-resistance state.

Topics: Animals; Appetite Depressants; Drug Resistance; Energy Metabolism; Female; Glucose; Gonadal Steroid Hormones; Hypogonadism; Leptin; Mice; Mice, Inbred C57BL; Obesity; Ovariectomy; Sex Factors; Weight Gain

High-fructose diets have been implicated in obesity via impairment of leptin signaling in humans and rodents. We investigated whether fructose-induced leptin resistance in mice could be used to study the metabolic consequences of fructose consumption in humans, particularly in children and adolescents. Male C57Bl/6 mice were weaned to a randomly assigned diet: high fructose, high sucrose, high fat, or control (sugar-free, low-fat). Mice were maintained on their diets for at least 14 weeks. While fructose-fed mice regularly consumed more kcal and expended more energy, there was no difference in body weight compared to control by the end of the study. Additionally, after 14 weeks, both fructose-fed and control mice displayed similar leptin sensitivity. Fructose-feeding also did not change circulating glucose, triglycerides, or free fatty acids. Though fructose has been linked to obesity in several animal models, our data fail to support a role for fructose intake through food lasting 3 months in altering of body weight and leptin signaling in mice. The lack of impact of fructose in the food of growing mice on either body weight or leptin sensitivity over this time frame was surprising, and important information for researchers interested in fructose and body weight regulation.

Topics: Administration, Oral; Animals; Basal Metabolism; Diet; Diet, High-Fat; Female; High Fructose Corn Syrup; Leptin; Male; Mice, Inbred C57BL; Obesity; Weight Gain

To understand adiponectin, leptin, insulin and ghrelin levels in preterm colostrum and mature milk and their influence on the growth and development of the premature infant.. The study subjects were divided into two groups: preterm group and control group. Specimens of colostrum and mature milk on 42nd day after delivery were collected, the general situation of maternal and infants growth parameters at birth and at postnatal 42 days were recorded. Leptin, adiponectin, insulin and ghrelin levels in colustrum and mature milk were determined and compared.. A total of 128 mother-infant pairs were involved. There were 128 specimens of colostrums (80 from preterm group, 48 from control group) and 94 specimens of mature milk(50 from premature group, 44 from control group). The levels of colostrum, mature milk adiponectin, leptin, and insulin were not significantly different between the 2 groups; ghrelin levels in colostrum and mature milk of premature group were significantly lower than those in control group (P = 0.038), adiponectin and leptin levels in colostrum were higher than those of the mature milk (P < 0.05), colostrum ghrelin levels were lower than those of mature milk (P < 0.05). Adiponectin, leptin, and ghrelin showed no significant difference between different gestational age groups ( ≤ 34 weeks group vs. > 34 weeks group). True insulin level of mature milk in 34 weeks group was higher than that of > 34 weeks group (29.3 vs. 21.6 mU/L, P = 0.045); true insulin level in colostrums in ≤ 34 weeks group was lower than that in mature milk (21.7 vs. 29.3 mU/L, P = 0.000). Adiponectin levels in colostrum and 42 days weight gain were negatively correlated (r = -0.362, P = 0.025) . Insulin level in mature milk had a negative correlation with birth weight (r = -0.319, P = 0.029) . Ghrelin levels in colostrum and birth weight, length, head circumference, head circumference on 42(nd) day were positively correlated (r = 0.271,0.261,0.360, P < 0.05); weight, length at 42(nd) day and ghrelin levels showed borderline positive correlation (P = 0.050, 0.058).. Many bioactive hormones in milk might participate in the regulation of suitable growth after birth. Premature birth affects hormone levels in breast milk. Breast feeding is very important in preterm infants.

Topics: Adiponectin; Birth Weight; Breast Feeding; Colostrum; Female; Gestational Age; Ghrelin; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Insulin; Leptin; Male; Milk, Human; Weight Gain

Studies in both humans and rodents suggest that maternal diabetes leads to a higher risk of the fetus developing impaired glucose tolerance and obesity during adulthood. However, the impact of hyperinsulinemia in the mother on glucose homeostasis in the offspring has not been fully explored. We aimed to determine the consequences of maternal insulin resistance on offspring metabolism and endocrine pancreas development using the LIRKO mouse model, which exhibits sustained hyperinsulinemia and transient increase in blood glucose concentrations during pregnancy. We examined control offspring born to either LIRKO or control mothers on embryonic days 13.5, 15.5, and 17.5 and postpartum days 0, 4, and 10. Control offspring born to LIRKO mothers displayed low birth weights and subsequently rapidly gained weight, and their blood glucose and plasma insulin concentrations were higher than offspring born to control mothers in early postnatal life. In addition, concentrations of plasma leptin, glucagon, and active GLP-1 were higher in control pups from LIRKO mothers. Analyses of the endocrine pancreas revealed significantly reduced β-cell area in control offspring of LIRKO mothers shortly after birth. β-Cell proliferation and total islet number were also lower in control offspring of LIRKO mothers during early postnatal days. Together, these data indicate that maternal hyperinsulinemia and the transient hyperglycemia impair endocrine pancreas development in the control offspring and induce multiple metabolic alterations in early postnatal life. The relatively smaller β-cell mass/area and β-cell proliferation in these control offspring suggest cell-autonomous epigenetic mechanisms in the regulation of islet growth and development.

Topics: Animals; Animals, Newborn; Blood Glucose; Cell Proliferation; Diabetes, Gestational; Disease Models, Animal; Female; Glucagon; Glucagon-Like Peptide 1; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Resistance; Insulin-Secreting Cells; Islets of Langerhans; Leptin; Mice; Organ Size; Phenotype; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Weight Gain

To determine whether rats reaching the same body mass, having been fed either a low-fat (LFD) or a high-fat diet (HFD), differ in white adipose tissue (WAT) deposition.. In experiment 1, 22 Sprague-Dawley rats of the same age were divided into 11 rats with body mass below the batch median and fed a HFD, and 11 above the median and fed a LFD. In experiment 2, 20 Sprague-Dawley rats of the same age and starting body mass were randomised to either a HFD or LFD. When all groups reached similar final body mass, WAT was quantified using magnetic resonance imaging (MRI), dissection, and plasma leptin.. In experiment 1, both groups reached similar final body mass at the same age; in experiment 2 the HFD group reached similar final body mass earlier than the LFD group. There were no significant differences in WAT as assessed by MRI or leptin between the HFD and LFD groups in both experiments. Dissection revealed a trend for higher retroperitoneal and epididymal adiposity in the HFD groups in both experiments.. We conclude that at similar body mass, adiposity is independent of the macronutrient composition of the feeding regimen used to achieve it.

Topics: Adipose Tissue, White; Adiposity; Age Factors; Animals; Diet; Diet, Fat-Restricted; Diet, High-Fat; Dietary Fats; Energy Intake; Epididymis; Leptin; Male; Obesity; Peritoneum; Random Allocation; Rats, Sprague-Dawley; Weight Gain

We investigated the associations of the LEP-2548A/G and HTR2C-759C/T polymorphisms with long-term clozapine-induced weight changes and baseline BMI in chronic patients with schizophrenia.. A total of 113 patients receiving clozapine for at least 1 year were enrolled. Body weight was measured cross-sectionally and data on body weight just before starting clozapine were retrospectively extracted from medical records.. Clozapine-induced change in BMI was correlated inversely with the baseline BMI (P<0.001, ρ=-0.347). The LEP-2548A/G polymorphism was associated significantly with the change in BMI (F=4.380, P=0.015) during clozapine use; those with the AA genotype had the highest BMI gain (1.4±3.1 kg/m), followed by those with the AG (-0.2±3.3 kg/m) and GG (-1.6±3.4 kg/m) genotypes. We also found a significant association between the leptin genotype and BMI at baseline (F=3.499, P=0.034); those with the AA genotype had the lowest baseline BMI (23.4±4.3 kg/m), followed by those with the AG (24.1±4.4 kg/m) and GG (28.8±7.3 kg/m) genotypes. In the case of the HTR2C-759C/T polymorphism, we found a trend in which T alleles were more prevalent in male patients with up to 7% increase in BMI than in those with a greater than 7% increase in BMI [12/54 (22.7%) vs. 1/27 (3.7%); Fisher's exact test: P=0.051].. This study shows an inverse correlation between the baseline BMI and change in BMI during long-term clozapine use in patients with schizophrenia, and the LEP-2548A/G polymorphism was associated significantly with both these measures.

Topics: Adult; Antipsychotic Agents; Body Mass Index; Chronic Disease; Clozapine; Humans; Leptin; Middle Aged; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2C; Schizophrenia; Weight Gain

Excessive consumption of protein that leads to increased blood levels of insulin-like growth factor-1 (IGF-1) is an important risk factor for high growth velocity and obesity in formula-fed infants. However, it is not clear whether these factors can explain the high growth velocity in breast-fed infants.. To study the possible links between the growth velocity in breast-fed infants and the levels of protein, IGF-1 and other hormones, which regulate energy homeostasis, in mothers' breast milk.. We studied 103 mother-infant pairs. Their daily breast milk intake and level of IGF-1, leptin, ghrelin, adiponectin, protein and fat in breast milk were measured at 1, 2 and 3 months of lactation. The infant group was divided into three subgroups of low, normal and high weight gain tertiles.. The breast milk consumed by the infants with high weight gain contained higher levels of IGF-1 than that consumed by those with low weight gain at all periods studied (p = 0.032 at 3 months of lactation), and ghrelin levels were higher at 1 and 2 months and leptin levels at 2 and 3 months of lactation (p < 0.05). A positive correlation was observed between the breast milk IGF-1 level and infant weight gain (r = 0.294, p = 0.043). Total daily breast milk, fat and hormone intake was also higher in the high weight gain group compared to the low weight gain group.. One of the reasons for the high growth velocity in breast-fed infants may be the enhanced levels of the studied hormones in breast milk.

Topics: Adiponectin; Adult; Breast Feeding; Child Development; Female; Ghrelin; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Insulin-Like Growth Factor I; Leptin; Male; Milk, Human; Surveys and Questionnaires; Weight Gain

Eating at a time when the internal circadian clock promotes sleep is a novel risk factor for weight gain and obesity, yet little is known about mechanisms by which circadian misalignment leads to metabolic dysregulation in humans. We studied 14 adults in a 6-d inpatient simulated shiftwork protocol and quantified changes in energy expenditure, macronutrient utilization, appetitive hormones, sleep, and circadian phase during day versus nightshift work. We found that total daily energy expenditure increased by ∼4% on the transition day to the first nightshift, which consisted of an afternoon nap and extended wakefulness, whereas total daily energy expenditure decreased by ∼3% on each of the second and third nightshift days, which consisted of daytime sleep followed by afternoon and nighttime wakefulness. Contrary to expectations, energy expenditure decreased by ∼12-16% during scheduled daytime sleep opportunities despite disturbed sleep. The thermic effect of feeding also decreased in response to a late dinner on the first nightshift. Total daily fat utilization increased on the first and second nightshift days, contrary to expectations, and carbohydrate and protein utilization were reduced on the second nightshift day. Ratings of hunger were decreased during nightshift days despite decreases in 24-h levels of the satiety hormones leptin and peptide-YY. Findings suggest that reduced total daily energy expenditure during nightshift schedules and reduced energy expenditure in response to dinner represent contributing mechanisms by which humans working and eating during the biological night, when the circadian clock is promoting sleep, may increase the risk of weight gain and obesity.

Topics: Adult; Analysis of Variance; Circadian Rhythm; Eating; Electromyography; Energy Metabolism; Female; Ghrelin; Humans; Leptin; Male; Melatonin; Obesity; Peptide YY; Risk Factors; Sleep; Sleep Deprivation; Sleep Stages; Time Factors; Wakefulness; Weight Gain; Work Schedule Tolerance

Soybean-derived PC is an essential cell membrane phospholipid that is composed of unsaturated fatty acids, including oleic acid. The present study aimed to evaluate the potential alleviation effects of soybean PC on high fat diet (HFD)-induced obesity and its related complications.. We fed C57BL/6 mice a HFD for 12 weeks and administered PC orally for 8 or 12 weeks at different doses. At the end of the experiment, blood was prepared for biochemical analysis and leptin ELISA. Aorta, epididymal and mesenteric fat and liver were removed surgically, weighed and observed for histological or immunohistochemical changes.. PC significantly prevented body weight gain and lipid accumulation and alleviated hyperlipidemia by decreasing triglyceride (TG) and total cholesterol (TC) levels and the atherogenic index in serum or by increasing the HDL/TC ratio. Aortic apoE expression and serum leptin levels were suppressed by PC treatment in the HFD-induced obese mouse model. Elevated serum aspartate aminotransferase and alanine aminotransferase levels in HFD-fed mice were decreased in the PC groups. PC treatment significantly decreased HFD-induced liver weight and hepatic lipid accumulation.. PC treatment alleviated HFD-induced obese status and obesity-related complications such as hyperlipidemic changes that induce cardiovascular disease and NAFLD.

Topics: Adipocytes; Animals; Apolipoproteins E; Diet, High-Fat; Hyperlipidemias; Leptin; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; Phosphatidylcholines; Weight Gain

At a wide range of doses, rapamycin extends life span in mice. It was shown that intraperitoneal injections (i.p.) of rapamycin prevent weight gain in mice on high-fat diet (HFD). We further investigated the effect of rapamycin on weight gain in female C57BL/6 mice on HFD started at the age of 7.5 months. By the age of 16 and 23 months, mice on HFD weighed significantly more (52 vs 33 g; p = 0.0001 and 70 vs 38 g; p < 0.0001, respectively) than mice on low fat diet (LFD). The i.p. administration of 1.5 mg/kg rapamycin, 3 times a week every other week, completely prevented weight gain, whereas administration of rapamycin by oral gavash did not. Rapamycin given in the drinking water slightly decreased weight gain by the age of 23 months. In addition, metabolic parameters were evaluated at the age of 16 and 23 months, 6 and 13 days after last rapamycin administration, respectively. Plasma leptin levels strongly correlated with body weight, (P < 0.0001, r=0.86), suggesting that the difference in weight was due to fat tissue mass. Levels of insulin, glucose, triglycerides and IGF1 were not statistically different in all groups, indicating that these courses of rapamycin treatment did not impair metabolic parameters at least after rapamycin discontinuation. Despite rapamycin discontinuation, cardiac levels of phospho-S6 and pAKT(S473) were low in the i.p.-treated group. This continuous effect of rapamycin can be explained by prevention of obesity in the i.p. group. We conclude that intermittent i.p. administration of rapamycin prevents weight gain without causing gross metabolic abnormalities. Intermittent gavash administration minimally affected weight gain. Potential clinical applications are discussed.

Topics: Animals; Blood Glucose; Diet, High-Fat; Female; Immunosuppressive Agents; Injections, Intraperitoneal; Insulin; Leptin; Mice; Mice, Inbred C57BL; Obesity; Phosphorylation; Proto-Oncogene Proteins c-akt; Ribosomal Protein S6 Kinases; Sirolimus; Triglycerides; Weight Gain

To examine associations of perinatal and 3-year leptin with weight gain and adiposity through 7 years.. In Project Viva, plasma leptin from mothers at 26-28 weeks' gestation (n = 893), umbilical cord vein at delivery (n = 540), and children at 3 years (n = 510) was assessed in relation to BMI z-score, waist circumference, skinfold thicknesses, and dual X-ray absorptiometry body fat.. 50.1% of children were male and 29.5% non-white. Mean (SD) maternal, cord, and age 3 leptin concentrations were 22.9 (14.2), 8.8 (6.4), and 1.8 (1.7) ng/ml, respectively, and 3- and 7-year BMI z-scores were 0.46 (1.00) and 0.35 (0.97), respectively. After adjusting for parental and child characteristics, higher maternal and cord leptin were associated with less 3-year adiposity. For example, mean 3-year BMI z-score was 0.5 lower (95% CI: -0.7, -0.2; P-trend = 0.003) among children whose mothers' leptin concentrations were in the top versus bottom quintile. In contrast, higher age 3 leptin was associated with greater weight gain and adiposity through age 7 [e.g., change in BMI z-score from 3 to 7 years was 0.2 units (95% CI: -0.0, 0.4; P-trend =0.05)].. Higher perinatal leptin was associated with lower 3-year adiposity, whereas higher age 3 leptin was associated with greater weight gain and adiposity by 7 years.

Topics: Absorptiometry, Photon; Adipose Tissue; Adiposity; Body Mass Index; Child; Child, Preschool; Female; Fetal Blood; Humans; Leptin; Linear Models; Male; Mothers; Obesity; Pediatric Obesity; Pregnancy; Pregnancy Trimester, Second; Prospective Studies; Skinfold Thickness; Waist Circumference; Weight Gain

The presence of appetite hormones, namely glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and leptin in breast milk may be important in infant feeding regulation and infant growth. This study evaluated whether concentrations of GLP-1, PYY, and leptin change across a single feeding (from fore- to hindmilk), and are associated with maternal and infant anthropometrics.. Thirteen postpartum women (mean ± SD: 25.6 ± 4.5 years, 72.0 ± 11.9 kg) provided fore- and hindmilk samples 4-5 weeks after delivery and underwent measurements of body weight and composition by Dual X-ray Absorptiometry. GLP-1, PYY, and leptin concentrations were measured using radioimmunoassay, and milk fat content was determined by creamatocrit.. Concentration of GLP-1 and content of milk fat was higher in hindmilk than foremilk (P ≤ 0.05). PYY and leptin concentrations did not change between fore- and hindmilk. Both leptin concentration and milk fat content were correlated with indices of maternal adiposity, including body mass index (r = 0.65-0.85, P < 0.02), and fat mass (r = 0.65-0.84, P < 0.02). Hindmilk GLP-1 was correlated with infant weight gain from birth to 6 months (r = -0.67, P = 0.034).. The presence of appetite hormones in breast milk may be important in infant appetite and growth regulation.

Topics: Absorptiometry, Photon; Adiposity; Adult; Appetite; Body Mass Index; Female; Glucagon-Like Peptide 1; Humans; Leptin; Milk, Human; Peptide YY; Postpartum Period; Radioimmunoassay; Weight Gain; Young Adult

The peel of the native Brazilian fruit jaboticaba is rich in anthocyanins, which are known for their anti-obesity effects in animal models. The aim of the present study was to evaluate the effects of freeze-dried jaboticaba peel powder (FDJPP) on a number of metabolic parameters in a model of diet-induced obesity. Mice (n 8 per group) were initially fed on a high-fat diet (HFD, 35% w/w) for 4 weeks and then switched to a HFD supplemented with FDJPP (1, 2 or 4% w/w) for an additional 6 weeks. Energy intake, weight loss, glucose tolerance, insulin resistance and lipid profile were determined, and the results were evaluated using ANOVA and Tukey’s tests. The FDJPP exerted no protective effect on HFD-induced weight gain, hyperleptinaemia and glucose intolerance. However, the supplementation was effective to reduce insulin resistance, as evidenced in the insulin tolerance test, and subsequently confirmed by improved signal transduction through the insulin receptor/insulin receptor substrate-1/Akt/forkhead box protein pathway and by the attenuation of HFD-induced inflammation in the liver, verified by lower expressions of IL-1b and IL-6 and decreased phosphorylated IkB-a protein levels in all jaboticaba-treated mice. These results suggest that FDJPP may exert a protective role against obesity-associated insulin resistance.

Topics: Analysis of Variance; Animals; Anthocyanins; Anti-Obesity Agents; Diet, High-Fat; Dietary Supplements; Fruit; Glucose Intolerance; Inflammation; Insulin; Insulin Resistance; Leptin; Liver; Male; Mice; Mice, Inbred Strains; Myrtaceae; Obesity; Phytotherapy; Plant Preparations; Powders; Receptor, Insulin; Signal Transduction; Weight Gain

It is suggested that antibiotherapy in infancy might program adult body composition and thus could be a determinant of obesity risk. Although not convincingly substantiated by existing literature, this assumption is plausible since antibiotics affect intestinal microbiota, whose composition in adulthood is potentially programmable during infancy and which is able to interact with both fat development and central control of appetite.. In order to substantiate the link between antibiotherapy and programming of adult body composition, the present study investigated the impact of a course of amoxicillin treatment in neonatal period on subsequent growth and body composition in rats.. Suckling rat pups were treated by oral gavage with an amoxicillin solution (150 mg·kg(-1)) or vehicle from postnatal day (PND)5 to PND15. All animals were fully weaned at PND21 then fed a standard diet until PND130. Animal growth and food intake were followed up until PND130, when body composition and plasma leptin were measured. Faecal microbiota was typified at regular intervals using real-time quantitative polymerase chain reaction.. Preweaning amoxicillin treatment affected the composition of the faecal microbiota of pups at PND21 but this impact did not sustain long beyond the antibiotic supplementation. Immediately after weaning, a transient increase in food intake (+11%) was noticed in amoxicillin-treated animals. However, no significant impact on either growth or body composition at adulthood was observed.. In a neonatal animal model there is no evidence of a programming of adult body weight and composition by wide-spectrum antibiotic treatment in early life.

Topics: Adiposity; Administration, Oral; Age Factors; Amoxicillin; Animals; Animals, Newborn; Anti-Bacterial Agents; Body Composition; DNA, Bacterial; Eating; Feces; Female; Intestines; Lactation; Leptin; Male; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Risk Assessment; Weight Gain

Wild rice (WR) is a very nutritious grain that has been used to treat diabetes in Chinese medicinal practice. City diet (CD) is based on the diet consumed by Asian area residents in modern society, which is rich in saturated fats, cholesterol and carbohydrates. The present study was aimed at evaluating the effects of replacing white rice and processed wheat starch of CD with WR as the chief source of dietary carbohydrates on insulin resistance in rats fed with a high-fat/cholesterol diet. Except the rats of the low-fat (LF) diet group, the rats of the other three groups, including to high-fat/cholesterol (HFC) diet, CD and WR diet, were fed with high-fat/cholesterol diets for eight weeks. The rats fed with CD exhibited higher weight gain and lower insulin sensitivity compared to the rats consuming a HFC diet. However, WR suppressed high-fat/cholesterol diet-induced insulin resistance. WR decreased liver homogenate triglyceride and free fatty acids levels, raised serum adiponectin concentration and reduced serum lipocalin-2 and visfatin concentrations. In addition, the WR diet potently augmented the relative expressions of adiponectin receptor 2, peroxisome proliferator-activated receptors, alpha and gamma, and abated relative expressions of leptin and lipocalin-2 in the tissues of interest. These findings indicate that WR is effective in ameliorating abnormal glucose metabolism and insulin resistance in rats, even when the diet consumed is high in fat and cholesterol.

Topics: Adiponectin; Animals; Cholesterol, Dietary; Diet, High-Fat; Dietary Carbohydrates; Fatty Acids, Nonesterified; Gene Expression; Glucose; Insulin Resistance; Leptin; Lipocalins; Liver; Male; Nicotinamide Phosphoribosyltransferase; Oryza; Poaceae; Rats; Rats, Sprague-Dawley; Receptors, Adiponectin; Triglycerides; Triticum; Weight Gain

Stearoyl-coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that catalyzes the biosynthesis of monounsaturated fatty acids from saturated fatty acids. Recently, SCD1 down-regulation has been implicated in the prevention of obesity, and the improvement of insulin and leptin sensitivity. In this study, we examined the effect of fucoxanthin, a marine carotenoid, on hepatic SCD1 in obese mouse models of hyperleptinemia KK-A(y) and leptin-deficiency ob/ob. In KK-A(y) mice, providing a diet containing 0.2 % fucoxanthin for 2 weeks markedly suppressed SCD1 mRNA and protein expressions in the liver. The fatty acid composition of liver lipids was also affected by an observed decrease in the ratio of oleic acid to stearic acid. Furthermore, serum leptin levels were significantly decreased in hyperleptinemia KK-A(y) mice after 2 weeks of fucoxanthin feeding. However, the suppressive effects of fucoxanthin on hepatic SCD1 and body weight gain were not observed in ob/ob mice. These results show that fucoxanthin down-regulates SCD1 expression and alters fatty acid composition of the liver via regulation of leptin signaling in hyperleptinemia KK-A(y) mice but not in leptin-deficient ob/ob mice.

Topics: Animals; Blood Glucose; Down-Regulation; Fatty Acids; Female; Leptin; Liver; Mice; Mice, Obese; Obesity; RNA, Messenger; Seaweed; Signal Transduction; Stearoyl-CoA Desaturase; Weight Gain; Xanthophylls

Complete leptin deficiency is associated with weight gain and extreme obesity, according to studies of animals and of monogenic obesity in humans. It is still a matter of debate whether relative leptin deficiency plays a physiologic role in adiposity regulation in free-living humans. We hypothesized that leptin levels would be associated with subsequent weight changes in healthy normal-weight young adults. Our prospective cohort involved 150 healthy young adults (114 women and 36 men) followed over their years of study at the Université de Sherbrooke. Anthropometric measurements, fasting blood samples, 3-day food diaries, and a physical activity questionnaire were collected at baseline. Leptin levels were measured with radioimmunoassay. Associations between baseline leptin levels and subsequent anthropometric changes were assessed with multivariable linear regression models to account for adiposity at baseline, food intake, and energy expenditure. Over the 2-year follow-up, changes in body mass index (BMI) ranged from -0.8 to +2.6 kg·m(-2) in men (mean BMI change, +0.6 kg·m(-2)) and from -2.5 to +3.7 kg·m(-2) in women (mean BMI change, +0.1 kg·m(-2)). Lower leptin levels at baseline were associated with a higher risk of weight gain in women (r = -0.24; p = 0.01 for change in BMI) and in men (r = -0.27, p = 0.11), even after accounting for baseline BMI, total daily caloric intake, and energy expenditure (p = 0.02). In the subsample measured at 4 years (n = 63), baseline leptin levels were not associated with 4-year weight changes. Lower leptin levels are associated with a higher risk of weight gain over 2 years in healthy young adults.

Topics: Adult; Body Mass Index; Humans; Leptin; Obesity; Prospective Studies; Weight Gain; Young Adult

Omentin-1, a visceral fat depot-specific secretory protein, is inversely correlated with obesity and insulin resistance. We investigated, in rats, the effects of chronic omentin-1 administration (8 μg/kg, intraperitoneally, once daily for 14-days) on feeding behavior and related hypothalamic peptides and neurotransmitters. Food intake and body weight were recorded daily throughout the study. We found a significantly increased food intake compared to controls, but only in days 10-14, while body weight significantly increased since day 12 (P<0.05). Compared with vehicle, omentin-1 treatment led to a significant reduction in both cocaine and amphetamine-regulated transcript (CART) (P<0.05) and corticotrophin releasing hormone (CRH) (P<0.05) gene expression, while pro-opiomelanocortin (POMC), agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A gene expression were not modified with respect to vehicle-treated rats. We also found an increase in hypothalamic levodopa (l-dopa) (P<0.05) and norepinephrine (NE) (P<0.01) synthesis, without any effect on dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) metabolism. Furthermore, in hypothalamic synaptosomes, omentin-1 (10-100 ng/ml) stimulated basal NE release (ANOVA, P<0.0001; post hoc, P<0.001 vs. vehicle), in a dose-dependent manner, leaving unaffected both basal and depolarization-induced DA and 5-HT release. Finally, when synaptosomes were co-perfused with leptin and omentin-1, we observed that leptin was able to reverse omentin-1-induced stimulation of NE. In conclusion, the orexigenic effects of omentin-1 could be related, at least in part, to decreased CART and CRH gene expression and increased NE synthesis and release in the hypothalamus.

Topics: Animals; Appetite Stimulants; Corticotropin-Releasing Hormone; Cytokines; Energy Intake; Feeding Behavior; Gene Expression; Gene Silencing; GPI-Linked Proteins; Hypothalamus; Lectins; Leptin; Male; Nerve Tissue Proteins; Neurotransmitter Agents; Norepinephrine; Rats; Rats, Wistar; Synaptosomes; Weight Gain

The molecular mechanisms involved in the development of obesity and related complications remain unclear. Here, we report that obese mice and human subjects have increased activity of neutrophil elastase (NE) and decreased serum levels of the NE inhibitor α1-antitrypsin (A1AT, SerpinA1). NE null (Ela2(-/-)) mice and A1AT transgenic mice were resistant to high-fat diet (HFD)-induced body weight gain, insulin resistance, inflammation, and fatty liver. NE inhibitor GW311616A reversed insulin resistance and body weight gain in HFD-fed mice. Ela2(-/-) mice also augmented circulating high molecular weight (HMW) adiponectin levels, phosphorylation of AMP-activated protein kinase (AMPK), and fatty acid oxidation (FAO) in the liver and brown adipose tissue (BAT) and uncoupling protein (UCP1) levels in the BAT. These data suggest that the A1AT-NE system regulates AMPK signaling, FAO, and energy expenditure. The imbalance between A1AT and NE contributes to the development of obesity and related inflammation, insulin resistance, and liver steatosis.

Topics: Adiponectin; Adipose Tissue, Brown; alpha 1-Antitrypsin; AMP-Activated Protein Kinase Kinases; Animals; Diet, High-Fat; Energy Metabolism; Fatty Acids; Fatty Liver; Hep G2 Cells; Humans; Inflammation; Insulin Resistance; Ion Channels; Leptin; Leukocyte Elastase; Liver; Metabolome; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Mice, Transgenic; Mitochondrial Proteins; Obesity; Oxidation-Reduction; Phosphorylation; Piperidines; Protein Kinases; Uncoupling Protein 1; Weight Gain

Dietary supplement may potentially help to fight obesity and other metabolic disorders such as insulin-resistance and low-grade inflammation. The present study aimed to test whether supplementation with Agaricus blazei murill (ABM) extract could have an effect on diet-induced obesity in rats.. Wistar rats were fed with control diet (CD) or high-fat diet (HF) and either with or without supplemented ABM for 20 weeks.. HF diet-induced body weight gain and increased fat mass compared to CD. In addition HF-fed rats developed hyperleptinemia and insulinemia as well as insulin resistance and glucose intolerance. In HF-fed rats, visceral adipose tissue also expressed biomarkers of inflammation. ABM supplementation in HF rats had a protective effect against body weight gain and all study related disorders. This was not due to decreased food intake which remained significantly higher in HF rats whether supplemented with ABM or not compared to control. There was also no change in gut microbiota composition in HF supplemented with ABM. Interestingly, ABM supplementation induced an increase in both energy expenditure and locomotor activity which could partially explain its protective effect against diet-induced obesity. In addition a decrease in pancreatic lipase activity is also observed in jejunum of ABM-treated rats suggesting a decrease in lipid absorption.. Taken together these data highlight a role for ABM to prevent body weight gain and related disorders in peripheral targets independently of effect in food intake in central nervous system.

Topics: Agaricus; Animals; Biomarkers; Blood Glucose; Body Composition; Calorimetry, Indirect; Diet, High-Fat; Dietary Fats; Dietary Supplements; Energy Metabolism; Gastrointestinal Tract; Glucose Intolerance; Inflammation; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipase; Male; Microbiota; Obesity; Probiotics; Rats; Rats, Wistar; Subcutaneous Fat, Abdominal; Weight Gain

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

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

Pathological changes associated with obesity are thought to contribute to GH deficiency. However, recent observations suggest that impaired GH secretion relative to excess calorie consumption contributes to progressive weight gain and thus may contribute to the development of obesity. To clarify this association between adiposity and GH secretion, we investigated the relationship between pulsatile GH secretion and body weight; epididymal fat mass; and circulating levels of leptin, insulin, non-esterified free fatty acids (NEFAs), and glucose. Data were obtained from male mice maintained on a standard or high-fat diet. We confirm the suppression of pulsatile GH secretion following dietary-induced weight gain. Correlation analyses reveal an inverse relationship between measures of pulsatile GH secretion, body weight, and epididymal fat mass. Moreover, we demonstrate an inverse relationship between measures of pulsatile GH secretion and circulating levels of leptin and insulin. The secretion of GH did not change relative to circulating levels of NEFAs or glucose. We conclude that impaired pulsatile GH secretion in the mouse occurs alongside progressive weight gain and thus precedes the development of obesity. Moreover, data illustrate key interactions between GH secretion and circulating levels of insulin and reflect the potential physiological role of GH in modulation of insulin-induced lipogenesis throughout positive energy balance.

Topics: Adiposity; Animals; Down-Regulation; Glucose; Growth Hormone; Humans; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Weight Gain

Synthetic glucocorticoids (sGCs) are administered to women threatening preterm labor. We have shown multigenerational endocrine and metabolic effects of fetal sGC exposure. We hypothesized that sGC exposure would alter the second filial generation (F2) offspring neonatal leptin peak that controls development of appetitive behavior with metabolic consequences.. F0 nulliparous ewes were bred to a single ram. Beginning at day 103 of gestation (term 150 days), dexamethasone (DEX) ewes received 4 injections of 2 mg DEX intramuscularly, 12 hours apart. Control ewes received saline. Ewes lambed naturally. At 22 months of age, F1 offspring were mated to produce F2 offspring. At 10 months of age, F2 female offspring were placed on an ad libitum feeding challenge for 12 weeks.. DEX F2 female offspring did not show a postnatal leptin peak and their plasma cortisol concentration was elevated in the first days of life. During the feeding challenge, DEX F2 offspring consumed 10% more feed and gained 20% more weight compared with control F2 offspring. At the end of the feeding challenge, DEX F2 offspring had greater adiposity compared with control F2 offspring. F2 sGC offspring showed impaired insulin secretion in response to an intravenous glucose tolerance test.. sGC administration to F0 mothers eliminates the neonatal leptin peak in F2 female offspring potentially by inhibition caused by elevated cortisol in the DEX F2 offspring. F2 offspring showed increased appetite, weight gain, and adiposity during an ad libitum feeding challenge accompanied by decreased insulin response to an intravenous glucose tolerance test.

Topics: Adiposity; Animals; Appetite; Dexamethasone; Feeding Behavior; Female; Glucocorticoids; Glucose; Glucose Intolerance; Glucose Tolerance Test; Hydrocortisone; Leptin; Pregnancy; Prenatal Exposure Delayed Effects; Sheep; Weight Gain

Obesity is an epidemic, calling for innovative and reliable pharmacological strategies. Here, we show that ShK-186, a selective and potent blocker of the voltage-gated Kv1.3 channel, counteracts the negative effects of increased caloric intake in mice fed a diet rich in fat and fructose. ShK-186 reduced weight gain, adiposity, and fatty liver; decreased blood levels of cholesterol, sugar, HbA1c, insulin, and leptin; and enhanced peripheral insulin sensitivity. These changes mimic the effects of Kv1.3 gene deletion. ShK-186 did not alter weight gain in mice on a chow diet, suggesting that the obesity-inducing diet enhances sensitivity to Kv1.3 blockade. Several mechanisms may contribute to the therapeutic benefits of ShK-186. ShK-186 therapy activated brown adipose tissue as evidenced by a doubling of glucose uptake, and increased β-oxidation of fatty acids, glycolysis, fatty acid synthesis, and uncoupling protein 1 expression. Activation of brown adipose tissue manifested as augmented oxygen consumption and energy expenditure, with no change in caloric intake, locomotor activity, or thyroid hormone levels. The obesity diet induced Kv1.3 expression in the liver, and ShK-186 caused profound alterations in energy and lipid metabolism in the liver. This action on the liver may underlie the differential effectiveness of ShK-186 in mice fed a chow vs. an obesity diet. Our results highlight the potential use of Kv1.3 blockers for the treatment of obesity and insulin resistance.

Topics: Adipose Tissue, Brown; Adiposity; Animals; Blood Glucose; Diet; Energy Intake; Energy Metabolism; Fatty Liver; Insulin Resistance; Kv1.3 Potassium Channel; Leptin; Lipids; Liver; Male; Mice; Mice, Inbred C57BL; Motor Activity; Obesity; Oxygen Consumption; Proteins; Weight Gain

Obesity is a chronic inflammatory disease and a risk factor for disorders such as heart disease, diabetes, and cancer. A high-fat diet (HFD), a risk factor for obesity, has also been associated with inflammatory bowel disease (IBD). A proinflammatory state characterized by systemic and local increases in cytokine and chemokine levels are noted in both obesity and IBD, but it is unclear whether obesity is a risk factor for IBD. To examine any association between obesity and IBD, we chose FVB.129P2- Abcb1a(tm1Bor)N7 (Mdr1a(-/-)) mice, because this strain develops IBD spontaneously with age without a chemical or bacterial "trigger." In addition, its background strain, FVB, has been used for diet-induced obesity studies. Mdr1a(-/-) mice and wild-type (WT) mice were fed a HFD (∼60% calories from fat) or a low-fat diet (LFD; ∼11% calories from fat) for 12 wk. Obesity phenotypes examined included body weight measurements, glucose metabolism changes, and adiposity at termination of the study. IBD was determined by clinical signs, necropsy, and histopathology. We found that compared with those fed the LFD, both the Mdr1a(-/-) and WT mice fed the HFD had greater weight gains and elevated plasma leptin concentrations (P < 0.0001). When all mice were analyzed, weight gain was also associated with inflammation in mesenteric fat (R(2) = 0.5; P < 0.0001) and mesenteric lymph nodes (R(2) = 0.4; P < 0.0001). In contrast, the HFD was not associated with IBD in WT mice, whereas it exacerbated spontaneous IBD in Mdr1a(-/-) mice (P = 0.012; Fisher's exact test). Although a HFD and obesity were not associated with IBD in WT mice, our studies suggest that they are likely risk factors for IBD in a genetically susceptible host, such as Mdr1a(-/-) mice.

Topics: Adipose Tissue; Adiposity; Animals; Diet; Diet, Fat-Restricted; Diet, High-Fat; Disease Models, Animal; Energy Intake; Fatty Liver; Glucose Tolerance Test; Inflammatory Bowel Diseases; Insulin Resistance; Leptin; Male; Mice; Mice, Knockout; Obesity; Weight Gain

Activation of brain melanocortin-4 receptors (MC4-R) by α-melanocyte-stimulating hormone (MSH) or inhibition by agouti-related protein (AgRP) regulates food intake and energy expenditure and can modulate neuroendocrine responses to changes in energy balance. To examine the effects of AgRP inhibition on energy balance, a small molecule, non-peptide compound, TTP2515, developed by TransTech Pharma, Inc., was studied in vitro and in rodent models in vivo. TTP2515 prevented AgRP from antagonizing α-MSH-induced increases in cAMP in HEK 293 cells overexpressing the human MC4-R. When administered to rats by oral gavage TTP2515 blocked icv AgRP-induced increases in food intake, weight gain and adiposity and suppression of T4 levels. In both diet-induced obese (DIO) and leptin-deficient mice, TTP2515 decreased food intake, weight gain, adiposity and respiratory quotient. TTP2515 potently suppressed food intake and weight gain in lean mice immediately after initiation of a high fat diet (HFD) but had no effect on these parameters in lean chow-fed mice. However, when tested in AgRP KO mice, TTP2515 also suppressed food intake and weight gain during HFD feeding. In several studies TTP2515 increased T4 but not T3 levels, however this was also observed in AgRP KO mice. TTP2515 also attenuated refeeding and weight gain after fasting, an effect not evident in AgRP KO mice when administered at moderate doses. This study shows that TTP2515 exerts many effects consistent with AgRP inhibition however experiments in AgRP KO mice indicate some off-target effects of this drug. TTP2515 was particularly effective during fasting and in mice with leptin deficiency, conditions in which AgRP is elevated, as well as during acute and chronic HFD feeding. Thus the usefulness of this drug in treating obesity deserves further exploration, to define the AgRP dependent and independent mechanisms by which TTP2515 exerts its effects on energy balance.

Topics: Adiposity; Administration, Oral; Agouti-Related Protein; alpha-MSH; Animals; Anti-Obesity Agents; Diet, High-Fat; Eating; Energy Metabolism; Humans; Leptin; Male; Mice; Mice, Knockout; Rats; Receptor, Melanocortin, Type 4; Thyroxine; Triiodothyronine; Weight Gain

We present our experiment about adding anthocyanins to the daily food of mice. Three kinds of anthocyanins (cyanidin-3-glucoside, cyanidin-3-rutinoside and pelargonidin-3-glucoside) purified from Chinese mulberry (Morus australis Poir) were evaluated for suppressing body weight gain of the male C57BL/6 mice fed with high-fat diet (HFD). The results from a 12-week experiment show that consumption of purified mulberry anthocyanins (MACN) of 40 or 200mg/kg can significantly inhibit body weight gain, reduce the resistance to insulin, lower the size of adipocytes, attenuate lipid accumulation and decrease the leptin secretion. Thus, dietary supplementation with MACN can protect against body weight gain of the diet-induced obese mice.

Topics: Animals; Anthocyanins; Body Weight; Diet, High-Fat; Dietary Supplements; Humans; Leptin; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Morus; Obesity; Plant Extracts; Weight Gain

Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10(-6)), CNR1 (P=9.6 × 10(-5)) and the leptin (LEP) promoter (P=1.4 × 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event.

Topics: Adolescent; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Amidohydrolases; Antipsychotic Agents; Body Weight; Child; Child Development Disorders, Pervasive; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Leptin; Male; Proteins; Receptor, Cannabinoid, CB1; Receptor, Melanocortin, Type 4; Risperidone; Weight Gain

Bariatric surgeries are hypothesized to produce weight loss and improve diabetes control by multiple mechanisms including gastric restriction and lower gut stimulation; the relative importance of these mechanisms remains poorly understood. We compared the effects of a typical foregut procedure, sleeve gastrectomy, (SG) with a primarily hindgut surgery, ileal transposition (IT), alone and together (SGIT), or sham manipulations, on food intake, body weight, gut hormones, glucose tolerance, and key markers of glucose homeostasis in peripheral tissues of adult male Sprague-Dawley rats (450-550 g, n = 7-9/group). SG, IT, and SGIT surgeries produced transient reduction in food intake and weight gain; the effects of SG and IT on intake and body weight were nonadditive. SG, IT, and SGIT surgeries resulted in increased tissue expression and plasma concentrations of the lower gut hormones glucagon-like peptide-1 and peptide YY and decreased plasma glucose-dependent insulinotropic peptide, insulin, and leptin concentrations. Despite transient effects on intake and weight gain, the SG, IT, and SGIT surgeries produced a significant improvement in glucose tolerance. In support of glycemic improvements, the protein abundance of key markers of glucose metabolism (e.g., GLUT4, PKA, IRS-1) in muscle and adipose tissue were increased, whereas the expression of key gluconeogenic enzyme in liver (G-6-Pase) were decreased following the surgeries. Therefore, our data suggest that enhanced lower gut stimulation following SG, IT, and SGIT surgeries leads to transient reduction in food intake and weight gain together with enhanced secretion of lower gut hormones and improved glucose clearance by peripheral tissues.

Topics: Adipose Tissue, White; Animals; Bariatric Surgery; Biomarkers; Carbohydrate Metabolism; Energy Intake; Gastrectomy; Gastrointestinal Hormones; Glucose; Glucose Intolerance; Ileum; Insulin; Insulin Secretion; Intestinal Mucosa; Leptin; Liver; Male; Muscle, Skeletal; Random Allocation; Rats; Rats, Sprague-Dawley; Vitamin K; Weight Gain

The use of antipsychotic drugs has started a new era in the treatment of psychotic disorders. Nevertheless, they cause complications in the long-term treatment, which is mainly weight gain. In this study, we investigated circulating levels of hypothalamic neuropeptides, which are related to appetite regulation, neuropeptide Y (NPY), α-melanocyte-stimulating hormone (α-MSH), cocaine- and amphetamine-regulated transcript (CART), and leptin, in first-attack psychotic patients who were treated with an atypical antipsychotic drug, risperidone, for 4 weeks. We used a case-control association design to compare the neuropeptides in the control group versus before and after treatment of the patient group. Samples were obtained from psychotic patients who were admitted to the Psychiatry Outpatient Clinics, Gulhane School of Medicine, Ankara, Turkey. When compared with the control group, NPY and α-MSH plasma levels of psychotic patients were severely reduced, and the CART levels were substantially increased when they were first diagnosed (before treatment). However, the patients' body mass index and circulating leptin levels were markedly high after the treatment. Circulating levels of those neurohormones were not significantly changed between before and after treatment of the patients. These data demonstrate that peripheral α-MSH and NPY, although reflecting only secretion from peripheral organs, nevertheless, may provide an insight into the patients sympathetic tone and also suggest change of their appetite regulation. α-Melanocyte-stimulating hormone, NPY, and CART plasma levels may be used as a predictor of weight gain in the early treatment of the patients along with the leptin levels.

Topics: alpha-MSH; Antipsychotic Agents; Appetite Regulation; Body Mass Index; Case-Control Studies; Humans; Hypothalamus; Leptin; Male; Nerve Tissue Proteins; Neuropeptide Y; Risperidone; Treatment Outcome; Weight Gain; Young Adult

Leptin and adiponectin play important roles in carbohydrate and lipid metabolism in different species. Information is limited on the effects of diet, weight gain, and fat mass on their concentrations in cats. This study compared fasting and postprandial blood leptin and total adiponectin concentrations before and after 8 wk of ad libitum feeding to promote weight gain in adult cats (n = 32) fed either a low-carbohydrate, high-protein (23% and 47% ME) or a high-carbohydrate, low-protein (51% and 21% ME) diet. There were significant effects of total, abdominal, and nonabdominal fat mass, but not diet or body weight, on mean 24-h and peak leptin (P < 0.01); observed increases in mean and peak leptin were greatest for abdominal fat mass (50% and 56% increase for every extra 100 g, respectively). After weight gain, postprandial leptin concentration increased markedly relative to when cats were lean, and the duration of the increase was longer after a mean weight gain of 37% with the low-carbohydrate, high-protein diet group compared with 17% with the high-carbohydrate, low-protein group (P ≤ 0.01). Adiponectin was lower than fasting at some time points during the postprandial period in both groups (P ≤ 0.05). For both fasting and mean 24-h adiponectin, there was no significant diet effect (P ≥ 0.19) or changes in weight gain relative to when cats were lean (P ≥ 0.29). In conclusion, fat mass, and not diet, has a large effect on postprandial leptin but not adiponectin concentrations in cats.

Topics: Abdominal Fat; Adiponectin; Animals; Body Composition; Cats; Diet; Dietary Carbohydrates; Dietary Proteins; Fasting; Humans; Leptin; Postprandial Period; Weight Gain

Specific methylation of appetite-related genes in leukocytes could serve as a useful biomarker to predict weight regain after an energy restriction program. We aimed to evaluate whether the pre-intervention DNA methylation patterns involved in the epigenetic control of appetite-regulatory genes in leukocytes are associated with the weight regain process. Eighteen men who lost ≥5% of body weight after an 8-week nutritional intervention were categorized as "regainers" (≥10% weight regain) and "non-regainers" (<10% weight regain) 32weeks after stopping dieting. At baseline, leukocytes were isolated and DNA was analyzed for epigenetic methylation patterns of appetite-related gene promoters by MALDI-TOF mass spectrometry. Regainers showed higher methylation levels than non-regainers in proopiomelanocortin (POMC) CpG sites +136bp and +138bp (fold change from non-regainers=26%; p=0.020) and lower methylation of the whole analyzed region of neuropeptide Y (NPY; fold change from non-regainers=-22%; p=0.033), as well as of several individual NPY-promoter CpG sites. Importantly, total baseline NPY methylation was associated with weight-loss regain (r=-0.76; p<0.001), baseline plasma ghrelin levels (r=0.60; p=0.011) and leptin/ghrelin ratio (r=-0.52; p=0.046). Lower methylation levels of POMC CpG sites +136bp and +138bp were associated with success in weight-loss maintenance (odds ratio=0.042 [95% CI 0.01-0.57]; p=0.018), whereas lower total methylation levels in NPY promoter were associated with higher risk of weight regain (odds ratio=14.0 [95% CI 1.13-172]; p=0.039). Therefore, the study of leukocyte methylation levels reflects a putative epigenetic regulation of NPY and POMC, which might be implicated in the weight regain process and be used as biomarkers for predicting weight regain after dieting.

Topics: CpG Islands; DNA Methylation; Ghrelin; Humans; Leptin; Leukocytes; Male; Neuropeptide Y; Obesity; Pro-Opiomelanocortin; Promoter Regions, Genetic; Receptors, Leptin; Weight Gain

Leptin plays a critical role in the central regulation of bone mass. Ghrelin counteracts leptin. In this study, we investigated the effect of chronic intracerebroventricular administration of ghrelin on bone mass in Sprague-Dawley rats (1.5 μg/day for 21 days). Rats were divided into control, ghrelin ad libitum-fed (ghrelin ad lib-fed), and ghrelin pair-fed groups. Ghrelin intracerebroventricular infusion significantly increased body weight in ghrelin ad lib-fed rats but not in ghrelin pair-fed rats, as compared with control rats. Chronic intracerebroventricular ghrelin infusion significantly increased bone mass in the ghrelin pair-fed group compared with control as indicated by increased bone volume percentage, trabecular thickness, trabecular number and volumetric bone mineral density in tibia trabecular bone. There was no significant difference in trabecular bone mass between the control group and the ghrelin ad-lib fed group. Chronic intracerebroventricular ghrelin infusion significantly increased the mineral apposition rate in the ghrelin pair-fed group as compared with control. In conclusion, chronic central administration of ghrelin increases bone mass through a mechanism that is independent of body weight, suggesting that ghrelin may have a bone anabolic effect through the central nervous system.

Topics: Animals; Appetite; Bone and Bones; Bone Density; Drug Administration Schedule; Eating; Ghrelin; Injections, Intraventricular; Leptin; Male; Radiography; Rats; Rats, Sprague-Dawley; Weight Gain

Betaine (BET) reduces diet-induced liver lipid accumulation, and may relieve obesity-related metabolic disturbances. The aim of our study was to analyze metabolite alterations after supplementation of BET, polydextrose (PDX, a soluble dietary fiber), or their combination (BET PDX) via drinking water to C57BL/6J mice fed a high-fat (HF) diet.. BET supplementation increased BET levels in plasma, muscle, and liver (p < 0.05), and the nontargeted LC-MS metabolite profiling revealed an increase in several metabolites in the carnitine biosynthesis pathway after BET supplementation both in liver and muscle. These included carnitine and acetylcarnitine (1.4-fold, p < 0.05), propionylcarnitine and γ-butyrobetaine (1.5-fold, p < 0.05), and several other short-chain acylcarnitines (p < 0.05) in muscle. These changes were slightly higher in the BET PDX group. Furthermore, BET reduced the HF diet induced accumulation of triglycerides in liver (p < 0.05). The supplementations did not attenuate the HF diet induced increase in body weight gain or the increase in adipose tissue mass. Instead, the combination of BET and PDX tended to increase adiposity.. Our results suggest that increased availability of BET in different tissues, especially in muscle, after BET supplementation has an impact on carnitine metabolism, and this could further explain the link between BET and lipid metabolism.

Topics: Acetylcarnitine; Adipose Tissue; Adiposity; Animals; Betaine; Blood Glucose; Carnitine; Chromatography, Liquid; Diet, High-Fat; Dietary Supplements; Fasting; Glucans; Insulin; Leptin; Lipid Metabolism; Liver; Male; Mass Spectrometry; Metabolomics; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Obesity; Triglycerides; Weight Gain

Leptin is an adipocyte-secreted hormone that regulates energy homeostasis, while its role in fetal programming remains poorly understood. We aimed to evaluate the effect of maternal weight status on cord blood leptin levels and their combined effect on fetal growth.. We included 638 mother-child pairs from the prospective mother-child cohort 'Rhea' study in Crete, Greece with singleton pregnancies, providing cord blood serum samples for leptin analysis and complete data on birth outcomes. Multivariable logistic and linear regression models were used adjusting for confounders. Generalised additive models were used to explore the form of the relationship between cord leptin and continuous birth outcomes.. Log cord leptin was positively associated with birthweight {β-coef: 176.5 [95% confidence interval (CI): 133.0, 220.0] }, ponderal index (β-coef: 1.0 [95% CI: 0.6, 1.4] ) and gestational age (β-coef: 0.7 [95% CI: 0.5, 0.8] ). Excessive weight gain during pregnancy was associated with a threefold increased risk for cord hyperleptinaemia {relative risk (RR): 3.0, [95% CI: 1.5, 6.3] }. Maternal pre-pregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m(2) ] increased the risk of giving birth to a hyperleptinaemic neonate (RR: 2.1 [95% CI: 1.4, 3.2] and the effect of log leptin on birthweight (β-coef: 219.1 [95% CI: 152.3, 285.9] compared with women with a BMI <25 kg/m(2) (β-coef: 150.5 [95% CI: 93.1, 207.9].. Higher cord blood leptin levels are associated with increased size at birth and gestational age, while maternal pre-pregnancy BMI and weight gain during pregnancy represent significant indicators of cord blood leptin.

Topics: Adult; Body Mass Index; Body Weight; Cohort Studies; Female; Fetal Blood; Fetal Development; Gestational Age; Greece; Humans; Leptin; Mothers; Pregnancy; Prospective Studies; Regression Analysis; Weight Gain

Recent research suggests that cannabinoid receptor CB1 antagonists can affect appetite and body weight gain, although their influence on other parameters related to metabolic syndrome is not well documented. The present study was designed to assess the effects of chronic treatment with the CB1 receptor inverse agonist AM 251 (3 mg/kg for 3 weeks) in obese and lean Zucker rats on parameters related to metabolic syndrome.. Four groups of rats were used: lean Zucker rats, untreated obese Zucker rats, AM 251-treated obese Zucker rats and a pair-fed obese Zucker rat experimental group which received the same amount of food as that consumed by the animals treated with AM251. Food intake, body weight gain, energy expenditure, plasma biochemical parameters, leptin, insulin and hepatic status markers were analysed.. Daily injection of AM 251 in obese Zucker rats produced a marked and sustained decrease in daily food intake and body weight and a considerable increase in energy expenditure in comparison with untreated obese Zucker rats. AM 251 administration to obese rats significantly reduced plasma levels of glucose, leptin, AST, ALT, Gamma GT, total bilirubin and LDL cholesterol whereas HDL cholesterol plasma levels increased. The results also showed a decrease in liver/weight body ratio and total fat content in the liver. The main effects of AM251 (3 mg/kg) found in this study were not observed in pair-fed obese animals, highlighting the additional beneficial effects of treatment with AM 251. The results obtained in obese rats can be interpreted as a decrease in leptin and insulin resistance, thereby improving glucose and lipid metabolism, alleviating the steatosis present in the metabolic syndrome and thus favourably modifying plasma levels of hepatic biomarkers.. Our results indicate that the cannabinoid CB1 inverse agonist AM 251 represents a promising therapeutic strategy for the treatment of obesity and metabolic syndrome.

Topics: Animals; Biomarkers; Cannabinoid Receptor Antagonists; Eating; Energy Metabolism; Fatty Liver; Insulin; Insulin Resistance; Leptin; Lipid Metabolism; Liver; Male; Metabolic Syndrome; Obesity; Piperidines; Pyrazoles; Rats; Rats, Zucker; Receptor, Cannabinoid, CB1; Weight Gain

To investigate whether the effects of diet-induced obesity in mothers are passed on to their offspring fed a control diet in a gender-specific manner.. Mother mice received either standard chow (SC; 17% energy from fat) or high-fat (HF; 49% energy from fat) diet for eight weeks pre-pregnancy until lactation. After weaning (at 21 days of age), offspring received SC diet and were divided into four groups according to the mother's diet (Mo): male Mo-SC, female Mo-SC, male Mo-HF, and female Mo-HF. Stereology, Elisa and western blotting were performed.. HF diet-fed mothers were overweight, and had metabolic abnormalities, all of which were found in their adult offspring. Male Mo-HF offspring had higher cholesterol, triglycerides, leptin and insulin levels and lower circulating adiponectin than female Mo-HF offspring. Mo-HF offspring of both genders had higher expression of tumor necrosis factor-alpha, interleukin-6 and leptin and lower expression of adiponectin than Mo-SC offspring; however, male Mo-HF were more affected than female Mo-HF offspring for these variables, demonstrating sexual dimorphism.. Exposure to HF diet is effective in inducing obesity and metabolic alterations in mothers, and this phenotype can be passed on to their offspring. An adverse pattern in the body fat distribution in males probably has favored the intensification of a pro-inflammatory profile compared with females. In adulthood, the male offspring responds to the maternal obesity more than the female offspring, indicating a relevant sexual dimorphism that is a novel finding in this animal study.

Topics: Adipose Tissue; Animals; Blood Glucose; Blood Pressure; Body Fat Distribution; Diet, High-Fat; Energy Intake; Female; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; Sex Characteristics; Weight Gain

Perfluorooctane sulfonate (PFOS), which belongs to the degradation product of many perfluorinated compounds, is on the list of persistent organic pollutants (POPs) and is currently detected in both wildlife and humans. The consequence of gestational and lactational exposure to PFOS on prediabetes effect in offspring was investigated in rats in the present study. Maternal rats were treated with vehicle, 0.5 mg/kg/day or 1.5 mg/kg/day PFOS respectively from gestation day 0 to postnatal day 21. The glucose and lipid metabolism effects were investigated on the offspring in adulthood. The gestational and lactational exposure to PFOS led to low body weight from birth to weaning, and evoked signs of a prediabetic state, with elevated fasting serum insulin and leptin level, impaired glucose tolerance, though the fasting serum glucose and glycosylated serum protein level were normal. Abnormal lipid homeostasis was also observed by the phenomenon of hepatic steatosis and increased gonadal fat pad weight. However, the circulating serum level of fasting triglyceride and cholesterol level were no different from controls. Our results suggested that developmental exposure to PFOS may contribute to glucose and lipid metabolic disorder in adulthood.

Topics: Adipose Tissue; Alkanesulfonic Acids; Animals; Animals, Newborn; Environmental Pollutants; Fatty Liver; Female; Fluorocarbons; Glucose; Glucose Intolerance; Homeostasis; Insulin; Lactation; Leptin; Lipid Metabolism; Male; Maternal Exposure; Prediabetic State; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Triglycerides; Weight Gain

Accelerated infant growth is associated with an altered, mostly adverse adult cardiometabolic risk profile. The importance of genetic and environmental factors to these associations is unclear.. The objective was to examine the importance of genetic and environmental factors in the associations between infant growth and adult cardiometabolic risk factors (anthropometric characteristics, lipids, insulin sensitivity, leptin, blood pressure, and fibrinogen) in twins.. Cardiometabolic risk factors were assessed in 240 twin pairs (aged 18-34 y) from the East Flanders Prospective Twin Survey. Infant growth was defined as change in weight z score. We regressed intrapair differences in growth during 4 growth windows (0-1, 1-6, 6-12, and 12-24 mo) against intrapair differences in the risk factors in monozygotic and dizygotic twins separately.. Within monozygotic twin pairs only, associations between infant growth and most adult lipids, glucose, leptin, and blood pressure (eg, systolic blood pressure: b = 5.95 mm Hg per change in z score, P = 0.01 in monozygotic twins; b = -1.64, P = 0.82 in dizygotic twins from 12 to 24 mo) were found. Within dizygotic twin pairs only, associations between growth and triglycerides and fibrinogen (eg, fibrinogen: b = 0.07 ln mg/dL per change in z score, P = 0.31 in monozygotic twins; b = 0.79, P = 0.01 in dizygotic twins from 0 to 1 mo) were identified. Most associations showed a detrimental effect of accelerated growth, but beneficial associations were also identified (eg, total-to-high-density-lipoprotein cholesterol ratio: b = -0.22 per change in z score from 1 to 6 mo, P = 0.008 in monozygotic twins).. Our data showed that environmental factors play a role in the associations between infant growth and most adult lipids, glucose, leptin, and blood pressure, whereas genetic factors are involved regarding triglycerides and fibrinogen.

Topics: Adolescent; Adult; Belgium; Blood Glucose; Blood Pressure; Child, Preschool; Environment; Female; Fibrinogen; Heart Diseases; Humans; Infant; Infant, Newborn; Insulin Resistance; Leptin; Lipids; Male; Metabolic Diseases; Prospective Studies; Risk Factors; Triglycerides; Twins; Twins, Dizygotic; Twins, Monozygotic; Weight Gain

Adipose tissue (AT)-specific inflammation is considered to mediate the pathological consequences of obesity and macrophages are known to activate inflammatory pathways in obese AT. Because cyclooxygenases play a central role in regulating the inflammatory processes, we sought to determine the role of hematopoietic cyclooxygenase-1 (COX-1) in modulating AT inflammation in obesity.. Bone marrow transplantation was performed to delete COX-1 in hematopoietic cells. Briefly, female wild type (wt) mice were lethally irradiated and injected with bone marrow (BM) cells collected from wild type (COX-1+/+) or COX-1 knock-out (COX-1-/-) donor mice. The mice were fed a high fat diet for 16 weeks.. The mice that received COX-1-/- bone marrow (BM-COX-1-/-) exhibited a significant increase in fasting glucose, total cholesterol and triglycerides in the circulation compared to control (BM-COX-1+/+) mice. Markers of AT-inflammation were increased and were associated with increased leptin and decreased adiponectin in plasma. Hepatic inflammation was reduced with a concomitant reduction in TXB2 levels. The hepatic mRNA expression of genes involved in lipogenesis and lipid transport was increased while expression of genes involved in regulating hepatic glucose output was reduced in BM-COX-1-/- mice. Finally, renal inflammation and markers of renal glucose release were increased in BM-COX-1-/- mice.. Hematopoietic COX-1 deletion results in impairments in metabolic homeostasis which may be partly due to increased AT inflammation and dysregulated adipokine profile. An increase in renal glucose release and hepatic lipogenesis/lipid transport may also play a role, at least in part, in mediating hyperglycemia and dyslipidemia, respectively.

Topics: Adiponectin; Adipose Tissue; Animals; Biomarkers; Blotting, Western; Bone Marrow Cells; Bone Marrow Transplantation; Cyclooxygenase 1; Diet, High-Fat; Eating; Female; Fluorescent Antibody Technique; Inflammation; Kidney; Leptin; Liver; Macrophages; Mice; Mice, Knockout; Obesity; Real-Time Polymerase Chain Reaction; Weight Gain

Maternal high-fat (HF) diet has long-term consequences on the metabolic phenotype of the offspring. Here, we determined the effects of postweaning exercise in offspring of rat dams fed HF diet during gestation and lactation. Pregnant Sprague-Dawley rats were maintained on chow or HF diet throughout gestation and lactation. All pups were weaned onto chow diet on postnatal day (PND) 21. At 4 wk of age, male pups were given free access to running wheels (RW) or remained sedentary (SED) for 3 wk, after which all rats remained sedentary, resulting in four groups: CHOW-SED, CHOW-RW, HF-SED, and HF-RW. Male HF offspring gained more body weight by PND7 compared with CHOW pups and maintained this weight difference through the entire experiment. Three weeks of postweaning exercise did not affect body weight gain in either CHOW or HF offspring, but reduced adiposity in HF offspring. Plasma leptin was decreased at the end of the 3-wk running period in HF-RW rats but was not different from HF-SED 9 wk after the exercise period ended. At 14 wk of age, intracerebroventricular injection of leptin suppressed food intake in CHOW-SED, CHOW-RW, and HF-RW, while it did not affect food intake in HF-SED group. At death, HF-RW rats also had higher leptin-induced phospho-STAT3 level in the arcuate nucleus than HF-SED rats. Both maternal HF diet and postweaning exercise had effects on hypothalamic neuropeptide and receptor mRNA expression in adult offspring. Our data suggest that postweaning exercise improves central leptin sensitivity and signaling in this model.

Topics: Adiposity; Animal Nutritional Physiological Phenomena; Animals; Blood Glucose; Brain; Diet, High-Fat; Eating; Female; Gene Expression Regulation; Glucose Tolerance Test; Injections, Intraventricular; Insulin; Lactation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Neuropeptides; Obesity; Phosphorylation; Physical Exertion; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide; RNA, Messenger; Sedentary Behavior; Signal Transduction; STAT3 Transcription Factor; Weaning; Weight Gain

We investigated the effect of timing of food intake on growth in common carp (Cyprinus carpio L.). Juvenile carp were demand-fed for 22 days using a computerized pendulum feeder that registered meal requests. Controls were pair-fed at 10:00 h, both groups were kept at 12L:12D (lights on at 06:30 h). Demand-fed fish displayed highest food intake at 22:00 h, and the lowest at 10:00. After 22 days, demand-fed fish had grown by 20% of their initial body weight, compared to 4% of the pair-fed control. Plasma cortisol levels in demand-fed fish were remarkably low and stable, whereas in the control group levels had increased 60-fold at 10:00 h compared to 22:00 h. Hepatic mRNA expression of leptin-a1 and leptin-a2 also differed markedly between groups and time points, with leptin-a2 expression being lowest in the demand-fed group at the time point of lowest food intake. We conclude that timing of food intake is an important determinant of endocrine status, growth and welfare.

Topics: Animals; Carps; Eating; Feeding Behavior; Female; Hydrocortisone; Leptin; Liver; Male; Weight Gain

Maternal obesity increases the risk of obesity in offspring, and obesity is accompanied by an increase in blood leptin levels. The "yellow" mutation at the mouse agouti locus (A(y)) increases blood leptin levels in C57BL preobese pregnant mice without affecting other metabolic characteristics. We investigated the influence of the A(y) mutation or leptin injection at the end of pregnancy in C57BL mice on metabolic phenotypes and the susceptibility to diet-induced obesity (DIO) in offspring. In both C57BL-A(y) and leptin-treated mice, the maternal effect was more pronounced in male offspring. Compared with males born to control mothers, males born to A(y) mothers displayed equal food intake (FI) but decreased body weight (BW) gain after weaning, equal glucose tolerance, and enhanced FI-to-BW ratios on the standard diet but the same FI and BW on the high-fat diet. Males born to A(y) mothers were less responsive to the anorectic effect of exogenous leptin and less resistant to fasting (were not hyperphagic and gained less weight during refeeding after food deprivation) compared with males born to control mothers. However, all progeny displayed equal hypothalamic expression of Agouti gene-related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (POMC) and equal plasma leptin and glucose levels after food deprivation. Leptin injections in C57BL mice on day 17 of pregnancy decreased BW in both male and female offspring but inhibited FI and DIO only in male offspring. Our results show that hyperleptinemia during pregnancy has sex-specific long-term effects on energy balance regulation in progeny and does not predispose offspring to developing obesity.

Topics: Agouti-Related Protein; Animals; Body Composition; Body Weight; Eating; Energy Metabolism; Female; Hypothalamus; Leptin; Mice; Mice, Inbred C57BL; Neuropeptide Y; Obesity; Phenotype; Pregnancy; Pregnancy Complications; Pro-Opiomelanocortin; Sex Factors; Weight Gain

Weight gain and metabolic abnormalities are common side effects of antipsychotic treatment. Retinoids have been suggested as promising substances to suppress obesity. This study has investigated the effects of a retinoid agonist AM-80 on olanzapine-induced weight gain and metabolic changes in rats.. Female Sprague-Dawley rats (7 weeks) were treated with AM-80 (1 mg/kg/day, subcutaneously) and/or olanzapine (4 mg/kg/day, intraperitoneally) for 21 days. Body weight and food/water intake were measured daily. The open field (OFT) and prepulse inhibition (PPI) tests were done on days 18 and 21, respectively. Animals were sacrificed on day 22 to measure weight of adipose tissues and serum levels of adiponectin and leptin levels.. Olanzapine significantly increased body weight, food/water intake and the mass of inguinal adipose tissue (IAT) compared to vehicle-treated rats. AM-80 demonstrated significant inhibition of weight gain. No significant effect of olanzapine or AM-80 was found on behaviors or serum adiponectin/leptin levels.. These findings suggests that AM-80 is a potential therapeutic agent to attenuate weight gain and metabolic side effects associated with olanzapine.

Topics: Adiponectin; Adiposity; Animals; Antipsychotic Agents; Benzoates; Benzodiazepines; Body Weight; Drinking; Eating; Female; Leptin; Motor Activity; Olanzapine; Rats; Retinoids; Sensory Gating; Tetrahydronaphthalenes; Weight Gain

Patients with anorexia nervosa (AN) are often observed to have high levels of physical activity, which do not necessarily diminish after a successful therapy. Previous studies have shown that body fat tissue recovery in these patients is associated with a disproportional restoration of the adipocyte hormone, leptin. Therefore, we wondered whether the individual variation in physical activity in AN patients prior to treatment may be related to body fat percentage and plasma leptin level outcome.. Body fat percentage, leptin serum, and physical activity levels (accelerometer) were measured in adolescents with an (n=37, age 13 to 17.5 years) at initial assessment, at the end of study participation (median 12 months), and at one-year follow-up.. Accelerometer data were used to split the patients in two groups: those with low (n=26) and those with high levels of physical activity (HLPA, n=11). These groups did not differ in terms of age, IQ, presence of menses, BMI and season of admission. The HLPA group was characterized by a longer total duration of illness. Physical activity levels during therapy decreased for the group with initially HLPA and increased for the group with low levels of physical activity (to comparable levels). Physical activity remained stable after one year. The increase in body fat percentage and leptin levels were dependent on the recovery status; however, recovered patients with initially HLPA had significantly higher fat mass during the follow-up.. HLPA, an important modulator of AN progression in adolescents, can be successfully diminished by therapeutic intervention. Among recovered patients, those with initially HLPA had higher fat mass levels than those with low levels of physical activity. This finding suggests that HLPA are an important modulator of the body composition recovery mechanism.

Topics: Adipose Tissue; Adolescent; Anorexia Nervosa; Body Composition; Body Mass Index; Female; Humans; Leptin; Motor Activity; Weight Gain

Our objective was to evaluate changes in serum leptin levels during pregnancy in overweight/obese and non-obese women and to assess total and percent weight gain during pregnancy as possible factors that influence leptin levels.. In a prospective study of 42 low-risk pregnant women receiving prenatal care, we assessed serum leptin levels at gestational weeks 9-12, 25-28, and 34-37. Based on their pre-pregnancy body mass indices (BMIs), the cohort was divided into: non-overweight (BMI <25 kg/m(2)) and overweight/obese (BMI ≥ 25 kg/m(2)) subjects.. We found a progressive increase in maternal weight gain during pregnancy in both groups. There was also a progressive increase in leptin levels in the 2 strata; however, the increase was significantly higher in the non-overweight patient group. We found that non-overweight pregnant women had a noticeably larger total weight gain. When analyzing the percent weight gain during pregnancy compared to the pre-pregnancy weight, the non-overweight group had a significantly greater percent weight gain than the overweight/obese group.. Our results suggest that the greater increase in leptin levels in non-overweight pregnant women can be explained by the higher percent weight gain in this group compared to overweight/obese women. These findings suggest that controlling the percent weight gain may be an important preventive measure when controlling leptin levels during pregnancy and subsequent medical complications.

Topics: Adult; Analysis of Variance; Anthropometry; Brazil; Female; Gestational Age; Humans; Leptin; Obesity; Overweight; Pregnancy; Prospective Studies; Weight Gain

To determine whether daidzein improves insulin resistance by modifying weight gain, visceral fat accumulation, blood lipids and serum cytokines levels in ovariectomized Sprague-Dawley rats.. Twenty-eight 12-week-old female rats were divided into three groups: the sham-operated group (SHAM) (n =10), the ovariectomized group receiving daidzein therapy (DAID) (n =10), and the ovariectomized control group (Control) (n =8). The rats in the DAID group received 50 mg/kg daidzein via gavage daily. Weight and food intake were recorded every 2 weeks. All of the animals were euthanized 12 weeks after ovariectomy, after which their fasting insulin, glucose, blood lipids, estradiol, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), adiponectin and leptin levels were measured.. After 12 weeks, the ovariectomized rats demonstrated an increase in their body weight and visceral fat; compared to the SHAM rats, the ovariectomized rats also experienced a significant increase in their serum IL-6 levels and insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR) (p <0.05). Daidzein therapy decreased weight gain, visceral fat, the HOMA-IR index and IL-6 levels that were induced by ovariectomy. Rats which had received daidzein therapy had lower levels of TNF-α, leptin and blood lipids (except for high density lipoprotein cholesterol) than the other two groups. IL-6 levels positively correlated with the HOMA-IR index in all of the rats after adjustment for body weight (r =0.495; p =0.016).. We conclude that daidzein can improve insulin resistance induced by ovariectomy by decreasing weight gain, visceral fat accumulation, blood lipids, TNF-α, leptin and IL-6 levels.

Topics: Analysis of Variance; Animals; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Female; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Isoflavones; Leptin; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Triglycerides; Tumor Necrosis Factor-alpha; Weight Gain

The effects of maternal moderate-low physical training on postnatal development, glucose homeostasis and leptin concentration in adult offspring subjected to a low-protein diet during the perinatal period were investigated. Male Wistar rats (aged 150 d old) were divided into four groups according to maternal group: untrained (NTp, n 8); trained (Tp, n 8); untrained with a low-protein diet (NT+LPp, n 8); trained with a low-protein diet (T+LPp, n 8). The trained mothers were subjected to a protocol of moderate physical training over a period of 4 weeks (treadmill, 5 d/week, 60 min/d, at 65 % VO(2max)) before mating. At pregnancy, the intensity and duration of exercise was progressively reduced (50-20 min/d, at 65-30 % VO(2max)). The low-protein diet groups received an 8 % casein diet, and their peers received a 17 % casein diet during gestation and lactation. The pups' birth weight and somatic growth were recorded weekly up to the 150th day. Fasting blood glucose, cholesterol, serum leptin concentration, glucose and insulin tolerance tests were evaluated. The Tp animals showed no changes in somatic and biochemical parameters, while the NT+LPp group showed a greater abdominal circumference, hyperglycaemia, hypercholesterolaemia, glucose intolerance and lower plasma leptin. In the T+LPp animals, all of those alterations were reversed except for plasma leptin concentration. In conclusion, the effects of a perinatal low-protein diet on growth and development, glucose homeostasis and serum leptin concentration in the offspring were attenuated in pups from trained mothers.

Topics: Animals; Behavior, Animal; Birth Weight; Diet, Protein-Restricted; Female; Fetal Development; Fetal Growth Retardation; Hypercholesterolemia; Hyperglycemia; Insulin Resistance; Lactation; Leptin; Male; Maternal Behavior; Maternal Nutritional Physiological Phenomena; Motor Activity; Muscle, Skeletal; Pregnancy; Random Allocation; Rats; Rats, Wistar; Weight Gain

Conjugated linoleic acid (CLA) has been extensively studied during the last two decades with regard to its effects on controlling body composition. As a cognate to CLA, conjugated nonadecadienoic acid (CNA) has been previously reported to reduce body fat more effectively than CLA. However, it is not known whether CNA supplementation can influence adult-onset obesity. Thus, the purpose of this study was to evaluate the effects of dietary CNA on the prevention of adult-onset inactivity-induced obesity using nescient basic helix-loop-helix 2 knockout (N2KO) mice. CNA supplementation at 0.1 w/w% level starting in the preobese state significantly prevented the reduction of voluntary movement and the increase in weight gain in N2KO mice during the experimental period compared to wild-type animals. In both wild-type and N2KO mice, respiratory exchange ratio was significantly reduced by CNA treatment during light and dark cycles, and dietary CNA significantly increased energy expenditure in N2KO mice. Selected gene expression profiles in white adipose tissue, muscle or liver showed a beneficial action of CNA on lipid metabolism and energy expenditure. These findings suggest that CNA could prevent adult-onset obesity by enhancing voluntary activity and energy expenditure in N2KO mice.

Topics: Adipose Tissue; Adipose Tissue, White; Animals; Basic Helix-Loop-Helix Transcription Factors; Body Composition; Cholesterol, HDL; Cholesterol, LDL; Diet, High-Fat; Dietary Supplements; Energy Metabolism; Fatty Acids, Unsaturated; Female; Glucose Tolerance Test; Leptin; Lipid Metabolism; Liver; Mice; Mice, Knockout; Motor Activity; Muscle, Skeletal; Obesity; RNA, Messenger; Triglycerides; Weight Gain

Previous studies have shown relationships between personality styles and markers of serotonergic functioning, but data on patients with anorexia nervosa (AN) are scarce.. The personality styles and disorder inventory was administered to 47 acute patients with anorexia nervosa (acAN), 27 weight-recovered patients (recAN) and 72 healthy controls (HC) aged between 14 and 21 years. Platelet monoamine oxidase (MAO-B) activity was assayed with [14C]-β-phenylethylamine as substrate.. AcAN had significant elevated scores on 9 of the 14 personality style subscales when compared to HC, whereas recAN were largely normal. Platelet MAO-B activity and "ambitious/narcissistic" scores correlated negatively in acAN. In recAN we found positive correlations between MAO-B and personality subscores.. The inverse relationship between a cluster B personality style and MAO-B activity in acAN is in accordance with studies in other patient populations. In contrast, positive associations between problematic personality styles and MAO-B activity in recAN combined with the overall decreased MAO-B activity in this group adds to the existing evidence suggesting a general dysfunction of the serotonergic system as a trait marker for AN.

Topics: Adolescent; Anorexia Nervosa; Biomarkers; Blood Platelets; Body Mass Index; Carbon Radioisotopes; Case-Control Studies; Female; Humans; Leptin; Monoamine Oxidase; Personality; Phenethylamines; Weight Gain; Young Adult

Polyphenols have been reported to prevent chronic diseases such as cardiovascular diseases, cancers, diabetes and neurodegenerative diseases. The objective of the study was to conduct a screening for potential anti-obesity polyphenolic plant extracts using a diet-induced animal model. Rats were fed a high-fat-sucrose (HFS) diet with or without supplementation of different polyphenolic plant extracts (almond, apple, cinnamon, orange blossom, hamamelis, lime blossom, grape vine, and birch) for 56-64 days.. Body weight gain was lower in rats supplemented with apple, cinnamon, hamamelis and birch extracts as compared to HFS non-supplemented group. Moreover, apple and cinnamon extracts prevented the increase in fat mass promoted by the HFS diet. Insulin resistance, estimated by the homostatic model assessment-insulin resistance (HOMA-IR) index, was reduced in rats fed apple, cinnamon, hamamelis and birch extracts. Apple extract also prevented the HFS-induced hyperglycaemia and hyperleptinaemia.. Only apple and cinnamon extracts were finally considered as potentially important anti-obesogenic extracts, due to their body fat-lowering effects, while the improvement of obesity-related metabolic complications by apple polyphenols highlights this extract as a promising functional food ingredient for the management of obesity and its metabolic complications.

Topics: Adipose Tissue, White; Adiposity; Animals; Anti-Obesity Agents; Antioxidants; Cinnamomum zeylanicum; Dietary Sucrose; Dietary Supplements; Fruit; Hyperglycemia; Insulin Resistance; Leptin; Male; Malus; Obesity; Plant Bark; Plant Extracts; Polyphenols; Random Allocation; Rats; Rats, Wistar; Weight Gain

There is overwhelming evidence that experiences during early life could have long-term health consequences. However, the role of early nutrition in programming obesity and leptin resistance is still poorly understood.. We aimed at determining whether nutritional intakes in early life are associated with body composition and hormonal status at 20 years.. Healthy infants participating in the two-decade-long prospective ELANCE (Etude Longitudinale Alimentation Nutrition Croissance des Enfants) study were examined at 10 months and 2 years. At 20 years, weight, height, subscapular and triceps skinfold thicknesses, fat mass (FM) and fat-free mass (FFM) assessed via bioelectrical impedance analysis, and serum leptin concentration were recorded in 73 subjects still participating in the follow-up.. In adjusted linear regression models, an increase by 100 kcal in energy intake at 2 years was associated with higher subscapular skinfold thickness (β=6.4% SF, 95% confidence interval 2.53-10.30, P=0.002) and higher FFM (0.50 kg, 0.06-0.95, P=0.03) at 20 years. An increase by 1% energy from fat at 2 years was associated with lower subscapular skinfold thickness (-2.3% SF, -4.41 to -0.18, P=0.03), lower FM (-0.31 kg, -0.60 to -0.01, P=0.04) and lower serum leptin concentration (-0.21 μg l(-1), -0.39 to -0.03, P=0.02) at 20 years.. Low-fat intake in early life was negatively associated with body fat (particularly at the trunk site) and serum leptin concentration at 20 years, suggesting that early low-fat intake could increase the susceptibility to develop overweight and leptin resistance at later ages. These findings substantiate current recommendations against restricting fat intake in early life and open new directions for investigating the origin of obesity.

Topics: Adipose Tissue; Biomarkers; Body Height; Body Mass Index; Body Weight; Child, Preschool; Diet Records; Disease Susceptibility; Energy Intake; Female; Follow-Up Studies; France; Humans; Infant; Infant Nutritional Physiological Phenomena; Leptin; Male; Nutritional Status; Obesity; Prospective Studies; Skinfold Thickness; Weight Gain; Young Adult

Rats given sugar-sweetened drinks can develop glucose intolerance, insulin resistance and dyslipidaemia. The aim of this study was to investigate whether such metabolic disruptions and also possible weight gain induced by chronic sucrose consumption could be attenuated by low-volume exercise.. Using a 2 × 2 factorial design, rats were given free access for 57 days to either a 10% sucrose solution (Suc and SucEx) or water only (Con and ConEx), while exercise rats (SucEx and ConEx) received 20-min treadmill training every 3 days. Caloric intake and body weight were measured throughout this dietary intervention. Oral glucose tolerance tests were performed on days 29 and 54. Plasma insulin, triglycerides and leptin were also measured, together with post-mortem measures of retroperitoneal fat pads and liver triglycerides.. In groups given sucrose, exercise reduced calorie consumption, reduced weight gain and decreased leptin relative to non-exercised controls. Exercise was found to improve glucose tolerance and insulin action at day 29, but not day 54.. Low-volume exercise can be effective in preventing weight gain in sucrose-fed rats, probably via reduction of subcutaneous fat, but prevention of the glucose intolerance and dyslipidaemia produced by sucrose consumption may be transient.

Topics: Animals; Blood Glucose; Energy Intake; Glucose Intolerance; Glucose Tolerance Test; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Liver; Male; Obesity; Physical Conditioning, Animal; Rats; Rats, Wistar; Sedentary Behavior; Sucrose; Triglycerides; Weight Gain

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

The prototypic second messenger cyclic AMP (cAMP) is essential for controlling cellular metabolism, including glucose and lipid homeostasis. In mammals, the majority of cAMP functions are mediated by cAMP-dependent protein kinase (PKA) and exchange proteins directly activated by cAMP (Epacs). To explore the physiological functions of Epac1, we generated Epac1 knockout mice. Here we report that Epac1 null mutants have reduced white adipose tissue and reduced plasma leptin levels but display heightened leptin sensitivity. Epac1-deficient mice are more resistant to high-fat diet-induced obesity, hyperleptinemia, and glucose intolerance. Furthermore, pharmacological inhibition of Epac by use of an Epac-specific inhibitor reduces plasma leptin levels in vivo and enhances leptin signaling in organotypic hypothalamic slices. Taken together, our results demonstrate that Epac1 plays an important role in regulating adiposity and energy balance.

Topics: Adipose Tissue, White; Adiposity; Animals; Cyclic AMP; Diet, High-Fat; Gene Knockout Techniques; Glucose; Glucose Tolerance Test; Guanine Nucleotide Exchange Factors; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Signal Transduction; Weight Gain

Fatty acid (FA) composition and desaturase indices are associated with obesity and related metabolic conditions. However, it is unclear to what extent desaturase activity in different lipid fractions contribute to obesity susceptibility. Our aim was to test whether desaturase activity and FA composition are linked to an obese phenotype in rats that are either obesity prone (OP) or resistant (OR) on a high-fat diet (HFD).. Two groups of Sprague-Dawley rats were given ad libitum (AL-HFD) or calorically restricted (HFD-paired; pair fed to calories consumed by chow-fed rats) access to a HFD. The AL-HFD group was categorized into OP and OR sub-groups based on weight gain over 5 weeks. Five different lipid fractions were examined in OP and OR rats with regard to proportions of essential and very long-chain polyunsaturated FAs: linoleic acid (LA), alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and the stearoyl-CoA desaturase 1 (SCD-1) product 16:1n-7. FA ratios were used to estimate activities of the delta-5-desaturase (20:4n-6/20:3n-6), delta-6-desaturase (18:3n-6/18:2n-6), stearoyl-CoA desaturase 1 (SCD-1; 16:1n-7/16:0, SCD-16 and 18:1n-9/18:0, SCD-18), de novo lipogenesis (16:0/18:2n-6) and FA elongation (18:0/16:0). Fasting insulin, glucose, adiponectin and leptin concentrations were measured in plasma.. After AL-HFD access, OP rats had a significantly higher SCD-16 index and 16:1n-7 proportion, but a significantly lower LA proportion, in subcutaneous adipose tissue (SAT) triacylglycerols, as well as significantly higher insulin and leptin concentrations, compared with OR rats. No differences were found between the two phenotypes in liver (phospholipids; triacylglycerols) or plasma (cholesterol esters; phospholipids) lipid fractions or for plasma glucose or adiponectin concentrations. For the desaturase indices of the HFD-paired rats, the only significant differences compared with the OP or OR rats were higher SCD-16 and SCD-18 indices in SAT triacylglycerols in OP compared with HFD-paired rats.. The higher SCD-16 may reflect higher SCD-1 activity in SAT, which in combination with lower LA proportions may reflect higher insulin resistance and changes in SAT independent of other lipid fractions. Whether a lower SCD-16 index protects against diet-induced obesity is an interesting possibility that warrants further investigation.

Topics: Adiponectin; alpha-Linolenic Acid; Animals; Blood Glucose; Caloric Restriction; Delta-5 Fatty Acid Desaturase; Diet, High-Fat; Dietary Fats; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acid Desaturases; Insulin; Leptin; Linoleic Acid; Lipogenesis; Liver; Male; Obesity; Rats; Rats, Sprague-Dawley; Stearoyl-CoA Desaturase; Subcutaneous Fat; Triglycerides; Weight Gain

Across species obesity is associated with several disorders but in companion animals little information is available on the impact of chronic obesity on immune competence. The aim of the present study was to investigate whether weight gain and stable obese bodyweight affects the immune cell response. Obesity was induced in eight adult healthy beagle dogs (weight gain group; WGG) by a weight gain period (WGP) of 47 weeks, which was immediately followed by a period (stable period: SP) of stable obesity of 26 weeks. Eight adult healthy beagle dogs were included as a control group (CG) and remained at their ideal bodyweight throughout the entire study. Body composition was measured at five intervening time-points. Concentration of serum leptin and inflammatory cytokines, functionality of lymphocytes and phagocytic activity of neutrophils and monocytes were evaluated at ten intervening time-points. Serum leptin concentration was rising during the WGP in the WGG but went to lower concentrations during the SP. At the end of long-term weight gain, a decreased mitogen-induced proliferation of T-lymphocytes was noted but this alteration seemed to be transient after stabilization of bodyweight. This finding may imply an altered immune response for dogs with different energy balances. However, no systemic low grade inflammation or alteration in other immune cell functions was observed. Consequently it is suggested that the change in energy balance during the onset of obesity (becoming obese versus being obese), evokes an additional obesity-related disorder in dogs, i.e. impaired T-lymphocyte immune function.

Topics: Animals; Case-Control Studies; Cell Proliferation; Chronic Disease; Cytokines; Dog Diseases; Dogs; Energy Intake; Female; Leptin; Lymphocyte Activation; Male; Obesity; T-Lymphocytes; Weight Gain

Prader-Willi Syndrome is the most common syndromic form of human obesity and is caused by the loss of function of several genes, including MAGEL2. Mice lacking Magel2 display increased weight gain with excess adiposity and other defects suggestive of hypothalamic deficiency. We demonstrate Magel2-null mice are insensitive to the anorexic effect of peripherally administered leptin. Although their excessive adiposity and hyperleptinemia likely contribute to this physiological leptin resistance, we hypothesized that Magel2 may also have an essential role in intracellular leptin responses in hypothalamic neurons. We therefore measured neuronal activation by immunohistochemistry on brain sections from leptin-injected mice and found a reduced number of arcuate nucleus neurons activated after leptin injection in the Magel2-null animals, suggesting that most but not all leptin receptor-expressing neurons retain leptin sensitivity despite hyperleptinemia. Electrophysiological measurements of arcuate nucleus neurons expressing the leptin receptor demonstrated that although neurons exhibiting hyperpolarizing responses to leptin are present in normal numbers, there were no neurons exhibiting depolarizing responses to leptin in the mutant mice. Additional studies demonstrate that arcuate nucleus pro-opiomelanocortin (POMC) expressing neurons are unresponsive to leptin. Interestingly, Magel2-null mice are hypersensitive to the anorexigenic effects of the melanocortin receptor agonist MT-II. In Prader-Willi Syndrome, loss of MAGEL2 may likewise abolish leptin responses in POMC hypothalamic neurons. This neural defect, together with increased fat mass, blunted circadian rhythm, and growth hormone response pathway defects that are also linked to loss of MAGEL2, could contribute to the hyperphagia and obesity that are hallmarks of this disorder.

Topics: Adiposity; Animals; Antigens, Neoplasm; Arcuate Nucleus of Hypothalamus; Circadian Rhythm; Growth Hormone; Humans; Hyperphagia; Leptin; Mice; Neurons; Obesity; Prader-Willi Syndrome; Pro-Opiomelanocortin; Proteins; Receptors, Leptin; Weight Gain

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

There is growing evidence that vagus nerve stimulation (VNS) exerts a suppressive effect on both short- and long-term feeding in animal models. We previously showed that VNS with high-frequency (10 Hz) electrical impulses decreased food intake and body weight in rats. In the present study, we investigated the effect of VNS with a low frequency (1 Hz) on the serum lipid concentrations, feeding behavior and appetite in rats fed a high-fat diet. The levels of appetite-regulating peptides were also assessed. Adult male Wistar rats were subcutaneously implanted with a microstimulator (MS) and fed a high-fat diet throughout the entire study period (42 days). The left vagus nerve was stimulated subdiaphragmatically by rectangular electrical pulses (10 ms, 200 mV, 1 Hz, 12 h a day) generated by the MS. The daily food intake and body weight were measured each morning. At the end of the experiments, the serum glucose, cholesterol, triglycerides, low-density lipoproteins, high-density lipoproteins, ghrelin, leptin and nesfatin-1 concentrations were measured. The adipose tissue content was evaluated by the assessment of the weight of the epididymal fat pads. Chronic VNS significantly decreased food intake, body weight gain and epididymal fat pad weight. VNS also lowered the total plasma cholesterol concentrations and triglyceride levels. Finally, the serum concentrations of nesfatin-1 were elevated, leptin levels were decreased, and ghrelin levels remained unchanged after VNS. The study demonstrates that chronic electrical VNS exerts anorexigenic effects, lowering the blood concentration of lipids. Increased nesfatin-1 levels may contribute to these effects.

Topics: Adipose Tissue; Adult; Animals; Body Weight; Cholesterol; Diet, High-Fat; Eating; Humans; Leptin; Male; Models, Animal; Obesity; Rats; Rats, Wistar; Triglycerides; Vagus Nerve; Vagus Nerve Stimulation; Weight Gain

Chronic stress and diet can independently or in concert influence the body's homeostasis over time. Thus, it is crucial to investigate the interplay of these parameters to gain insight into the evolution of stress-induced metabolic and eating disorders.. C57BL/6J mice were subjected to chronic psychosocial (mixed model of social defeat and overcrowding) stress in combination with either a high- or low-fat diet for three or six weeks. To determine the evolution of stress and dietary effects, changes in body weight, caloric intake and caloric efficiency were determined as well as circulating leptin, insulin, glucose and corticosterone levels and social avoidance behaviour.. Exposure to stress for three weeks caused an increase in weight gain, in caloric intake and in caloric efficiency only in mice on a low-fat diet. However, after six weeks, only stressed mice on a high-fat diet displayed a pronounced inhibition of body weight gain, accompanied by reduced caloric intake and caloric efficiency. Stress decreased circulating leptin levels in mice on a low-fat diet after three weeks and in mice on a high-fat diet after three and six weeks of exposure. Plasma levels of insulin and markers of insulin resistance were blunted in mice on high-fat diet following six weeks of stress exposure. Social avoidance following chronic stress was present in all mice after three and six weeks.. This study describes the evolution of the chronic effects of social defeat/overcrowding stress in combination with exposure to high- or low-fat diet. Most importantly, we demonstrate that a six week chronic exposure to social defeat stress prevents the metabolic effects of high-fat diet, by inhibiting an increase in weight gain, caloric intake and efficiency and insulin resistance as well as in plasma leptin and insulin levels. This study highlights the importance of considering the chronic aspects of both parameters and their time-dependent interplay.

Topics: Animals; Blood Glucose; Body Weight; Chronic Disease; Corticosterone; Crowding; Diet, High-Fat; Energy Intake; Insulin; Interpersonal Relations; Leptin; Male; Mice; Mice, Inbred C57BL; Social Dominance; Social Environment; Stress, Psychological; Weight Gain

The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such as reproduction and immune responses. Accumulating evidence suggests that leptin plays a role in human pathologies, such as autoimmune diseases and cancer, thus providing a rationale for the development of leptin antagonists. In the present study, we generated and evaluated a panel of neutralizing nanobodies targeting the LR (leptin receptor). A nanobody comprises the variable domain of the naturally occurring single-chain antibodies found in members of the Camelidae family. We identified three classes of neutralizing nanobodies targeting different LR subdomains: i.e. the CRH2 (cytokine receptor homology 2), Ig-like and FNIII (fibronectin type III) domains. Only nanobodies directed against the CRH2 domain inhibited leptin binding. We could show that a nanobody that targets the Ig-like domain potently interfered with leptin-dependent regulation of hypothalamic NPY (neuropeptide Y) expression. As a consequence, daily intraperitoneal injection increased body weight, body fat content, food intake, liver size and serum insulin levels. All of these characteristics resemble the phenotype of leptin and LR-deficient animals. The results of the present study support proposed models of the activated LR complex, and demonstrate that it is possible to block LR signalling without affecting ligand binding. These nanobodies form new tools to study the mechanisms of BBB (blood-brain barrier) leptin transport and the effect of LR inhibition in disease models.

Topics: Adipose Tissue; Animals; Antibodies; Camelids, New World; Gene Expression Regulation; HEK293 Cells; Humans; Hyperinsulinism; Leptin; Liver; Mice; Mice, Inbred C57BL; Nanostructures; Neuropeptide Y; Organ Size; Protein Binding; Protein Structure, Tertiary; Receptors, Leptin; Signal Transduction; Weight Gain

Hypothalamic insulin inhibits food intake, preventing obesity. High-fat feeding with polyunsaturated fats may be obesogenic, but their effect on insulin action has not been elucidated. The present study evaluated insulin hypophagia and hypothalamic signaling after central injection in rats fed either control diet (15% energy from fat) or high-fat diets (50% energy from fat) enriched with either soy or fish oil. Soy rats had increased fat pad weight and serum leptin with normal body weight, serum lipid profile and peripheral insulin sensitivity. Fish rats had decreased body and fat pad weight, low leptin and corticosterone levels, and improved serum lipid profile. A 20-mU dose of intracerebroventricular (ICV) insulin inhibited food intake in control and fish groups, but failed to do so in the soy group. Hypothalamic protein levels of IR, IRS-1, IRS-2, Akt, mTOR, p70S6K and AMPK were similar among groups. ICV insulin stimulated IR tyrosine phosphorylation in control (68%), soy (36%) and fish (34%) groups. Tyrosine phosphorylation of the pp185 band was significantly stimulated in control (78%) and soy (53%) rats, but not in fish rats. IRS-1 phosphorylation was stimulated only in control rats (94%). Akt serine phosphorylation was significantly stimulated only in control (90%) and fish (78%) rats. The results showed that, rather than the energy density, the fat type was a relevant aspect of high-fat feeding, since blockade of hypothalamic insulin signal transmission and insulin hypophagia was promoted only by the high-fat soy diet, while they were preserved in the rats fed with the high-fat fish diet.

Topics: Adipose Tissue; Animals; Diet, High-Fat; Dietary Fats; Energy Intake; Fish Oils; Glycine max; Hypothalamus; Insulin; Insulin Resistance; Leptin; Male; Phosphorylation; Rats; Rats, Wistar; Signal Transduction; Soybean Oil; Weight Gain

To investigate the effect of a new soluble fiber, namely cationic hydroxyethyl cellulose (cHEC), on weight loss and metabolic disorders associated with obesity using a high-fat diet-induced obese mouse model.. Obese male C57BL/6J (B6) mice were fed high-fat (60% kcal) diets supplemented with cHEC for 5 weeks. Body weight, energy intake, mesenteric adipose and liver weights, plasma cholesterol, plasma insulin, glucose, adiponectin, and leptin were assessed to determine the effects of cHEC. Hepatic and fecal lipids were also analyzed to investigate the effect of cHEC on lipid absorption and metabolism.. Supplementation of the high-fat diet with cHEC resulted in significant weight loss in obese mice. In addition, significant decreases were seen in mesenteric adipose and liver weights, as well as concentrations of plasma cholesterol and hepatic lipids. A significant improvement in glucose homeostasis, insulin sensitivity, and leptin concentrations were observed at 4% cHEC. Moreover, increases in fecal excretion of total bile acids, sterols, and fats indicated altered fat absorption when cHEC was supplemented in the diet.. We have shown in the present study that cHEC reduces body weight, improves insulin sensitivity, and prevents the development of metabolic syndrome. Furthermore, the effects of cHEC on glucose and lipid homeostasis in B6 mice are mediated by improvements in leptin sensitivity resulting from reduced fat absorption.

Topics: Adiponectin; Animals; Cellulose; Disease Models, Animal; Glucose; Insulin; Leptin; Lipids; Male; Mice; Mice, Inbred C57BL; Obesity; Weight Gain

Peripheral blockade of cannabinoid CB(1) receptors has been proposed as a safe and effective therapy against obesity, putatively devoid of the adverse psychiatric side effects of centrally acting CB(1) receptor antagonists. In this study we analysed the effects of LH-21, a peripherally acting neutral cannabinoid receptor antagonist with poor brain penetration, in an animal model of diet-induced obesity.. To induce obesity, male Wistar rats were fed a high-fat diet (HFD; 60 kcal% fat) whereas controls received a standard diet (SD; 10 kcal% fat). Following 10 weeks of feeding, animals received a daily i.p. injection of vehicle or 3 mg·kg(-1) LH-21 for 10 days. Plasma and liver samples were used for biochemical analyses whereas visceral fat-pad samples were analysed for lipid metabolism gene expression using real-time RT-PCR. In addition, the potential of LH-21 to interact with hepatic cytochrome P450 isoforms and cardiac human Ether-à-go-go Related Gene (hERG) channels was evaluated.. LH-21 reduced feeding and body weight gain in HFD-fed animals compared with the control group fed SD. In adipose tissue, this effect was associated with decreased gene expression of: (i) leptin; (ii) lipogenic enzymes, including SCD-1; (iii) CB(1) receptors; and (iv) both PPARα and PPARγ. Although there were no significant differences in plasma parameters between HFD- and SD-fed rats, LH-21 did not seem to induce hepatic, cardiac or renal toxicity.. These results support the hypothesis that treatment with the peripherally neutral acting CB(1) receptor antagonist, LH-21, may promote weight loss through modulation of visceral adipose tissue.

Topics: Animals; Anti-Obesity Agents; Brain; Diet, High-Fat; Eating; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Gene Expression; HEK293 Cells; Humans; Intra-Abdominal Fat; Leptin; Lipogenesis; Liver; Male; Mice; Mice, Knockout; Obesity; PPAR alpha; PPAR gamma; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Triazoles; Weight Gain

Combination therapies are becoming increasingly important for the treatment of high blood pressure. Little is known about whether double blockade of angiotensin II (AT(1) ) receptors and angiotensin-converting enzyme (ACE) exert synergistic metabolic effects.. Spontaneously hypertensive rats were allowed to choose between palatable chocolate bars and standard chow and were simultaneously treated with the AT(1) blocker telmisartan (8 mg·kg(bw) (-1) ·day(-1) ), the ACE inhibitor ramipril (4 mg·kg(bw) (-1) ·day(-1) ) or a combination of the two (8 + 4 mg·kg(bw) (-1) ·day(-1) ) for 12 weeks.. Although food-dependent energy intake was increased by telmisartan and telmisartan + ramipril compared with ramipril or controls, body weight gain, abundance of fat and plasma leptin levels were decreased. Increased insulin levels in response to an oral glucose tolerance test were comparably attenuated by telmisartan and telmisartan + ramipril, but not by ramipril. During an insulin tolerance test, glucose utilization was equally as effectively improved by telmisartan and telmisartan + ramipril. In response to a stress test, ACTH, corticosterone and glucose increased in controls. These stress reactions were attenuated by telmisartan and telmisartan + ramipril.. The combination of telmisartan + ramipril was no more efficacious in regulating body weight and glucose homeostasis than telmisartan alone. However, telmisartan was more effective than ramipril in improving metabolic parameters and in reducing body weight. The association between the decrease in stress responses and the diminished glucose levels after stress supports our hypothesis that the ability of telmisartan, as an AT(1) receptor blocker, to alleviate stress reactions may contribute to its hypoglycaemic actions.

Topics: Adipose Tissue; Adrenocorticotropic Hormone; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzimidazoles; Benzoates; Blood Glucose; Blood Pressure; Corticosterone; Drug Therapy, Combination; Feeding Behavior; Heart Rate; Leptin; Male; Obesity; Ramipril; Rats; Rats, Inbred SHR; Telmisartan; Weight Gain

1. Overconsumption of fructose produces glucose intolerance, autonomic abnormalities and renal dysfunction and may be related to the worldwide epidemic of obesity and diabetes. 2. Experiments were conducted to determine whether the time period (light or dark) of fructose consumption influenced the pathological consequences. C57BL mice were given standard chow and assigned to one of three groups: (i) control (n = 10), which received water over a 24 h period; (ii) FL (n = 11), which received 10% fructose solution during the 12 h light period; and (iii) FD (n = 11), which received 10% fructose solution during the 12 h dark period. 3. There was a time related increase in body weight for all groups (P < 0.01, 2 vs 6 wks). There was a greater increase in body fat in the FL group compared with the control and FD groups. The changes in adiposity occurred even though the total caloric intake was not significantly different among the groups (approximately 18 kcal/day). Total fluid (water + fructose) consumption was greater in the FD and FL groups compared with control at 6 weeks. Significant increases were noted for plasma insulin and leptin at 8 weeks, with highest levels in the FL compared with FD group (P < 0.05). There were no significant changes in glucose, glucose tolerance, cholesterol, triglycerides or adiponectin. 4. The results of the present study suggest that there is a mismatch in caloric consumption, metabolism and adiposity as related to the light-dark cycle of fructose consumption. These findings have clinical implications in the control of bodyweight, abdominal fat accumulation and Type 2 diabetes.

Topics: Adipose Tissue, White; Adiposity; Animals; Cardiovascular Diseases; Cell Size; Cholesterol; Circadian Rhythm; Feeding Behavior; Fructose; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Random Allocation; Risk Factors; Triglycerides; Weight Gain

Soybean is known to have an anti-obesity effect. We compared the anti-obesity effect of doenjang, a fermented soybean paste, with that of nonfermented soybeans in rats. Steamed soybeans and doenjang (steamed soybeans fermented and aged for 10 months) were sampled and freeze-dried. Male Sprague-Dawley rats were fed basal (BA) (5% fat), high fat (HF) (30% fat), HF+steamed soybeans (SOY), or HF+doenjang (DJ) diet ad libitum for 8 weeks. HF significantly increased body weight gain, liver weight, hepatic triglyceride (TG) and cholesterol levels, and epididymal fat pad weight compared with BA. Compared with HF, body weight gain and hepatic TG and cholesterol levels were significantly lower in SOY and DJ groups, but they were not significantly different from each other. DJ significantly reduced visceral fat weight and epididymal adipocyte size compared with HF, whereas SOY resulted in a mild reduction without significance. This was possibly because DJ showed lowered fatty acid synthase (FAS) activity and elevated carnitine palmitoyltransferase (CPT)-1 activity in liver tissue more than SOY. SOY and DJ did not affect serum total and high-density lipoprotein-cholesterol levels compared with HF; however, DJ significantly lowered the atherogenic index and serum leptin level. In conclusion, doenjang, a fermented soybean product, was more effective than soybeans for preventing diet-induced visceral fat accumulation, possibly because of its greater effects on CPT-1 activity stimulation and FAS activity suppression. These effects may be due in part to the higher content of aglycone isoflavones in doenjang.

Topics: Adipocytes; Animals; Anti-Obesity Agents; Atherosclerosis; Carnitine O-Palmitoyltransferase; Cholesterol; Diet, High-Fat; Dietary Fats; Fatty Acid Synthases; Fermentation; Glycine max; Intra-Abdominal Fat; Isoflavones; Leptin; Liver; Male; Obesity; Organ Size; Phytotherapy; Rats; Rats, Sprague-Dawley; Seeds; Soy Foods; Triglycerides; Weight Gain

The roles of adiponectin and leptin in the early stages of life are poorly understood. We previously studied longitudinal changes in these adipocytokines from birth to 12 months of age. The aim of this investigation was to evaluate the correlation between cord serum adipocytokine levels and postnatal growth by 3 years of age.. A questionnaire was sent to obtain the general physical measurements of 3-year-olds from 56 healthy newborn infants born at a gestational age of 35 weeks or more; 45 valid responses were obtained. The correlations between variables, including cord serum adipocytokine levels at birth and general physical measurements at 3 years, were investigated.. Body mass index (BMI) Z-score gain from birth to 3 years was negatively correlated with birthweight SD scores (β=-0.395, P= 0.019) and gestational age (β=-0.557, P= 0.016), and positively correlated with cord serum adiponectin levels (β= 0.253, P= 0.043). BMI Z-score gain from birth to 6 months was negatively correlated with only birthweight SD score (β=-0.442, P= 0.017). Cord serum leptin levels were not a significant predictor of BMI Z-scores gain in our subjects. BMI Z-scores at 6 months, 12 months, and 3 years of age were not related to cord serum adiponectin or leptin levels.. Birthweight SD score, gestational age, and cord serum adiponectin levels are significant predictors of BMI Z-score gain from birth to 3 years of age in Japanese infants.

Topics: Adiponectin; Birth Weight; Body Mass Index; Child, Preschool; Female; Fetal Blood; Humans; Infant, Newborn; Leptin; Male; Pregnancy; Regression Analysis; Surveys and Questionnaires; Weight Gain

Pups of normally nourished dams that are cross-fostered after birth to dams fed a low-protein (8% by weight) diet (postnatal low protein (PLP)) grow slower during the suckling period and remain small and lean throughout adulthood. At weaning, they have increased expression in the arcuate nucleus (ARC) of the hypothalamus of the orexigenic neuropeptide Y (NPY) and decreased expression of pro-opiomelanocortin, the precursor of anorexigenic melanocortins.. We investigated, using third ventricle administration, whether 3-month-old male PLP rats display altered sensitivity to leptin with respect to food intake, NPY and the melanocortin 3/4-receptor agonist MTII, and using in situ hybridization or laser capture microdissection of the ARC followed by RT-PCR, whether the differences observed were associated with changes in the hypothalamic expression of NPY or the leptin receptor, NPY receptors and melanocortin receptors.. PLP rats were smaller and had reduced percentage body fat content and plasma leptin concentration compared with control rats. Leptin (5 μg) reduced food intake over 0-48 h more in PLP than control rats (P<0.05). Submaximal doses of NPY increased the food intake less in PLP rats than in controls, whereas submaximal doses of MTII reduced the food intake more in PLP rats. Maximal responses did not differ between PLP and control rats. Leptin and melanocortin-3 receptor (MC3R) expression were increased in both ARC and ventromedial hypothalamic nuclei in PLP animals compared with the controls. MC4R, NPY Y1R, Y5R and NPY expression were unchanged.. Postnatal undernourishment results in food intake in adult rats being more sensitive to reduction by leptin and melanocortins, and less sensitive to stimulation by NPY. We propose that this contributes to increased leptin sensitivity and resistance to obesity. Increased expression of ObRb and MC3R may partly explain these findings but other downstream mechanisms must also be involved.

Topics: Animals; Animals, Newborn; Arcuate Nucleus of Hypothalamus; Body Weight; Disease Susceptibility; Eating; Gene Expression Regulation; Leptin; Male; Neuropeptide Y; Obesity; Rats; Rats, Wistar; Receptor, Melanocortin, Type 3; Thinness; Time Factors; Weight Gain

Leptin has been thought to work as a mediator for body weight control by inhibiting food intake. Leptin, however, cannot prevent obesity induced by a high-fat diet (HFD) probably because of leptin resistance. We investigated daily feeding and weight gain when ordinary chow (OC) was changed to a HFD in male rats. Food intake, by weight, significantly increased the next day, but gradually decreased until at 20 days the HFD intake contained the same calories as consumed by the OC-fed control rats. The reduction in food intake occurred only during the night without change of preference for the HFD, even after leptin resistance had developed. Nonetheless, the HFD-fed rats gained more weight than the controls. From the present experiment, it is concluded that leptin resistance does not induce hyperphagia, and suggested that body weight is not regulated to be constant.

Topics: Animals; Diet, High-Fat; Dietary Fats; Drug Resistance; Eating; Energy Intake; Food Preferences; Hyperphagia; Leptin; Male; Rats; Rats, Wistar; Weight Gain

High-fat (HF) diets trigger an increase in adipose tissue and body weight (BW) and disordered eating behavior. Our study deals with the hypothesis that circadian distribution of energy intake is more relevant for BW dynamics than diet composition. Four-week-old mice were exposed for 8 wk to a HF diet and compared with animals receiving control chow. HF mice progressively increased BW, decreased the amount of nocturnal (1800-0900 h) calories (energy or food intake) (30%) and increased diurnal (0900-1800 h) caloric intake (energy or food intake), although total daily intake was identical between groups. Animals were killed at 3-h intervals and plasma insulin, leptin, corticosterone, glucose, and fatty acid levels quantified. Adipose tissue was weighed, and enzymatic activities integral to the pentose phosphate pathway (PPP) assayed in lumbar adipose tissue. Phosphorylated AMP-dependent protein kinase and fatty acid synthase were quantified by Western blotting. In HF mice, there was a shift in the circadian oscillations of plasma parameters together with an inhibition of PPP activity and a decrease in phosphorylated AMP-dependent protein kinase and fatty acid synthase. In a second experiment, HF mice were forced to adhere to a circadian pattern of food intake similar to that in control animals. In this case, BW, adipose tissue, morning plasma parameters and PPP activity appeared to be normal. These data indicate that disordered feeding behavior can trigger BW gain independently of food composition and daily energy intake. Because PPP is the main source of reduced nicotinamide adenine dinucleotide phosphate, we suggest that PPP inhibition might be an early marker of adipose dysfunction in diet-induced obesity.

Topics: Adipose Tissue; Adiposity; Animals; Circadian Rhythm; Corticosterone; Dietary Fats; Energy Metabolism; Fatty Acids, Nonesterified; Hyperphagia; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; NADP; Overweight; Pentose Phosphate Pathway; Weight Gain

Glucocorticoids (GCs) are potent pharmacological agents used to treat a number of immune conditions. GCs are also naturally occurring steroid hormones (e.g. cortisol, corticosterone) produced in response to stressful conditions that are thought to increase the preference for calorie dense 'comfort' foods. If chronically elevated, GCs can contribute to the development of type 2 diabetes mellitus (T2DM), although the mechanisms for the diabetogenic effects are not entirely clear. The present study proposes a new rodent model to investigate the combined metabolic effects of elevated GCs and high-fat feeding on ectopic fat deposition and diabetes development. Male Sprague-Dawley rats (aged 7-8 weeks) received exogenous corticosterone or wax (placebo) pellets, implanted subcutaneously, and were fed either a standard chow diet (SD) or a 60% high-fat diet (HFD) for 16 days. Animals given corticosterone and a HFD (cort-HFD) had lower body weight and smaller relative glycolytic muscle mass, but increased relative epididymal mass, compared with controls (placebo-SD). Cort-HFD rats exhibited severe hepatic steatosis and increased muscle lipid deposition compared with placebo-SD animals. Moreover, cort-HFD animals were found to exhibit severe fasting hyperglycemia (60% increase), hyperinsulinemia (80% increase), insulin resistance (60% increase) and impaired β-cell response to oral glucose load (20% decrease) compared with placebo-SD animals. Thus, a metabolic syndrome or T2DM phenotype can be rapidly induced in young Sprague-Dawley rats by using exogenous GCs if a HFD is consumed. This finding might be valuable in examining the physiological and molecular mechanisms of GC-induced metabolic disease.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adipose Tissue; Adiposity; Animals; Body Composition; Circadian Rhythm; Corticosterone; Diabetes Mellitus, Experimental; Diet, High-Fat; Disease Models, Animal; Energy Intake; Fasting; Feeding Behavior; Glucocorticoids; Hyperglycemia; Hyperinsulinism; Hyperphagia; Insulin; Insulin Resistance; Leptin; Male; Muscular Atrophy; Rats; Receptors, Glucocorticoid; Triglycerides; Weight Gain

It is clear that the prenatal and early neonatal environments are important for determining the metabolic equilibrium in the adult animal, with prenatal/neonatal leptin levels being at least one of the factors involved. Leptin modulates hypothalamic development and, in particular, the neuronal circuits involved in metabolic control. We have recently reported that maternal deprivation (MD) for 24 h on postnatal day (PND) 9 modifies trophic factors and markers of cell turnover and neuronal maturation in the hypothalamus, as well as body weight and circulating leptin levels at PND13, with long- term effects on weight gain and circulating metabolic hormones in the adult. Moreover, these responses are sexually dimorphic. During MD, a dramatic decline in leptin levels is observed; thus, we aimed to determine which of the previously observed changes in markers of hypothalamic development might be attributed to the decline in this metabolic signal. Accordingly, male and female rats were treated with a pegylated leptin antagonist on PND9. In both sexes, hypothalamic signal transducer and activator of transcription 3 activation in response to acute leptin treatment was blocked by the antagonist. In females, hypothalamic mRNA levels for brain-derived neurotrophic factor, cocaine- and amphetamine-regulated transcript and the leptin receptor were increased, as were nestin and vimentin levels. There was also an increase in cell death in the hypothalamus, with a shift towards an anti-apoptotic balance in the Bcl2/BAX ratio. No hypothalamic effects were seen in males. Because antagonism of the actions of leptin at this specific neonatal stage affects hypothalamic cell turnover and maturation in a sex-specific manner, changes in this hormone, at least at this postnatal age, may differentially affect hypothalamic development in males and females, and may explain some of the reported sexually dimorphic responses to modifications in the early nutritional environment.

Topics: Animals; Animals, Newborn; Female; Hormone Antagonists; Hypothalamus; Intercellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptides; Polyethylene Glycols; Rats; Rats, Wistar; Receptors, Leptin; Sex Characteristics; STAT3 Transcription Factor; Weight Gain

Overweight in dogs is, as in other companion animals, a major risk factor for several metabolic disorders. However, it is not yet known whether immunity is challenged by increased body weight in dogs. The aim of this study was to investigate the effect of a short-term increase in body weight on immunological variables in adult healthy beagle dogs. Sixteen dogs, divided into a control group (CG) and weight gain group (WGG), were included. During a period of 13 weeks, the CG was fed at maintenance energy requirement (MER), whereas the WGG received a double amount of food. After 13 weeks, blood samples were taken for immunological and biochemical analyses. Weight gain and increased body condition score in the WGG were accompanied by a significant higher leptin concentration. Weight gain increased the number of lymphocytes and immunoglobulins A and M and was responsible for a higher proliferation of peripheral blood mononuclear cells (PBMC). Short-term increase of body weight thus seems to trigger immunological variables in dogs.

Topics: Animals; Dogs; Eating; Female; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Leptin; Leukocytes, Mononuclear; Lymphocyte Subsets; Male; Neutrophils; Oxidative Stress; Reactive Oxygen Species; Weight Gain

Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr(-/-) mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr(-/-)) mice, the Ldlr(-/-)Fxr(-/-) double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr(-/-) background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr(-/-) mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr(-/-) mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob(-/-)Fxr(-/-) mice that were deficient in both Leptin and Fxr. On a chow diet, ob(-/-)Fxr(-/-) mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (<11 months old) Ob(-/-)Fxr(-/-) mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions.

Topics: Adipose Tissue, Brown; Adiposity; Animals; Carcinoma; Cell Transformation, Neoplastic; Diet, High-Fat; Dietary Fats; Energy Metabolism; Female; Gene Knockout Techniques; Glucose Intolerance; Intestinal Absorption; Leptin; Liver; Liver Neoplasms; Male; Mice; Mice, Knockout; Mice, Obese; Muscle, Skeletal; Obesity; Receptors, Cytoplasmic and Nuclear; Sex Factors; Weight Gain

Cigarettes smoke (CS) limits food intake and body weight increase. Ghrelin and leptin are hormones regulating appetite and energy balance. While ghrelin increases food intake and causes a positive energy balance, leptin decreases food intake and enhances a negative energy balance. To investigate the possible role of ghrelin and leptin regarding the negative energy balance caused by CS, 10-week old male Wistar rats (n = 10) were exposed to CS from 30 cigarettes twice a day for 5 days a week for four weeks. In the smoking group, food intake and body weight gain were less than those in the non-smoking group (n = 10) during the entire CS exposure. In the smoking group, the plasma levels of acyl ghrelin were significantly higher (75.9 ± 5.1 fmol/ml versus 46.5 ± 3.3 fmol/ml, p < 0.01), while those of leptin were significantly lower than those in the non-smoking group (434.9 ± 41.1 ng/ml versus 744.0 ± 45.4 ng/ml, p < 0.01) after the final CS exposure. However, the plasma des-acyl ghrelin levels were not affected by CS exposure. These results suggested that acyl ghrelin and leptin levels in plasma may change to compensate for the negative energy balance by CS.

Topics: Animals; Carboxyhemoglobin; Eating; Ghrelin; Hydrogen Peroxide; Leptin; Male; Rats; Rats, Wistar; Smoking; Weight Gain

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

Obesity is associated with alterations in upper airway collapsibility during sleep. Obese, leptin-deficient mice demonstrate blunted ventilatory control, leading us to hypothesize that (1) obesity and leptin deficiency would predispose to worsening neuromechanical upper airway function and that (2) leptin replacement would acutely reverse neuromuscular defects in the absence of weight loss. In age-matched, anesthetized, spontaneously breathing C57BL/6J (BL6) and ob(-)/ob(-) mice, we characterized upper airway pressure-flow dynamics during ramp decreases in nasal pressure (P(N)) to determine the passive expiratory critical pressure (P(CRIT)) and active responses to reductions in P(N), including the percentage of ramps showing inspiratory flow limitation (IFL; frequency), the P(N) threshold at which IFL developed, maximum inspiratory airflow (Vi(max)), and genioglossus electromyographic (EMG(GG)) activity. Elevations in body weight were associated with progressive elevations in P(CRIT) (0.1 ± 0.02 cmH(2)O/g), independent of mouse strain. P(CRIT) was also elevated in ob(-)/ob(-) compared with BL6 mice (1.6 ± 0.1 cmH(2)O), independent of weight. Both obesity and leptin deficiency were associated with significantly higher IFL frequency and P(N) threshold and lower VI(max). Very obese ob(-)/ob(-) mice treated with leptin compared with nontreated mice showed a decrease in IFL frequency (from 63.5 ± 2.9 to 30.0 ± 8.6%) and P(N) threshold (from -0.8 ± 1.1 to -5.6 ± 0.8 cmH(2)O) and increase in VI(max) (from 354.1 ± 25.3 to 659.0 ± 71.8 μl/s). Nevertheless, passive P(CRIT) in leptin-treated mice did not differ significantly from that seen in nontreated ob(-)/ob(-) mice. The findings suggest that weight and leptin deficiency produced defects in upper airway neuromechanical control and that leptin reversed defects in active neuromuscular responses acutely without reducing mechanical loads.

Topics: Animals; Disease Models, Animal; Electromyography; Infusions, Subcutaneous; Leptin; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Pressure; Pulmonary Ventilation; Recombinant Proteins; Respiratory Mechanics; Sleep Apnea, Obstructive; Tidal Volume; Weight Gain

Increased availability of fatty acids released from insulin-resistant adipose tissue may lead to excess fatty acid uptake in nonadipose organs, including the heart. Accumulation of toxic fatty acid intermediates may affect cardiac function. Our aim was to identify to which extent high-fat diet feeding leads to alterations in cardiac function and whether this depends on gender and (or) duration of high-fat diet feeding. Male and female C57Bl/6J mice (n = 8 per group) of 12 to 16 weeks old were fed a low-fat (10% energy) or high-fat (45% energy) lard diet for 6 or 12 weeks. Plasma lipid levels, echocardiography, and left ventricular pressure-volume relationships were obtained at 2, 1, and 0 weeks before termination, respectively. In both male and female mice, the high-fat diet increased body weight and plasma lipid content. At 10 weeks, significant increases were observed for plasma total cholesterol (males: +44%; females: +86%), phospholipids (+16% and +34%), and triglycerides (+27% and +53%) (all p < 0.001). In male mice, but not in female mice, the high-fat diet significantly affected cardiac function at 12 weeks with increased end-systolic volume (25.4 ± 6.2 vs. 17.0 ± 6.7 µL, p < 0.05), increased end-systolic pressure (72.1 ± 6.9 vs. 63.6 ± 6.9 mm Hg, p < 0.01), and decreased ejection fraction (61.2% ± 4.5% vs. 68.1% ± 3.7%, p < 0.01), indicating reduced systolic function. Multiple linear regression analysis indicated a significant diet-gender interaction for end-systolic volume and ejection fraction. In conclusion, high-fat diet feeding increased body weight and plasma lipid levels in male and in female mice, but resulted in impairment of cardiac function only in males.

Topics: Adipose Tissue; Animals; Cholesterol; Diet, High-Fat; Dietary Fats; Echocardiography; Fatty Acids, Nonesterified; Female; Heart; Insulin; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Phospholipids; Sex Factors; Triglycerides; Weight Gain

Fenretinide (FEN), a ligand of retinol binding protein 4 (RBP4), has been suggested as a measure to reduce insulin resistance and its associated disorders such as obesity, and fatty liver by reducing serum RBP4. We investigated whether there is another possible mechanism by which fenretinide reduces insulin resistance and fatty liver in genetically obese (ob/ob) mice. Male obese mice fed a high-fat diet (45% of calories from fat) were divided into two groups (n=13 each). One (FEN) received fenretinide (20 mg/kg body weight, intraperitoneally) and the other (O) received vehicle three times weekly for 24 d. C57BL/6J mice fed a normal-fat diet (16% of calories from fat) were used as a control (C; n=13). No changes in fat weight and serum leptin level could be observed in FEN mice. Lower plasma RBP4 was observed in FEN mice compared with O mice. Fenretinide improved whole-body insulin sensitivity based on glucose and insulin tolerance tests and the homeostasis model assessment of insulin resistance. Fenretinide decreased the plasma lipid (triglyceride, cholesterol, and free-fatty acid) levels, hepatic TG level, and histological steatosis score. The mechanism by which fenretinide prevents fatty liver may be explained by an increased plasma adiponectin level, increased activation of hepatic AMP-activated protein kinase, and the expression of peroxisome proliferator-activated protein-α and peroxisomal acyl-CoA oxidase, which promote fat oxidation. FEN alleviated insulin resistance and fatty liver in obese mice and thus may act as an anti-lipidemic and anti-diabetic drug.

Topics: Adiponectin; Adipose Tissue, White; Alanine Transaminase; Animals; Aspartate Aminotransferases; Diet, High-Fat; Fatty Liver; Fenretinide; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Leptin; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Prealbumin; Retinol-Binding Proteins, Plasma; Weight Gain

The exact mechanism of weight gain (WG) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with idiopathic Parkinson's disease remains unknown.. To investigate a possible involvement of ghrelin, neuropeptide Y (NPY) and leptin in WG after DBS.. Twenty-three Parkinson patients were submitted for body composition measurements and blood sampling 3 days before, and 3 and 6 months after STN DBS. Peripheral concentrations of ghrelin, NPY, and leptin were determined, as well as the L-dopa equivalent daily dose. Patients were clinically evaluated using the Unified Parkinson's Disease Rating Scale.. Three months after surgery, a significant WG was observed (3.09 ± 5.00 kg; p = 0.007) with no further increase at 6 months. Three months postoperatively, NPY circulating levels increased significantly (p = 0.05), while the increase of ghrelin levels reached statistical significance at 6 months (p = 0.001). WG was significantly associated with changes of ghrelin and leptin levels at 3 and 6 months, respectively.. STN DBS seems to temporarily dysregulate the hypothalamic secretion of NPY and ghrelin. The variation of weight may be attributed to an increased production of ghrelin and leptin. A possible neuroprotective role of DBS, exerted through the increase of ghrelin levels, should be further studied.

Topics: Aged; Body Composition; Deep Brain Stimulation; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Neuropeptide Y; Parkinson Disease; Subthalamic Nucleus; Treatment Outcome; Weight Gain

Antipsychotic-induced weight gain (AIWG) is a serious side-effect of antipsychotic medication leading to metabolic syndrome and increased cardiovascular morbidity. Unfortunately, there are still no valid predictors to assess an individual's risk to gain weight. Previous studies have indicated an impact of genetic variation in the genes encoding leptin, LEP, and leptin receptor, LEPR, on AIWG, but results have not been conclusive. Thus, we investigated polymorphisms in both genes for an association with AIWG.. A total of 181 schizophrenic and schizoaffective patients treated with various antipsychotics were included. In a small subset of patients, leptin plasma levels were additionally obtained. Five polymorphisms in LEP and LEPR (LEP: rs7799039 (-2548G/A polymorphism), rs10954173, rs3828942; LEPR: rs1327120, rs1137101 (Q223R polymorphism) were genotyped using TaqMan assays. Statistical association with % weight change from baseline weight was performed using ANCOVA with baseline weight as covariate.. ANCOVA showed a non-significant trend for genotype association of the rs7799039 marker (p=.068). No significant association of the other LEP and LEPR SNPs with AIWG was detected. However, we found a significant association between a haplotype of LEP rs7799039G-rs10954173G-rs3828942G (p=.035) and AIWG. The rs7799039 G-allele (p=.042) and G-allele of rs3828942 (p=.032) were associated with higher weight gain.. Our study supports the hypothesis of an impact of LEP gene variation on AIWG. Limitations of our study include heterogeneous samples, short treatment duration and multiple comparisons. Our findings were compared to previous studies in detail in order to provide the readers with a more conclusive picture. However, further studies are warranted including more gene variants and interaction analyses with other genes of the leptin-melanocortin pathway.

Topics: Adult; Alleles; Antipsychotic Agents; Female; Gene-Environment Interaction; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Leptin; Male; Middle Aged; Polymorphism, Genetic; Receptors, Leptin; Schizophrenia; Weight Gain

We aimed to assess the mechanisms responsible for hyperphagia and metabolic alterations caused by maternal moderate caloric restriction during gestation. Male and female offspring of control and 20% caloric-restricted rats (CR) were studied. They were fed a normal-fat diet until 4 months of age and then moved to a high-fat diet until 6 months of age. Blood parameters and expression of selected genes in hypothalamus, retroperitoneal white adipose tissue (rWAT) and liver were analyzed at 25 days and 6 months of age. Plasma leptin was measured during suckling. Levels of proteins involved in insulin and leptin signaling were determined at 6 months of age. CR ate more calories than controls, but only males gained more weight. A peak in plasma leptin was found in 9-day-old controls, but was absent in CR. Twenty-five-day-old CR showed lower insulin receptor mRNA levels in hypothalamus, rWAT and liver, and long-form leptin receptor (ObRb) in hypothalamus. At the age of 6 months, homeostatic model assessment for insulin resistance index was higher in CR than controls, and CR males also displayed hyperleptinemia. Adult CR also showed lower ObRb mRNA levels in the hypothalamus (only females, but both showed altered neuropeptide Y/proopiomelanocortin mRNA ratio), rWAT and liver (males), and a decrease of protein kinase C zeta levels in rWAT (females) and liver (males) and of phosphorylated signal transducer and activator of transcription 3 in liver (females). These results suggest that CR animals are programmed for insulin and central leptin resistance, which may explain the dysregulation of appetite and other metabolic alterations, favoring obesity development, although only manifested in males. These early programming effects could be associated with the absence of leptin surge during lactation.

Topics: Adipose Tissue, White; Animals; Animals, Newborn; Caloric Restriction; Eating; Fasting; Female; Gene Expression; Hypothalamus; Insulin Resistance; Lactation; Leptin; Liver; Male; Maternal Nutritional Physiological Phenomena; Neuropeptide Y; Pregnancy; Pro-Opiomelanocortin; Rats; Receptor, Insulin; Receptors, Leptin; Weight Gain

Both overnutrition and an incorrect nutrient balance have contributed to the rise in obesity. Moreover, it is now clear that poor nutrition during early life augments the possibility of excess weight gain in later years. Our aim was to determine how neonatal overnutrition affects later responses to a sucrose-enriched diet and whether this varies depending upon when the diet is introduced in postnatal life. Male Wistar rats raised in litters of four or 12 pups were given a 33% sucrose solution instead of water from weaning (day 21) or postnatal day (PND) 65. All rats received normal chow ad libitum until they were euthanized on PND 80. Body weight (BW) and food and liquid intake were monitored throughout the study. Fat mass, adipocyte morphology, serum biochemical and hormonal parameters, and hypothalamic neuropeptide mRNA levels were measured at study termination. Neonatal overnutrition increased food intake, BW, and leptin levels, induced adipocyte hypertrophy, and decreased total ghrelin levels. The sucrose-enriched diet increased total energy intake, adipose accrual, and leptin, adiponectin, and acylated ghrelin levels but decreased BW. Most of these responses were accentuated in neonatally overnourished rats, which also had increased insulin and triglyceride levels. However, long-term sucrose intake induced adipocyte hypertrophy in rats from normal-sized litters but not in neonatally overfed rats. The results reported here indicate that neonatal overnutrition increases the detrimental response to a diet rich in sucrose later in life. Moreover, the timing and duration of the exposure to a sucrose-enriched diet alter the adverse metabolic outcomes.

Topics: Adiponectin; Adipose Tissue; Animals; Animals, Newborn; Blood Proteins; Body Composition; Cholesterol; Corticosterone; Diet; Dietary Sucrose; Eating; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Nonesterified; Female; Ghrelin; Glucose Tolerance Test; Glycerol; Insulin; Leptin; Male; Overnutrition; Pregnancy; Radioimmunoassay; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Weight Gain

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

At puberty, type 1 diabetes (T1D) among young girls can lead to excess body weight, insulin resistance, deterioration of glycaemic control and dyslipidaemia. Although biological factors contribute largely to such metabolic dysfunction, little is known of the role of behavioural factors such as physical activity and diet.. This study investigated the association between metabolic dysfunction measured after a 12-h overnight fast and behavioural factors, including diet (4-day diary) and physical activity (validated questionnaire), in 19 postmenarchal adolescent girls with T1D compared with 19 healthy girls.. T1D girls displayed higher levels of fat mass, insulin resistance (higher plasma glucose, serum leptin and waist-to-hip ratios) and dyslipidaemia (higher LDL-C and apolipoprotein B levels, lower HDL-C and apolipoprotein A-1 levels). Also, contrary to what is usually observed in T1D adults, serum adiponectin, an important vessel protector, was not raised in T1D adolescent girls compared with healthy controls. Quantity and quality of dietary macronutrient intakes as well as physical activity levels were comparable in both groups, although the T1D girls with the poorest metabolic profiles reported having the healthiest diets (fewer total calories, more protein and less carbohydrates). However, in T1D girls, less physical activity and more time spent watching television were associated with poorer metabolic profiles (higher waist-to-hip ratios, fat mass and leptin levels, and lower adiponectin, HDL-C and apolipoprotein A-1 levels).. Collectively, these data suggest that physical inactivity is linked to metabolic dysfunction to a greater extent than unhealthy dietary habits in postmenarchal T1D adolescent girls.

Topics: Adolescent; Adolescent Behavior; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Diet Records; Energy Intake; Exercise; Fasting; Feeding Behavior; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Leptin; Menarche; Overweight; Quality of Life; Risk Factors; Surveys and Questionnaires; Waist-Hip Ratio; Weight Gain

The G protein-coupled receptor 83 (GPR83) was recently demonstrated in warm sensitive neurons (WSN) of the hypothalamic preoptic area (POA) that participate in temperature homeostasis. Thus, we investigated whether GPR83 may have a role in regulating core body temperature (CBT) by reducing its expression in the POA. Dissipation of energy in the form of heat is the primary mode of energy expenditure in mammals and can ultimately affect energy homeostasis. Thus, we also measured the level of important regulators of metabolism. Downregulation of GPR83 was obtained by lentiviral short-hairpin RNAs (shGPR83) vectors designed and selected for their ability to reduce GPR83 levels in vitro. Mice received POA injection of shGPR83 or non-silencing vectors and were monitored for CBT, motor activity, food intake body weight and circulating levels of IGF-1, insulin, leptin and adiponectin. Down-regulation of GPR83 in the POA resulted in a small (0.15°C) but significant reduction of CBT during the dark/active cycle of the day. Temperature reduction was followed by increased body weight gain independent of caloric intake. shGPR83 mice also had increased level of circulating adiponectin (31916±952 pg/mL vs. 23474±1507 pg/mL, P<.01) while no change was observed for insulin, IGF-1 or leptin. GPR83 may participate in central thermoregulation and the central control of circulating adiponectin. Further work is required to determine how GPR83 can affect POA WSN and what are the long term metabolic consequences of its down-regulation.

Topics: Adiponectin; Amino Acid Sequence; Animals; Base Sequence; Body Temperature Regulation; Down-Regulation; Insulin-Like Growth Factor I; Leptin; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Preoptic Area; Receptors, G-Protein-Coupled; RNA, Small Interfering; Weight Gain

The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns.

Topics: Adipogenesis; Adiponectin; Adipose Tissue, White; Animals; Gene Expression Regulation; Genetic Markers; Leptin; Lipogenesis; Lipolysis; Male; Mice; Mice, Inbred C57BL; Physical Conditioning, Animal; Weight Gain

There is evidence that some atypical antipsychotics, including olanzapine, can produce unwanted metabolic side effects, weight gain and diabetes. However, neuronal correlates of change related to food information processing have not been investigated with these medications. We studied the effect of a pharmacological manipulation with an antipsychotic known to cause weight gain on metabolites, cognitive tasks and neural correlates related to food regulation. We used functional magnetic resonance imaging in conjunction with a task requiring visual processing of appetitive stimuli in schizophrenic patients and healthy controls before and after 16 weeks of antipsychotic medication with olanzapine. In patients, the psychological and neuronal changes associated following the treatment correlated with appetite control measures and metabolite levels in fasting blood samples. After 16 weeks of olanzapine treatment, the patients gained weight, increased their waist circumference, had fewer positive schizophrenia symptoms, a reduced ghrelin plasma concentration and an increased concentration of triglycerides, insulin and leptin. In premotor area, somatosensory cortices as well as bilaterally in the fusiform gyri, the olanzapine treatment increased the neural activity related to appetitive information in schizophrenic patients to similar levels relative to healthy individuals. However, a higher increase in sensitivity to appetitive stimuli after the treatment was observed in insular cortices, amygdala and cerebellum in schizophrenic patients as compared with healthy controls. Furthermore, these changes in neuronal activity correlated with changes in some metabolites and cognitive measurements related to appetite regulation.

Topics: Adult; Antipsychotic Agents; Appetite; Benzodiazepines; Brain Mapping; Case-Control Studies; Female; Ghrelin; Humans; Insulin; Leptin; Magnetic Resonance Imaging; Male; Neurons; Olanzapine; Schizophrenia; Statistics, Nonparametric; Weight Gain

Blockade of opioidergic neurotransmission contributes to reduction in body weight. However, how such blockade affects body weight gain (BWG) attributed to second generation antipsychotic agents (SGAs) has not yet been established. Here we examined the effects of an opioid receptor antagonist, naltrexone (NTX), on food intake and BWG associated with an SGA, olanzapine (OL). Four groups of Wistar Han IGS rats were treated for 28 days with either OL (2 mg/kg twice daily, intraperitoneal (IP)), a combination of OL (2 mg/kg twice daily, IP) + extended-release NTX (50 mg/kg, one-time, intramuscular (IM)), extended-release NTX (50 mg/kg, one-time, IM) or vehicle and their food intake and body weight were measured daily for the first nine days and every other day thereafter. Food intake and BWG that were increased by OL were decreased by the added NTX while NTX alone had no significant effects on food intake or on BWG. Plasma leptin concentrations were significantly elevated in the three groups receiving pharmacological agents, but did not differ among each other, suggesting that changes in leptin secretion and/or clearance alone would not explain the food intake and the body weight findings. Our results extend prior reports on anorexigenic effects of opioid antagonists by demonstrating that such effects may generalize to food intake increases and BWG arising in the context of OL pharmacotherapy.

Topics: Animals; Antipsychotic Agents; Appetite Depressants; Appetite Regulation; Behavior, Animal; Benzodiazepines; Delayed-Action Preparations; Drug Interactions; Energy Intake; Feeding Behavior; Female; Injections, Intramuscular; Injections, Intraperitoneal; Leptin; Naltrexone; Narcotic Antagonists; Olanzapine; Random Allocation; Rats; Rats, Wistar; Weight Gain

Olanzapine, an atypical antipsychotic drug with affinities for dopamine, serotonin, and histamine binding sites appears to be associated with substantial weight gain and metabolic alterations. The aim of this study was to evaluate weight gain and metabolic alterations in rats treated with olanzapine on a hypercaloric diet.. We used 40 rats divided into 4 groups: Group 1, standard food and water conditions (control); Group 2, standard diet plus olanzapine; Group 3, cafeteria diet (hypercaloric); and Group 4, olanzapine plus cafeteria diet. Olanzapine was administered by gavage at a dose of 3 mg/kg for 9 weeks. RESULTS There were no significant changes in the cholesterol levels in any group. Glucose levels increased in Group 3 by the fourth week. Triglyceride levels were altered in group 2 toward the end of the experiment. Leptin levels decreased in Groups 2 and 4. Complex II activity in the muscles and liver was altered in Group 2 (muscle), and Groups 2, 3, and 4 (liver). Complex IV activity was altered only in the liver in Group 2, without significant alterations within the muscles.. These results suggest that olanzapine is correlated with weight gain and the risks associated with obesity.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Energy Metabolism; Leptin; Male; Olanzapine; Random Allocation; Rats; Rats, Wistar; Weight Gain

The link between obesity, hyperleptinemia, and development of cardiovascular disease is not completely understood. Increases in leptin have been shown to impair leptin signaling via caveolin-1-dependent mechanisms. However, the role of hyperleptinemia versus impaired leptin signaling in adipose tissue is not known.. To determine the presence and significance of leptin-dependent increases in adipose tissue caveolin-1 expression in humans.. We designed a longitudinal study to investigate the effects of increases in leptin on adipose tissue caveolin-1 expression during weight gain in humans. Ten volunteers underwent 8 weeks of overfeeding, during which they gained an average weight of 4.1±1.4 kg, with leptin increases from 7±3.8 to 12±5.7 ng/mL. Weight gain also resulted in changes in adipose tissue caveolin-1 expression, which correlated with increases in leptin (rho=0.79, P=0.01). In cultured human white preadipocytes, leptin increased caveolin-1 expression, which in turn impaired leptin cellular signaling. Functionally, leptin decreased lipid accumulation in differentiating human white preadipocytes, which was prevented by caveolin-1 overexpression. Further, leptin decreased perilipin and fatty acid synthase expression, which play an important role in lipid storage and biogenesis.. In healthy humans, increases in leptin, as seen with modest weight gain, may increase caveolin-1 expression in adipose tissue. Increased caveolin-1 expression in turn impairs leptin signaling and attenuates leptin-dependent lowering of intracellular lipid accumulation. Our study suggests a leptin-dependent feedback mechanism that may be essential to facilitate adipocyte lipid storage during weight gain.

Topics: Adipocytes, White; Adipose Tissue, White; Adult; Caveolin 1; Cells, Cultured; Feedback, Physiological; Female; Humans; Hyperphagia; Leptin; Lipid Metabolism; Longitudinal Studies; Male; Signal Transduction; Stem Cells; Weight Gain; Young Adult

GSK3β (glycogen synthase kinase 3β) is a ubiquitous kinase that plays a key role in multiple intracellular signalling pathways, and increased GSK3β activity is implicated in disorders ranging from cancer to Alzheimer's disease. In the present study, we provide the first evidence of increased hypothalamic signalling via GSK3β in leptin-deficient Lep(ob/ob) mice and show that intracerebroventricular injection of a GSK3β inhibitor acutely improves glucose tolerance in these mice. The beneficial effect of the GSK3β inhibitor was dependent on hypothalamic signalling via PI3K (phosphoinositide 3-kinase), a key intracellular mediator of both leptin and insulin action. Conversely, neuron-specific overexpression of GSK3β in the mediobasal hypothalamus exacerbated the hyperphagia, obesity and impairment of glucose tolerance induced by a high-fat diet, while having little effect in controls fed standard chow. These results demonstrate that increased hypothalamic GSK3β signalling contributes to deleterious effects of leptin deficiency and exacerbates high-fat diet-induced weight gain and glucose intolerance.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Base Sequence; Diet, High-Fat; DNA Primers; Eating; Glucose; Glucose Intolerance; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Humans; Hypothalamus; Leptin; Male; Mice; Mice, Knockout; Obesity; Signal Transduction; Weight Gain

In addition to contemporary lifestyle factors that contribute to the increased obesity prevalence worldwide, early nutrition is associated with sustained effects on later life obesity. We hypothesized that physical properties of dietary lipids contribute to this nutritional programming. We developed a concept infant formula (IMF) with large, phospholipid-coated lipid droplets (Nuturis; Danone Research, Paris, France) and investigated its programming effect on metabolic phenotype later in life.. Male C57Bl/6j mice were fed a control formula (Control IMF) or Nuturis (Concept IMF) diet between postnatal day (PN)16 and PN42. All mice were subsequently fed a Western-style diet (WSD) until PN126. Body composition was monitored repeatedly by dual-energy X-ray absorptiometry between PN42 and PN126.. Concept IMF slightly increased lean body mass as compared with Control IMF at PN42 but did not affect fat mass. Upon 84 d of WSD feeding, the Concept IMF group showed reduced fat accumulation as compared with Control IMF. In addition, fasting plasma leptin, resistin, glucose, and lipids were significantly lower in the Concept IMF group.. Large phospholipid-coated lipid droplets in young mice reduced fat accumulation and improved metabolic profile in adulthood. These data emphasize that physical properties of early dietary lipids contribute to metabolic programming.

Topics: Absorptiometry, Photon; Adiposity; Aging; Animal Nutritional Physiological Phenomena; Animals; Biomarkers; Blood Glucose; Dietary Fats; Eating; Fasting; Humans; Infant; Infant Formula; Leptin; Male; Mice; Mice, Inbred C57BL; Nutritional Status; Particle Size; Phospholipids; Resistin; Weight Gain

We observed whether the anti-obesity activity of yeast hydrolysate (YH) was due to the alteration of lipid-regulating enzyme activities.. Male ICR mice were divided into four groups: a normal diet group (ND; 4.2% fat), a high-fat diet group (HF; 27.7% fat), an HF group treated orally with 0.5% or 1% YH in the drinking water (HF+YH0.5; 27.7% fat and HF+YH1; 27.7% fat).. After 5 weeks, the YH groups (HF+YH0.5=3.92±0.17 g/100 g BW and HF+YH1=3.76±0.13 g/100 g BW) had significantly lower levels of epididymal fats compared to the HF group (4.91±0.29 g/100 g BW; p<0.05). YH supplementation produced a decrease in serum triglycerides and low-density lipoprotein cholesterol concentrations and body weight gain, and produced a dose-dependent significant increase in serum ghrelin compared with the HF group (p<0.05). Hepatic glucose-6-phosphate dehydrogenase (G6PD) activity was inhibited by YH supplementation compared with the HF group, and mice treated orally with 1% YH exhibited a significant decrease in hepatic malic enzyme (ME) activity compared to obese mice treated with the vehicle (HF=10.44±2.74 nmol/min/mg protein vs. HF+YH1=6.68±2.23 nmol/min/mg protein; p<0.05).. YH supplementation suppressed body fat accumulation by attenuating fatty acid synthesis through the downregulation of hepatic G6PD and ME activities.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Cholesterol, LDL; Diet, High-Fat; Down-Regulation; Ghrelin; Glucosephosphate Dehydrogenase; Leptin; Lipid Metabolism; Lipogenesis; Liver; Malate Dehydrogenase; Male; Mice; Mice, Inbred ICR; Protein Hydrolysates; Triglycerides; Weight Gain; Yeasts

The purpose of this study was to evaluate whether conjugated linoleic acid (CLA) exposure during the developmental period increases voluntary activity, which would influence obesity outcome later in life. The effects of dietary supplementation of 0.5% CLA in a high fat diet were evaluated in nescient basic helix-loop-helix 2 (Nhlh2) knock-out (N2KO) mice, which is a unique animal model representing inactivity-induced obesity in a pre-obese condition. Male wild type and N2KO mice were fed either control or CLA (0.5%) diet for 8 weeks. As expected, control diet fed N2KO animals showed greater body weight with decreased physical activity in the late stage of the experimental period compared with wild type control. Dietary CLA significantly decreased body weight and adipose depots in both wild type and N2KO mice, and the body weights of both genotypes fed CLA were similar during the experimental period. CLA exposure during the developmental period significantly improved the impairment of physical activity in N2KO mice, but the wild type did not show any effect of CLA. In both genotypes, CLA significantly reduced serum triglycerides levels and down-regulated the mRNA expressions of CCAAT/enhancer binding protein α (C/EBPα) and leptin in white adipose tissue. These findings suggest that early CLA exposure could prevent obesity with improved voluntary physical activity in N2KO mice.

Topics: Adiposity; Animals; Basic Helix-Loop-Helix Transcription Factors; CCAAT-Enhancer-Binding Protein-alpha; Down-Regulation; Leptin; Linoleic Acids, Conjugated; Male; Mice; Mice, Knockout; Obesity; Physical Exertion; RNA, Messenger; Triglycerides; Weight Gain

Environmental factors, such as photoperiod and temperature, play an important role in the regulation of an animal's physiology and behavior. In the present study, we examined the effects of short photoperiod (SD, 8L:16D) on body mass as well as on several physiological, hormonal, and biochemical measures indicative of thermogenic capacity, to test our hypothesis that short photoperiod stimulates increases thermogenic capacity and energy intake in tree shrews. At the end, these tree shrews (SD) had a significant higher body mass, energy intake, cytochrome C oxidase (COX) activity and uncoupling protein-1 (UCP1) content, serum tri-iodothyronine (T(3)) and thyroxine (T(4)) compared to LD (16L:8D) tree shrews. However, there were no significant differences in serum leptin and melatonin between the two groups. Together, these data suggest tree shrews employ a strategy of maximizing body growth and increasing energy intake in response to cues associated with short photoperiod.

Topics: Adaptation, Physiological; Adipose Tissue, Brown; Animals; Basal Metabolism; Body Composition; Cell Respiration; Electron Transport Complex IV; Energy Intake; Ion Channels; Leptin; Male; Melatonin; Mitochondria; Mitochondrial Proteins; Organ Size; Photoperiod; Seasons; Thermogenesis; Tupaiidae; Uncoupling Protein 1; Weight Gain

Chronic partial sleep loss is associated with obesity and metabolic syndrome in humans. We used rats with lesions in the ventrolateral preoptic area (VLPO), which spontaneously sleep about 30% less than intact rats, as an animal model to study the consequences of chronic partial sleep loss on energy metabolism.. Adult male Sprague-Dawley rats (300-365 g).. We ablated the VLPO in rats using orexin-B-saporin and instrumented them with electrodes for sleep recordings. We monitored their food intake and body weight for the next 60 days and assessed their sleep-wake by 24-h EEG/EMG recordings on day 20 and day 50 post-surgery. On day 60, after blood samples were collected for metabolic profiling, the animals were euthanized and the brains were harvested for histological confirmation of the lesion site.. VLPO-lesioned animals slept up to 40% less than sham-lesioned rats. However, they showed slower weight gain than sham-lesioned controls, despite having normal food intake. An increase in plasma ghrelin and a decrease in leptin levels were observed, whereas plasma insulin levels remained unaffected. As expected from leaner animals, plasma levels of glucose, cholesterol, triglycerides, and C-reactive protein were reduced in VLPO-lesioned animals.. Chronic partial sleep loss did not lead to obesity or metabolic syndrome in rats. This finding raises the question whether adverse metabolic outcomes associated with chronic partial sleep loss in humans may be due to factors other than short sleep, such as circadian disruption, inactivity, or diet during the additional waking hours.

Topics: Animals; Blood Glucose; Body Weight; C-Reactive Protein; Energy Metabolism; Ghrelin; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Obesity; Rats; Sleep Deprivation; Weight Gain

Maternal deprivation (MD) during neonatal life has diverse long-term effects, including affectation of metabolism. Indeed, MD for 24 hours during the neonatal period reduces body weight throughout life when the animals are maintained on a normal diet. However, little information is available regarding how this early stress affects the response to increased metabolic challenges during postnatal life. We hypothesized that MD modifies the response to a high fat diet (HFD) and that this response differs between males and females. To address this question, both male and female Wistar rats were maternally deprived for 24 hours starting on the morning of postnatal day (PND) 9. Upon weaning on PND22 half of each group received a control diet (CD) and the other half HFD. MD rats of both sexes had significantly reduced accumulated food intake and weight gain compared to controls when raised on the CD. In contrast, when maintained on a HFD energy intake and weight gain did not differ between control and MD rats of either sex. However, high fat intake induced hyperleptinemia in MD rats as early as PND35, but not until PND85 in control males and control females did not become hyperleptinemic on the HFD even at PND102. High fat intake stimulated hypothalamic inflammatory markers in both male and female rats that had been exposed to MD, but not in controls. Reduced insulin sensitivity was observed only in MD males on the HFD. These results indicate that MD modifies the metabolic response to HFD intake, with this response being different between males and females. Thus, the development of obesity and secondary complications in response to high fat intake depends on numerous factors.

Topics: Animals; Animals, Newborn; Blood Glucose; Body Weight; Diet, High-Fat; Eating; Environment; Female; Insulin; Leptin; Male; Maternal Deprivation; Neuropeptide Y; Obesity; Rats; Rats, Wistar; Sex Characteristics; Triglycerides; Weaning; Weight Gain

Phenolic compounds and flavonoids ameliorate bodyweight, blood glucose, and serum lipid profile. Since seabuckthorn (Hippophae rhamnoides L.) is known as a rich source of isoflavones and flavonoids, we hypothesized that ethanolic extract of seabuckthorn leaves (SL) may have anti-obesity and hypoglycemic effects. To investigate the effect of ethanolic extract of SL, 32 C57BL/6J mice were randomly divided into 4 dietary groups, containing 8 mice in each group: normal diet group; high-fat diet (HD) control group; high-fat diet with SL extract, 500 mg/kg body weight (BW) (SL1) group; and high-fat diet with SL extract, 1000 mg/kg BW (SL2) group. After 13 weeks, it was observed that oral administration of SL extract significantly reduced the energy intake; BW gain; epididymal fat pad weight; hepatic triglyceride, hepatic, and serum total cholesterol levels; and serum leptin levels in the SL groups compared to the HD group. However, differences in serum triglyceride and insulin levels in the SL groups were not significant in comparison to the HD group. The hepatic mRNA expression of peroxisome proliferator-activated receptor (PPAR) α and carnitine palmitoyltransferase 1 along with PPAR-γ were significantly increased in SL groups, whereas the level of acetyl-CoA carboxylase was significantly reduced in SL groups compared to HD group. Our results indicated that SL is effective in preventing BW gain and fat accumulation in the liver; it also reduced adipose tissue mass, hepatic lipid profile, and serum leptin level in the mouse. Together, these observations suggest that SL is a potential agent to study in the management of obesity and related disorders.

Topics: Acetyl-CoA Carboxylase; Adipogenesis; Adipose Tissue; Administration, Oral; Animals; Anti-Obesity Agents; Carnitine O-Palmitoyltransferase; Cholesterol; Diet, High-Fat; Down-Regulation; Energy Intake; Flavonoids; Hippophae; Insulin; Leptin; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Phytotherapy; Plant Extracts; PPAR alpha; PPAR gamma; Random Allocation; RNA, Messenger; Triglycerides; Weight Gain

Considering the explosive increase in obesity worldwide, there must be an unknown mechanism(s) promoting energy accumulation under conditions of overnutrition. We identified a feed-forward mechanism favoring energy storage, originating in hepatic glucokinase (GK) upregulation. High-fat feeding induced hepatic GK upregulation, and hepatic GK overexpression dose-dependently decreased adaptive thermogenesis by downregulating thermogenesis-related genes in brown adipose tissue (BAT). This intertissue (liver-to-BAT) system consists of the afferent vagus from the liver and sympathetic efferents from the medulla and antagonizes anti-obesity effects of leptin on thermogenesis. Furthermore, upregulation of endogenous GK in the liver by high-fat feeding was more marked in obesity-prone than in obesity-resistant strains and was inversely associated with BAT thermogenesis. Hepatic GK overexpression in obesity-resistant mice promoted weight gain, while hepatic GK knockdown in obesity-prone mice attenuated weight gain with increased adaptive thermogenesis. Thus, this intertissue energy-saving system may contribute to determining obesity predisposition.

Topics: Adipose Tissue, Brown; Animals; Diet, High-Fat; Glucokinase; Glycogen; Leptin; Liver; Mice; Mice, Inbred C57BL; Neurons; Obesity; RNA Interference; RNA, Small Interfering; Signal Transduction; Thermogenesis; Up-Regulation; Weight Gain

Organotin compounds such as tributyltin (TBT) have been used worldwide in agriculture and industry as biocides, heat stabilizers, and chemical catalysts. However, few studies addressing the effects of TBT on growth and metabolism have been reported. This study was conducted to investigate the effects of TBT at low doses (0.5, 5, and 50 μg/kg) on body weight gain in male mice exposed as from puberty and to determine the alterations in related hormones. The results showed that exposure to TBT for 45 days resulted in an increase in body weight gain and hepatic steatosis accompanied with hyperinsulinemia and hyperleptinemia. Reduction of hepatic adiponectin levels in a dose-dependent manner was related to the lipid increase in the liver. These results suggest that chronic and repeat exposure to low doses of TBT can result in obesity and hepatic steatosis and induce the occurrence of insulin and leptin resistance.

Topics: Adipose Tissue; Animals; Dose-Response Relationship, Drug; Environmental Pollutants; Fatty Liver; Growth and Development; Hormones; Hyperinsulinism; Leptin; Liver; Male; Mice; Obesity; Trialkyltin Compounds; Weight Gain

Hyperprolactinemia might be related to weight gain, metabolic syndrome (MS), and insulin resistance (IR). Treatment with dopamine agonist (DA) has been shown to reduce body weight and improve metabolic parameters. The objectives of this study were to determine the prevalence of obesity, overweight, MS, and IR in patients with prolactinoma before and after therapy with DA and to evaluate the relation between prolactin (PRL), body weight, fat distribution, leptin levels, IR, and lipid profile before treatment. In addition, we investigated the correlation of the reduction in PRL levels with weight loss and metabolic profile improvement. Twenty-two patients with prolactinoma completed 6 months of treatment with DA. These patients were submitted to clinical (BMI, waist circumference, blood pressure (BP)), laboratory evaluation (leptin, glucose, low-density lipoprotein (LDL)-cholesterol, and triglyceride (TG) levels) and abdominal computed tomography (CT) before and after treatment. The statistical analyses were done by nonparametric tests. At the beginning of the study, the prevalence of obesity, overweight, MS, and IR was 45, 27, 27, and 18%, respectively. After 6 months of treatment with DA, PRL levels normalized, but no significant difference in BMI was observed. However, there was a significant decrease on homeostasis model assessment of insulin resistance (HOMA(IR)) index, glucose, LDL-cholesterol, and TG levels. This study suggests a possible involvement of prolactinoma on the prevalence of obesity. We should consider that DA may be effective on improving metabolic parameters, and we speculate that a period longer than 6 months of treatment is necessary to conclude whether this drug can interfere in the body weight of patients with prolactinoma.

Topics: Adult; Aftercare; Aged; Blood Glucose; Body Composition; Body Mass Index; Body Weight; Bromocriptine; Cabergoline; Cholesterol, HDL; Cholesterol, LDL; Dopamine Agonists; Ergolines; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Metabolome; Middle Aged; Obesity; Prevalence; Prolactinoma; Waist Circumference; Weight Gain; Young Adult

To determine the extent to which known prenatal and perinatal predictors of childhood obesity also predict weight gain in early infancy.. We studied 690 infants participating in the prospective cohort Project Viva. We measured length and weight at birth and at 6 months. Using multivariable linear regression, we examined relationships of selected maternal and infant factors with change in weight-for-length z-score (WFL-z) from 0 to 6 months.. Mean (standard deviation) change in WFL-z from 0 to 6 months was 0.23 (1.11), which translates to 4500 grams gained from birth to 6 months of life in an infant with average birth weight and length. After adjustment for confounding variables and birth weight-for-gestational age z-score (-0.28 [95% confidence interval, -0.37, -0.19] per unit), cord blood leptin (-0.40 [95%confidence interval, -0.61, -0.19] per 10 ng/mL), and gestational diabetes -0.50 [95%confidence interval, -0.88, -0.11] versus normal glucose tolerance)were each associated with slower gain in WFL-z from 0 to 6 months.. Higher neonatal leptin and gestational diabetes predicted slower weight gain in the first 6 months of life. The hormonal milieu of the intrauterine environment may determine growth patterns in early infancy and thus later obesity.

Topics: Biomarkers; Blood Glucose; Body Height; Body Mass Index; Child Development; Cohort Studies; Confidence Intervals; Diabetes, Gestational; Female; Fetal Blood; Follow-Up Studies; Gestational Age; Glucose Intolerance; Glucose Tolerance Test; Humans; Infant; Infant, Newborn; Leptin; Male; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Pregnancy; Prospective Studies; Regression Analysis; Sensitivity and Specificity; Time Factors; Weight Gain

Diabetic obesity is associated with increased fracture risk in adults and adolescents. We find in both adolescent and adult mice dramatically inferior mechanical properties and structural quality of cortical bone, in agreement with the human fracture data, although some aspects of the response to obesity appear to differ by age.. The association of obesity with bone is complex and varies with age. Diabetic obese adolescents and adult humans have increased fracture risk. Prior studies have shown reduced mechanical properties as a result of high-fat diet (HFD) but do not fully address size-independent mechanical properties or structural quality, which are important to understand material behavior.. Cortical bone from femurs and tibiae from two age groups of C57BL/6 mice fed either HFD or low-fat diet (LFD) were evaluated for structural and bone turnover changes (SEM and histomorphometry) and tested for bending strength, bending stiffness, and fracture toughness. Leptin, IGF-I, and non-enzymatic glycation measurements were also collected.. In both young and adult mice fed on HFD, femoral strength, stiffness, and toughness are all dramatically lower than controls. Inferior lamellar and osteocyte alignment also point to reduced structural quality in both age groups. Bone size was largely unaffected by HFD, although there was a shift from increasing bone size in obese adolescents to decreasing in adults. IGF-I levels were lower in young obese mice only.. While the response to obesity of murine cortical bone mass, bone formation, and hormonal changes appear to differ by age, the bone mechanical properties for young and adult groups are similar. In agreement with human fracture trends, adult mice may be similarly susceptible to bone fracture to the young group, although cortical bone in the two age groups responds to diabetic obesity differently.

Topics: Aging; Animals; Biomechanical Phenomena; Blood Glucose; Body Composition; Bone and Bones; Bone Density; Diabetes Mellitus, Experimental; Diet, High-Fat; Femur; Glycation End Products, Advanced; Insulin-Like Growth Factor I; Leptin; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Obesity; Osteoporotic Fractures; Tibia; Weight Gain

Weight gain is a well-known unwanted effect of valproic acid (VPA) therapy. Studies on VPA-associated changes of homeostatic hormones remain limited and controversial. Allopregnanolone (AP) is a circulating neuroactive steroid involved in modulation of behavioral activities whose serum levels are increased in obese children. The aim of the present study was to determine whether VPA therapy affects leptin and AP circulating levels in prepubertal girls with epilepsy. One-hundred and one patients were divided into four groups: epileptic patients with VPA-associated obesity (n = 21); lean epileptic patients under VPA therapy (n = 35); healthy obese children (n = 23), and healthy lean children (n = 22). Patients with VPA-associated obesity had significantly enhanced blood concentrations of AP (p = 0.001) and leptin (p = 0.007) than lean subjects. There were no differences in leptin and AP plasma levels between patients with VPA-associated obesity and obese controls (p = 0.45 and p = 0.10, respectively), as there were no differences between lean patients under VPA therapy and lean healthy controls (p = 0.06). In patients under VPA therapy, both plasma leptin and AP levels were significantly correlated with BMI (r = 0.074, p = 0.02, and r = 0.084, p = 0.01, respectively). Plasma leptin concentrations were not correlated with AP levels (r = 0.023, p = 0.13). In conclusion, a correlation between obesity and neuroactive steroids was shown. It remains to be established whether the increased circulating level of AP is a secondary effect of anxiolytic-sedative processes occurring in subjects with obesity-related emotional and behavioral anomalies, or plays a central role in determining abnormal eating behaviors.

Topics: Anticonvulsants; Child; Epilepsy; Female; Humans; Immunoassay; Leptin; Male; Obesity; Pregnanolone; Valproic Acid; Weight Gain

A recent population-based genome-wide association study has revealed that the Niemann-Pick C1 (NPC1) gene is associated with early-onset and morbid adult obesity. Concurrently, our candidate gene-based mouse growth study performed using the BALB/cJ NPC1 mouse model (Npc1) with decreased Npc1 gene dosage independently supported these results by suggesting an Npc1 gene-diet interaction in relation to early-onset weight gain. To further investigate the Npc1 gene in relation to weight gain and metabolic features associated with insulin resistance, we interbred BALB/cJ Npc1(+/-) mice with wild-type C57BL/6J mice, the latter mouse strain commonly used to study aspects of diet-induced obesity and insulin resistance. This breeding produced a hybrid (BALB/cJ-C57BL/6J) Npc1(+/-) mouse model with increased susceptibility to weight gain and insulin resistance. The results from our study indicated that these Npc1(+/-) mice were susceptible to increased weight gain characterized by increased whole body and abdominal adiposity, adipocyte hypertrophy and hepatic steatosis in the absence of hyperphagia. Moreover, these Npc1(+/-) mice developed abnormal metabolic features characterized by impaired fasting glucose, glucose intolerance, hyperinsulinemia, hyperleptinemia and dyslipidemia marked by an increased concentration of cholesterol and triacylglycerol associated with low-density lipoprotein and high-density lipoprotein. The overall results are consistent with a unique Npc1 gene-diet interaction that promotes both weight gain and metabolic features associated with insulin resistance. Therefore, the NPC1 gene now represents a previously unrecognized gene involved in maintaining energy and metabolic homeostasis that will contribute to our understanding concerning the current global epidemic of obesity and type 2 diabetes mellitus.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Diet; Disease Models, Animal; Fatty Liver; Haploinsufficiency; Humans; Insulin; Insulin Resistance; Intracellular Signaling Peptides and Proteins; Leptin; Magnetic Resonance Imaging; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Niemann-Pick C1 Protein; Proteins; Triglycerides; Weight Gain

Leptin, the product of the Lep gene, reports levels of adiposity to the hypothalamus and other regulatory cells, including pituitary somatotropes, which secrete GH. Leptin deficiency is associated with a decline in somatotrope numbers and function, suggesting that leptin may be important in their maintenance. This hypothesis was tested in a new animal model in which exon 17 of the leptin receptor (Lepr) protein was selectively deleted in somatotropes by Cre-loxP technology. Organ genotyping confirmed the recombination of the floxed LepR allele only in the pituitary. Deletion mutant mice showed a 72% reduction in pituitary cells bearing leptin receptor (LEPR)-b, a 43% reduction in LEPR proteins and a 60% reduction in percentages of immunopositive GH cells, which correlated with reduced serum GH. In mutants, LEPR expression by other pituitary cells was like that of normal animals. Leptin stimulated phosphorylated Signal transducer and activator of transcription 3 expression in somatotropes from normal animals but not from mutants. Pituitary weights, cell numbers, IGF-I, and the timing of puberty were not different from control values. Growth curves were normal during the first 3 months. Deletion mutant mice became approximately 30-46% heavier than controls with age, which was attributed to an increase in fat mass. Serum leptin levels were either normal in younger animals or reflected the level of obesity in older animals. The specific ablation of the Lepr exon 17 gene in somatotropes resulted in GH deficiency with a consequential reduction in lipolytic activity normally maintained by GH and increased adiposity.

Topics: Absorptiometry, Photon; Alleles; Animals; Body Composition; Energy Metabolism; Female; Gene Expression Regulation; Insulin; Integrases; Leptin; Male; Mice; Obesity; Pituitary Gland; Pituitary Hormones; Receptors, Leptin; Weight Gain

Obesity is a complex genetic and behavioural disorder arising from the improper integration of peripheral signals at central autonomic centres. For the hypothalamus to respond to dynamic physiological alterations, it must retain a degree of plasticity throughout life. Evidence is mounting that an intricate balance between matrix metalloproteinase (MMP)-mediated extracellular matrix proteolysis and tissue inhibitor of metalloproteinase (TIMP)-mediated proteolysis inhibition contributes to tissue remodelling. However, few studies have examined the role of MMPs/TIMPs in hypothalamic remodelling and energy homeostasis. To determine the contribution of TIMP-2 to the hypothalamic regulation of feeding, body mass and food consumption were monitored in TIMP-2 knockout (KO) mice fed a standard chow or high-fat diet (HFD). TIMP-2 KO mice of both sexes gained more weight than wild-type (WT) mice, even when fed the chow diet. Before the onset of obesity, TIMP-2 KO mice were hyperphagic, without increased orexigenic or decreased anorexigenic neuropeptide expression, but leptin resistant (i.e. reduced leptin-induced anorexigenic response and signal transducer and activator of transcription 3 activation). HFD exacerbated weight gain and hyperleptinaemia. In addition, proteolysis was increased in the arcuate nucleus of TIMP-2 KO mice. These data suggest a role for TIMP-2 in hypothalamic control of feeding and energy homeostasis.

Topics: Animals; Appetite Regulation; Diet; Drug Resistance; Eating; Energy Metabolism; Extracellular Matrix; Female; Hyperphagia; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein Processing, Post-Translational; Tissue Inhibitor of Metalloproteinase-2; Weight Gain

OBJECTIVES - Determine whether bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson's disease (PD) is associated with an increase in neuropeptide Y (NPY) and/or resistance to inhibition by leptin in relation to post-surgery weight gain. MATERIALS AND METHODS - This prospective study included 20 patients who underwent bilateral STN-DBS and 17 who refused surgery. Data were obtained at baseline, 3 and 6 months on neurological and nutritional status, including determination of body mass index (BMI) and serum NPY and leptin levels. RESULTS -  NPY and leptin levels changed over time, with a distinct pattern. The BMI increase at 6 months was greater in the surgical group (5.5 ± 6.3% vs 0.5 ± 3.5%; P = 0.035). Medical group exhibited a reduction in leptin level (-2.0 ± 4.3 ng/ml) and a consequent increase in NPY level (72.4 ± 58.7 pmol/ml). However, STN-DBS patients showed an increase in leptin (3.1 ± 5.0 ng/ml; P = 0.001 vs medical group) and also in NPY (12.1 ± 53.6 pmol/ml; P = 0.022 vs medical group) levels, which suggests resistance to inhibition by leptin. Rise in NPY level correlated with higher stimulation voltages. CONCLUSIONS -  Bilateral STN-DBS causes disruption of the melanocortin system, probably related to diffusion of the electric current to the hypothalamus. This mechanism may in part explain the weight gain of patients with PD after surgery.

Topics: Aged; Body Mass Index; Electric Stimulation Therapy; Female; Humans; Leptin; Male; Melanocortins; Middle Aged; Neuropeptide Y; Parkinson Disease; Prospective Studies; Subthalamic Nucleus; Treatment Outcome; Weight Gain

Circadian (daily) rhythms are present in almost all plants and animals. In mammals, a brain clock located in the hypothalamic suprachiasmatic nucleus maintains synchrony between environmental light/dark cycles and physiology and behavior. Over the past 100 y, especially with the advent of electric lighting, modern society has resulted in a round-the-clock lifestyle, in which natural connections between rest/activity cycles and environmental light/dark cycles have been degraded or even broken. Instances in which rapid changes to sleep patterns are necessary, such as transmeridian air travel, demonstrate negative effects of acute circadian disruption on physiology and behavior. However, the ramifications of chronic disruption of the circadian clock for mental and physical health are not yet fully understood. By housing mice in 20-h light/dark cycles, incongruous with their endogenous ∼24-h circadian period, we were able to model the effects of chronic circadian disruption noninvasively. Housing in these conditions results in accelerated weight gain and obesity, as well as changes in metabolic hormones. In the brain, circadian-disrupted mice exhibit a loss of dendritic length and decreased complexity of neurons in the prelimbic prefrontal cortex, a brain region important in executive function and emotional control. Disrupted animals show decreases in cognitive flexibility and changes in emotionality consistent with the changes seen in neural architecture. How our findings translate to humans living and working in chronic circadian disruption is unknown, but we believe that this model can provide a foundation to understand how environmental disruption of circadian rhythms impacts the brain, behavior, and physiology.

Topics: Animals; Behavior, Animal; Biological Clocks; Blood Glucose; Body Temperature; Brain; Circadian Clocks; Circadian Rhythm; Energy Metabolism; Humans; Insulin; Leptin; Male; Maze Learning; Mice; Mice, Inbred C57BL; Motor Activity; Neurons; Photoperiod; Prefrontal Cortex; Weight Gain

Gastric leptin and cholecystokinin (CCK) act on vagal afferents to induce cardiovascular effects and reflex inhibition of splanchnic sympathetic nerve discharge (SSND) and may act cooperatively in these responses. We sought to determine whether these effects are altered in animals that developed obesity in response to a medium high-fat diet (MHFD). Male Sprague-Dawley rats were placed on a low-fat diet (LFD; n = 8) or a MHFD (n = 24) for 13 wk, after which the animals were anesthetized and artificially ventilated. Arterial pressure was monitored and blood was collected for the determination of plasma leptin and CCK. SSND responses to leptin (15 μg/kg) and CCK (2 μg/kg) administered close to the coeliac artery were evaluated. Collectively, MHFD animals had significantly higher plasma leptin but lower plasma CCK levels than LFD rats (P < 0.05), and this corresponded to attenuated or reversed SSND responses to CCK (LFD, -21 ± 2%; and MHFD, -12 ± 2%; P < 0.05) and leptin (LFD, -6 ± 2%; and MHFD, 4 ± 1%; P < 0.001). Alternatively, animals on the MHFD were stratified into obesity-prone (OP; n = 8) or obesity-resistant (OR; n = 8) groups according to their weight gain falling within the upper or lower tertile, respectively. OP rats had significantly higher resting arterial pressure, adiposity, and plasma leptin but lower plasma CCK compared with LFD rats (P < 0.05). The SSND responses to CCK or leptin were not significantly different between OP and OR animals. These results demonstrate that a high-fat diet is associated with blunted splanchnic sympathoinhibitory responses to gastric leptin and CCK and may impact on sympathetic vasomotor mechanisms involved in circulatory control.

Topics: Adiposity; Animals; Blood Circulation; Blood Pressure; Cholecystokinin; Dietary Fats; Leptin; Male; Rats; Rats, Sprague-Dawley; Splanchnic Nerves; Weight Gain

Circulating levels of matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitor of metalloproteinases (TIMPs), are altered in human obesity and may contribute to its pathology. TIMP-2 exerts MMP-dependent (MMP inhibition and pro-MMP-2 activation) and MMP-independent functions. To assess the role of TIMP-2 in a murine model of nutritionally induced obesity, weight gain in wild-type and TIMP-2 deficient [knockout (KO)] mice fed a chow or high-fat diet (HFD) was determined. The effects of diet on glucose tolerance and insulin sensitivity, as well as pancreatic β-cell and adipocyte physiology, were assessed. Chow-fed TIMP-2 KO mice of both sexes became obese but maintained relatively normal glucose tolerance and insulin sensitivity. Obesity was exacerbated on the HFD. However, HFD-fed male, but not female, TIMP-2 KO mice developed insulin resistance with reduced glucose transporter 2 and pancreatic and duodenal homeobox 1 levels, despite increased β-cell mass and hyperplasia. Thus, although β-cell mass was increased, HFD-fed male TIMP-2 KO mice develop diabetes likely due to β-cell exhaustion and failure. TIMP-2 mRNA, whose expression was greatest in sc adipose tissue, was down-regulated in HFD-fed wild-type males, but not females. Furthermore, HFD increased membrane type 1-MMP (MMP-14) expression and activity in male, but not female, sc adipose tissue. Strikingly, MMP-14 expression increased to a greater extent in TIMP-2 KO males and was associated with decreased adipocyte collagen. Taken together, these findings demonstrate a role for TIMP-2 in maintaining extracellular matrix integrity necessary for normal β-cell and adipocyte physiology and that loss of extracellular matrix integrity may underlie diabetic and obesogenic phenotypes.

Topics: Adipocytes; Adipose Tissue; Animals; Blotting, Western; Dietary Fats; Female; Immunoenzyme Techniques; Insulin Resistance; Insulin-Secreting Cells; Leptin; Male; Matrix Metalloproteinase 14; Mice; Mice, Knockout; Microscopy, Confocal; Microscopy, Fluorescence; Obesity; Polymerase Chain Reaction; Sex Factors; Tissue Inhibitor of Metalloproteinase-2; Weight Gain

Various dietary carbohydrates have been linked to obesity and altered adipose metabolism; however, the influences of honey vs common sweeteners have not been fully explored. We hypothesized that in comparison with sucrose, a honey-based diet would promote lower weight gain, adiposity, and related biomarkers (leptin, insulin, and adiponectin) as well as a better blood lipid profile. Thirty-six male Sprague-Dawley rats (228.1 ± 12.5 g) were equally divided by weight into 2 groups (n = 18) and provided free access to 1 of 2 diets of equal energy densities differing only in a portion of the carbohydrate. Diets contained 20% carbohydrate (by weight of total diet) from either clover honey or sucrose. After 33 days, epididymal fat pads were excised and weighed, and blood was collected for analyses of serum concentrations of lipids, glucose, and markers of adiposity and inflammation. Body weight gain was 14.7% lower (P ≤ .05) for rats fed honey, corresponding to a 13.3% lower (P ≤ .05) consumption of food/energy, whereas food efficiency ratios were nearly identical. Epididymal fat weight was 20.1% lower (P ≤ .05) for rats fed honey. Serum concentrations of triglycerides and leptin were lower (P ≤ .05) by 29.6% and 21.6%, respectively, and non-high-density lipoprotein cholesterol was higher (P ≤ .05) by 16.8% for honey-fed rats. No significant differences in serum total cholesterol, high-density lipoprotein cholesterol, adiponectin, C-reactive protein, monocyte chemoattractant protein-1, glucose, or insulin were detected. These results suggest that in comparison with sucrose, honey may reduce weight gain and adiposity, presumably due to lower food intake, and promote lower serum triglycerides but higher non-high-density lipoprotein cholesterol concentrations.

Topics: Adiponectin; Adipose Tissue; Adiposity; Animals; Biomarkers; Blood Glucose; Body Weight; C-Reactive Protein; Chemokine CCL2; Diet; Dietary Carbohydrates; Eating; Energy Intake; Honey; Insulin; Leptin; Male; Obesity; Rats; Rats, Sprague-Dawley; Sucrose; Triglycerides; Weight Gain

Recent studies reported the impact of leptin on peripheral insulin sensitivity and glucose utilization. However, little is known concerning the effect of central leptin on hypothalamic and hepatic insulin efficiency. This study aimed to determine the consequence of chronic intra-cerebroventricular (ICV) leptin or murine leptin antagonist (MLA) infusion on hypothalamic and hepatic insulin signaling pathways, in rats. A 2-week central leptin infusion enhanced insulin-dependent Akt phosphorylation in the liver without changing PTP-1B protein expression, associated to insulin receptor (IR) upregulation and reduced IRS-1 phosphorylation on Ser302 residue. In the hypothalamus, a chronic ICV leptin infusion induced PTP-1B associated with a specific decrease in insulin-dependent Akt phosphorylation. In contrast, a chronic MLA infusion did not alter IR and PTP-1B expressions in hypothalamus and liver. Our results underline a brain leptin-dependent increase in hepatic insulin efficiency as mirrored by IR up-regulation, increased insulin-dependent Akt phosphorylation and reduced IRS-1 phosphorylation on Ser302 residue.

Topics: Animals; Blood Glucose; Brain; Eating; Insulin; Insulin Receptor Substrate Proteins; Leptin; Liver; Male; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Proto-Oncogene Proteins c-akt; Rats; Receptor, Insulin; Recombinant Proteins; RNA, Messenger; STAT3 Transcription Factor; Transcription, Genetic; Weight Gain

Hypothalamic leptin gene therapy normalizes the mosaic skeletal phenotype of leptin-deficient ob/ob mice. However, it is not clear whether increased hypothalamic leptin alters bone metabolism in animals already producing the hormone. The objective of this study was to evaluate the long duration effects of recombinant adeno-associated virus-rat leptin (rAAV-Lep) hypothalamic gene therapy on weight gain and bone metabolism in growing and skeletally mature leptin-replete female Sprague-Dawley rats. Rats were either unoperated or implanted with cannulas in the third ventricle of the hypothalamus and injected with either rAAV-Lep or rAAV-GFP (control vector encoding green fluorescent protein) and maintained on standard rat chow fed ad libitum for either 5 or 10 weeks (starting at 3 months of age) or 18 weeks (starting at 9 months of age). Tibias, femurs, or lumbar vertebrae were analyzed by micro-computed tomography and/or histomorphometry. In comparison with age-matched rAAV-GFP rats, rAAV-Lep rats maintained a lower body weight for the duration of studies. At 5 weeks after vector administration, rAAV-Lep rats had lower cancellous bone volume and bone marrow adiposity but higher osteoblast perimeter compared with nonoperated controls. However, these values did not differ between the two groups at 10 weeks after vector administration. Differences in cancellous bone volume and architecture were not detected between the rAAV-Lep and rAAV-GFP groups at either time point. Also, rAAV-Lep had no negative effects on bone in the 9-month-old skeletally mature rats at 18 weeks after vector administration. We hypothesize that the transient reductions in bone mass and bone marrow adiposity at 5 weeks after vector administration were due to hypothalamic surgery. We conclude that increased hypothalamic leptin, sufficient to prevent weight gain, has minimal specific effects (rAAV-Lep versus rAAV-GFP) on bone metabolism in normal female rats.

Topics: Animals; Bone and Bones; Bone Development; Dependovirus; Female; Genetic Therapy; Genetic Vectors; Hypothalamus; Injections, Intraventricular; Leptin; Radiography; Rats; Rats, Sprague-Dawley; Recombination, Genetic; Time Factors; Weight Gain

Preclinical and clinical data suggest modulating effects of appetite-regulating hormones and stress perception on food intake. Nicotine intake also interferes with regulation of body weight. Especially following smoking cessation gaining weight is a common but only partially understood consequence. The aim of this study was to examine the interaction between smoking habits, the appetite regulating hormone leptin, negative affectivity, and stress vulnerability on eating behavior in a clinical case-control study under standardized conditions. In a large population-based study sample, we compared leptin and cortisol plasma concentrations (radioimmunoassay) between current tobacco smokers with high cognitive restraint and disinhibition in eating behavior and smokers scoring low in both categories as assessed with the Three Factor Eating Questionnaire (TFEQ; Stunkard & Messick, 1985). As a measure for smoking effects on the stress axis, the saliva cortisol concentrations were compared before and after nicotine smoking. Additionally, stress perception was assessed with the Perceived Stress Scale (PSS), symptoms of depression and anxiety with the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI). In smokers showing high cognitive restraint and disinhibition we found significantly higher leptin concentrations than in the group of smokers scoring low in both categories. Furthermore there was a significant group difference in saliva cortisol concentrations after nicotine intake. Smokers showing high cognitive restraint and disinhibition were also characterized by significantly higher scores in the STAI, the PSS and the BDI. Our results suggest that smokers with a pathological eating behavior show an impaired neuroendocrine regulation of appetite and are prone to experience higher levels of stress and negative affectivity. This interaction of behavioral and neuroendocrinological factors may constitute a high risk condition for gaining weight following smoking cessation.

Topics: Adult; Anxiety; Case-Control Studies; Feeding Behavior; Female; Humans; Hydrocortisone; Leptin; Male; Middle Aged; Risk; Saliva; Smoking; Smoking Cessation; Stress, Psychological; Surveys and Questionnaires; Weight Gain; Young Adult

Klotho is a multifunctional protein involved in numerous biological functions, ranging from mineral ion metabolism to signaling activities. Recent studies have identified klotho as a target gene for peroxisome proliferator-activated receptor-γ (PPAR-γ), a master regulator of adipocyte differentiation, and an adipogenesis-promoting factor. In a similar line of observation, eliminating klotho function from mice resulted in the generation of lean mice with almost no detectable fat tissue. In contrast to the klotho-knockout mice (11.7±0.3 g at 9 wk), leptin-deficient (ob/ob) mice are severely obese (49.3±0.6 g at 9 wk), due to excessive fat accumulation. To study the in vivo role of klotho in obesity, we have generated and characterized ob/ob mice lacking klotho activity [ob/ob-klotho double-knockout (DKO) mice]. The ob/ob mice started to get bigger from 3 wk onward and gained almost 2 times more weight than their wild-type (WT) counterparts (WT vs. ob/ob: 34.8±1.3 vs. 65.5±1.2 g at 21 wk). The generated ob/ob-klotho DKO mice were not only viable throughout their adulthood but also showed markedly reduced fat tissue accumulation compared to their ob/ob littermates. The ob/ob-klotho DKO mice had significantly (P<0.01) less retroperitoneal, mesenteric, and epididymal fat accumulation, compared to their ob/ob counterparts. Similarly, the fatty liver that was consistently observed in the ob/ob mice was eliminated in the ob/ob-klotho DKO mice. Such structural improvement in the liver was also evident from markedly reduced fasting blood glucose levels in ob/ob-klotho DKO mice, compared to their ob/ob counterparts (ob/ob vs. ob/ob-klotho DKO: 266 ± 36 vs. 65±2 mg/dl). Finally, to study whether the absence of klotho can induce resistance to high-fat-diet-induced obesity, we provided a high-fat (60%) diet to klotho-knockout mice and compared them with normal-fat (20%) diet-fed klotho-knockout mice. No significant difference in body weight was detected in klotho-knockout mice fed either the normal-fat diet or high-fat diet, while WT mice fed the high-fat diet gradually gained body weight, compared to the normal-fat-diet-fed counterparts. The results of our dietary and genetic manipulation studies provide in vivo evidence for a role of klotho in obesity and offer a novel target to manipulate obesity and associated complications.

Topics: Adipose Tissue; Animals; Blood Glucose; Cholesterol; Diet; Dietary Fats; Fatty Liver; Gene Expression; Glucose; Glucuronidase; Klotho Proteins; Leptin; Liver; Longevity; Mice; Mice, Knockout; Obesity; PPAR gamma; Triglycerides; Weight Gain

Although the umami compound monosodium glutamate (MSG) is a widely used flavor enhancer, controversy still persists regarding the effects of MSG intake on body weight. It has been claimed, in particular, that chronic MSG intake may result in excessive body weight gain and obesity. In this study we assessed the effects of chronic (16 weeks) ad libitum MSG on body weight and metabolism of C57BL6/J mice. Adult male mice were divided in four experimental groups and fed with either a low-fat (LF) or high-fat (HF) diet and with either two bottles of plain water or one bottle containing 1% MSG and another one containing water according to a factorial design. Mice were monitored weekly for body weight and food/fluid intake for 15 weeks. At the end of the experiments, the circulating levels of leptin, insulin, total protein, total cholesterol, triglyceride, blood urea nitrogen, and non-esterified fatty acids were also analyzed. Our results show that MSG intake did not influence body weight in either LF or HF groups. Interestingly, although animals overall displayed strong preferences for MSG against water, preferences were relatively higher in LF compared to HF group. Consistent with the body weight data, while significant differences in leptin, insulin, total cholesterol, and non-esterified fatty acids were found between HF and LF groups, such an effect was not influenced by MSG intake. Finally, indirect calorimetry measurements revealed similar energy expenditure levels between animals being presented water only and MSG only. In summary, our data does not support the notion that ad libitum MSG intake should trigger the development of obesity or other metabolic abnormalities.

Topics: Analysis of Variance; Animals; Basal Metabolism; Blood Glucose; Blood Proteins; Blood Urea Nitrogen; Calorimetry, Indirect; Cholesterol; Diet; Drinking; Eating; Fatty Acids, Nonesterified; Glycogen; Insulin; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Sodium Glutamate; Triglycerides; Weight Gain

An imbalance in appetite-regulating neuropeptides of the central nervous system has been associated with anorexia nervosa (AN), but the mechanisms of action are poorly understood. Agouti-related protein (AGRP), an orexigenic mediator of the hypothalamus, increases food intake and decreases energy expenditure in times of negative energy balance. The aim of the present study was to investigate AGRP in acute and fully weight-restored patients with AN, as well as during weight gain.. Plasma AGRP and leptin levels were assessed using an enzyme-linked immunosorbent assay kit in a total of 175 female participants, including 75 patients with acute AN, 37 weight-restored AN patients and 63 healthy controls. Of the patients with acute AN, 33 were reassessed after partial weight gain.. In weight-restored AN patients plasma AGRP levels were similar to those in healthy controls, whereas in patients with acute AN, AGRP was elevated. AGRP was inversely correlated with indicators of undernutrition such as body mass index and plasma leptin. In addition, AGRP levels normalized during weight gain of longitudinally assessed AN patients.. Our results underline the significance of undernutrition and hypoleptinemia for the interpretation of peripheral AGRP concentrations. This provides support for the hypothesis that abnormal AGRP plasma levels in AN patients reflect undernutrition, rather than disease-specific traits.

Topics: Adolescent; Adult; Agouti-Related Protein; Analysis of Variance; Anorexia Nervosa; Biomarkers; Body Mass Index; Case-Control Studies; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Malnutrition; Weight Gain; Young Adult

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

Peripheral administration of a specific neurokinin-1 receptor (NK-1R) antagonist to mice leads to reduced weight gain and circulating levels of insulin and leptin after high-fat diet (HFD). Here, we assessed the contribution of substance P (SP) and NK-1R in diet-induced obesity using NK-1R deficient [knockout (KO)] mice and extended our previous findings to show the effects of SP-NK-1R interactions on adipose tissue-associated insulin signaling and glucose metabolic responses. NK-1R KO and wild-type (WT) littermates were fed a HFD for 3 wk, and obesity-associated responses were determined. Compared with WT, NK-1 KO mice show reduced weight gain and circulating levels of leptin and insulin in response to HFD. Adiponectin receptor mRNA levels are higher in mesenteric fat and liver in NK-1 KO animals compared with WT, after HFD. Mesenteric fat from NK-1R KO mice fed with HFD has reduced stress-activated protein kinase/c-Jun N-terminal kinase and protein kinase C activation compared with WT mice. After glucose challenge, NK-1R KO mice remove glucose from the circulation more efficiently than WT and pair-fed controls, suggesting an additional peripheral effect of NK-1R-mediated signaling on glucose metabolism. Glucose uptake experiments in isolated rat adipocytes showed that SP directly inhibits insulin-mediated glucose uptake. Our results further establish a role for SP-NK-1R interactions in adipose tissue responses, specifically as they relate to obesity-associated pathologies such as glucose intolerance and insulin resistance. Our results highlight this pathway as an important therapeutic approach for type 2 diabetes.

Topics: Adipose Tissue; Animals; Dietary Fats; Female; Glucose; Humans; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Rats; Rats, Inbred F344; Receptors, Neurokinin-1; Signal Transduction; Substance P; Weight Gain

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

Weight gain is a frequently occurring serious somatic adverse effect of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight.. To determine whether LEPR Q223R, LEP -2548G/A and HTR2C -759C/T polymorphisms are associated with obesity and weight change in patients using atypical antipsychotic drugs.. A longitudinal study design was used in a naturalistic setting. The study population included 141 patients, all of whom were using an atypical antipsychotic drug. The body mass index was measured twice. Primary outcome measures were obesity at the moment of first measurement and body mass index change during treatment. Determinants were the LEPR Q223R (rs1137101), the LEP -2548G/A SNP (rs7799039) and the HTR2C -759C/T (rs3813929) polymorphisms.. Of the 141 included patients, 35 (24.8%) were obese. In females, presence of the LEPR 223R allele was associated with an increased risk of obesity (47.6 vs 17.6%; p = 0.03). In males this association was not found. None of the SNPs were significantly associated with weight change during treatment.. The LEPR Q223R polymorphism may be a risk factor for obesity in women with a psychotic disorder treated with atypical antipsychotic drugs. This is in line with earlier findings of our group.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Antipsychotic Agents; Body Mass Index; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Infant; Infant, Newborn; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Psychotic Disorders; Receptor, Serotonin, 5-HT2C; Receptors, Leptin; Weight Gain; Young Adult

Appetizers based on different spices/herbs are highly acceptable but evaluation of their functionality needs more attention. The present study, investigated the effects of appetizers on food consumption, weight gain, and leptin levels in male Wistar rats. Three appetizers, namely ginger beverage, ajowan beverage, and karpurvalli beverage were administered to groups of rats. The fasting leptin levels ranged from 0.75 to 2.5 ng/ml, while weights were in the range of 147-201 g. Decreased (3.4-10.8%) leptin levels following the consumption of appetizers indicated their appetizing effect, with a greater reduction (p<0.05) for ginger beverage and karpurvalli beverage. Weight gain after 10 days was 7.68% in the control group whereas it was 11.20 and 13.26% in rats fed with ginger and karpurvalli beverages, respectively. However, food consumption was higher in all the appetizer groups than in the controls.

Topics: Animals; Appetite; Appetite Stimulants; Beverages; Body Weight; Eating; Fasting; Food; Food Technology; Leptin; Male; Rats; Rats, Wistar; Spices; Weight Gain; Zingiber officinale

Mechanisms underlying obesity-related vascular dysfunction are unclear. This study examined the effect of diet-induced obesity on expression and function of large conductance Ca(2+)-activated potassium channel (BK(Ca)) in rat pressurized small resistance vessels with myogenic tone. Male Sprague-Dawley rats fed a cafeteria-style high fat diet (HFD; ∼30% energy from fat) for 16-20 wk were ∼30% heavier than controls fed standard chow (∼13% fat). Obesity did not alter BK(Ca) α-subunit function or α-subunit protein or mRNA expression in vessels isolated from the cremaster muscle or middle-cerebral circulations. In contrast, BK(Ca) β(1)-subunit protein expression and function were significantly reduced in cremaster muscle arterioles but increased in middle-cerebral arteries from obese animals. Immunohistochemistry showed α- and β(1)-subunits were present exclusively in the smooth muscle of both vessels. Cremaster muscle arterioles from obese animals showed significantly increased medial thickness, and media-to-lumen ratio and pressurized arterioles showed increased myogenic tone at 30 mmHg, but not at 50-120 mmHg. Myogenic tone was not affected by obesity in middle-cerebral arteries. The BK(Ca) antagonist iberiotoxin constricted both cremaster muscle and middle-cerebral arterioles from control rats; this effect of iberiotoxin was abolished in cremaster muscle arteries only from obese rats. Diet-induced obesity has contrasting effects on BK(Ca) function in different vascular beds, through differential effects on β(1)-subunit expression. However, these alterations in BK(Ca) function had little effect on overall myogenic tone, suggesting that the mechanisms controlling myogenic tone can be altered and compensate for altered BK(Ca) expression and function.

Topics: Animals; Arterioles; Blotting, Western; Cerebral Arteries; Diet; Dietary Fats; Energy Intake; Heart Rate; Hyperinsulinism; Hypertension; Immunohistochemistry; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Leptin; Male; Microscopy, Electron; Muscle Tonus; Muscle, Skeletal; Obesity; Potassium Channels; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Reverse Transcriptase Polymerase Chain Reaction; Weight Gain

Fetal growth restriction followed by accelerated postnatal growth contributes to impaired metabolic function in adulthood. The extent to which these outcomes may be mediated centrally within the hypothalamus, as opposed to in the periphery within the digestive tract, remains unknown. In a sheep model, we achieved intrauterine growth restriction experimentally by maternal nutrient restriction (R) that involved a 40% reduction in food intake through late gestation. R offspring were then either reared singly to accelerate postnatal growth (RA) or as twins and compared with controls also reared singly. From weaning, all offspring were maintained indoors until adulthood. A reduced litter size accelerated postnatal growth for only the first month of lactation. Independently from postnatal weight gain and later fat mass, R animals developed insulin resistance as adults. However, restricted accelerated offspring compared with both the control accelerated and restricted restricted offspring ate less and had higher fasting plasma leptin as adults, an adaptation which was accompanied by changes in energy sensing and cell proliferation within the abomasum. Additionally, although fetal restriction down-regulated gene expression of mammalian target of rapamycin and carnitine palmitoyltransferase 1-dependent pathways in the abomasum, RA offspring compensated for this by exhibiting greater activity of AMP-activated kinase-dependent pathways. This study demonstrates a role for perinatal nutrition in the peripheral control of food intake and in energy sensing in the gastric mucosal and emphasizes the importance of diet in early life in regulating energy metabolism during adulthood.

Topics: Abomasum; Adiposity; AMP-Activated Protein Kinases; Animals; Caloric Restriction; Carnitine O-Palmitoyltransferase; Cell Proliferation; Energy Metabolism; Female; Fetal Growth Retardation; Gastric Mucosa; Gene Expression Regulation; Insulin Resistance; Lactation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Pregnancy; Random Allocation; RNA, Messenger; Sheep; TOR Serine-Threonine Kinases; Weight Gain

Leptin is an adipose-derived hormone that signals to inform the brain of nutrient status; loss of leptin signaling results in marked hyperphagia and obesity. Recent work has identified several groups of neurons that contribute to the effects of leptin to regulate energy balance, but leptin receptors are distributed throughout the brain, and the function of leptin signaling in discrete neuronal populations outside of the hypothalamus has not been defined. In the current study, we produced mice in which the long form of the leptin receptor (Lepr) was selectively ablated using Cre-recombinase selectively expressed in the hindbrain under control of the paired-like homeobox 2b (Phox2b) promoter (Phox2b Cre Lepr(flox/flox) mice). In these mice, Lepr was deleted from glucagon-like 1 peptide-expressing neurons resident in the nucleus of the solitary tract. Phox2b Cre Lepr(flox/flox) mice were hyperphagic, displayed increased food intake after fasting, and gained weight at a faster rate than wild-type controls. Paradoxically, Phox2b Cre Lepr(flox/flox) mice also exhibited an increased metabolic rate independent of a change in locomotor activity that was dependent on food intake, and glucose homeostasis was normal. Together, these data support a physiologically important role of direct leptin action in the hindbrain.

Topics: Animals; Cholecystokinin; Eating; Energy Metabolism; Gene Expression Regulation; Glucagon-Like Peptide 1; Glucose; Homeostasis; Hyperphagia; Infusions, Intraventricular; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Neurons; Receptors, Leptin; Solitary Nucleus; Weight Gain

We previously showed that peptides containing leptin sequences 1-33 or 61-90 are taken up by the rat brain. We now report the effects of these peptides on food intake and body weight in mature rats. Peptides were infused intravenously for 4weeks, using Alzet minipumps. Dosages were 20μg/kg/day in experiment I, and 60μg/kg/day in experiment 2. In experiment 1, female rats receiving peptides 1-33 and 61-90 each underwent an approximate doubling of the weight gain of control rats. These peptides also increased food intake in female rats. Peptide 15-32, which has a lesser degree of brain uptake, gave a smaller weight gain. Peptide 83-108, which is not taken up by the brain, had no effect on weight gain or food intake. Similar results were obtained in experiment 2. In male rats, however, none of the peptides caused significant changes in food intake or body weight. This was at least partly due to the fact that all male rats underwent vigorous weight increases. We conclude that peptides 1-33 and 61-90 acted as leptin antagonists, stimulating food intake and body weight increases, at least in female rats. These peptides may lead to clinical applications in conditions such as anorexia and cachexia.

Topics: Animals; Drug Evaluation, Preclinical; Eating; Female; Leptin; Male; Peptide Fragments; Rats; Weight Gain

Hypothalamic obesity (HO) is a major and unsolved problem in patients with medial hypothalamic lesions and is associated with hyperinsulinemia and hyperleptinemia. The purpose of this study was to create a rodent model that mimics metabolic changes in HO for use in therapeutic testing. Female Sprague-Dawley rats were used to test the individual and combined effects of two types of medial hypothalamic lesions: arcuate nucleus (ARC) lesions by injection of monosodium glutamate at neonatal age, and ventromedial nucleus (VMN) lesions by passing an anodal current through an electrode placed in the VMN at age 80 days. Adiposity in ARC-lesioned animals was associated with decreased food intake and stunted growth, while VMN lesions were associated with hyperphagia but not reduced growth. The greatest weight gain (weight at age 200 days 712 +/- 65 vs. 451 +/- 19 g in controls), hyperphagia (food intake 10 days following surgery 33 +/- 0.8 vs. 18.5 +/- 0.7 g/day in sham-treated rats), hyperinsulinemia and hyperleptinemia occurred in rats that received both ARC and VMN lesions. Thus, the combined medial hypothalamic lesions result in an obesity phenotype similar to that of patients that suffer from HO and are consequently more suitable for testing potential therapeutics for this disorder than lesions of single hypothalamic nuclei.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Brain; Disease Models, Animal; Female; Hyperinsulinism; Hyperphagia; Hypothalamic Diseases; Insulin; Leptin; Obesity; Rats; Rats, Sprague-Dawley; Sodium Glutamate; Ventromedial Hypothalamic Nucleus; Weight Gain

The objective of this study was to investigate the cause of valproate (VPA)-associated weight gain in children.. Eighteen children (10.94 ± 3.78 years) with epilepsy were assigned to VPA therapy. Serum levels of glucose, insulin, cortisol, leptin, neuropeptide Y (NPY), galanin and ghrelin were assessed before (month 0) and after 18 months of therapy. Eighteen age- and gender-matched patients (10.78 ± 3.95 years) were enrolled as the control group.. Excess per capita weight of 2.3 kg was determined in the children receiving VPA over 18 months compared to the control group. In these patients, a statistically significant increase in standardized weight score, Homeostasis Model Assessment index, serum leptin, NPY and galanin values was determined at the 18th month compared to those before VPA treatment and in the control group, and there was also a significant decrease in ghrelin values.. Increased serum levels of leptin, NPY and galanin play an important role in VPA-associated weight gain in children. While ghrelin is not directly associated with weight gain, its serum levels decline as a response to weight gain.

Topics: Adolescent; Child; Child, Preschool; Epilepsy; Galanin; Ghrelin; Humans; Hydrocortisone; Insulin; Leptin; Neuropeptide Y; Valproic Acid; Weight Gain

The success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the effect of olanzapine administration on the regulation of hypothalamic mechanisms controlling food intake, namely neuropeptide expression and AMP-activated protein kinase (AMPK) phosphorylation in rats. Our results show that subchronic exposure to olanzapine upregulates neuropeptide Y (NPY) and agouti related protein (AgRP) and downregulates proopiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC). This effect was evident both in rats fed ad libitum and in pair-fed rats. Of note, despite weight gain and increased expression of orexigenic neuropeptides, subchronic administration of olanzapine decreased AMPK phosphorylation levels. This reduction in AMPK was not observed after acute administration of either olanzapine or clozapine. Overall, our data suggest that olanzapine-induced hyperphagia is mediated through appropriate changes in hypothalamic neuropeptides, and that this effect does not require concomitant AMPK activation. Our data shed new light on the hypothalamic mechanism underlying antipsychotic-induced hyperphagia and weight gain, and provide the basis for alternative targets to control energy balance.

Topics: Agouti-Related Protein; Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Arcuate Nucleus of Hypothalamus; Benzodiazepines; Clozapine; Feeding Behavior; Female; Gene Expression Regulation; Hyperphagia; Hypothalamus; Injections, Intraventricular; Insulin; Intracellular Signaling Peptides and Proteins; Leptin; Neuropeptide Y; Neuropeptides; Olanzapine; Orexins; Phosphorylation; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Ribonucleotides; Signal Transduction; Weight Gain

The potential health benefits of tea have long been studied. This study examined the role of powdered sea buckthorn leaf tea (SLT) in high-fat diet-induced obese mice. The mice were fed two different doses of SLT (1% and 5%, wt/wt) for six weeks. SLT suppressed body weight gain in a dose-dependent manner and significantly reduced visceral fat, plasma levels of leptin, triglyceride and total cholesterol and ALT activity compared with the high-fat-fed control mice. SLT also decreased hepatic triglyceride and cholesterol concentrations and lipid accumulation, whereas elevated fecal lipid excretion. High-fat feeding resulted in simultaneously decreasing hepatic FAS and G6PD activities and increasing PAP, β-oxidation and CPT activities. However, SLT supplementation during high-fat feeding led to a significant decrease in PAP, β-oxidation and CPT activities with a simultaneous increase in G6PD activity. The hepatic CYP2E1 activity and hepatic and erythrocyte lipid peroxides were significantly lowered with SLT supplements. Hepatic and erythrocyte SOD and CAT activities were also increased with SLT supplements in a dose-dependent manner, whereas GSH-Px activity was increased in erythrocytes only. These results indicate that SLT has potential anti-visceral obesity and antioxidant effects mediated by the regulation of lipid and antioxidant metabolism in high-fat diet-induced obese mice.

Topics: Animals; Antioxidants; Body Weight; Dietary Fats; Hippophae; Leptin; Male; Mice; Mice, Inbred ICR; Obesity, Abdominal; Powders; Tea; Weight Gain

Recent studies have reported the preventive effects of probiotics on obesity. Among commensal bacteria, bifidobacteria is one of the most numerous probiotics in the mammalian gut and are a type of lactic acid bacteria. The aim of this study was to assess the antiobesity and lipid-lowering effects of Bifidobacterium spp. isolated from healthy Korean on high fat diet-induced obese rats.. Thirty-six male Sprague-Dawley rats were divided into three groups as follows: (1) SD group, fed standard diet; (2) HFD group, fed high fat diet; and (3) HFD-LAB group, fed high fat diet supplemented with LAB supplement (B. pseudocatenulatum SPM 1204, B. longum SPM 1205, and B. longum SPM 1207; 108 ~ 109 CFU). After 7 weeks, the body, organ, and fat weights, food intake, blood serum levels, fecal LAB counts, and harmful enzyme activities were measured.. Administration of LAB reduced body and fat weights, blood serum levels (TC, HDL-C, LDL-C, triglyceride, glucose, leptin, AST, ALT, and lipase levels), and harmful enzyme activities (β-glucosidase, β-glucuronidase, and tryptophanase), and significantly increased fecal LAB counts.. These data suggest that Bifidobacterium spp. used in this study may have beneficial antiobesity effects.

Topics: Alanine Transaminase; alpha-Amylases; Animals; Anti-Obesity Agents; Aspartate Aminotransferases; beta-Glucosidase; Bifidobacterium; Blood Glucose; Dietary Fats; Feces; Glucuronidase; Hypolipidemic Agents; Leptin; Lipase; Lipids; Male; Obesity; Probiotics; Rats; Rats, Sprague-Dawley; Tryptophanase; Urease; Weight Gain

We investigated the anti-obesity effect of abietic acid in mice fed a high-fat diet with emphasis on changes in adipogenesis in epididymal adipose tissues. Male C57BL/6J mice were divided into four groups and fed a normal diet, a high-fat diet (HFD), or HFD plus oral administration of abietic acid (20 mg/kg of body weight/day [LA] or 40 mg/kg of body weight/day [HA]) for 8 weeks. Compared with the HFD group, mice orally administered 40 mg of abietic acid/kg of body weight/day exhibited significantly decreased body weight and adipose tissue weights. Serum triglyceride concentrations in the HA group were significantly lower than those in the HFD group, as were the levels of serum insulin and leptin. Hematoxylin and eosin staining revealed that epididymal adipose tissue mass was decreased by abietic acid administration. Abietic acid also inhibited the protein expression of sterol regulatory element-binding protein-1c, CCAAT/enhancer-binding protein α, and CD36 in epididymal adipose tissues, which are up-regulated by HFDs. These data demonstrate that abietic acid has an anti-obesity effect in mice mediated by the regulation of adipogenesis.

Topics: Abietanes; Adipogenesis; Adipose Tissue, White; Adiposity; Animals; Anti-Obesity Agents; CCAAT-Enhancer-Binding Protein-alpha; CD36 Antigens; Dietary Fats; Dose-Response Relationship, Drug; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Random Allocation; Sterol Regulatory Element Binding Protein 1; Triglycerides; Weight Gain

Alterations in plasma leptin and adiponectin concentrations are associated with an adverse metabolic profile in obese children.. To simultaneously assess multiple factors with possible effects on plasma leptin and adiponectin concentrations in healthy, non-obese children.. We studied 170 healthy non-obese children (86 males, age 10+1.5 years), with available medical records from birth.. Plasma leptin and adiponectin concentrations were assessed by immunoassay. The ratio of current weight/birth weight (WBWR) was used as an index of children growth from birth. Children's intensity of physical activity and parental characteristics were also assessed.. Leptin was positively associated with WBWR (p<0.0001); parental smoking (analysis of variance, ANOVA; p-=0.03) and parental obesity (ANOVA; p<0.001) were negatively associated with breastfeeding (p<0.01) and children's access to exercise (p<0.0001). Adiponectin was negatively associated with WBWR (p<0.0001) and parental smoking (p=0.04), with an additive negative effect of parental smoking status and parental obesity on children's adiponectin levels (ANOVA; p=0.02).. Children's and parental factors are related and could possibly influence leptin and adiponectin concentrations in healthy non-obese children. Early preventive strategies that target both children and parents could improve the profile of adipocytokine in these children.

Topics: Adiponectin; Birth Weight; Body Mass Index; Body Weight; Cardiovascular Diseases; Child; Child Development; Female; Greece; Humans; Leptin; Male; Motor Activity; Obesity; Parents; Reference Values; Risk Factors; Tobacco Smoke Pollution; Weight Gain

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

The adipokine leptin has been detected in human breast milk, but its effect on postnatal growth and development remains largely unclear. We hypothesized that leptin could affect infant's body weight gain during early lactation in the first 6 mo of life. Therefore, we evaluated leptin levels in maternal serum and breast milk of 23 healthy, lactating mothers and their neonates in a prospective, longitudinal study. Leptin concentration was quantified by a commercially available human leptin RIA. Our results showed that leptin levels in breast milk were 22-fold lower than in maternal serum, but both parameters were positively correlated to each other (r = 0.431, p = 0.001) and to maternal BMI (serum: r = 0.512, p < 0.001; milk: r = 0.298, p < 0.001) over 6 mo of lactation. A negative association was found between breast milk leptin levels during the first week after delivery and the infant weight gain from the end of the first to the sixth month (r = -0.681, p = 0.007). This suggests that milk-borne leptin provides a link between maternal body composition and infant growth and development and plays a critical role in regulating appetite and food intake during early infancy.

Topics: Adult; Body Composition; Child Development; Female; Humans; Infant; Infant, Newborn; Lactation; Leptin; Longitudinal Studies; Milk, Human; Radioimmunoassay; Statistics, Nonparametric; Weight Gain

Weight gain has been reported in patients with Parkinson's disease (PD) treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). To evaluate the influence of STN-DBS on weight changes, we studied food-related hormones.. Anthropometric parameters and food-related hormones (leptin, adiponectin, resistin, ghrelin, cortisol, insulin, and thyroid stimulating hormone) were measured in 27 patients with STN-DBS during a 12 month period following electrode implantation.. Besides marked motor improvements on STN-DBS, PD patients significantly gained weight. The mean weight gain at 12 months was 5.2±(SD)5.8 kg. A significant decrease in cortisol levels compared to baseline appeared at month 2 and persisted at 12 months (p<0.01, corrected), with no significant changes in other hormones tested.. Changes in peripheral food-related hormones do not appear to cause weight gain in PD patients. Direct effects of STN-DBS on hypothalamic catabolic/anabolic peptide balance remain hypothetical and necessitate further elucidation.

Topics: Adiponectin; Adult; Aged; Deep Brain Stimulation; Eating; Female; Ghrelin; Hormones; Humans; Hydrocortisone; Hypothalamus; Insulin; Leptin; Male; Middle Aged; Parkinson Disease; Resistin; Subthalamic Nucleus; Thyrotropin; Weight Gain

The aim of this study was to determine the association between cord blood adiponectin and leptin and early infant growth at one year in small for gestational age (SGA) and appropriate for gestational age (AGA) infants.. In this prospective study adiponectin and leptin concentrations were determined in cord blood of (i) AGA newborns (n = 44) and (ii) SGA newborns (n = 24). At one year of age, height and weight were measured. Linear regression analysis was used to determine which factors were associated with anthropometric measurements at the age of one year.. (i) SGA neonates had a significantly lower median cord blood adiponectin and leptin than AGA neonates; (ii) among SGA neonates, cord blood adiponectin concentrations were negatively correlated with body weight at one year, weight gain after one year and with BMI at one year; and (iii) among AGA neonates cord blood adiponectin concentrations were negatively correlated with body weight at one year, weight gain after one year and with BMI at one year.. The disparity in cord blood adiponectin and leptin concentrations between SGA and AGA neonates suggests a role for adipokines in fetal growth.

Topics: Adiponectin; Body Height; Body Mass Index; Body Weight; Child Development; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Leptin; Male; Prospective Studies; Weight Gain

To determine associations between weight gain induced by antipsychotic and the polymorphisms of HTR2C gene -759C/T and -697G/C, histamine-1 receptor gene, leptine gene -2548G/A, and adiponectin gene +276G/T and +45T/G.. In the case-matched study, 85 patients who gained more than 7% of their pre-drug body weight served as the study group and another 85 patients who gained less than 7% of their pre-drug body weight served as the control group. The ligation diction reaction technique was used to analyze the frequencies of the -759C/T and -697G/C polymorphism of the HTR2C gene, -2548A/G polymorphism of leptin gene, +276G/T and +45T/G polymorphism of adiponectin gene and glu349asp polymorphism of H1 receptor gene.. The presence of the -759C allele, -697G allele, -2548A allele and +276G allele was significantly higher in the study group than that in the control group (P<0.05).. The -759C/T and -697G/C polymorphisms of the promoter region of 5HT(2)C receptor gene, -2548A/G polymorphisms of leptin gene and +276G/T polymorphisms of adiponectin gene may be associated with the antipsychotic induced weight gain. The glu349asp polymorphisms of histamine-1 receptor gene is not associated with antipsychotic induced weight gain.

Topics: Adiponectin; Adolescent; Adult; Antipsychotic Agents; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2C; Schizophrenia; Weight Gain; Young Adult

The neuroendocrine and metabolic effects of leptin have been extensively researched since the discovery, and the later identification, of the leptin gene mutated within the ob/ob mouse. Leptin is required for optimal health in a number of physiological systems (e.g. fertility, bone density, body weight regulation). Despite the extensive leptin literature and many observations of leptin's cyclical pattern over the 24-hour day, few studies have specifically examined how the circadian rhythm of leptin may be essential to leptin signaling and health. Here we present data indicating that a rhythmic leptin profile (e.g. 1 peak every 24 hours) leads to excessive weight gain during desynchronized feeding whereas non-rhythmic leptin provided in a continuous manner does not lead to excessive body weight gain under similar feeding conditions. This study suggests that feeding time can interact with leptin's endogenous rhythm to influence metabolic signals, specifically leading to excessive body weight gains during 'wrongly' timed feeding.

Topics: Animals; Body Weight; Circadian Rhythm; Feeding Behavior; Leptin; Male; Mice; Mice, Obese; Obesity; Periodicity; Weight Gain

Prediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).. Systemic inflammation and glycemia influence circadian blood pressure variability.. Dahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α)] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP) and heart rate (HR) were recorded by telemetry every 5 minutes during both sleep (day) and active (night) periods. Pulse pressure (PP) was calculated (PP = SBP-DBP).. [mean(SEM)]: The AD fed group displayed significant increase in body weight (after 90 days; p < 0.01). Fasting glucose, adipokine (leptin and adiponectin) concentrations significantly increased (at 90 and 172 days; all p < 0.05), along with a trend for increased concentrations of systemic pro-inflammatory cytokines (MCP-1 and TNF-α) on day 90. The AD fed group, with significantly higher FG, also exhibited significantly elevated circadian (24-hour) overall mean SBP, DBP, PP and HR (all p < 0.05).. These data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system) which generate abnormal CBPV.

Topics: Adiponectin; Animals; Biomarkers; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Chemokine CCL2; Circadian Rhythm; Diet, High-Fat; Disease Models, Animal; Heart Rate; Inflammation; Inflammation Mediators; Leptin; Prediabetic State; Rats; Rats, Inbred Dahl; Telemetry; Time Factors; Tumor Necrosis Factor-alpha; Weight Gain

We previously investigated the effects of an aqueous extract of maté (mate) tea, made from the leaves of Ilex paraguariensis, on the diabesity and metabolic syndrome features in a mouse model. Mate induced significant decreases in body weight (BW), body mass index, and food intake (FI). In this study, to verify the mode of action of mate on FI and consequently on BW, we examined the anorexic effects of mate on the appetite and satiety markers glucagon-like peptide 1 (GLP-1) and leptin in high-fat diet-fed ddY mice. GLP-1 is a peptide signal generated by the gastrointestinal tract, which regulates appetite and influences BW, whereas leptin is an afferent signal from the periphery to the brain in a homeostatic feedback loop that regulates adipose tissue mass, thus leading to decreased appetite and FI and increased energy expenditure. Chronic administration of mate (50, 100 mg/kg) for 3 weeks significantly reduced FI, BW, and ameliorated blood fats, liver fats, and adipose tissue. Mate induced significant increases in GLP-1 levels and leptin levels compared with the control. Acute administration of major constituents of mate showed significant increases in GLP-1 levels by dicaffeoyl quinic acids and matesaponins, and significant induction of satiety by caffeoyl quinic acids and caffeine in ddY mice. These findings suggest that mate may induce anorexic effects by direct induction of satiety and by stimulation of GLP-1 secretion and modulation of serum leptin levels.

Topics: Animals; Anti-Obesity Agents; Beverages; Diet, High-Fat; Dipeptidyl Peptidase 4; Disease Models, Animal; Eating; Fatty Acids; Glucagon-Like Peptide 1; Ilex paraguariensis; Leptin; Liver; Male; Mice; Obesity; Phytotherapy; Plant Extracts; Plant Leaves; Satiation; Triglycerides; Weight Gain

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is upregulated in a variety of tissues in obesity. It is still unclear as to whether NADPH oxidase upregulation in a specific tissue is part of a systemic response. Here we analyzed the expression pattern of NADPH oxidase in vascular, adipose, and kidney tissues in a rat model of diet-induced obesity. After weaning, rats were fed either a normal or high-fat diet for 12 weeks. The high-fat diet resulted in 20% increased body weight. In the aorta, Nox4 expression was increased by three-fold in obese rats. Upregulations of p22phox and p47phox in adipose, and Nox4, p22phox, and p47phox in kidney were observed in obesity. Marked increases in plasma leptin and insulin were observed, with more modest changes in adiponectin in obese rats. The average systolic blood pressure in the obese group was 11 mmHg higher than that of lean rats (P < 0.005). There was a significant correlation between blood pressure and aortic Nox4 expression (P < 0.01). In cultured vascular smooth muscle cells, adiponectin reduced the expression of Nox4 in a protein kinase A-dependent manner. Our results suggest that upregulation of NADPH oxidase in multiple tissues during obesity appears to be a systemic response. At least in vitro, adiponectin may have a protective antioxidant role by suppressing vascular NADPH oxidase expression. The association between NADPH oxidase Nox4 expression in the vasculature and the elevated blood pressure in obesity requires further investigation.

Topics: Adiponectin; Adipose Tissue, White; Animals; Antioxidants; Aorta, Thoracic; Blood Pressure; Cells, Cultured; Diet, High-Fat; Disease Models, Animal; Enzyme Activation; Insulin; Kidney; Leptin; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NADPH Oxidase 4; NADPH Oxidases; Obesity; Rats; Rats, Sprague-Dawley; Up-Regulation; Weight Gain

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

Obesity in human was found mainly due to the poor transportation of leptin through brain-blood barrier (BBB), called as leptin resistance. To produce a leptin capable of penetrating BBB, we have added Tat-PTD(9) to the C terminal of leptin to construct a fusion protein. The fusion Tat-leptin and native leptin genes were synthesized by single-step insertion of a polymerase chain reaction and expressed in Escherichia coli BL21 (Rosseta). The expressing products were purified and renatured by Ni-NTA affinity chromatography, and identified by the molecular size in SDS-PAGE gel and by its immunoreactivity to specific antibody with Western-blotting assay. To bio-functionally evaluate the fusion protein, Balb/c mice fed with high-fat diet (HFD) were given Tat-leptin, leptin or saline for 19 days. The immunohistochemical staining showed the increases in positive stains for the leptin in the region of hypothalamus of the HFD mice with either Tat-leptin or leptin as compared to saline group, but the staining intensity and frequency in the group with Tat-leptin were stronger and higher than those in the group with leptin. Furthermore, the most efficiency in preventing the body-weight gain caused by HFD was found in Tat-leptin group among these three groups. These results suggest that Tat-modified leptin may become a great potential candidate for the prevention or therapy of obese patients.

Topics: Animals; Anti-Obesity Agents; Blood-Brain Barrier; Dietary Fats; Drug Delivery Systems; Genes, tat; Hypothalamus; Immunohistochemistry; Leptin; Male; Mice; Mice, Inbred BALB C; Obesity; Peptide Fragments; Polymerase Chain Reaction; Random Allocation; Recombinant Fusion Proteins; tat Gene Products, Human Immunodeficiency Virus; Time Factors; Tissue Distribution; Weight Gain

A diet rich in whole grain cereals is suggested to protect against type 2 diabetes and facilitate body weight regulation. However, little is known about the impact of different cereals and the underlying mechanisms. The objective of this study was to compare the long-term metabolic effects of diets supplemented with whole grain wheat or whole grain rye in the C57BL/6J mouse.. Mice were fed the whole grain supplements in a low-fat background diet for 22 wk. Oral and intravenous glucose tolerance tests were performed during the study and in vitro insulin secretion assays were performed at the end of the study. Body weight, energy intake, body fat content, and plasma parameters were measured during the study.. A dietary supplement of whole grain rye suppressed body weight gain and resulted in significantly decreased adiposity, plasma leptin, total plasma cholesterol, and triacylglycerols compared with a supplement of whole grain wheat. Also, a slight improvement in insulin sensitivity was observed in the rye group compared with the wheat group. The decreases in body weight and adiposity were observed in the absence of differences in energy intake.. Long-term administration of whole grain rye evokes a different metabolic profile compared with whole grain wheat in the C57BL/6J mouse, the primary difference being that whole grain rye reduces body weight and adiposity compared with whole grain wheat. In addition, whole grain rye slightly improves insulin sensitivity and lowers total plasma cholesterol.

Topics: Adiposity; Animals; Body Weight; Cholesterol; Dietary Carbohydrates; Dietary Supplements; Edible Grain; Female; Insulin Resistance; Leptin; Mice; Mice, Inbred C57BL; Obesity; Secale; Triglycerides; Triticum; Weight Gain

We investigated the relationship between plasma insulin-like growth factor I (IGF-I), leptin, active ghrelin levels, and postnatal growth in very low birth weight (VLBW) infants.. Plasma IGF-I, leptin, and active ghrelin levels were measured at birth and at 2, 4, 6 and 8 weeks after birth in 61 VLBW infants, including 31 appropriate-for-gestational-age (AGA) and 30 small-for-gestational-age (SGA) infants.. Insulin-like growth factor I levels were the lowest at birth, but increased gradually over the first 8 weeks of life. IGF-I was positively correlated with body weight, body length and body mass index at all time points. Leptin levels did not change over the study period. Ghrelin levels were significantly lower at birth; however, there were no significant differences between the levels after 2 weeks of age. Leptin and ghrelin levels were not correlated with anthropometrical measures. IGF-I levels at birth were significantly lower in SGA than in AGA infants, but the leptin and ghrelin levels were not significantly different between the two groups.. Insulin-like growth factor I is related to length and weight gain in the prenatal and the early postnatal periods in VLBW infants, but this does not appear to be the case for leptin and ghrelin.

Topics: Analysis of Variance; Body Height; Female; Ghrelin; Growth; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Infant, Very Low Birth Weight; Insulin-Like Growth Factor I; Leptin; Male; Statistics, Nonparametric; Weight Gain

Teenagers are susceptible to delivering small-for-gestational-age (SGA) infants. Previous studies suggest that maternal growth may contribute, as a result of preferential nutrient partitioning to the mother. We investigated the impact of maternal growth on birthweight in pregnant teenagers in the UK, and examined endocrine mediators of nutrient partitioning.. A prospective observational multicentre study, About Teenage Eating, conducted between 2004 and 2007.. Four hospitals in socially-deprived areas of Manchester and London.. A total of 500 pregnant adolescents (14-18 years of age) with a singleton pregnancy were recruited at 10-21 weeks of gestation, with follow-up studies on 368 subjects. A cohort of 80 pregnant adults (25-40 years of age) provided a control group for determining growth.. Skeletal growth, weight gain and skinfold thickness were measured from first to third trimester, together with maternal levels of micronutrients and metabolic hormones: insulin-like growth factor (IGF) system and leptin. Dietary analyses were performed.. SGA birth.. Maternal growth was not associated with SGA birth: growing mothers delivered more large-for-gestational-age infants (OR 2.51; P < 0.05). Growers had greater weight gain (P < 0.001), fat accrual (P < 0.001) and red cell folate concentrations (P < 0.01) than non-growers. Maternal IGF-I (P < 0.01) and leptin (P < 0.001) were positively associated with maternal and fetal growth, whereas IGF-I (P < 0.001) was negatively associated. Teenagers that were underweight at booking or with low weight gain were at greater risk of SGA birth.. Maternal growth was not detrimental to fetal growth in this UK population of teenagers. Greater weight gain and higher concentrations of IGF-I in growing teenagers may provide anabolic drive for maternal and fetal growth.

Topics: Adolescent; Adult; England; Enzyme-Linked Immunosorbent Assay; Female; Fetal Development; Folic Acid; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Knee; Leptin; Micronutrients; Pregnancy; Pregnancy in Adolescence; Prenatal Nutritional Physiological Phenomena; Prospective Studies; Weight Gain

The human proteins ciliary neurotrophic factor (CNTF) and interleukin-6 (IL6) and their receptors share structural homology with leptin and its receptor. In addition, uncoupling protein-2 (UCP2) has been shown to participate the regulation of leptin on food intake. All three proteins are active in the hypothalamus. Experiments have shown that CNTF and IL6, like leptin, can influence body weight in humans and animals, while the effect of UCP2 is not consistent. In a Dutch general population (n=545) we investigated associations of CNTF (null G/A, rs1800169), IL6 (174 G/C, rs1800795) and UCP2 (A55V, rs660339 and del/ins) polymorphisms with weight gain using interaction graphs and logistic regression analysis. The average follow-up period was 6.9 years. Individuals who gained weight (n=264) were compared with individuals who remained stable in weight (n=281). In women the CNTF polymorphism (odds ratio (OR)=2.15, 95%CI: 1.27-3.64, p=0.004) and in men the IL6 polymorphism by itself (OR=2.26, 95%CI: 1.08-4.75, p=0.03) or in combination with the CNTF polymorphism, were associated with weight gain. Furthermore, CNTF and IL6 polymorphisms in interaction with UCP2 polymorphisms had similar strong effects on weight gain in women and men, respectively. All observed effects were statistically shown to be independent of serum leptin level. These results are incorporated in a biological model for weight regulation with upstream effects of CNTF and IL6, and downstream effects of UCP2. The results of this study suggest a novel mechanism for weight regulation that is active in both women and men, but strongly influenced by sex.

Topics: Adult; Anthropometry; Chi-Square Distribution; Ciliary Neurotrophic Factor; Cohort Studies; Confidence Intervals; Entropy; Female; Gene Frequency; Genotype; Humans; Interleukin-6; Ion Channels; Leptin; Male; Mitochondrial Proteins; Odds Ratio; Polymorphism, Single Nucleotide; Sex Factors; Uncoupling Protein 2; Weight Gain; 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

The postpartum phase following gestational diabetes (GDM) is characterised by subtle metabolic defects, including the beta cell dysfunction that is believed to mediate the increased future risk of type 2 diabetes in this patient population. Low circulating levels of adiponectin and increased leptin and C-reactive protein (CRP) have recently emerged as novel diabetic risk factors, although their relevance to GDM and subsequent diabetes has not been characterised. Thus, we sought to determine whether adiponectin, leptin and CRP levels during pregnancy relate to the postpartum metabolic defects linking GDM with type 2 diabetes.. Metabolic characterisation, including oral glucose tolerance testing, was undertaken in 487 women during pregnancy and at 3 months postpartum. Based on the antepartum OGTT, there were 137 women with GDM, 91 with gestational impaired glucose tolerance and 259 with normal glucose tolerance.. Adiponectin levels were lowest (p < 0.0001) and CRP levels highest (p = 0.0008) in women with GDM. Leptin did not differ between the glucose tolerance groups (p = 0.4483). Adiponectin (r = 0.41, p < 0.0001), leptin (r = -0.36, p < 0.0001) and CRP (r = -0.30, p < 0.0001) during pregnancy were all associated with postpartum insulin sensitivity (determined using the insulin sensitivity index of Matsuda and DeFronzo [IS(OGTT)]). Intriguingly, adiponectin levels were also related to postpartum beta cell function (insulinogenic index/HOMA of insulin resistance; r = 0.16, p = 0.0009). Indeed, on multiple linear regression analyses, adiponectin levels during pregnancy independently predicted both postpartum insulin sensitivity (t = 3.97, p < 0.0001) and beta cell function (t = 2.37, p = 0.0181), even after adjustment for GDM. Furthermore, adiponectin emerged as a significant negative independent determinant of postpartum fasting glucose (t = -3.01, p = 0.0027).. Hypoadiponectinaemia during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia, and hence may be relevant to the pathophysiology relating GDM with type 2 diabetes.

Topics: Adiponectin; Adult; Blood Glucose; Breast Feeding; C-Reactive Protein; Diabetes Mellitus, Type 2; Diabetes, Gestational; Ethnicity; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Insulin-Secreting Cells; Leptin; Parity; Postpartum Period; Pregnancy; Racial Groups; Risk Factors; Weight Gain

The geographic distribution of Japanese macaques includes populations with the most northern range of any primate species. Not surprisingly, females of this species are characterized by physiological adaptations and unique fat deposition mechanisms that facilitate their survival through the sometimes-harsh seasonal conditions of temperate climates, as well as sustaining the metabolic costs of mating, pregnancy, and lactation. Here, we explore the relationship between nutritional status, seasonality, and reproductive status using anthropometric and leptin measures from 14 captive female Japanese macaques. No seasonal patterns were found in the levels of leptin, but there were differences between seasons in anthropometric measures, specifically between the beginning and the end of the mating season. Females gained weight and accumulated energy reserves in fall to prepare for mating activity, and to survive the severe conditions of winter, which is also the period of gestation if pregnancy occurs. Lactating females had larger total skinfolds relative to nonlactating individuals, and females with older babies at the beginning of the mating season had larger abdominal skinfolds than did those with younger babies. There was a relationship between the likelihood of conception and nutritional status, with females that conceived during one mating season being in better condition at the end of their previous mating season. Together, these results suggest that, even in captive settings, seasonal breeding has a cost on the energetic demands of mating, and that higher condition (i.e. fatter) females could afford the demands of lactation and reproduced more rapidly.

Topics: Adiposity; Animals; Body Composition; Breeding; Energy Metabolism; Female; Japan; Lactation; Leptin; Macaca; Nutritional Status; Reproduction; Seasons; Skinfold Thickness; Weight Gain

Ovariectomized mice on a high fat diet represent a model of diet-induced obesity during estrogen deficiency. Here, we tested the hypothesis that sensitivity to centrally administered leptin in ovariectomized mice with diet-induced obesity could be restored by estrogen supplementation. Ovariectomized C57BL/6 female mice were fed either a standard or high fat diet until they were 27 weeks old. Ovariectomized mice on a high fat diet developed extreme obesity and hyperleptinemia and moderate hyperinsulinemia compared to those on a standard diet. For the last 4 weeks, 17beta-estradiol-3-benzoate or its vehicle was administered subcutaneously in a 4-day cyclic regimen. Finally, leptin or saline was injected into the third ventricle, and food intake and body weight were measured for 36 h. In ovariectomized mice fed a standard diet, the decrease in food intake and body weight was significant and was pronounced in 17beta-estradiol-3-benzoate-supplemented mice. The response to centrally injected leptin in ovariectomized mice on a high fat diet was insignificant, whereas in 17beta-estradiol-3-benzoate-supplemented mice, the effect was significant, particularly with respect to body weight. We showed for the first time that central insensitivity to leptin in ovariectomized diet-induced obese mice was restored with 17beta-estradiol-3-benzoate supplementation, which also attenuated most of the parameters of metabolic syndrome. Only circulating adiponectin, a peripheral insulin sensitivity marker, was lowered following 17beta-estradiol-3-benzoate administration in both high fat and standard diet-fed ovariectomized mice, despite of decreased or unchanged glycemia, respectively.

Topics: Animals; Body Weight; Diet; Dietary Fats; Dietary Supplements; Estradiol; Feeding Behavior; Female; Leptin; Mice; Mice, Inbred C57BL; Obesity; Ovariectomy; Weight Gain

The C57BL/6J (B6/J) male mouse represents a standard for diet-induced obesity (DIO) and is unique in expressing a loss-of-function nicotinamide nucleotide transhydrogenase (Nnt) gene. This mutation was associated with a marked reduction in glucose-stimulated insulin secretion from B6/J islets in vitro and moderately impaired glucose clearance in vivo. To assess the contribution of this Nnt mutation, we compared DIO responsiveness of Nnt-mutant B6/J males to Nnt wild-type C57BL/6NJ (B6/NJ) males over a 14-week period of feeding a high-fat (60% of calories) diet. Initial mean body weights at 6 weeks did not distinguish the substrains and both substrains were DIO-sensitive. However, B6/J males outgained the B6/NJ males, with a significant 3 g higher mean body weight at 20 weeks accompanied by significant increases in both lean and fat mass. Mean nonfasting serum glucose over time was also significantly higher in B6/J males, as was impairment of glucose tolerance assessed at 8 and 20 weeks of age. Serum leptin, but not insulin, was significantly higher in B6/J males over time. Potential contributions of the wild-type Nnt gene were demonstrable on a lower fat diet (10% of calories) where a significantly greater weight gain over time by B6/NJ males was correlated with a significantly higher serum insulin. In conclusion, DIO developed in response to 60% fat feeding regardless of Nnt allele status. Contribution of the B6/J-unique Nnt mutation was most evident in response to 10% fat feeding that resulted in reduced serum insulin and weight gain compared to B6/NJ males.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Fluid Compartments; Body Weight; Diet; Dietary Fats; Glucose Intolerance; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; NADP Transhydrogenases; Obesity; Weight Gain

The importance of hypertension treatment has expanded beyond blood pressure management to include additional risk factors, mainly diabetes. It was considered of interest to test the effect of telmisartan, an angiotensin receptor 1 antagonist and peroxisome proliferator activator receptor-gamma partial agonist, on Cohen-Rosenthal diabetic hypertensive nonobese (CRDH) rats, a unique model combining both pathologies. Its effect was examined on fat-derived and inflammatory agents in CRDH. To determine the extent of the drug's peroxisome proliferator activator receptor-gamma modulating beneficial metabolic actions, results were compared with those obtained with valsartan and rosiglitazone in CRDH and Cohen diabetic rat (CDR). Telmisartan and valsartan were given in drinking water at 3 and 12 mg/kg/d, whereas rosiglitazone (3 mg/kg/d) was given as food admixture for a period of 5 months. Blood pressure, glucose, insulin, adiponectin, leptin, and tumor necrosis factor alpha were examined. Telmisartan and valsartan significantly (P < .01) reduced blood pressure, whereas telmisartan and rosiglitazone considerably reduced blood glucose levels to normoglycemic levels (P < .01) in these 2 strains. Insulin levels were not affected by telmisartan and valsartan but were slightly reduced by rosiglitazone in CDR. In contrast to valsartan, adiponectin was significantly (60%, P < .01) increased by telmisartan in both CDR and CRDH, whereas rosiglitazone induced a 60% and 180% increase in CRDH and CDR animals, respectively, on day 30 of treatment. Co-treatment with GW9662 averted telmisartan-induced rise of adiponectin. Tumor necrosis factor alpha declined in telmisartan-treated rats, less so with rosiglitazone, but not valsartan. Telmisartan also induced downsizing of epididymal adipocytes compared with valsartan. Leptin levels were significantly increased by valsartan (P < .05) but reduced by telmisartan and rosiglitazone. The telmisartan-induced increase in adiponectin was most probably associated with a decrease in glucose and tumor necrosis factor alpha levels. Therefore, in addition to its hypotensive effect, telmisartan demonstrated beneficial thiazolidinedione-like effects.

Topics: Adiponectin; Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Benzoates; Blood Pressure; Humans; Hyperglycemia; Hypertension; Insulin; Insulin Resistance; Leptin; PPAR gamma; Rats; Rats, Inbred SHR; Rosiglitazone; Telmisartan; Thiazolidinediones; Tumor Necrosis Factor-alpha; Weight Gain

Cholecystokinin (CCK) is a satiation peptide released during meals in response to lipid intake; it regulates pancreatic digestive enzymes that are required for absorption of nutrients. We proposed that mice with a disruption in the CCK gene (CCK knockout [CCK-KO] mice) that were fed a diet of 20% butter fat would have altered fat metabolism.. We used quantitative magnetic resonance imaging to determine body composition and monitored food intake of CCK-KO mice using an automated measurement system. Intestinal fat absorption and energy expenditure were determined using a noninvasive assessment of intestinal fat absorption and an open circuit calorimeter, respectively.. After consuming a high-fat diet for 10 weeks, CCK-KO mice had reduced body weight gain and body fat mass and enlarged adipocytes, despite the same level of food intake as wild-type mice. CCK-KO mice also had defects in fat absorption, especially of long-chain saturated fatty acids, but pancreatic triglyceride lipase did not appear to have a role in the fat malabsorption. Energy expenditure was higher in CCK-KO than wild-type mice, and CCK-KO mice had greater oxidation of carbohydrates while on the high-fat diet. Plasma leptin levels in the CCK-KO mice fed the high-fat diet were markedly lower than in wild-type mice, although levels of insulin, gastric-inhibitory polypeptide, and glucagon-like peptide-1 were normal.. CCK is involved in regulating the metabolic rate and is important for lipid absorption and control of body weight in mice placed on a high-fat diet.

Topics: Adiposity; Animals; Biomarkers; Butter; Calorimetry; Cholecystokinin; Dietary Fats; Disease Models, Animal; Eating; Energy Metabolism; Fatty Acids; Intestinal Absorption; Leptin; Lipase; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Obesity; Time Factors; Weight Gain

In adults, adjustments in resting energy expenditure (REE) are used to defend energy balance against disturbance caused by over-and under-nutrition, and may be linked to changes in insulin resistance and leptin. Little is known of these associations in children. Our aim was to test the hypothesis that long-term weight gain in children is met with adaptive changes in resting energy expenditure, mediated by insulin resistance and/or leptin.. REE by indirect calorimetry, anthropometry, body composition by DEXA, insulin resistance (HOMA-IR) and serum leptin were measured annually in 232 children from the age of 7-10 y.. REE rose from 7 to 10 y, and the rise exceeded that predicted by the concurrent rise in fat and fat-free mass by 184 kcal/day in the boys and by 160 kcal/day in the girls. However, there were no significant relationships in either gender between this 'excess' rise in REE and change in body composition (r < or = 0.08, p > or = 0.42). The rise in both boys and girls was associated with, but not explained by, a rise in insulin resistance (p < or = 0.002). There was no association with serum leptin (p > or = 0.32).. The data do not support the hypothesis of adaptive changes in REE in pre-pubertal children, and insulin resistance explains very little of the pre-pubertal rise in REE. The rise in REE beyond that explained by changes in body composition may reflect an increase in energy requirements prior to puberty.

Topics: Absorptiometry, Photon; Aging; Anthropometry; Basal Metabolism; Body Composition; Calorimetry, Indirect; Child; Energy Metabolism; Female; Homeostasis; Humans; Insulin Resistance; Leptin; Longitudinal Studies; Male; Nutritional Requirements; Sex Characteristics; Weight Gain

Numerous clinical and experimental studies have linked stress to changes in risk factors associated with the development of physiological syndromes, including metabolic disorders. How different mediators of the stress response, such as corticosterone (CORT), influence these changes in risk remains unclear. Although CORT has beneficial short-term effects, long-term CORT exposure can result in damage to the physiological systems it protects acutely. Disruption of this important physiologic signal is observed in numerous disparate disorders, ranging from depression to Cushing's syndrome. Thus, understanding the effects of chronic high CORT on metabolism and physiology is of key importance. We explored the effects of 4-wk exposure to CORT dissolved in the drinking water on the physiology and behavior of male mice. We used this approach as a noninvasive way of altering plasma CORT levels while retaining some integrity in the diurnal rhythm present in normal animals. This approach has advantages over methods involving constant CORT pellets, CORT injections, or adrenalectomy. We found that high doses of CORT (100 microg/ml) result in rapid and dramatic increases in weight gain, increased adiposity, elevated plasma leptin, insulin and triglyceride levels, hyperphagia, and decreased home-cage locomotion. A lower dose of CORT (25 microg/ml) resulted in an intermediate phenotype in some of these measures but had no effect on others. We propose that the physiological changes observed in the high-CORT animals approximate changes observed in individuals suffering from the metabolic syndrome, and that they potentially serve as a model for hypercortisolemia and stress-related obesity.

Topics: Adipose Tissue, White; Adiposity; Adrenal Glands; Animals; Atrophy; Chemical Phenomena; Corticosterone; Disease Models, Animal; Dose-Response Relationship, Drug; Endocrine System; Glucose Intolerance; Hyperphagia; Insulin; Leptin; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Motor Activity; Thymus Gland; Triglycerides; Weight Gain

Ghrelin and GH secretagogues, including GH-releasing peptide (GHRP)-6, stimulate food intake and adiposity. Because insulin modulates the hypothalamic response to GH secretagogues and acts synergistically with ghrelin on lipogenesis in vitro, we analyzed whether insulin plays a role in the metabolic effects of GHRP-6 in vivo. Streptozotocin-induced diabetic rats received saline, GHRP-6, insulin, or insulin plus GHRP-6 once daily for 8 wk. Rats receiving saline suffered hyperglycemia, hyperphagia, polydipsia, and weight loss. Insulin, but not GHRP-6, improved these parameters (P < 0.001 for all), as well as the diabetes-induced increase in hypothalamic mRNA levels of neuropeptide Y and agouti-related peptide and decrease in proopiomelanocortin. Cocaine amphetamine-related transcript mRNA levels were also reduced in diabetic rats, with GHRP-6 inducing a further decrease (P < 0.03) and insulin an increase. Diabetic rats receiving insulin plus GHRP-6 gained more weight and had increased epididymal fat mass and serum leptin levels compared with all other groups (P < 0.001). In epididymal adipose tissue, diabetic rats injected with saline had smaller adipocytes (P < 0.001), decreased fatty acid synthase (FAS; P < 0.001), and glucose transporter-4 (P < 0.001) and increased hormone sensitive lipase (P < 0.001) and proliferator-activated receptor-gamma mRNA levels (P < 0.01). Insulin normalized these parameters to control values. GHRP-6 treatment increased FAS and glucose transporter-4 gene expression and potentiated insulin's effect on epididymal fat mass, adipocyte size (P < 0.001), FAS (P < 0.001), and glucose transporter-4 (P < 0.05). In conclusion, GHRP-6 and insulin exert an additive effect on weight gain and visceral fat mass accrual in diabetic rats, indicating that some of GHRP-6's metabolic effects depend on the insulin/glucose status.

Topics: Adipocytes; Agouti-Related Protein; Animals; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Experimental; Epididymis; Fats; Fatty Acid Synthases; Gene Expression; Ghrelin; Glucose Transporter Type 4; Growth Hormone; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Neuropeptide Y; Oligopeptides; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Weight Gain

Adipocyte fatty acid binding protein (a-FABP) has been suggested to play an important role in the pathogenesis of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance, and, possibly, other components of metabolic syndrome.. To determine circulating levels of a-FABP in preterm infants and examine possible associations of a-FABP with metabolic indices (serum lipids, glucose, and insulin levels, and homeostasis model assessment index of insulin resistance [HOMA-IR]), levels of leptin and adiponectin, anthropometric parameters and weight gain.. Prospective cohort study.. 55 healthy preterm (mean [SD] gestational age 32.8 [1.8] weeks) and 23 fullterm infants (reference group).. Serum a-FABP, lipids, glucose, insulin, leptin and adiponectin levels at 31.9 [10.4] days of life.. Serum a-FABP levels did not differ significantly between preterm and fullterm infants. A-FABP levels correlated positively with total-cholesterol [total-C] in both preterm and fullterm infants (beta=0.33; p=0.01 and beta=0.33; p=0.04, respectively). In addition to total-C, weight gain correlated independently with a-FABP levels in preterm infants (beta=0.36, p=0.01).. An association between a-FABP levels and indices of insulin resistance was not present in infants studied. As the development of insulin resistance in children born prematurely is possibly associated with weight gain in early postnatal life, follow-up of our study population is necessary to demonstrate whether a-FABP levels, shown to correlate with weight gain in preterm infants, are a predictive marker for the later development of insulin resistance in these infants.

Topics: Adiponectin; Blood Glucose; Cholesterol; Fatty Acid-Binding Proteins; Female; Homeostasis; Humans; Immunoenzyme Techniques; Infant, Newborn; Infant, Premature; Insulin; Insulin Resistance; Leptin; Male; Prospective Studies; Weight Gain

Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that high-capacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intra-paraventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT.

Topics: Adiposity; Animals; Dietary Fats; Energy Metabolism; Hypothalamus; Intracellular Signaling Peptides and Proteins; Leptin; Male; Muscle, Skeletal; Neuropeptides; Obesity; Orexins; Phosphoenolpyruvate Carboxykinase (GTP); Physical Conditioning, Animal; Rats; Running; Thermogenesis; Weight Gain

Interest in pharmacological intervention to combat metabolic syndrome and its complications is increasing as the prevalence of obesity is reaching epidemic proportions. The potential efficacy of drugs is often tested in animal models; however, the method of drug delivery is frequently overlooked and may act as a confounder due to stress. We hypothesized that long-term orogastric gavage would negatively influence the development of hepatic steatosis and the metabolic syndrome in a murine model of diet-induced obesity. C57BL/6J male mice were fed a high fat diet and were gavaged with a vehicle once or twice daily for 9 weeks. A group without orogastric gavaging served as control. A similar experiment was performed using leptin deficient ob/ob mice that were fed a standard diet for 4 weeks. Food intake was monitored, insulin resistance determined, and steatosis was assessed by histology and quantified via magnetic resonance spectroscopy. After 9 weeks, control C57BL/6J mice exhibited significantly more weight gain, insulin resistance and hepatic steatosis, compared to mice that were gavaged daily, or twice daily. This effect was likely due to decreased food consumption associated with gavage-induced stress. In contrast, the phenotype of leptin deficient ob/ob mice was not affected by orogastric gavage. Therefore, we concluded that orogastric gavage may lead to increased stress, thereby affecting food intake and the development of diet-induced obesity in a murine model. The effects of what may seem to be trivial laboratory routines, such as orogastric gavage, should be taken into account when designing animal studies for drug development.

Topics: Adiposity; Alanine Transaminase; Animals; Blood Glucose; Body Weight; Cholesterol; Dietary Fats; Eating; Energy Intake; Enteral Nutrition; Fasting; Fatty Liver; Insulin Resistance; Leptin; Liver; Magnetic Resonance Spectroscopy; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; Organ Size; Phenotype; Severity of Illness Index; Stress, Physiological; Time Factors; Triglycerides; Weight Gain

After a period of forced overfeeding, many individuals actively compensate for this weight gain by reducing food intake and maintaining this state of hypophagia well into the post-overfeeding period. Our central goal is to define the mechanism underlying this adaptive reduction in food intake. When male Long Evans rats were implanted with indwelling gastric cannula and overfed a liquid low-fat (10% fat) diet for 17 days, overfed rats exhibited increased weight gain (P<0.01) but decreased food intake, and this hypophagia persisted for 4-6 days post-overfeeding (P<0.05). Leptin levels were increased 8-fold by overfeeding (P<0.01), yet returned to baseline within 2 days post-overfeeding, despite the persistent hypophagia. Energy expenditure and oxygen consumption (VO2) were increased on the first day post-overfeeding (P<0.05), but subsequently normalized prior to the normalization of food intake. Lastly, in leptin receptor deficient Obese Zucker (fa/fa) rats, overfeeding produced a significant decrease in food intake during active overfeeding. However, food intake returned to near baseline levels within one day post-overfeeding. Contrastingly, food intake remained suppressed in lean controls for 6 days post-overfeeding. Thus intact leptin signaling is not required for the decrease in food intake that occurs during overfeeding, but the ability to maintain this hypophagia is substantially impaired in the absence of leptin signaling. In addition, this post-overfeeding leptin effect appears to occur despite the fact that leptin levels normalize relatively rapidly post-overfeeding.

Topics: Adaptation, Physiological; Animal Nutritional Physiological Phenomena; Animals; Eating; Energy Metabolism; Fats; Gene Expression; Hormones; Leptin; Male; Oxidation-Reduction; Oxygen Consumption; Rats; Rats, Long-Evans; Rats, Zucker; Weight Gain

The aim of this study was to determine the effect of the antioxidant vitamin E (VE) on adiponectin and leptin expression in obese rats. Thirty weaning male Sprague-Dawley rats were divided into three groups as follows: (1) a control group, fed with normal chow; (2) a diet-induced obesity group (DIO), fed with a high-fat diet and (3) an intervention group, fed with a high-fat diet supplemented with VE (350 mg/kg). After 10 weeks of being fed according to these group assignments, rats were weighed and euthanized. Blood and adipose tissues were then immediately collected; mRNA and protein levels of leptin and adiponectin were measured by realtime reverse transcription-polymerase chain reaction and Western blotting. Biomarkers of oxidative stress, including serum levels of 8-epi-prostaglandin-F(2)alpha (8-epi-PGF(2)alpha) and glutathione peroxidase activity, were also examined. Adiponectin and leptin levels were lower in the DIO group than in the control group. VE intervention increased the expression of both leptin and adiponectin (P values < 0.05). Association analysis showed that serum leptin levels correlated positively with body fat mass (r = 0.601, P < 0.05). Both serum leptin and adiponectin levels were associated with the presence of serum 8-epi-PGF2 alpha (leptin, r = 0.513, P < 0.05; adiponectin, r = -0.422, P < 0.05). Administration of VE decreases leptin and adiponectin expression in obese rats. This finding is consistent with the view that antioxidants can play an important role in the treatment of obesity-related diseases.

Topics: Adiponectin; Adipose Tissue; Animals; Antioxidants; Base Sequence; Biomarkers; Dietary Fats; Dinoprost; Disease Models, Animal; DNA Primers; Gene Expression; Glutathione Peroxidase; Leptin; Male; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; RNA, Messenger; Vitamin E; Weight Gain

High infancy weight gain is associated with increased body mass index (BMI) and insulin resistance (IR) in later life, but the association with later body composition has not been well explored. Appetite regulatory hormones may be programmed in early life, but data to support this are lacking.. We investigated the effect of weight gain in infancy on body composition, IR, leptin, ghrelin, and adiponectin at 17 y of age.. This was an observational study of 95 term and appropriate-for-gestational-age infants. We measured weight at birth and 9 mo of age and, for a subgroup (n = 60), at 3 and 6 mo of age. Changes in weight SD scores from 0 to 9, 0 to 3, 3 to 6, and 6 to 9 mo of age were calculated. Follow-up examinations at 10 and 17 y of age included body fat (BF) assessment by dual-energy X-ray absorptiometry scanning. We measured serum leptin, ghrelin adiponectin, and IR at 17 y of age.. Weight gain from 0 to 9 mo of age was positively associated with BMI (P < 0.003), percentage BF (P < 0.05), and percentage trunk fat (TF) (P < 0.03) but not with percentage TF relative to total BF, in childhood and adolescence, and most of these effects were explained by growth from 0 to 3 mo of age. Weight gains from 0 to 9 and 0 to 3 mo of age were not related to IR or leptin but were negatively associated with ghrelin and adiponectin corrected for BF at 17 y of age.. Our findings suggest that high weight gain in infancy, especially from 0 to 3 mo of age, has a role in programming both BF and concentrations of ghrelin and adiponectin in adolescence, whereas there was no effect on IR or leptin in this study.

Topics: Absorptiometry, Photon; Adiponectin; Adolescent; Appetite; Body Composition; Child Development; Cohort Studies; Female; Ghrelin; Humans; Infant; Insulin Resistance; Leptin; Male; Peptide Hormones; Prospective Studies; Sex Factors; Statistics, Nonparametric; Weight Gain

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

Maternal hypoprolactinemia at the end of lactation (a precocious weaning model) increases milk leptin transfer and results in overweight, leptin resistance, and secondary hypothyroidism at adulthood. We studied the effects of prolactin (PRL) inhibition during mid-lactation (a partial malnutrition model) on milk leptin transfer, leptinemia, body composition, and thyroid function. Lactating rats were treated with bromocryptine (BRO, 1 mg/twice daily) or saline on days 7, 8, and 9 of lactation. Offspring were sacrificed 10, 21, and 90 days after birth. After treatment, BRO-treated dams showed hypoprolactinemia and hyperleptinemia, and produced less milk with lower levels of lactose and higher milk triglycerides. Milk leptin levels were lower at weaning. Offspring of BRO-treated dams had lower body weight and length as well as less visceral fat during lactation and adulthood. Total fat was also lower at weaning and adult life, whereas total protein was higher at 90 days-old. BRO offspring presented lower serum T4 and TSH at 10 days-old and weaning, respectively. When adults, these rats exhibited hypoleptinemia, lower levels of thyroid hormones, and higher TSH. Early inhibition of PRL therefore leads to offspring malnutrition and affects subsequent growth. Also, inhibition of PRL during lactation predisposes offspring to hypothyroidism; however, when the inhibition occurs during late lactation, the hypothyroidism is secondary, whereas when it is restricted to mid-lactation, the thyroid hypofunction is primary. The programming effect of milk suppression thus depends on the developmental stage of offspring.

Topics: Adiposity; Aging; Animals; Bromocriptine; Feeding Behavior; Female; Hypothyroidism; Lactation; Leptin; Malnutrition; Milk; Obesity; Prolactin; Rats; Rats, Wistar; Thyroid Gland; Weight Gain

Investigating the effect of leptin on energy expenditure in undernutrition might lead to a better understanding of the role of leptin in regulating body weight in humans.. 73 underweight female adolescents with anorexia nervosa (AN) were compared with 23 healthy normal weight (nwC), and 9 overweight girls (OW); 37 AN were followed during 7 months of weight recovery. Resting energy expenditure (REE, by indirect calorimetry), body composition (fat mass, FM; lean tissue mass, LTM; by Dual-Energy X-Ray Absorptiometry) and plasma hormones of leptin and 3,5,3'-Triiodothyronine (T(3)) were measured.. In underweight, leptin, T(3) and REE adjusted for lean tissue mass (REE(LTM)) were decreased; in OW, FM and leptin were increased at unchanged T(3) and REE(LTM). There was a significant positive relation between FM and leptin at low and normal (AN, r(2) = 0.26; nwC, r(2) = 0.51, p < 0.001), but not at high adiposity. Leptin and REE(LTM) were positively associated in underweight (r(2) = 0.14, p = 0.001) but not in normal or overweight subjects. T(3) was linearly related to REE(LTM) over the whole range of adiposity (r(2) = 0.42, p < 0.001). With weight gain in AN (5.0 ± 3.5 kg) the relationship between leptin and REE(LTM) changed toward the conditions seen in normal weight controls.. At low adiposity the interrelated fall of leptin and REE reflect an adaptive mechanism to preserve body weight. High leptin production associated with excessive adiposity was without effect on metabolic adaptation.

Topics: Absorptiometry, Photon; Adipose Tissue; Adiposity; Adolescent; Anorexia Nervosa; Body Composition; Body Mass Index; Calorimetry, Indirect; Case-Control Studies; Energy Metabolism; Female; Humans; Leptin; Linear Models; Overweight; Rest; Thinness; Triiodothyronine; Weight Gain

Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy.. We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (HTR2C), insulin-induced gene 2 (INSIG2) and leptin (LEP).. We investigated the association of HTR2C, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (HTR2C: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests.. We report a significant association of three HTR2C SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs.. The results contribute to the accumulating evidence for an association of the X-chromosomal HTR2C gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased HTR2C gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism.

Topics: Adolescent; Adult; Aged; Alleles; Antipsychotic Agents; Case-Control Studies; Female; Genes, X-Linked; Genotype; Germany; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Logistic Models; Male; Membrane Proteins; Middle Aged; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT2C; Retrospective Studies; Schizophrenia; Weight Gain; Young Adult

In an acute treatment experiment, metformin (150, 300 mg/kg, per os (p.o.)) markedly reduced the consumption of a high-fat diet (HFD) (45 kcal% fat-containing diet) for 2 h after the HFD was given to the fasted male C57BL/6J (B6) mice. In addition, metformin at a higher dose increased plasma active glucagon-like peptide-1 (GLP-1) levels at 1 h after the HFD was given. On the other hand, pioglitazone (12 mg/kg, p.o.) slightly increased the food intake but did not affect active GLP-1 levels when given at 6 and 12 mg/kg, p.o. In a long-team experiment for 9 weeks, metformin treatment (0.25, 0.5% in the HFD) resulted in reduction of body weight gain and HFD intake. When wet weights of various body fat pads of each mouse were measured at 9 weeks after treatment, metformin markedly decreased these weights. However, pioglitazone treatment (0.01, 0.02% in the HFD) did not have obvious effects on these parameters. Oral glucose tolerance test was carried out after 20-h fasting at 4 weeks post-treatment. Whereas metformin treatment (0.25, 0.5%) markedly improved glucose intolerance, pioglitazone treatment (0.02%) slightly improved this parameter. At 9 weeks, both metformin and pioglitazone markedly improved hyperglycemia and hyperinsulinemia. Metformin treatment also improved hyperleptinemia, whereas pioglitazone was ineffective. These results indicate that metformin reduces body weight gain and improves glucose intolerance in HFD-induced obese diabetic B6 mice.

Topics: Animals; Blood Glucose; Body Weight; Dietary Fats; Energy Intake; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Hyperglycemia; Hyperinsulinism; Hypoglycemic Agents; Insulin; Leptin; Male; Metformin; Mice; Mice, Inbred C57BL; Obesity; Pioglitazone; Thiazolidinediones; Weight Gain

Because gut microbiota has recently attracted much attention as an environmental factor involved in the development of obesity, probiotics may be useful in preventing and/or improving obesity and its related disorders. The present study aimed to investigate the effects of Lactobacillus plantarum strain No. 14 (LP14), a bacterial strain reported to decrease body fat percentage in healthy volunteers, on adipocyte size in mice. Female C57BL/6 mice were fed either normal- or high-fat diet and administered intragastrically with LP14 (1 x 10(8) colony-forming units/mouse) or vehicle daily for 11 weeks. High dietary fat intake increased body weight gain, white adipose tissue weight, mean adipocyte size and serum total cholesterol and leptin concentrations, and decreased serum adiponectin concentration. In mice fed the high-fat diet, LP14 administration significantly reduced the mean adipocyte size and tended to reduce the white adipose tissue weight and serum total cholesterol and leptin concentrations as compared with the vehicle-administered mice. All mice had undetectable serum levels of conjugated linoleic acids that reportedly exert antiobesity action. In a separate experiment, LP14 ingestion had no influence on serum triacylglycerol accumulation following olive oil administration in Triton WR1339-treated mice, suggesting that dietary fat absorption is unaffected by LP14. In conclusion, we propose that LP14 may exert a beneficial effect on the onset of diet-induced obesity by reducing the cell size of white adipose tissues, and it seems unlikely that previously reported mechanisms for other bacterial strains are involved in the action of LP14.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Body Weight; Cholesterol; Dietary Fats; Female; Lactobacillus plantarum; Leptin; Mice; Mice, Inbred C57BL; Obesity; Triglycerides; Weight Gain

The effect of Eriobotrya japonica Lindl. (loquat) on insulin resistance was examined in mice fed a high-fat (HF) diet. First, the mice were divided randomly into two groups: the control (CON) group was fed a low-fat diet, whereas the experimental group was fed with a 45% HF diet for 10 weeks. After 6 weeks of induction, the HF group was subdivided into five groups and was given orally loquat or not for 4 weeks afterward. It was demonstrated that loquat was effective in ameliorating the HF diet-induced hyperglycemia, hyperleptinemia, hyperinsulinemia and hypertriglyceridemia, as well as in decreasing the levels of free fatty acid (FFA), but increasing the adipose PPARγ (peroxisomal proliferator-activated receptor γ) and hepatic PPARα mRNA levels. Loquat significantly decreased the body weight gain, weights of white adipose tissue and visceral fat accompanying the suppressed leptin mRNA levels. Loquat not only suppressed the hepatic mRNA levels of enzymes involved in fatty acid and triacylglycerol synthesis and lowered the sterol regulatory element binding protein-1c (SREBP-1c) mRNA level, but also affected fatty acid oxidation enzyme levels. These regulations may contribute to triacylglycerol accumulation in white adipose tissue. The findings provide a nutritional basis for the use of loquat as a functional food factor that may have benefits for the prevention of hyperlipidemia and diabetes.

Topics: Adipokines; Adipose Tissue; Administration, Oral; AMP-Activated Protein Kinases; Animals; Eriobotrya; Fatty Acids, Nonesterified; Glucose Tolerance Test; Hyperinsulinism; Hyperlipidemias; Hypertriglyceridemia; Insulin Resistance; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Phytotherapy; Plant Extracts; PPAR gamma; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Weight Gain

Topics: Appetite; Energy Intake; Homeostasis; Humans; Insulin; Leptin; Motor Activity; Weight Gain

The long prevailing view that obesity is generally associated with beneficial effects on the skeleton has recently been challenged. Apolipoprotein E (apoE) is known to influence both adipose tissue and bone. The goal of the current study was to examine the impact of apoE on the development of fat mass and bone mass in mice under conditions of diet-induced obesity (DIO). Four week-old male C57BL/6 (WT) and apoE-deficient (apoE(-/-)) mice received a control or a diabetogenic high-fat diet (HFD) for 16 weeks. The control-fed apoE(-/-) animals displayed less total fat mass and higher lumbar trabecular bone volume (BV/TV) than WT controls. When stressed with HFD to induce obesity, apoE(-/-) mice had a lower body weight, lower serum glucose, insulin and leptin levels and accumulated less white adipose tissue mass at all sites including bone marrow. While WT animals showed no significant change in BV/TV and bone formation rate (BFR), apoE deficiency led to a decrease of BV/TV and BFR when stressed with HFD. Bone resorption parameters were not affected by HFD in either genotype. Taken together, under normal dietary conditions, apoE-deficient mice acquire less fat mass and more bone mass than WT littermates. When stressed with HFD to develop DIO, the difference of total body fat mass becomes larger and the difference of bone mass smaller between the genotypes. We conclude that apoE is involved in an inverse regulation of bone mass and fat mass in growing mice and that this effect is modulated by diet-induced obesity.

Topics: Adipocytes; Adipose Tissue; Animals; Apolipoproteins E; Blood Glucose; Bone Marrow Cells; Bone Remodeling; Cell Proliferation; Diet; Dietary Fats; Epididymis; Insulin; Leptin; Lipids; Male; Mice; Mice, Inbred C57BL; Obesity; Organ Size; Spine; Subcutaneous Tissue; Viscera; Weight Gain

Because rearing rats in large litters (LLs) protects them from becoming obese, we postulated that LL rearing would protect rats selectively bred to develop diet-induced obesity (DIO) from becoming obese by overcoming their inborn central leptin resistance. Male and female DIO rats were raised in normal litters (NLs; 10 pups/dam) or LLs (16 pups/dam) and assessed for anatomical, biochemical, and functional aspects of leptin sensitivity at various ages when fed low-fat chow or a 31% fat high-energy (HE) diet. LL rearing reduced plasma leptin levels by postnatal day 2 (P2) and body weight gain by P8. At P16, LL DIO neonates had increased arcuate nucleus (ARC) binding of leptin to its extracellular receptors and at P28 an associated increase of their agouti-related peptide and alpha-MSH axonal projections to the paraventricular nucleus. Reduced body weight persisted and was associated with increased ARC leptin receptor binding and sensitivity to the anorectic effects of leptin, reduced adiposity, and enhanced insulin sensitivity in LL DIO rats fed chow until 10 wk of age. The enhanced ARC leptin receptor binding and reduced adiposity of LL DIO rats persisted after an additional 5 wk on the HE diet. Female LL DIO rats had similar reductions in weight gain on both chow and HE diet vs. normal litter DIO rats. We postulate that LL rearing enhances DIO leptin sensitivity by lowering plasma leptin levels and thereby increasing leptin receptor availability and that this both enhances the ARC-paraventricular nucleus pathway development and protects them from becoming obese.

Topics: Adiposity; Agouti-Related Protein; alpha-MSH; Animals; Animals, Newborn; Arcuate Nucleus of Hypothalamus; Body Weight; Breeding; Diet; Eating; Female; Gestational Age; Immunohistochemistry; Lactation; Leptin; Litter Size; Male; Obesity; Paraventricular Hypothalamic Nucleus; Protein Binding; Rats; Receptors, Leptin; Time Factors; Weaning; Weight Gain

Appetite-related hormones may play an important role in weight regain after obesity therapy.. Our objective was to investigate the potential involvement of ghrelin, leptin, and insulin plasma levels in weight regain after a therapeutic hypocaloric diet.. A group of obese/overweight volunteers (49 women and 55 men; 35 ± 7 yr; 30.7 ± 2.4 kg/m(2)) followed an 8-wk hypocaloric diet (-30% energy expenditure) and were evaluated again 32 wk after treatment. Body weight as well as plasma fasting ghrelin, leptin, and insulin concentrations were measured at three points (wk 0, 8, and 32).. After the 8-wk hypocaloric diet, the average weight loss was -5.0 ± 2.2% (P < 0.001). Plasma leptin and insulin concentrations decreased significantly, whereas ghrelin levels did not markedly change. In the group regaining more than 10% of the weight loss, leptin levels were higher (P < 0.01), whereas ghrelin levels were lower (P < 0.05). No differences were observed in insulin levels. Weight regain at wk 32 was negatively correlated with ghrelin and positively associated with leptin levels at baseline (wk 0) and endpoint (wk 8). These outcomes showed a gender-specific influence, being statistically significant among men for ghrelin and between women for leptin. Moreover, a decrease in ghrelin after an 8-wk hypocaloric diet was related to an increased risk for weight regain (odds ratio = 3.109; P = 0.008) whereas a greater reduction in leptin (odds ratio = 0.141; P = 0.001) was related to weight-loss maintenance.. Subjects with higher plasma leptin and lower ghrelin levels at baseline could be more prone to regain lost weight, and hormones levels could be proposed as biomarkers for predicting obesity-treatment outcomes.

Topics: Adult; Analysis of Variance; Biomarkers; Diet, Reducing; Female; Ghrelin; Humans; Insulin; Leptin; Male; Obesity; Overweight; Radioimmunoassay; Statistics, Nonparametric; Surveys and Questionnaires; Weight Gain

An increase in brain suppressor of cytokine signaling 3 (SOCS3) has been implicated in the development of both leptin and insulin resistance. Socs3 mRNA is localized throughout the brain, and it remains unclear which brain areas are involved in the effect of SOCS3 levels on energy balance. We investigated the role of SOCS3 expressed in the mediobasal hypothalamus (MBH) in the development of diet-induced obesity in adult rats. Socs3 mRNA was down-regulated by local injection of adeno-associated viral vectors expressing a short hairpin directed against Socs3, after which we determined the response to high-fat high-sucrose choice diet. In contrast to neuronal Socs3 knockout mice, rats with SOCS3 knockdown limited to the MBH showed increased body weight gain, larger amounts of white adipose tissue, and higher leptin concentrations at the end of the experiment. These effects were partly due to the decrease in locomotor activity, as 24 h food intake was comparable with controls. In addition, rats with Socs3 knockdown in the MBH showed alterations in their meal patterns: average meal size in the light period was increased and was accompanied by a compensatory decrease in meal frequency in the dark phase. In addition, neuropeptide Y (Npy) mRNA levels were significantly increased in the arcuate nucleus of Socs3 knockdown rats. Since leptin is known to stimulate Npy transcription in the absence of Socs3, these data suggest that knockdown of Socs3 mRNA limited to the MBH increases Npy mRNA levels, which subsequently decreases locomotor activity and alters feeding patterns.

Topics: Animals; Body Composition; Body Weight; Brain; Down-Regulation; Energy Metabolism; Feeding Behavior; Gene Knockdown Techniques; HEK293 Cells; Humans; Hypothalamus; Insulin; Leptin; Male; Neuropeptide Y; Obesity; Rats; Rats, Wistar; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Suppressor of Cytokine Signaling Proteins; Weight Gain

The adipokine hormone leptin triggers signals in the brain that ultimately lead to decreased feeding and increased energy expenditure. However, obesity is most often associated with elevated plasma leptin levels and leptin resistance. Suppressor of cytokine signaling (SOCS)-3 and protein-tyrosine phosphatase 1B (PTP-1B) are two endogenous inhibitors of tyrosine kinase signaling pathways and suppress both insulin and leptin signaling via different molecular mechanisms. Brain-specific inactivation of these genes individually in the mouse partially protects against diet-induced obesity (DIO) and insulin resistance. The aim of this study was to investigate possible genetic interactions between these two genes to determine whether combined reduction in these inhibitory activities results in synergistic, epistatic, or additive effects on energy balance control.. We generated mice with combined inactivation of the genes coding for SOCS-3 and PTP-1B in brain cells, examined their sensitivity to hormone action, and analyzed the contribution of each gene to the resulting phenotype.. Surprisingly, the Nestin-Cre mice used to mediate gene inactivation displayed a phenotype. Nonetheless, combined inactivation of SOCS-3 and PTP-1B in brain revealed additive effects on several parameters, including partial resistance to DIO and associated glucose intolerance. In addition, synergistic effects were observed for body length and weight, suggesting possible compensatory mechanisms for the absence of either inhibitor. Moreover, a SOCS-3-specific lean phenotype was revealed on the standard diet.. These results show that the biological roles of SOCS-3 and PTP-1B do not fully overlap and that targeting both factors might improve therapeutic effects of their inhibition in obesity and type 2 diabetes.

Topics: Animals; Crosses, Genetic; Energy Metabolism; Female; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation; Obesity; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Weight Gain

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

The aim of our study was to investigate the impact of typical and atypical antipsychotic drugs on leptin concentration in blood and changes in the receptor expression in the hypothalamus of male Wistar rats.. From the age of 13 to 18 weeks, three groups of 20 animals were fed an average dose of 3.5 + 0.03 mg/ kg body weight (BW) haloperidol; 30.6 + 0.22 mg/kg BW clozapine; or 14.9 + 0.13 mg/kg BW ziprasidone in ground food pellets containing 15% fat. Twenty control animals received no drugs. Blood samples were taken at week 14, 16, and 19. Locomotor activity and exploratory behavior were measured using the alcove test at weeks 15 and 17. The expression of the hypothalamic leptin receptor in rat brains was determined by using a Western blot.. Rats medicated with haloperidol and ziprasidone showed a significantly decreased percentage weight gain and food consumption. We observed no differences in the alcove test, but locomotor activity was significantly reduced in the haloperidol group. Except for rats in the clozapine and ziprasidone groups, after 2 weeks of drug application, we found no changes in the leptin blood concentrations among the four groups or animals within each group. Moreover, we did not find specific differences in hypothalamic leptin receptor expression among the groups.. We concluded that in male Wistar rats during this treatment period, the tested drugs did not act directly on the leptin regulatory system. We recommend further studies using long-term treatment of different rat strains.

Topics: Animals; Antipsychotic Agents; Blotting, Western; Clozapine; Eating; Exploratory Behavior; Haloperidol; Hypothalamus; Leptin; Male; Motor Activity; Piperazines; Rats; Rats, Wistar; Receptors, Leptin; Thiazoles; Time Factors; Weight Gain

Weight gain is an adverse metabolic effect in some children with epilepsy. The studies done to detect the effect of antiepileptic drugs and weight homeostatic hormones, insulin and leptin, were limited and controversial.. We evaluated the serum leptin and insulin as predictors of weight gain in children receiving long-term treatment with valproate (VPA), carbamazepine (CBZ), lamotrigine (LTG). This study included 90 patients (treated: 70; untreated: 20). Serum lipid profile, insulin and leptin were measured.. BMI, serum leptin and insulin were significantly elevated in VPA compared with controls, untreated patients and those treated with CBZ, LTG and combined therapy with LTG. Girls on VPA had higher BMI and leptin levels than boys. With VPA, serum insulin was correlated with BMI (r=0.625, p<0.01), leptin (r=0.823, p<0.001), treatment duration (r=0.775, p<0.01) and VPA dose (r=0.975, p<0.0001). Serum leptin was correlated with age (r=0.980, p<0.0001), BMI (r=0.704, p<0.01), serum insulin (r=0.823, p<0.001), LDL-c (r=0.630, p<0.01), HDL-c (r=-0.880, p<0.001), treatment duration (r=0.770, p<0.01) and VPA dose (r=0.970, p<0.001). BMI is correlated with serum insulin, leptin, LDL-c (r=0.835, p<0.001) and HDL-c (r=-0.955, p<0.0001).. Hyperinsulinemia and hyperleptinemia are common with VPA and marked among epileptic children who gained weight suggesting states of insulin and leptin resistances. These alterations were not demonstrated with CBZ or LTG. The relationship between VPA, leptin and weight seems to be gender specific. Serum leptin may serve as a sensitive parameter for weight gain and reduction with intervention programs during follow-up of girls with epilepsy.

Topics: Adolescent; Age Factors; Anticonvulsants; Body Mass Index; Carbamazepine; Case-Control Studies; Child; Epilepsy; Female; Humans; Hyperinsulinism; Insulin; Lamotrigine; Leptin; Lipids; Male; Predictive Value of Tests; Risk Assessment; Sex Factors; Triazines; Valproic Acid; Weight Gain

The aim of our study was to evaluate the influence of surgical removal of pheochromocytoma on the endocrine function of adipose tissue and subclinical inflammation as measured by circulating C-reactive protein (CRP) levels. Eighteen patients with newly diagnosed pheochromocytoma were included into study. Anthropometric measures, biochemical parameters, serum CRP, leptin, adiponectin and resistin levels were measured at the time of diagnosis and six months after surgical removal of pheochromocytoma. Surgical removal of pheochromocytoma significantly increased body weight, decreased both systolic and diastolic blood pressure, fasting blood glucose and glycated hemoglobin levels. Serum CRP levels were decreased by 50 % six months after surgical removal of pheochromocytoma (0.49+/-0.12 vs. 0.23+/-0.05 mg/l, p<0.05) despite a significant increase in body weight. Serum leptin, adiponectin and resistin levels were not affected by the surgery. We conclude that increased body weight in patients after surgical removal of pheochromocytoma is accompanied by an attenuation of subclinical inflammation probably due to catecholamine normalization. We failed to demonstrate an involvement of the changes in circulating leptin, adiponectin or resistin levels in this process.

Topics: Adiponectin; Adipose Tissue; Adrenal Gland Neoplasms; Adrenalectomy; Adult; Biomarkers; Blood Pressure; C-Reactive Protein; Down-Regulation; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Pheochromocytoma; Resistin; Treatment Outcome; Weight Gain

Small birth weight and excess of early protein intake are suspected to enhance later adiposity. The present study was undertaken to determine the impact of diets differing in protein content on short-term growth, adipose tissue development, and the insulin-like growth factor (IGF) system in piglets. Normal (NW) and small (SW) birth weight piglets were fed milk-replacers formulated to provide an adequate (AP) or a high protein (HP) supply between 7 and 28 d of age. The fractional growth rate was higher (p < 0.01) in SW than in NW piglets. At 7 d of age, the lower (p < 0.05) weight of perirenal adipose tissue relative to body mass in SW than in NW piglets did not involve significant changes in plasma IGF-I, leptin, or insulin-like growth factor binding protein levels, but involved differences (p < 0.05) in the expression of IGF-I and leptin in adipose tissue. Growth rates did not differ between AP and HP piglets. At 28 d of age, HP piglets had lower (p < 0.001) relative perirenal adipose tissue weight but did not differ clearly from AP piglets with regard to the IGF system. It remains to be determined whether piglets fed such a high protein intake will stay subsequently with a low adiposity.

Topics: Adipose Tissue; Adiposity; Age Factors; Aging; Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Birth Weight; Diet; Eating; Fetal Growth Retardation; Insulin-Like Growth Factor Binding Proteins; Leptin; Milk Proteins; Somatomedins; Swine; Weight Gain

Most previous studies investigating amino acid levels in anorexia nervosa (AN) have focused on acutely underweight patients. The present study assessed the availability of aromatic amino acids in the plasma of weight-recovered outpatients with AN (recAN) in comparison to acutely underweight AN patients (acAN) and healthy control woman (HCW).. Plasma tryptophan (TRP), tyrosine (TYR), and phenylalanine (PHEN) as well as leptin concentration were determined in 32 recAN, 32 acAN, and 32 HCW.. Both recAN and acAN patients showed significantly lower levels of TRP and PHEN when compared to HCW. TYR was reduced in acAN patients only.. Normal weight and normal leptin levels but lower availability of TRP and PHEN in recAN patients might indicate that outside a tightly controlled setting these patients still engage in abnormal eating patterns. Reduced peripheral availability of these precursor amino acids could impact on 5-HT and catecholamine functioning in the brain.

Topics: Acute Disease; Adolescent; Adult; Aged; Anorexia Nervosa; Child; Convalescence; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Leptin; Middle Aged; Phenylalanine; Tryptophan; Weight Gain; Young Adult

Important and novel roles for neuropeptide Y (NPY) signaling in the control of bone homeostasis have recently been identified, with deletion of either the Y1 or Y2 receptors resulting in a generalized increase in bone formation. Whereas the Y2 receptor-mediated anabolic response is mediated by a hypothalamic relay, the Y1-mediated response is likely mediated by osteoblastic Y1 receptors. The presence of Y1 receptors on osteoblasts and various other peripheral tissues suggests that, in addition to neuronal input, circulating factors may also interact with the Y1-mediated pathways. The skeletal and adipose tissue (peripheral and marrow) responses to Y1 receptor deficiency were examined after (1) leptin deficiency, (2) gonadectomy, and (3) hypothalamic NPY overexpression. Bone formation was consistently increased in intact Y1(-/-) mice. However, the hypogonadism of gonadectomy or leptin deficiency blocked this anabolism in male Y1(-/-) mice, whereas females remained unchanged. The Y1-mediated bone anabolic pathway thus seems to be dependent on the presence of intact androgen signaling. Y1 deficiency also led to increased body weight and/or adiposity in all experimental models, with the exception of male ob/ob, showing a general adipogenic effect of Y1 deficiency that is not dependent on androgens. Interestingly, marrow adipocytes were regulated differently than general adipose depots in these models. Taken together, this interaction represents a novel mechanism for the integration of endocrine and neural signals initiated in the hypothalamus and provides further insight into the coordination of bone and energy homeostasis.

Topics: Adipose Tissue; Adiposity; Animals; Blood Glucose; Body Weight; Bone and Bones; Bone Resorption; Female; Gene Deletion; Gonadal Steroid Hormones; Homeostasis; Leptin; Male; Mice; Neuropeptide Y; Obesity; Osteogenesis; Receptors, Neuropeptide Y; Signal Transduction; Thinness; Weight Gain

The offspring of high fat (HF) diet-fed rats display increased body weight during adulthood. However, it is not known whether the changes in appetite regulation in these animals occur in utero or postnatally. We investigated the effects of maternal obesity induced by a HF diet prior to and during pregnancy on leptin and insulin signaling and the expression of orexigenic and anorexigenic peptides in term fetal hypothalami. The consumption of a HF diet prior to and during pregnancy resulted in obesity in HF female rats; additionally, HF female rats exhibited hyperinsulinemia and hyperleptinemia which were exaggerated in late gestation compared with control female rats that were fed a standard rodent laboratory chow (LC). Term fetuses of HF female rats (FHF) also had significantly higher serum leptin and insulin levels compared with control fetuses (FLC) while there was no difference in average fetal weight between the two groups. FHF hypothalami showed elevated levels of mRNA and proteins for leptin long receptor and insulin receptor beta-subunit. However, the protein levels of signal transducers and activators of transcription-3 and insulin receptor substrate-2, the downstream signaling components of leptin and insulin signaling respectively were decreased. Also, FHF hypothalami had increased mRNA levels of neuropeptide Y and agouti-related polypeptide indicating that orexigenic neuropeptides in HF progeny are already upregulated by term fetal stage. Additionally, the mRNA levels of pro-opiatemelanocortin and melanocortin receptor-4 were also increased in the HF fetal hypothalami. These findings indicate potential programming effects of an altered intrauterine environment induced by HF diet consumption on appetite-regulating neuropeptides and leptin and insulin signaling in the late fetal period.

Topics: Animals; Blood Glucose; Diet; Dietary Fats; Female; Fetus; Hypothalamus; Insulin; Leptin; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Weight Gain

The health benefits of pomegranate consumption have recently received considerable scientific focus, with most studies examining fruit and/or juice consumption. Pomegranate seed oil (POMo) is a rich source of 9-cis, 11-trans conjugate linolenic acid (CLA), which may offset the side-effects associated with weight gain. Male, wild-type CD-1 mice were divided into one of three groups (twenty per group): high-fat (HF), HF+seed oil (HF + POMo) or lean control (LN). In HF and HF + POMo, mice were provided access ad libitum to a high-fat chow (60 % of energy from fat). HF + POMo was supplemented with 61.79 mg POMo/d. LN consumed a restricted low-fat (10 % of energy from fat) chow to maintain body weight within 5 % of initial weight. Plasma was analysed for biomarkers associated with cholesterol profile (total cholesterol, HDL and TAG), glucose sensitivity (glucose and insulin), adipose tissue accumulation (leptin and adiponectin) and systemic low-grade inflammation (C-reactive protein and haptoglobin). The key findings of this study were that weight gain was associated with an increase in biomarkers of cholesterol profile, glucose sensitivity, adipose tissue accumulation and systemic low-grade inflammation (P < 0.05). POMo only altered body weight accumulation, final body weight, leptin, adiponectin and insulin (P < 0.05). We found that despite a similar level of energy intake, HF mice had a greater concentration of leptin and a lower concentration of adiponectin compared to HF + POMo mice. POMo intake was associated with an improvement in insulin sensitivity, suggesting that risk of developing type 2 diabetes may have been reduced; however, CVD risk did not change.

Topics: Adiponectin; Animals; Biomarkers; Body Composition; C-Reactive Protein; Cholesterol; Diabetes Mellitus, Type 2; Dietary Fats; Dietary Fats, Unsaturated; Dietary Supplements; Energy Intake; Haptoglobins; Insulin; Leptin; Lythraceae; Male; Mice; Mice, Inbred Strains; Plant Oils; Random Allocation; Risk; Seeds; Weight Gain

The fuel-sensing enzyme AMP-activated protein kinase (AMPK) has been implicated in central nervous system control of energy balance. Hypothalamic AMPK activity is increased by food deprivation, and this elevation is inhibited by refeeding or by leptin treatment. The contribution of extrahypothalamic AMPK activity in energy balance control has not been addressed. Here, we investigate the effects of physiological state on the AMPK activity in hindbrain nucleus tractus solitarius (NTS) neurons because treatments that reduce energy availability in these neurons trigger behavioral, endocrine, and autonomic responses to restore energy balance. Food-deprived rats showed significantly increased AMPK activity in both NTS- and hypothalamus-enriched lysates compared with those that were ad libitum fed. Pharmacological inhibition of AMPK activity in medial NTS neurons, by intraparenchymal injection of compound C, suppressed food intake and body weight gain compared with vehicle. Fourth ventricle (4th i.c.v.) compound C delivery increased heart rate and spontaneous activity in free-moving rats. Suppression of AMPK activity has been implicated in leptin's anorectic action in the hypothalamus. Given the role of leptin signaling in food intake inhibition within the medial NTS, we also examined whether stimulation of hindbrain AMPK by 4th i.c.v. administration of 5-aminoimidazole-4-carboxamide-riboside (AICAR), an AMP-mimicking promoter of AMPK activity, could attenuate the inhibition of food intake by 4th i.c.v. leptin. The intake-suppressive effects of leptin (at 2 and 4 h) were completely reversed by AICAR. We conclude that 1) hindbrain AMPK activity contributes to energy balance control through regulation of food intake and energy expenditure, 2) leptin's intake-reducing effects in the NTS are mediated by AMPK, and 3) central nervous system AMPK controls whole-body homeostasis at anatomically distributed sites across the neuraxis.

Topics: Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Body Weight; Eating; Energy Metabolism; Homeostasis; Hypoglycemic Agents; Leptin; Male; Protein Kinase Inhibitors; Rats; Rats, Sprague-Dawley; Rhombencephalon; Ribonucleotides; Second Messenger Systems; Weight Gain

Maternal obesity accentuates offspring obesity in dams bred to develop diet-induced obesity (DIO) on a 31% fat, high energy (HE) diet but has no effect on offspring of diet-resistant (DR) dams. Only DIO dams became obese on HE diet when they and DR dams were fed 5% fat chow or HE diets throughout gestation and lactation. Leptin sensitivity of dissociated arcuate (ARC) and ventromedial (VMN) hypothalamic nucleus neurons from the 3- to 4-wk-old offspring was assessed using fura-2 calcium imaging to monitor leptin-induced changes in intracellular calcium ([Ca(2+)](i)) as an index of neuronal activity. At 0.1, 1, 10 fmol/l leptin, approximately 4 times more VMN and ARC neurons were excited than inhibited by leptin. In the VMN, leptin excited up to 41% fewer neurons, and these excited neurons were less sensitive to increasing doses of leptin in DIO compared with DR offspring. Also, maternal HE diet intake decreased the percentage of leptin-excited VMN neurons in both DIO and DR offspring and decreased the percentage of leptin-inhibited VMN neurons by 36% only in DIO offspring. In the ARC, there were no genotype or maternal diet effects on the percentage of ARC neurons excited by leptin. However, those DR neurons that were leptin excited were more sensitive to leptin than were those from DIO offspring. These data suggest that reduced responsiveness of DIO VMN neurons to leptin's excitatory effects may be an important contributing factor to the reduced anorectic and thermogenic leptin responsiveness of DIO rats in vivo.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Blood Glucose; Calcium Signaling; Diet; Dose-Response Relationship, Drug; Energy Intake; Genotype; Insulin; Leptin; Male; Neurons; Obesity; Rats; RNA, Messenger; Ventromedial Hypothalamic Nucleus; Weight Gain

To investigate whether change in leptin content of breast milk during lactation acts on neonatal body weight gain.. In total 15 lactating women and their 15 term infants were involved in the study. Breast milk and neonatal serum samples were obtained from the same women and their neonates on the 1st day and any day between the 21st and 30th days after birth. Breast milk and serum leptin concentrations were determined by radioimmunoassay. Anthropometric indexes of the infants were recorded.. The study was completed with 15 multiparious mothers aged 19-37 years and their infants. The mean collection time of the first samples after birth was 6.07 +/- 1.94 h. The leptin level in the mature milk was significantly higher than in the colostrum (p < 0.001). Neonatal weight and height were significantly increased on 21-30 lactation days compared to 1st day of lactation (p < 0.05 and p < 0.001, respectively). The leptin concentration in the mature milk was negatively correlated with delta BMI (r =-0.53; p < 0.05). The delta breast milk leptin concentration was also found to be inversely correlated with delta BMI (r =-0.529; p < 0.05).. The results of this study have suggested that change in the leptin content of breast milk during lactation might play a role in the regulation of weight gain in healthy neonates.

Topics: Adult; Body Mass Index; Breast Feeding; Colostrum; Female; Humans; Infant, Newborn; Leptin; Longitudinal Studies; Male; Milk, Human; Weight Gain; Young Adult

The role of cortisol in mediating basal metabolic rate (BMR) changes that accompany the adjustment of maternal body weight (BW) and body composition during pregnancy is unknown. We tested whether increase in BMR during pregnancy is explained by variations in cortisol secretion. Longitudinal changes in BW, fat mass (FM), fat-free mass (FFM), BMR, hormonal, and metabolic parameters in 31 parous Caucasian women at gestational weeks 12, 26, and 36 were examined. Individual differences (Delta) between the last and the first measurement occasions for each variable were calculated. By gestational week 36, BW and BMR increased while both FFM/FM and BMR/BW ratio decreased (P < 0.001 for all) suggesting higher proportion of FM accretion. Cortisol, leptin, and insulin-like growth factor-1 (IGF-1) concentration rose, whereas non-placental growth hormone (GH) and thyroid hormones declined (P < 0.001 for all). Insulin resistance changed; basal glucose (P < 0.001) and ghrelin (P < 0.014) declined, whereas insulin (P < 0.001), homeostatic model index (HOMA-IR) (P = 0.041), and free fatty acid (FFA) concentration (P = 0.007) increased. The elevation in BMR showed inverse correlations with DeltaBW (r = 0.37, P = 0.047) and Deltacortisol (r = -0.53, P = 0.004). Significant portion (51.6%) of the variation in BMR change was explained by increases of cortisol (27.1%), FFA (13.4%), and free triiodothyronine (11.1%). In conclusion, the changes in maternal cortisol concentration are in relationship with changes in BMR and BW, further suggesting that increased cortisol secretion during pregnancy could be linked with the maintenance of maternal BW and body composition.

Topics: Adult; Basal Metabolism; Blood Glucose; Body Composition; Fatty Acids, Nonesterified; Female; Gestational Age; Ghrelin; Growth Hormone; Humans; Hydrocortisone; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Pregnancy; Thyroid Hormones; Weight Gain

In rats selectively bred to develop diet-induced obesity (DIO) 3 wk of postweaning exercise reduces weight and adipose regain for 10 wk after exercise cessation, despite intake of 31% fat high-energy (HE) diet. To test the hypothesis that this effect is due to increased central leptin sensitivity, 4-wk-old DIO rats were fed the HE diet and left sedentary (Sed), exercised for 3 wk, and then remained sedentary for 10 additional weeks (Ex/Sed) or continued exercise for a full 13 wk (Ex). After 3 wk, leptin (5 mg/kg ip) induced a 36% decrease in 24-h food intake in Ex rats, while Sed rats had no change in 24-h intake. Ex rats also had 23% more leptin-induced phospho-STAT3 (pSTAT3)-expressing neurons in the arcuate nucleus (ARC) and 95% and 68% higher (125)I-labeled leptin receptor binding in the ventromedial and dorsomedial nuclei than did Sed rats, respectively. At 7 wk after onset, leptin decreased 24-h intake by 20% in Ex and 24% in Ex/Sed rats without altering Sed intake. After a total of 13 wk, compared with Sed rats, Ex and Ex/Sed rats had 58% and 38% less fat, respectively, but leptin failed to decrease food intake in any group. Nevertheless, Ex, but not Ex/Sed rats, still had 32% more ARC leptin-induced pSTAT3-expressing neurons than Sed rats. These data suggest that brief postweaning exercise in DIO rats that are inherently leptin resistant causes a sustained resistance to obesity on HE diet, which is, in part, due to increased central leptin sensitivity.

Topics: Adipose Tissue; alpha-MSH; Animals; Arcuate Nucleus of Hypothalamus; Blood Glucose; Body Temperature Regulation; Caloric Restriction; Diet; Eating; Extracellular Signal-Regulated MAP Kinases; Immunohistochemistry; Insulin; Leptin; Male; Obesity; Paraventricular Hypothalamic Nucleus; Physical Conditioning, Animal; Rats; Signal Transduction; STAT3 Transcription Factor; Telemetry; Weight Gain

Leptin and adiponectin are adipocyte-secreted hormones that regulate energy homeostasis and metabolism. Because their roles in the neonatal period and in early childhood are poorly understood, we aimed in this prospective cohort study to determine the extent to which umbilical cord blood leptin and adiponectin concentrations predict measures of adiposity and growth at 3 years of age.. We studied 588 children participating in the prospective prebirth cohort study Project Viva. We examined associations of cord blood leptin and adiponectin levels with weight changes during the first 6 months of life, 3-year circulating leptin and adiponectin concentrations, and the following adiposity-related outcomes at 3 years of age: BMI z score, height-for-age z score, and sums of triceps and subscapular skinfold thicknesses to represent overall adiposity, as well as subscapular/triceps skinfold ratio to represent central adiposity.. Cord blood leptin and adiponectin were each directly associated with the duration of gestation and birth weight for gestational age z scores. Cord blood leptin levels were negatively associated with change in weight-for-length, weight-for-age, and length-for-age z scores between birth and 6 months of age. Similarly, cord blood adiponectin was negatively associated with change in weight-for-length and weight-for-age z scores. After adjusting for several maternal and child factors related to obesity, each 10 ng/mL increment of cord blood leptin was associated with a reduction in BMI z score and higher leptin levels at 3 years but not with skinfold thicknesses. Each 10 microg/mL increment of cord blood adiponectin was positively associated with a higher subscapular skinfold thickness/triceps skinfold thickness ratio at 3 years.. Lower cord blood leptin levels are associated with smaller size at birth but more pronounced weight gain in the first 6 months of life and higher BMI at 3 years of age. Cord blood adiponectin levels are also directly associated with birth weight for gestational age, inversely associated with weight gain in the first 6 months of life, and predict an increase in central adiposity at age 3 years.

Topics: Adiponectin; Adiposity; Body Height; Body Mass Index; Child, Preschool; Female; Fetal Blood; Humans; Leptin; Male; Prospective Studies; Weight Gain

For experimental research on type 2 diabetes mellitus, a diet-induced obesity-dependent diabetes model developed using genetically normal animals is essential. However, attempts at feeding a high-fat diet (HFD) to major inbred strains of mice have not resulted in the establishment of an ideal model. Here, we show that BDF1 mice, the F(1) hybrids of C57BL/6 and DBA/2 normal strains, develop HFD-induced obesity-dependent diabetes. BDF1 mice fed a HFD gained weight rapidly and developed severe diabetes characterized by hyperglycemia, glucosuria, and elevation of hemoglobin A(1C) levels in 3 to 4 months. The glucose tolerance of the diabetic mice was significantly impaired, and the elevation of plasma insulin after a glucose load was significantly reduced. Isolated pancreatic islets of HFD-fed BDF1 mice showed decreased insulin content and a reduced insulin secretory response to higher concentrations of glucose. Immunohistochemical analysis of the pancreas showed reduced staining intensity to insulin and aberrant distribution of glucagon-positive cells in diabetic BDF1 mice. These observations suggest the cause of the diabetes in HFD-fed BDF1 mice to be dysfunction of the pancreatic beta-cells, which do not produce or secrete enough insulin to compensate for insulin resistance. BDF1 mice fed a HFD showing obesity-dependent diabetes are suggested to be an appropriate animal model of type 2 diabetes mellitus. This model would be useful for exploring the mechanism of obesity-dependent type 2 diabetes mellitus and evaluating antiobesity and antidiabetic drugs.

Topics: Animals; Blood Glucose; Cholesterol; Diabetes Mellitus, Type 2; Dietary Fats; Fatty Acids, Nonesterified; Glucose Tolerance Test; Glycosuria; Insulin; Insulin Secretion; Islets of Langerhans; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred Strains; Models, Biological; Obesity; Triglycerides; Weight Gain

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

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

Obesity seems to be linked to the hypothalamic involvement in craniopharyngioma. We evaluated the pre-surgery relationship between the degree of this involvement on magnetic resonance imaging and insulin resistance, as evaluated by the homeostasis model insulin resistance index (HOMA). As insulin-like growth factor 1, leptin, soluble leptin receptor (sOB-R) and ghrelin may also be involved, we compared their plasma concentrations and their link to weight change.. 27 children with craniopharyngioma were classified as either grade 0 (n = 7, no hypothalamic involvement), grade 1 (n = 8, compression without involvement), or grade 2 (n = 12, severe involvement).. Despite having similar body mass indexes (BMI), the grade 2 patients had higher glucose, insulin and HOMA before surgery than the grade 0 (P = 0.02, <0.05 and 0.02 respectively) and 1 patients (P < 0.02 and <0.03 for both insulin and HOMA). The grade 0 (5.8 +/- 4.9) and 1 (7.2 +/- 5.3) patients gained significantly less weight (kg) during the year after surgery than did the grade 2 (16.3 +/- 7.4) patients. The pre-surgery HOMA was positively correlated with these weight changes (P < 0.03). The data for the whole population before and 6-18 months after surgery showed increases in BMI (P < 0.0001), insulin (P < 0.005), and leptin (P = 0.0005), and decreases in sOB-R (P < 0.04) and ghrelin (P < 0.03).. The hypothalamic involvement by the craniopharyngioma before surgery seems to determine the degree of insulin resistance, regardless of the BMI. The pre-surgery HOMA values were correlated with the post-surgery weight gain. This suggests that obesity should be prevented by reducing inn secretion in those cases with hypothalamic involvement.

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Craniopharyngioma; Female; Ghrelin; Homeostasis; Hormone Replacement Therapy; Humans; Hydrocortisone; Hypophysectomy; Hypopituitarism; Hypothalamus; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Male; Models, Biological; Obesity; Pituitary Neoplasms; Receptors, Leptin; Retrospective Studies; Single-Blind Method; Thyroxine; Weight Gain

Leptin, a pleiotropic adipokine, is a central regulator of appetite and weight and a key immunomodulatory protein. Although inborn leptin deficiency causes weight gain, it is unclear whether induced leptin deficiency in adult wild-type animals would be orexigenic. Previous work with a potent competitive leptin antagonist did not induce a true metabolic state of leptin deficiency in mice because of a short circulating half-life. In this study, we increased the half-life of the leptin antagonist by pegylation, which resulted in significantly increased bioavailability and retaining of antagonistic activity. Mice administered the pegylated antagonist showed a rapid and dramatic increase in food intake with weight gain. Resulting fat was confined to the mesenteric region with no accumulation in the liver. Serum cholesterol, triglyceride, and hepatic aminotransferases remained unaffected. Weight changes were reversible on cessation of leptin antagonist treatment. The mechanism of severe central leptin deficiency was found to be primarily caused by blockade of transport of circulating leptin across the blood-brain barrier with antagonisms at the arcuate nucleus playing a more minor role. Altogether we introduce a novel compound that induces central and peripheral leptin deficiency. This compound should be useful in exploring the involvement of leptin in metabolic and immune processes and could serve as a therapeutic for the treatment of cachexia.

Topics: Adipose Tissue; Animals; Blood-Brain Barrier; Eating; Female; Humans; Leptin; Male; Polyethylene Glycols; Weight Gain

1. A total of 320-d-old Ross broilers were used in a 6-week study to investigate the effects of feeding lower energy and protein diets from d 8 to 14 on growth performance, blood profiles, and gene expression of leptin and myostatin. 2. Broilers were randomly allotted to 4 treatments, each treatment applied to 4 pens with 20 birds in each. During first week, all the birds were fed on a common starter diet (13.4 MJ ME/kg, 230 g/kg CP and 11.0 g/kg lysine). The birds were then subjected to their respective treatment diets from d 8 to 14. Treatment diets comprised two ME levels, 13.4 and 12.0 MJ/kg, each with two levels of CP, 230 and 184 g/kg. This was followed by feeding common starter and finisher diets for the last 4 weeks. 3. Dietary protein reduction resulted in poor performance and feed efficiency while energy reduction resulted in poor feed efficiency between d 8 and 14. From d 14 to 42 birds previously fed diets lower in energy and protein showed similar body weight gain and feed intake to well-fed birds. Moreover from d 8 to 14, birds fed on energy and protein-reduced diets had lower nutrient metabolisability coefficients. 4. The blood urea nitrogen (BUN) and relative weights of heart and breast muscle were lower in birds fed protein-reduced diets while energy reduction resulted in lower plasma glucose, abdominal fat and intestinal weight at d 14. At d 42, birds fed on the protein-reduced diets had lower BUN, breast muscle weight and small intestine length, while feeding on the energy-reduced diets resulted in lower abdominal fat. 5. Upregulated myostatin mRNA expression in breast muscle and downregulation of leptin mRNA expression in abdominal fat were observed in birds fed on protein and energy-reduced diets, respectively. 6. In conclusion, early nutrient reduction affected growth performance and produced lesser abdominal fat in broilers. Moreover, early energy and/or protein reduction could change muscle and fat metabolism by regulating the expressions of myostatin and leptin.

Topics: Amino Acids; Animals; Blood Urea Nitrogen; Caloric Restriction; Chickens; Diet, Protein-Restricted; Dietary Fats; Dietary Proteins; Digestion; Eating; Gene Expression; Glutamic Acid; Ileum; Leptin; Muscle, Skeletal; Myostatin; Organ Size; Weight Gain

We investigated whether regular decaffeinated green tea intake could modulate body weight in an experimental model of obesity. Male leptin-deficient (ob/ob) mice and their C57BL/6J lean littermates (4 weeks of age; n 20/genotype) were assigned randomly to receive either decaffeinated green tea or vehicle, for 6 weeks. Body weights were recorded weekly and fluid intake was measured at each replacement. Blood was collected from the heart into collection tubes, with Li(+)-heparin as the anticoagulant. Administration of decaffeinated green tea to ob/ob mice significantly slowed their rate of weight gain, as compared with animals that were fed buffer alone. This effect is apparent after only 1 week of supplementation. No significant difference was recorded between C57BL/6J lean mice administrated decaffeinated green tea and those given buffer alone. Decaffeinated green tea consumption by ob/ob mice was also associated with significantly lower cholesterolemia, triglyceridemia, and adiponectin concentration. Fecal lipids did not change significantly throughout the experiment. In conclusion, administration of decaffeinated green tea might contribute to weight control and provides an opportunity for through-the-day consumption, without the excitatory effects of caffeine.

Topics: Adiponectin; Animals; Anti-Obesity Agents; Caffeine; Catechin; Cholesterol; Feces; Hyperlipidemias; Hypolipidemic Agents; Leptin; Lipid Metabolism; Lipids; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Plant Preparations; Tea; Triglycerides; Weight Gain

Adipocyte fatty acid binding protein (A-FABP) has been suggested to play an important role in fat metabolism linking obesity and the metabolic syndrome. Increasing A-FABP plasma levels were observed during greatest weight loss after bariatric surgery suggesting that A-FABP may indicate changes in fat mass in dynamic situations.. As there are no data on weight gain, we investigated the effect of refeeding anorexic patients on body composition and A-FABP plasma levels.. Parameters of glucose and lipid metabolism as well as plasma levels of leptin and A-FABP were prospectively assessed in 16 female patients with anorexia nervosa during inpatient weight restoration. Body composition was determined by multifrequency body impedance analysis.. After 28 days, fat mass increased from 4.4 +/- 2.5 kg at baseline to 5.5 +/- 2.2 kg (P < 0.01), constituting 40% of total weight gain. Conversely, A-FABP concentrations decreased from 32.56 +/- 35.59 ng/ml at baseline to 21.27 +/- 13.68 ng/ml (P < 0.05), which corresponds to a significant decrease in the proportion of A-FABP per kilogram fat mass from 7.86 +/- 5.23 to 4.09 +/- 2.12 ng/ml/kg (P

Topics: Adipocytes; Adolescent; Adult; Anorexia Nervosa; Body Composition; Body Mass Index; Bulimia Nervosa; Electric Impedance; Enzyme-Linked Immunosorbent Assay; Fatty Acid-Binding Proteins; Female; Humans; Leptin; Matched-Pair Analysis; Middle Aged; Regression Analysis; Weight Gain; Young Adult

Topics: Antipsychotic Agents; Apoptosis; Central Nervous System; Humans; Leptin; Metabolic Syndrome; Neuroprotective Agents; Psychotic Disorders; Schizophrenia; Weight Gain

Infusion of insulin acutely stimulates leptin production and chronic insulin treatment is associated with elevated serum leptin levels and body weight in subjects with type 2 diabetes.. The objective of the study was to investigate the relationship between insulin administration, leptin levels, and weight gain in subjects with type 2 diabetes.. This was a post hoc analysis of two randomized, controlled trials.. The study was conducted at an outpatient clinic.. Subjects included 35 (study 1) and 32 (study 2) poorly controlled oral hypoglycemic agent (OHA)-treated type 2 diabetic subjects.. Study 1: subjects were investigated during a hyperinsulinemic, euglycemic glucose clamp and 12 months after being randomly allocated to start insulin or continue on OHAs. Study 2: 1 yr treatment with either OHAs and lifestyle intervention or insulin with or without concomitant lifestyle intervention.. Changes in serum leptin levels during clamp and during 1 yr of treatment in relationship to changes in body weight.. Study 1: during acute insulin infusion leptin levels increased by 10% (P < 0.001). During 1 yr of insulin therapy, mean body weight increased by 6%, whereas the fasting leptin levels increased by 108% (both P < 0.001). The weight gain observed at 1 yr correlated with the increase in leptin levels observed during the clamp (r = 0.62, P = 0.003). Study 2: mean body weight increased by 4% (P < 0.01), whereas leptin levels increased by 56% (P < 0.001) during 1 yr of insulin treatment and the increase in leptin preceded the increase in body weight.. Significant correlations were observed between insulin's effect on serum leptin levels and the increase in weight that accompanied insulin therapy.

Topics: Adult; Aged; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glucose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Leptin; Male; Middle Aged; Signal Transduction; Weight Gain

Poorly controlled diabetes is associated with hormonal imbalances, including decreased prolactin production partially due to increased lactotroph apoptosis. In addition to its metabolic actions, ghrelin inhibits apoptosis in several cell types. Thus, we analyzed ghrelin's effects on diabetes-induced pituitary cell death and hormonal changes. Six weeks after onset of diabetes in male Wistar rats (streptozotocin 70 mg/kg), minipumps infusing saline or 24 nmol ghrelin/day were implanted (jugular). Rats were killed two weeks later. Ghrelin did not modify body weight or serum glucose, leptin or adiponectin, but increased total ghrelin (P<0.05), IGF-I (P<0.01) and prolactin (P<0.01) levels. Ghrelin decreased cell death, iNOS and active caspase-8 (P<0.05) and increased prolactin (P<0.05), Bcl-2 (P<0.01) and Hsp70 (P<0.05) content in the pituitary. In conclusion, ghrelin prevents diabetes-induced death of lactotrophs, decreasing caspase-8 activation and iNOS content and increasing anti-apoptotic pathways such as pituitary Bcl-2 and Hsp70 and serum IGF-I concentrations.

Topics: Adiponectin; Animals; Apoptosis; Biomarkers; Body Weight; Caspases; Cytoprotection; Diabetes Mellitus, Experimental; Ghrelin; HSP70 Heat-Shock Proteins; In Situ Nick-End Labeling; Insulin; Insulin-Like Growth Factor I; Lactotrophs; Leptin; Nitric Oxide Synthase Type II; Prolactin; Proto-Oncogene Proteins c-bcl-2; Rats; Weight Gain; X-Linked Inhibitor of Apoptosis Protein

Diets high in trans fats are associated with an increased risk of cardiovascular disease and components of the metabolic syndrome. The influence of these toxic fatty acids on the development of nonalcoholic fatty liver disease has not been significantly examined. Therefore, we sought to compare the effect of a murine diet high in trans fat to a standard high-fat diet that is devoid of trans fats but high in saturated fats. Male AKR/J mice were fed a calorically identical trans fat diet or standard high-fat diet for 10 days, 4 wk, and 8 wk. Serum alanine aminotransferase (ALT), lipid, insulin, and leptin levels were determined and the quantitative insulin-sensitivity check index (QUICKI) was calculated as a measure of insulin resistance. Additionally, hepatic triglyceride content and gene expression of several proinflammatory genes were assessed. By 8 wk, trans fat-fed mice exhibited higher ALT values than standard high-fat-fed mice (126 +/- 16 vs. 71 +/- 7 U/l, P < 0.02) despite similar hepatic triglyceride content at each time point. Trans fat-fed mice also had increased insulin resistance compared with high-fat-fed mice at 4 and 8 wk with significantly higher insulin levels and lower QUICKI values. Additionally, hepatic interleukin-1beta (IL-1beta) gene expression was 3.6-fold higher at 4 wk (P < 0.05) and 5-fold higher at 8 wk (P < 0.05) in trans fat-fed mice compared with standard high-fat-fed mice. Trans fat feeding results in higher ALT values, increased insulin resistance, and elevated IL-1beta levels compared with standard high-fat feeding.

Topics: Alanine Transaminase; Animals; Cholesterol; Dietary Fats; Fatty Liver; Inflammation Mediators; Insulin; Insulin Resistance; Interleukin-1beta; Leptin; Liver; Male; Mice; Oleic Acid; Oleic Acids; Severity of Illness Index; Time Factors; Trans Fatty Acids; Triglycerides; Up-Regulation; Weight Gain

Renin-angiotensin system is involved in homeostasis processes linked to renal and cardiovascular system and recently has been linked to metabolic syndrome. We analyzed the influence of long term angiotensin I converting enzyme (ACE) inhibitor enalapril treatment in normotensive adult Wistar rats fed with standard or palatable hyperlipidic diets. Our results show that long term enalapril treatment decreases absolute food intake, serum leptin concentration and body weight gain. Moreover, in adipose tissue, enalapril treatment led to decreased ACE activity, enhanced the expression of peroxisome proliferator activated receptor gamma, adiponectin, hormone-sensitive lipase, fatty acid synthase, catalase and superoxide dismutase resulting in prolonged life span. On the other hand, the ACE inhibitor was not able to improve the transport of leptin through the blood brain barrier or to alter the sensitivity of this hormone in the central nervous system. The effect of enalapril in decreasing body weight gain was also observed in older rats. In summary, these results extend our previous findings and corroborate data from the literature regarding the beneficial metabolic effects of enalapril and show for the first time that this ACE inhibitor prolongs life span in rats also fed with palatable hyperlipidic diet, an action probably correlated with adipose tissue metabolic modulation and body weight reduction.

Topics: Adiponectin; Adipose Tissue; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Catalase; Eating; Enalapril; Energy Intake; Fatty Acid Synthases; Insulin; Leptin; Longevity; Male; PPAR gamma; Random Allocation; Rats; Rats, Wistar; Sterol Esterase; Superoxide Dismutase; Time Factors; Weight Gain

l-Glutamate is a multifunctional amino acid involved in taste perception, intermediary metabolism, and excitatory neurotransmission. In addition, recent studies have uncovered new roles for l-glutamate in gut-brain axis activation and energy homeostasis. l-Glutamate receptors and their cellular transduction molecules have recently been identified in gut epithelial cells. Stimulation of such l-glutamate receptors by luminal l-glutamate activates vagal afferent nerve fibers and then parts of the brain that are targeted directly or indirectly by these vagal inputs. Notably, 3 areas of the brain-the medial preoptic area, the hypothalamic dorsomedial nucleus, and the habenular nucleus-are activated by intragastric l-glutamate but not by glucose or sodium chloride. Furthermore, the chronic, ad libitum ingestion of a palatable solution of monosodium l-glutamate (1% wt:vol) by rats has also been found to reduce weight gain, fat deposition, and plasma leptin concentrations compared with rats that ingest water alone. No difference in food intake was observed. Such effects may also be vagally mediated. Together, such findings contribute to the growing knowledge base that indicates that l-glutamate signaling via taste and gut l-glutamate receptors may influence multiple physiologic functions, such as thermoregulation and energy homeostasis.

Topics: Adiposity; Animals; Brain; Diet; Energy Metabolism; Enteric Nervous System; Gastrointestinal Tract; Glutamic Acid; Leptin; Rats; Receptors, Glutamate; Signal Transduction; Sodium Glutamate; Vagus Nerve; Water; Weight Gain

This study investigated the effects of different planes of nutrition in early pregnancy (EP) and mid-pregnancy (MP) of crossbred ewes on carcass characteristics of male offspring and reproductive performance of female offspring. During EP (d 1 to 39 after synchronized mating) ewes were allocated 60% (low, L-EP), 100% (medium, M-EP), or 200% (high, H-EP) of their energy requirements for maintenance. Between d 40 and 90 (MP), ewes were then allocated 80% (M-MP) or 140% (H-MP) of their maintenance energy requirement. After d 90, all ewes were fed to fully meet energy requirements for late pregnancy. Male offspring (n = 83) were reared on a grass-based system and slaughtered at 42, 46, or 50 kg of BW. Female offspring (n = 60) were reared on a grass-based system, mated at 8 mo, and performance recorded until weaning of their first lamb crop. Concentrations of leptin, an adiposity indicator, in female offspring varied with the plane of maternal nutrition in early pregnancy. The L-EP offspring had greater leptin concentrations than H-EP offspring (P = 0.04), with M-EP offspring showing intermediate concentrations. Reproductive performance of female offspring was not affected by maternal plane of nutrition (P > or = 0.16). Female H-EP offspring gave birth to heavier lambs (generation 2 offspring) than M-EP (P = 0.006) with L-EP offspring intermediate. Male offspring of L-EP dams showed a trend toward poorer carcass conformation (P = 0.06) and increased fat classification (P = 0.07), consistent with increased fat depths over the loin (P = 0.02). There was a significant interaction between plane of nutrition in early pregnancy and mid-pregnancy for female offspring BW at 2 mo postmating and 16 wk postlambing (P < or = 0.04), and for male offspring perinephric and retroperitoneal fat and tissue depth (P < or = 0.02). For dams offered diet L-EP during early pregnancy, diet H-MP gave heavier offspring with more perinephric and retroperitoneal fat. In contrast, for dams offered diet H-EP during EP, diet M-MP gave offspring that were heavier or fatter or both. Maintenance level of nutrition in EP followed by M-MP or H-MP treatments resulted in offspring intermediate in fatness and BW. The data indicate that adaptations in EP and MP to compensate for nutritional deprivation or nutritional excess can alter the BW, adiposity, conformation, and leptin concentrations of offspring. Such changes have potential to alter health and lifetime productive performance.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Dietary Supplements; Female; Leptin; Male; Meat; Pregnancy; Pregnancy, Animal; Selenium; Sheep; Weight Gain

Endocannabinoids (EC) are involved in regulating energy homeostasis, particularly in promoting hyperphagia and the consumption of a palatable diet. We have previously shown that rats given a high-fat (HF) diet display a transient hyperphagia that is normalized by a process partially dependent on leptin. We now propose that the induction of this hyperphagia is mediated, at least partially, by the EC signaling system. Obesity, including diet-induced and age-related, is associated with dysregulation of the EC system, and obese rodent models are hypersensitive to a cannabinoid-1 (CB1) receptor antagonist. This suggests that aged rats will be more responsive to the anorectic effects of a CB1 receptor antagonist. To test this, we examined the responsiveness to CB1 receptor antagonist, AM251, in young and aged rats during two experimental paradigms. First, we administered AM251 simultaneously with the introduction of an HF diet. Second, AM251 treatment began after the establishment of diet-induced obesity. Responses were measured by changes in body weight and composition, calorie intake, serum leptin, and biochemical indicators. The results demonstrated three key findings. 1) CB1 receptor activity contributes to the hyperphagia seen with the introduction of an HF diet. 2) Increased AM251 sensitivity and efficacy is increased with age and HF feeding, with the greatest responsiveness observed in HF-fed, aged rats. 3) AM251 sensitivity is elevated to a greater extent with HF diet than with established obesity. Thus, both age and an HF diet are associated with enhanced anorectic responses to AM251, but the underlying mechanism of these responses remains speculative.

Topics: Age Factors; Animals; Appetite Depressants; Body Composition; Dietary Fats; Energy Intake; Hyperphagia; Ion Channels; Leptin; Male; Mitochondrial Proteins; Obesity; Piperidines; Pyrazoles; Rats; Rats, Inbred F344; Receptor, Cannabinoid, CB1; STAT3 Transcription Factor; Uncoupling Protein 1; Weight Gain

Overfeeding increases adipose tissue mass and leptin production and up-regulates the renin-angiotensin system in adipose tissue in rodents. Here, we determined the effect of chronic treatment with the renin inhibitor, aliskiren, in a model of diet-induced obesity in mice, on: (i) body weight, adipose tissue weight and plasma leptin; (ii) food intake and caloric efficiency; and (iii) angiotensin II (Ang II) in adipose tissue.. Four-week-old C57BL/6J mice (n= 40) received aliskiren (50 mg.kg(-1).day(-1); 6 weeks) by means of a subcutaneous osmotic Alzet minipump. Animals were given either a low-fat (10% kcal from fat) or a high-fat diet (45% kcal from fat) during this period. Food-intake and body-weight variation were monitored during treatment.. In addition to a decrease of plasma renin activity, aliskiren reduced body-weight gain, adipose pads and plasma leptin concentration, independent of the diet. In adipose tissue, local concentrations of Ang II were also reduced by aliskiren.. Aliskiren limited the gain of adiposity in young mice. This effect was not due to changes in food intake or caloric efficiency and might be related to a down-regulation of the local renin-angiotensin system in adipose tissue. These effects were accompanied by reduced plasma leptin levels. As Ang II favours differentiation of adipocytes, it is possible that the decreased adipose tissue was linked to changes in adipocyte size and number.

Topics: Adipose Tissue; Adiposity; Amides; Animals; Dietary Fats; Eating; Energy Intake; Fumarates; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Organ Size; Renin; Renin-Angiotensin System; Weight Gain

Women with epilepsy often suffer from weight gain. A similar phenomenon is seen in female rats that are kindled from the amygdala. Interestingly, it has been reported that kindling of the left amygdala causes more weight gain than kindling of the right amygdala. The present study was designed to confirm and extend that effect.. Female Wistar rats were kindled from the left or right basolateral amygdala to a criterion of 40 stage 5 seizures. Control subjects were handled but not stimulated. Subjects were weighed weekly for the duration of the study. Twenty-four hours following the last kindled seizure, kindled subjects and their yoked controls were sacrificed and their brains and serum were extracted.. Kindled subjects weighed significantly more than controls at the end of the kindling procedure and had significantly higher serum levels of leptin. No laterality effects were seen in either weight gain or leptin levels, however.. Amygdala kindling increases weight gain and serum leptin levels in rats, but in the present study no laterality effects were seen.

Topics: Amygdala; Analysis of Variance; Animals; Body Weight; Disease Progression; Electric Stimulation; Electrodes, Implanted; Estrous Cycle; Female; Functional Laterality; Kindling, Neurologic; Leptin; Rats; Rats, Wistar; Seizures; Weight Gain

Post-menopausal osteoporosis is considered to be an inflammatory process, in which numerous pro-inflammatory and T-cell-derived cytokines play a bone-destructive role. IL-17A is the signature cytokine of the pro-inflammatory Th17 population and plays dichotomous roles in diseases that affect bone turnover. Although IL-17A promotes bone loss in rheumatoid arthritis, it is protective against pathogen-induced bone destruction in a periodontal disease model. We used a model of ovariectomy-induced osteoporosis (OVX) in IL-17 receptor (IL-17RA)(-/-) mice to evaluate the role of the IL-17A in bone loss caused by estrogen deficiency. Unexpectedly, IL-17RA(-/-) mice were consistently and markedly more susceptible to OVX-induced bone loss than controls. There were no changes in prototypical Th1, Th2 or Th17 cytokines in serum that could account for increased bone loss. However, IL-17RA(-/-) mice exhibited constitutively elevated leptin, which further increased following OVX. Consistently, IL-17A and IL-17F treatment of 3T3-L1 pre-adipocytes inhibited adipogenesis, leading to reduced production of leptin. In addition to its role in regulating metabolism and satiety, leptin can regulate bone turnover. Accordingly, these data show that IL-17A negatively regulates adipogenesis and subsequent leptin expression, which correlates with increased bone destruction during OVX.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Bone Density; Cytokines; Down-Regulation; Estrogens; Female; Interleukin-17; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Osteoporosis; Ovariectomy; Receptors, Interleukin-17; Signal Transduction; Spine; Tumor Necrosis Factor-alpha; Weight Gain

Obesity-associated activation of inflammatory pathways represents a key step in the development of insulin resistance in peripheral organs, partially via activation of TLR4 signaling by fatty acids. Here, we demonstrate that palmitate acting in the central nervous system (CNS) inhibits leptin-induced anorexia and Stat3 activation. To determine the functional significance of TLR signaling in the CNS in the development of leptin resistance and diet-induced obesity in vivo, we have characterized mice deficient for the TLR adaptor molecule MyD88 in the CNS (MyD88(DeltaCNS)). Compared to control mice, MyD88(DeltaCNS) mice are protected from high-fat diet (HFD)-induced weight gain, from the development of HFD-induced leptin resistance, and from the induction of leptin resistance by acute central application of palmitate. Moreover, CNS-restricted MyD88 deletion protects from HFD- and icv palmitate-induced impairment of peripheral glucose metabolism. Thus, we define neuronal MyD88-dependent signaling as a key regulator of diet-induced leptin and insulin resistance in vivo.

Topics: Animals; Central Nervous System; Diet; Dietary Fats; Eating; Energy Metabolism; Enzyme Activation; Female; Glucose; Homeostasis; Humans; I-kappa B Kinase; Insulin; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Activity; Myeloid Differentiation Factor 88; Obesity; Palmitic Acid; Signal Transduction; Weight Gain

As the use of atypical antipsychotics in children and adolescents has increased, concerns have been raised about their long-term safety. We aimed to investigate the association between risperidone-induced weight gain, leptin concentration, and the leptin gene (LEP) -2548G/A variants in youths.. Medically healthy 7- to 17-year-old children and adolescents, in extended naturalistic treatment with risperidone, were recruited through pediatric psychiatry clinics. Anthropometric measures and laboratory testing were conducted. Growth and medication history was obtained from the medical record. The effect of the LEP genotypes on leptin concentration and on the slopes of the weight and body mass index (BMI) Z-score curves before and after the onset of risperidone treatment was investigated .. In 74 individuals, chronically treated with risperidone, the A allele was associated with higher leptin concentration at low weight and BMI Z-scores. There was no effect of the LEP genotypes on weight or BMI Z-scores before risperidone was started. Afterwards, however, the A-allele carriers showed a steeper rate of increase in weight and BMI Z-scores. As a result, the GG-genotype carriers were 2.5 times less likely to be overweight/obese (i.e. having a BMI above the 85th percentile). This genetic effect on risperidone-associated weight gain did not extend to weight loss related to psychostimulants.. The LEP - 2548G/A variants seem to moderate the weight-altering effect of risperidone but not psychostimulants. This may be related to genetic differences in tissue sensitivity to leptin, resulting in differential body composition.

Topics: Adolescent; Antipsychotic Agents; Base Sequence; Child; DNA Primers; Female; Humans; Leptin; Male; Polymerase Chain Reaction; Risperidone; Weight Gain

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

The regulation of weight of a body--is an actual problem of modern medicine. The significant part of patients with pathology of gastro-intestinal tract suffers of an increasing weight of a body. In economically advanced countries, including Russia, on the average each third inhabitant has an increasing weight of a body. Last researches shows, that the adipose tissue is not only a place of storage of power stocks, but also analogue endocryne body. The most part of peptides, participating in regulation of food behaviour, in a place of primary development in adipose cells, has been named adipokines. It is possible to attribute to them leptin. The purpose of our research was specification of influence of leptin level on character of a pathology of gastro-pancreato-duodenal zone. Under our supervision there were patients with diseases of gastro-pancreato-duodenal zone: chronic pancreatitis, duodenal ulcer, gastroduodenitis. It was revealed most increasing value of leptin in the patients with combination of chronic pancreatitis and duodenal ulcer.

Topics: Eating; Female; Gastrointestinal Diseases; Humans; Leptin; Male; Pancreatitis, Chronic; Weight Gain

The stress response is known to lead to behavioral and metabolic changes. Exposure to chronic stress can promote the development of physiological and behavioral dysfunctions, including alterations in feeding behavior. The aim of this study was to verify whether chronic restraint stress alters the consumption of a highly palatable, highly caloric diet (chocolate), chronically offered to the animals. Male rats ate more chocolate than females, and they also exhibited a higher weight gain, abdominal fat deposition, and higher plasma levels of total cholesterol, LDL-cholesterol and glucose. The stress exposure decreased body weight, increased adrenal weight and decreased plasma insulin levels. Overall, female rats had lower plasma insulin levels and chocolate consumption prevented the increased adrenal gland weight after exposure to chronic stress, suggesting a reduction of stress effects induced by palatable food consumption. Taken together, these results suggest a peculiar metabolic pattern, related to energy store and expenditure, in stressed animals receiving a palatable diet. Since these effects were sex-specific, we may also propose that females and males subjected to restraint stress and chocolate consumption are differentially affected.

Topics: Abdominal Fat; Adrenal Glands; Animals; Behavior, Animal; Blood Glucose; Cacao; Energy Intake; Energy Metabolism; Female; Habituation, Psychophysiologic; Handling, Psychological; Insulin; Leptin; Lipids; Male; Organ Size; Random Allocation; Rats; Rats, Wistar; Sex Factors; Stress, Psychological; Time Factors; Weight Gain

Gene-targeted deletion of the voltage-gated potassium channel, Kv1.3, results in 'super-smeller' mice that have altered firing patterns of mitral cells in the olfactory bulb, modified axonal targeting to glomerular synaptic units, and behaviorally have an increased ability to detect and discriminate odors. Moreover, the Kv1.3-null mice weighed less than their wild-type counterparts, have modified ingestive behaviors, and are resistant to fat deposition following a moderately high-fat dietary regime. In this study, we investigate whether or not gene-targeted deletion of Kv1.3 (Shaker family member) can abrogate weight gain in a genetic model of obesity, the melanocortin-4 receptor-null mouse (MC4R-null).. Mice with double gene-targeted deletions of Kv1.3 and MC4R were generated by interbreeding Kv1.3 (Kv)- and MC4R-null mouse lines to homozygosity. Developmental weights, nose to anus length, fat pad weight, fasting serum chemistry, oxygen consumption, carbon dioxide respiration, locomotor activity and caloric intake were monitored in control, Kv-null, MC4R-null and Kv/MC4R-null mice. Physiological and metabolic profiles were acquired at postnatal day 60 (P60) in order to explore changes linked to body weight at the reported onset of obesity in the MC4R-null model.. Gene-targeted deletion of Kv1.3 in MC4R-null mice reduces body weight by decreasing fat deposition and subsequent fasting leptin levels, without changing the overall growth, fasting blood glucose or serum insulin. Gene-targeted deletion of Kv1.3 in MC4R-null mice significantly extended lifespan and increased reproductive success. Basal or light-phase mass-specific metabolic rate and locomotor activity were not affected by genetic deletion of Kv1.3 in MC4R-null mice but dark-phase locomotor activity and mass-specific metabolism were significantly increased resulting in increased total energy expenditure.. Gene-targeted deletion of Kv1.3 can reduce adiposity and total body weight in a genetic model of obesity by increasing both locomotor activity and mass-specific metabolism.

Topics: Adiposity; Animals; Blood Glucose; Calorimetry, Indirect; Disease Models, Animal; Drinking; Energy Intake; Female; Fertility; Gene Deletion; Growth; Homeostasis; Insulin; Kv1.3 Potassium Channel; Leptin; Locomotion; Longevity; Male; Mice; Mice, Knockout; Obesity; Oxygen Consumption; Receptor, Melanocortin, Type 4; Weight Gain

Monosodium l-glutamate (MSG), an umami taste substance, may be a key molecule coupled to a food intake signaling pathway, possibly mediated through a specific l-glutamate (GLU) sensing mechanism in the gastrointestinal tract. Here we investigated the effect of the spontaneous ingestion of a 1% MSG solution and water on food intake and body weight in male Sprague-Dawley rats fed diets of varying caloric density, fat and carbohydrate contents. Fat mass and lean mass in the abdomen, blood pressure, and several blood metabolic markers were also measured. Rats given free access to MSG and water showed a high preference (93-97%) for the MSG solution, regardless of the diet they consumed. Rats ingesting MSG had a significantly smaller weight gain, reduced abdominal fat mass, and lower plasma leptin levels, compared to rats ingesting water alone. Naso-anal length, lean mass, food and energy intakes, blood pressure, blood glucose, and plasma levels of insulin, triglyceride, total cholesterol, albumin, and GLU were not influenced by the ingestion of the MSG solution. These same effects were observed in a study of adult rats. Together, these results suggest that MSG ingestion reduces weight gain, body fat mass, and plasma leptin levels. Moreover, these changes are likely to be mediated by increased energy expenditure, not reduced energy intake or delayed development. Conceivably, these effects of MSG might be mediated via gut GLU receptors functionally linked to afferent branches of the vagus nerve in the gut, or the afferent sensory nerves in the oral cavity.

Topics: Abdominal Fat; Age Factors; Analysis of Variance; Animals; Animals, Newborn; Blood Pressure; Circadian Rhythm; Eating; Female; Food Additives; Glucose Tolerance Test; Leptin; Linear Models; Magnetic Resonance Imaging; Male; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Sex Factors; Sodium Glutamate; Subcutaneous Fat; Weight Gain

Weight gain is a major side effect of antipsychotic treatment. Some atypical antipsychotic agents have profound effects on weight. Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that seem to play an important role in the regulation of food intake, energy metabolism, and body weight are leptin and ghrelin. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. In this present study it is aimed to compare the effects of five different atypical antipsychotic medications on leptin and ghrelin.. 112 patients who were treated either with clozapine (n=20), olanzapine (n=28), risperidone (n=22), quetiapine (n=20) or amisulpride (n=22) as monotherapy for at least one year and age, gender, and body mass index (BMI) matched control group (n=23) were assessed cross-sectionally. Ghrelin and leptin levels were measured with enzyme-immunoassay.. When fasting serum leptin levels were compared between groups, control group had the highest mean value (9.2+/-6.7) and amisulpride group had the lowest mean value (3.7+/-2.1) but still there was no statistically significant difference between six groups (F=1993, p=0.084). In the comparison of the mean values of fasting serum ghrelin levels there was a statistically significant difference between groups (F=11,473, p=0.00). In post-hoc analysis it was seen that the control group had the lowest ghrelin level (194.5+/-86.8). Quetiapine treated group (378.1+/-260.4) had similar fasting serum ghrelin levels to control group. All the other antipsychotic treatment groups had significantly higher levels of fasting serum ghrelin compared to control group, highest in amisulpride treated group (597.0+/-150.0).. The weight-gain side effect of atypical antipsychotics can be related with the orexigenic effect of elevated serum ghrelin rather than leptin deficit. Among the five widely used atypical antipsychotics quetiapine is the only one which does not elevate the ghrelin level.

Topics: Adolescent; Adult; Age Factors; Aged; Antipsychotic Agents; Appetite; Body Mass Index; Carbohydrate Metabolism; Eating; Female; Ghrelin; Humans; Leptin; Lipid Metabolism; Male; Middle Aged; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Weight Gain

Leptin-resistant rats, when given a high-fat (HF) diet, have a delayed normalization of caloric intake and greater weight gain than those on a chow diet. Because aged, obese rats are leptin resistant, these data predict that they will also have a delayed normalization of caloric intake and exacerbated weight gain when provided a HF diet. To investigate this hypothesis, along with the consequences of a HF diet on voluntary wheel running, we compared various ages of rats on a HF or chow diet. HF-fed young rats spontaneously divided into diet-induced obese and diet-resistant rats. However, all aged rats were susceptible to the weight-gaining effects of HF feeding. Rate of initial weight gain was proportional to age, and peak caloric intake on the HF diet and the days required to normalize caloric intake to basal levels increased with age. Responsiveness to peripheral leptin before HF feeding revealed a dose-response decrease in food intake and body weight in the young but no responses in the aged to even the highest dose, 0.5 mg/day. In addition, both age and HF feeding decreased the tendency for wheel running, suggesting the propensity for inactivity with age and HF feeding may contribute to age-related obesity and accelerate the rate of diet-induced obesity. These results demonstrate that aged rats are more susceptible to the detrimental effects of a HF diet.

Topics: Adipose Tissue, Brown; Age Factors; Aging; Animals; Body Composition; Dietary Fats; Disease Models, Animal; Dose-Response Relationship, Drug; Energy Intake; Hyperphagia; Hypothalamus; Ion Channels; Leptin; Male; Mitochondrial Proteins; Motor Activity; Obesity; Physical Conditioning, Animal; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Rats; Rats, Inbred F344; RNA, Messenger; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Uncoupling Protein 1; Weight Gain

The aim of present study is to evaluate the effects of Garcinia cambogia on the mRNA levels of the various genes involved in adipogenesis, as well as on body weight gain, visceral fat accumulation, and other biochemical markers of obesity in obesity-prone C57BL/6J mice. Consumption of the Garcinia cambogia extract effectively lowered the body weight gain, visceral fat accumulation, blood and hepatic lipid concentrations, and plasma insulin and leptin levels in a high-fat diet (HFD)-induced obesity mouse model. The Garcinia cambogia extract reversed the HFD-induced changes in the expression pattern of such epididymal adipose tissue genes as adipocyte protein aP2 (aP2), sterol regulatory element-binding factor 1c (SREBP1c), peroxisome proliferator-activated receptor gamma2 (PPARgamma2), and CCAT/enhancer-binding protein alpha (C/EBPalpha). These findings suggest that the Garcinia cambogia extract ameliorated HFD-induced obesity, probably by modulating multiple genes associated with adipogenesis, such as aP2, SREBP1c, PPARgamma2, and C/EBPalpha in the visceral fat tissue of mice.

Topics: Adipogenesis; Adiposity; Animals; Dietary Fats; Garcinia cambogia; Gene Expression Profiling; Gene Expression Regulation; Insulin; Intra-Abdominal Fat; Leptin; Lipids; Mice; Mice, Inbred C57BL; Plant Extracts; Weight Gain

Topics: Adult; Fatty Acids, Nonesterified; Female; Hormone Replacement Therapy; Humans; Hyperinsulinism; Leptin; Linear Models; Lipid Metabolism; Male; Mutation, Missense; Recombinant Proteins; Weight Gain

Gyeongshingangjeehwan (GGEx), which comprises Liriope platyphylla F.T. Wang & T. Tang (Liliaceae), Platycodongrandiflorum A. DC. (Campanulaceae), Schisandrachinensis K. Koch (Magnoliaceae), and Ephedra sinica Stapf (Ephedraceae), has traditionally been used as an anti-obesity drug in Korean local clinics, although there is no evidence concerning the scientific analyses of its effects and mechanism(s) of action. Thus, we investigated the effects of GGEx on obesity, as well as the mechanism by which GGEx functions, in Otsuka Long-Evans Tokushima Fatty (OLETF) male rats. Compared with obese OLETF control rats, administration of GGEx for 8 weeks significantly decreased food intake and plasma leptin levels as well as body weight gain and abdominal fat in OLETF rats. GGEx treatment not only decreased circulating triglycerides, but also inhibited lipid accumulation in the liver. GGEx increased the hepatic mRNA levels of PPARalpha target genes responsible for fatty acid beta-oxidation. Consistent with the in vivo data, GGEx elevated PPARalpha reporter gene expression in NMu2Li liver cells. These results suggest that GGEx may effectively prevent obesity and hypertriglyceridemia in part through the inhibition of feeding and the activation of hepatic PPARalpha.

Topics: Abdominal Fat; Animals; Anti-Obesity Agents; Cell Line; Eating; Gene Expression Regulation; Genes, Reporter; Leptin; Liver; Male; Medicine, Korean Traditional; Mice; Obesity; Plants, Medicinal; PPAR alpha; Rats; Rats, Inbred OLETF; Rats, Long-Evans; RNA, Messenger; Triglycerides; Weight Gain

It has been suggested that increased fructose intake is associated with obesity. We hypothesized that chronic fructose consumption causes leptin resistance, which subsequently may promote the development of obesity in response to a high-fat diet. Sprague-Dawley rats were fed a fructose-free control or 60% fructose diet for 6 mo and then tested for leptin resistance. Half of the rats in each group were then switched to high-fat diet for 2 wk, while the other half continued on their respective diets. Chronic fructose consumption caused leptin resistance, while serum leptin levels, weight, and adiposity were the same as in control rats that were leptin responsive. Intraperitoneal leptin injections reduced 24-h food intake in the fructose-free group (73.7 +/- 6.3 vs. 58.1 +/- 8 kcal, P = 0.02) but had no effect in fructose-fed rats (71.2 +/- 6.6 vs. 72.4 +/- 6.4 kcal, P = 0.9). Absence of anorexic response to intraperitoneal leptin injection was associated with 25.7% decrease in hypothalamic signal transducer and activator of transcription 3 phosphorylation in the high-fructose-fed rats compared with controls (P = 0.015). Subsequent exposure of the fructose-mediated, leptin-resistant rats to a high-fat diet led to exacerbated weight gain (50.2 +/- 2 g) compared with correspondingly fed leptin-responsive animals that were pretreated with the fructose-free diet (30.4 +/- 5.8 g, P = 0.012). Our data indicate that chronic fructose consumption induces leptin resistance prior to body weight, adiposity, serum leptin, insulin, or glucose increases, and this fructose-induced leptin resistance accelerates high-fat induced obesity.

Topics: Animals; Blotting, Western; Body Composition; Dietary Fats; Drug Synergism; Fructose; Hypothalamus; Insulin; Leptin; Male; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Sweetening Agents; Weight Gain

Cocaine- and amphetamine-regulated transcript (CART) codes for a hypothalamic neuropeptide, CART (55-102), which inhibits food intake. Intracerebroventricular injection of CART (55-102) reduces appetite, but also results in motor abnormalities. More recently, studies have demonstrated that administration of CART directly into the paraventricular nucleus (PVN) increases food intake. To investigate the role of CART in the regulation of energy balance in the PVN, we used recombinant adeno-associated virus (rAAV) to overexpress CART in the PVN.. Male Wistar rats were injected with either rAAV-encoding CART (rAAV-CART) or rAAV-encoding enhanced green fluorescent protein (rAAV-EGFP) as a control. Food intake and body weight were measured regularly. Animals were fed on normal-chow diet for the first 93 days of the study. After this point, they were fed on high-fat diet. Animals were killed 138 days postinjection and blood and tissues were collected for analysis.. Overexpression of CART in the PVN resulted in increased cumulative food intake and body weight gain compared with rAAV-EGFP controls when fed normal chow. These changes became significant at day 65 and 79, respectively and were accentuated on a high-fat diet. A 4% increase in food intake was observed in rAAV-CART animals on a normal-chow diet and a 6% increase when fed a high-fat diet. At the end of the study, rAAV-CART-treated animals had higher circulating leptin concentrations in accord with their higher body weight.. These data provide further evidence that hypothalamic CART plays an orexigenic role.

Topics: Adipose Tissue; Animals; Appetite Regulation; Behavior, Animal; Dependovirus; Dietary Fats; Eating; Genetic Vectors; Ion Channels; Leptin; Male; Mitochondrial Proteins; Nerve Tissue Proteins; Neuropeptides; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; RNA, Messenger; Thyrotropin; Time Factors; Transduction, Genetic; Uncoupling Protein 1; Up-Regulation; Weight Gain

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

Low birth weight resulting from intrauterine growth retardation (IUGR) is a risk factor for further development of metabolic diseases. The pig appears to reproduce nearly all of the phenotypic pathological consequences of human IUGR and is likely to be more relevant than rodents in studies of neonatal development. In the present work, we characterized the model of low-birth-weight piglets with particular attention to the hypothalamic leptin-sensitive system, and we tested whether postnatal leptin supplementation can reverse the precocious signs of adverse metabolic programming. Our results demonstrated that 1) IUGR piglets present altered postnatal growth and increased adiposity; 2) IUGR piglets exhibit abnormal hypothalamic distribution of leptin receptors that may be linked to further disturbance in food-intake behavior; and 3) postnatal leptin administration can partially reverse the IUGR phenotype by correcting growth rate, body composition, and development of several organs involved in metabolic regulation. We conclude that IUGR may be characterized by altered leptin receptor distribution within the hypothalamic structures involved in metabolic regulation and that leptin supplementation can partially reverse the IUGR phenotype. These results open interesting therapeutic perspectives in physiopathology for the correction of defects observed in IUGR.

Topics: Adipocytes, White; Adipose Tissue, White; Animals; Animals, Newborn; Birth Weight; Blood Glucose; Body Composition; Body Size; Body Weight; Female; Fetal Growth Retardation; Gene Expression; Hypothalamus; In Situ Hybridization; Leptin; Receptors, Leptin; Sus scrofa; Triglycerides; Weight Gain

Topics: Animals; Blotting, Western; Dietary Fats; Drug Synergism; Fructose; Leptin; Male; Rats; Rats, Sprague-Dawley; Sweetening Agents; Triglycerides; Weight Gain

Leptin dysregulation has been implicated in the body weight gain and metabolic dysfunction observed with the second generation antipsychotic drugs (SGAD) olanzapine and clozapine.. This study quantified the frequency of subjects with abnormal correlation between leptin and the body mass index controlling for gender (defined as being out of the upper or lower 95% confidence interval in the regression line when combining each group with the drug-free subjects) after prolonged treatment with olanzapine (n=126), clozapine (n=62), first generation antiypsychotics (n=91), other SGAD (n=22), other psychotropic drugs (n=65) and drug-free subjects (n=229).. None of the analysis was significant (p>0.05). In fact, in 17 out of 20 comparisons, the drug-free group had numerically higher frequencies of outliers than the corresponding treatment group. There were 28 outliers (4.7% of the total sample). In agreement with previous studies, cross-sectional analysis did not report gross alterations in serum leptin levels during olanzapine or clozapine administration.. Longitudinal studies should focus on leptin regulation early on treatment, on the frequency of abnormal leptin receptor sensitivity and/or specific polymorphisms in the leptin allele and on several confounding factors in order to design personalized preventive and therapeutic measures.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Clozapine; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Male; Mental Disorders; Middle Aged; Olanzapine; Outliers, DRG; Receptors, Leptin; Schizophrenia; Sex Factors; Weight Gain

Physical inactivity is often associated with positive energy balance and fat gain.. We aimed to assess whether energy intake in excess of requirement activates systemic inflammation and antioxidant defenses and accelerates muscle atrophy induced by inactivity.. Nineteen healthy male volunteers were studied before and at the end of 5 wk of bed rest. Subjects were allowed to spontaneously adapt to decreased energy requirement (study A, n = 10) or were provided with an activity-matched diet (study B, n = 9). Groups with higher (HEB) or lower (LEB) energy balance were identified according to median values of inactivity-induced changes in fat mass (DeltaFM, assessed by bioelectrical impedance analysis).. In pooled subjects (n = 19; median DeltaFM: 1.4 kg), bed rest-mediated decreases in fat-free mass (bioelectrical impedance analysis) and vastus lateralis thickness (ultrasound imaging) were significantly greater (P < 0.03) in HEB(AB) (-3.8 +/- 0.4 kg and -0.32 +/- 0.04 cm, respectively) than in LEB(AB) (-2.3 +/- 0.5 kg and -0.09 +/- 0.04 cm, respectively) subjects. In study A (median DeltaFM: 1.8 kg), bed rest-mediated increases in plasma leptin, C-reactive protein, and myeloperoxidase were greater (P < 0.04) in HEB(A) than in LEB(A) subjects. Bed rest-mediated changes of glutathione synthesis rate in eythrocytes (l-[3,3-(2)H(2)]cysteine incorporation) were greater (P = 0.03) in HEB(A) (from 70 +/- 19 to 164 +/- 29%/d) than in LEB(A) (from 103 +/- 23 to 84 +/- 27%/d) subjects.. Positive energy balance during inactivity is associated with greater muscle atrophy and with activation of systemic inflammation and of antioxidant defenses. Optimizing caloric intake may be a useful strategy for mitigating muscle loss during period of chronic inactivity.

Topics: Adipose Tissue; Adult; Bed Rest; Biomarkers; Body Composition; C-Reactive Protein; Electric Impedance; Energy Intake; Energy Metabolism; Erythrocytes; Glutathione; Humans; Inflammation; Leptin; Lipid Metabolism; Male; Muscular Atrophy; Nutritional Requirements; Oxidation-Reduction; Oxidative Stress; Risk Factors; Weight Gain

Despite a better overall tolerance as compared to classical antipsychotics, atypical antipsychotics are not devoid of side-effects, notably metabolic factors (weight gain, alteration of lipid and glucose profile). These side-effects are very troubling concerning long term morbidity and mortality and may also influence compliance towards drugs. The department of psychiatry of the Hospital University Centre has established a guideline on the clinical monitoring of patients receiving atypical antipsychotics, based on recently published consensus, which will be presented here. In addition, recent studies show that weight gain and metabolic alterations induced by this type of medication may be influenced by the genetic background of the patients. Such studies should allow, in the near future, to adapt the treatment for each patient.

Topics: Antidepressive Agents, Second-Generation; Glucose Intolerance; Humans; Leptin; Metabolic Syndrome; Pharmacogenetics; Receptors, Leptin; Weight Gain

The aim of the present study was to investigate the anthropometric and endocrine characteristics of subjects with amenorrhea related to eating disorders after weight recovery, in order to identify factors connected with the resumption of menses.. Clinical data, body composition parameters and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, cortisol, leptin and insulin were assessed in two groups of young women classified according to menstrual status after weight rehabilitation: 43 subjects who displayed persistent amenorrhea and 34 who resumed menses. Univariate and multivariate logistic regression analyses were used to examine the relationships between the different parameters and menstrual recovery.. The patients who resumed menses had low initial weight and BMI, and a greater difference between current and initial BMI (DeltaBMI), than those with amenorrhea. No differences were observed in lean mass, body fat or bone density between the two groups. Moreover, the reduction in FSH and the increase in LH, insulin and leptin emerged as significant predictors of menstrual recovery. Increased DeltaBMI and insulin continued to be positive predictors in the multivariate analysis.. Following weight rehabilitation, the individual's metabolic set point before weight loss and the current insulin levels appear significant in predicting the reactivation of reproductive function.

Topics: Adolescent; Adult; Amenorrhea; Body Composition; Body Mass Index; Feeding and Eating Disorders; Female; Follicle Stimulating Hormone; Humans; Hydrocortisone; Insulin; Leptin; Luteinizing Hormone; Menstruation; Ovary; Prognosis; Recovery of Function; Thyroid Hormones; Weight Gain; Young Adult

Persistent suppression of hyperinsulinemia in genetically obese (fa/fa) Zucker rats by diazoxide (DZ) reduces food intake and weight gain; improves insulin sensitivity, glycemic control, and lipid profile; and enhances beta(3)-adrenergic function and lipolysis in adipose tissue. The aim of this study was to elucidate the effects of DZ on basal metabolic rate (BMR), fat oxidation, and adrenergic function of lean and obese Zucker rats. Diazoxide (150 mg/kg/d) or vehicle (control) was administered for 4 weeks in 7-week-old obese and lean Zucker rats (n = 8-9 per subgroup). Animals underwent indirect calorimetry, body composition analysis, and determination of uncoupling proteins (UCPs) messenger RNA (mRNA) in brown and white adipose tissues (BAT and WAT) and skeletal muscle (SM), beta(3)-adrenergic receptor (AR) mRNA in BAT and WAT, beta(2)-AR in SM as well as WAT, and SM adenylate cyclase (AC) activity at the completion of study. Diazoxide treatment decreased food intake, weight gain, and body fat in obese rats (P < .01). Although DZ treatment lowered fasting plasma glucose, insulin, leptin, adiponectin, and lipids in obese rats (P < .01), it increased adiponectin-leptin ratio (P < .01). Plasma adiponectin-leptin ratio was inversely correlated with fat mass in obese and lean rats (r = -0.86, P < .0001). Diazoxide treatment resulted in higher BMR and fat oxidation rate in obese compared with control animals (P < .01), without any effect in lean animals. Furthermore, plasma adiponectin was inversely correlated with BMR (-0.56, P < .001) and lipid oxidation rate (-0.61, P < .0005) and was positively correlated with nonprotein respiratory quotient (r = 0.41, P < .01) in obese and lean rats. This was associated with increased beta(3)-AR mRNA expression in BAT and WAT (P < .01), UCP-1 and UCP-3 in BAT and AC activity in WAT (P < .02), and AC activity in SM of DZ obese rats compared with controls (P < .01), without significant change in SM beta(2)-AR mRNA expressions. Diazoxide attenuation of hyperinsulinemia decreased the rate of weight gain but enhanced insulin sensitivity, BMR, and fat oxidation in obese rats. This was associated with increased receptor- and non-receptor-mediated adrenergic function in adipose and muscle tissues in obese rats, respectively. These metabolic changes in obese Zucker rats suggest that antiobesity effects of DZ appear to be not only through its anorectic effect, modification of disturbed insulin metabolism, and inhibition of lipogen

Topics: Adenylyl Cyclases; Animals; Basal Metabolism; Blood Glucose; Body Composition; Calorimetry, Indirect; Diazoxide; Energy Metabolism; Female; Insulin; Ion Channels; Leptin; Lipid Metabolism; Mitochondrial Proteins; Obesity; Oxidation-Reduction; Rats; Rats, Zucker; Receptors, Adrenergic, beta-3; RNA, Messenger; Uncoupling Protein 1; Uncoupling Protein 3; Weight Gain

Topics: Anorexia Nervosa; Body Mass Index; Child; Female; Fluid Therapy; Ghrelin; Heart Rate; Hematocrit; Hospitalization; Humans; Hypotension; Insulin; Leptin; Nutritional Support; Social Support; Weight Gain

Soy protein regulates adiponectin and peroxisome proliferator-activated receptor alpha (PPARalpha) in some species, but the effect of dietary soy protein on adiponectin and PPARalpha in the pig has not been studied. Therefore, the objective of this study was to determine whether soya bean meal reduction or replacement influences serum adiponectin, adiponectin mRNA, serum metabolites and the expression of PPARalpha and other genes involved in lipid deposition. Thirty-three pigs (11 pigs per treatment) were subjected to one of three dietary treatments: (i) reduced crude protein (CP) diet containing soya bean meal (RCP-Soy), (ii) high CP diet containing soya bean meal (HCP-Soy) or (iii) high CP diet with corn gluten meal replacing soya bean meal (HCP-CGM) for 35 days. Dietary treatment had no effect on overall growth performance, feed intake or measures of body composition. There was no effect of dietary treatment on serum adiponectin or leptin. Dietary treatment did not affect the abundance of the mRNAs for adiponectin, PPARalpha, PPARgamma2, lipoprotein lipase or fatty acid synthase in adipose tissue. The mRNA expression of PPARalpha, PPARgamma2, lipoprotein lipase or fatty acid synthetase in loin muscle was not affected by dietary treatment. In liver tissue, the relative abundance of PPARalpha mRNA was greater (p < 0.05) in pigs fed the HCP-Soy diets when compared to pigs fed RCP-Soy or HCP-CGM diets. Hepatic mRNA expression of acyl-CoA oxidase or fatty acid synthase was not affected by dietary treatment. Western blot analysis indicated that hepatic PPARalpha protein levels were decreased (p < 0.05) in pigs fed the RCP-Soy diets when compared to pigs fed the HCP-Soy diets. These data suggest that increasing the soy protein content of swine diets increases hepatic expression of PPARalpha without associated changes in body composition.

Topics: Adiponectin; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Body Composition; Dietary Proteins; Dose-Response Relationship, Drug; Energy Intake; Gene Expression Regulation; Leptin; Liver; PPAR alpha; PPAR gamma; Random Allocation; Soybean Proteins; Swine; Weight Gain

Rapid growth in infancy may be associated with later onset childhood obesity. The aim in this study was to evaluate the relationships of adipokines to growth of infants at 6-10 months of age and to serum insulin, glucose, and auxological parameters of infants and their mothers.. Thirty-seven healthy term AGA formula fed infants, 21 males, mean age 7.0 +/- 1.2 (SD) months, were evaluated during a nutritional assessment at a county health department. Length, weight, head circumference, waist circumference, mid-arm circumference, and subscapular skin fold and triceps skin fold thickness were determined. Mothers were weighed and their height measured, birth weight recorded from clinic records, and the infant's dietary history reviewed. Following finger stick for assessment of hemoglobin, a bedside blood glucose was determined and 250 microl of additional serum taken for assay of total adiponectin, high molecular weight (HMW) adiponectin (n=12), leptin, and insulin.. The infants' total adiponectin to leptin ratio correlated significantly with the change in body weight from birth to mid-infancy (r = 0.349, p < 0.05). The mean total adiponectin was 34.2 - 16.6 microg/ml (n=37), mean HMW adiponectin 12.2 +/- 9.0 microg/ml (n=12), mean HMW/total adiponectin ratio 34.3 +/- 17.6%, and mean leptin 1.3 +/- 1.2 ng/ml. Neither total nor HMW adiponectin, leptin, nor the leptin/adiponectin ratio, correlated with serum insulin, glucose/insulin ratio, hemoglobin, birth weight, or auxological determinations of the infants or mothers.. As leptin and adiponectin are both insulin sensitizing hormones that change inversely with acquisition of body fat, and the leptin/adiponectin ratio correlates significantly with weight gain in mid-infancy, we postulate that this ratio might provide a marker relating to infantile growth and later adiposity.

Topics: Adiponectin; Adipose Tissue; Adiposity; Biomarkers; Body Mass Index; Body Weight; Cohort Studies; Female; Humans; Infant; Insulin; Leptin; Male; Nutrition Assessment; Skinfold Thickness; Weight Gain

Antipsychotic-induced weight gain has important effects on treatment compliance and long-term health. Several reports have indicated that a -2548A/G single-nucleotide polymorphism (SNP) of the leptin gene is associated with antipsychotic-induced weight gain. We hypothesized that there is a similar relationship between the -2548A/G SNP and olanzapine-induced weight gain. A total of 74 Korean schizophrenic patients were examined. Their weight was measured before starting olanzapine and after long-term treatment lasting for at least 3 months. The weight gain was significantly higher for patients with the AG genotype than for those with the AA genotype (p=0.029). Analysis of covariance also showed the difference of weight gain was still significant when adjusted for sex and treatment duration (p=0.046). This finding supports the presence of a relationship between the -2548A/G SNP of the leptin gene and weight gain in Korean schizophrenic patients receiving olanzapine treatment.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Female; Gene Frequency; Genotype; Humans; Korea; Leptin; Male; Middle Aged; Olanzapine; Polymorphism, Single Nucleotide; Schizophrenia; Weight Gain

To determine if tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). IL-6 gene expression is influenced by amount and source of dietary fat, 30 weanling female rats were randomly assigned to a moderate-fat soybean oil (MFS; 22% of total energy fed as fat), high-fat (HF) soybean oil (HFS; 39% of total energy fed as fat), or HF tallow (HFT; 39% of total energy fed as fat) diet treatments. Oral glucose tolerance tests (OGTT) were conducted serially over 10 weeks of treatment. HFT and HFS rats gained more weight and had greater body fat than the MFS rats fed similar amounts of energy. Both groups of HF-fed rats had greater (P<.05) insulin resistance (homeostasis model assessment) than MFS-fed rats. TNF-alpha mRNA abundance quantified by real-time reverse transcriptase-polymerase chain reaction was greater (P<.05) in liver and lower (P<.05) in adipose tissue in HFT compared to HFS and MFS rats. There were positive correlations (P<.05) between hepatic TNF-alpha mRNA and insulin resistance, and negative correlations between insulin sensitivity and hepatic TNF-alpha mRNA and hepatic IL-6 mRNA. During Week 3 and Week 6 OGTTs, hyperinsulinemic responses were observed in the HFT group, after which, on Week 9, insulin secretion was diminished in response to the OGTT, suggesting impaired pancreatic insulin secretion. HFS rats exhibited insulin resistance on Week 9 OGTT. In summary, an HFT diet fed to growing female rats caused insulin resistance associated with increased hepatic TNF-alpha mRNA leading to pancreatic insufficiency. Early-onset insulin resistance related to the inflammatory process in obesity is influenced by the amount and type of fat in the diet.

Topics: Animals; Cytokines; Dietary Fats; Female; Gene Expression; Glucose Tolerance Test; Hyperinsulinism; Insulin; Insulin Resistance; Interleukin-1; Leptin; Liver; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha; Weaning; Weight Gain

This study was designed to determine whether (1) protein type and (2) the dietary carbohydrate to lipid content affected daily energy intake, body weight and adiposity in rats receiving high-protein diets ad libitum over a 25 d period. Each of the ten groups (n 8) consumed ad libitum one of the diets described below. A normal protein diet (P14C56L30, containing whole milk protein) and nine high-protein diets were used. The composition of the high-protein diets varied in terms of two parameters: macronutrient composition and protein type. Three macronutrient compositions (P55C35L10, P55C15L30 and P55L45) combined with three protein types (Milk, Whey and betaLac) allowed us to test nine diets. The results show that both protein type (betaLac > Whey > Milk) and the carbohydrate to lipid ratio (P55L45>P55C35L10 or P55C15L30) modulated reductions in energy intake, body weight and adiposity in rats receiving high-protein diets ad libitum, when compared with rats fed a normal diet under the same conditions. By contrast, blood lipid profiles were mainly influenced by the carbohydrate to lipid ratio (P55C15L30>P55L45 or P55C35L10). Moreover, betaLac protein was also the most efficient in tending to preserve lean body mass at the expense of fat mass, and improve blood metabolism hormones (insulin, leptin). Taken together, the present results show that whey-derived protein sources, and particularly beta-lactoglobulin-enriched fraction, are of considerable value because of their ability to reduce both body weight gain and the adiposity index.

Topics: Adiposity; Animals; Body Composition; Dietary Carbohydrates; Dietary Proteins; Energy Intake; Insulin; Lactoglobulins; Leptin; Lipids; Male; Milk Proteins; Rats; Rats, Wistar; Weight Gain; Whey Proteins

Mice with a targeted disruption of bombesin receptor subtype-3 (BRS-3 KO) develop hyperphagia, obesity, hypertension, and impaired glucose metabolism. However, the factors contributing to their phenotype have not been clearly established. To determine whether their obesity is a result of increased food intake or a defect in energy regulation, we matched the caloric intake of BRS-3 KO mice to wild-type (WT) ad libitum (ad lib)-fed controls over 21 wk. Although BRS-3 KO ad lib-fed mice were 29% heavier, the body weights of BRS-3 KO pair-fed mice did not differ from WT ad lib-fed mice. Pair-feeding BRS-3 KO mice normalized plasma insulin but failed to completely reverse increased adiposity and leptin levels. Hyperphagia in ad lib-fed KO mice was due to an increase in meal size without a compensatory decrease in meal frequency resulting in an increase in total daily food intake. An examination of neuropeptide Y, proopiomelanocortin, and agouti-related peptide gene expression in the arcuate nucleus revealed that BRS-3 KO mice have some deficits in their response to energy regulatory signals. An evaluation of the satiety effects of cholecystokinin, bombesin, and gastrin-releasing peptide found no differences in feeding suppression by these peptides. We conclude that hyperphagia is a major factor leading to increased body weight and hyperinsulinemia in BRS-3 KO mice. However, our finding that pair-feeding did not completely normalize fat distribution and plasma leptin levels suggests there is also a metabolic dysregulation that may contribute to, or sustain, their obese phenotype.

Topics: Adiposity; Animals; Body Weight; Bombesin; Cholecystokinin; Eating; Energy Metabolism; Gastrin-Releasing Peptide; Glucose; Hyperinsulinism; Hyperphagia; Hypothalamus; Insulin; Leptin; Male; Mice; Mice, Knockout; Obesity; Receptors, Bombesin; Satiation; Weight Gain

Chronic antiepileptic therapy with valproic acid (VPA) is associated with increased body weight and insulin resistance in adults and children. Attempts to determine the underlying pathophysiologic mechanisms have failed. Adipocytokines have recently been defined as a link between glucose and fat metabolism. We herein demonstrate that VPA-associated overweight is accompanied by lower adiponectin and higher leptin concentrations in children. The absence of any relationship with visfatin concentration does not suggest a role of this novel insulin-mimetic hormone in VPA-associated metabolic alterations. Therefore, adiponectin and leptin but not visfatin may be considered as potential regulators of glucose and fat metabolism during VPA-therapy.

Topics: Adiponectin; Adipose Tissue; Age Factors; Anticonvulsants; Blood Glucose; Child; Epilepsy; Female; Humans; Insulin Resistance; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Valproic Acid; Weight Gain

Recent studies support a link between stress and the increased consumption of palatable foods. However, there has been a noted lack of genetic models to examine predisposing factors of overweight, obesity, and binge eating, particularly the role that stress sensitivity might play in the development of these conditions. We have examined the effects of chronic stress exposure on macronutrient choice preferences in a genetic mouse model of stress sensitivity (corticotropin-releasing factor receptor-2 deficient mice). Mice were provided with high fat, high protein, and high carbohydrate diets during exposure to chronic variable stress (CVS). Mice given free access to these diets during CVS selected a greater proportion of their calories in the form of the high fat diet compared to non-stressed mice. Apparent genotypic differences in high protein and high carbohydrate preferences were also diminished during the stress exposure. Stress-sensitive mice showed reduced weight gain and caloric efficiency during CVS, indicating a role for this phenotype in energy balance. When the preferred high fat diet was provided under limited access, stress-sensitive mice showed an increase in high fat consumption during CVS that was not observed in wild type mice, indicating a potential role for stress sensitivity in stress-induced bingeing. These studies support an involvement of stress pathways in macronutrient selection where stress selectively elevates the intake of a preferred high fat diet. Based on the alterations in caloric efficiency, increases in stress sensitivity may further predispose an organism toward altered energy balance in times of stress.

Topics: Adipose Tissue, Brown; Analysis of Variance; Animals; Blood Glucose; Corticosterone; Diet; Eating; Energy Intake; Food; Food Preferences; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Corticotropin-Releasing Hormone; Stress, Psychological; Time Factors; Weight Gain

Pituitary Fshb concentrations increase markedly and selectively beginning on Postnatal Day 20 in the male rat. To evaluate the factors potentially responsible for this rise in FSH, we adjusted the time of weaning, which is generally also on Day 20. Male rat pups were provided nutrients by suckling only and were weaned to laboratory chow earlier (Day 17) or later (Day 23) than normally performed in animal facilities (Day 20). Between ages 17 and 29 days, significant increases were seen in serum LH (1.4-fold) and FSH (2.4-fold) levels; pituitary expression of Lhb (5.4-fold), Fshb (21.3-fold), and inhibin beta B (Inhbb, 2.26-fold) mRNAs; and testicular expression of Inhbb (10-fold) mRNA. Concurrently, significant decreases occurred in serum inhibin B levels (1.8-fold); pituitary adenylate cyclase-activating polypeptide (Adcyap1, 4.2-fold), total follistatin (Fst, 3.5-fold), and Fst isoform 288 (5.6-fold) mRNAs; and testicular expression of inhibin beta A (8.2-fold) mRNA. Early weaning significantly increased serum FSH but not LH and increased pituitary expression of Fshb and GnRH receptor (Gnrhr) mRNAs but not Lhb. Early weaning also significantly decreased serum inhibin B but increased testicular expression of the Inhbb subunit. Early weaning also caused pituitary expression of Fst and Adcyap1 to decline earlier than in the control group. Immediately after weaning, growth accelerated substantially, and the time of weaning produced significant and differential effects on circulating leptin levels that were not related to indices of FSH production. From these observations, we propose the novel hypothesis that the increase in growth rate subsequent to weaning signals circulating inhibin B levels to fall and pituitary Adcyap1 and consequently Fst expression to decrease, and that these events together facilitate the rise in Fshb and Gnrhr expression by increasing pituitary activin signaling.

Topics: Aging; Animals; Female; Follicle Stimulating Hormone; Follicle Stimulating Hormone, beta Subunit; Follistatin; Inhibins; Leptin; Luteinizing Hormone, beta Subunit; Male; Pituitary Adenylate Cyclase-Activating Polypeptide; Pituitary Gland; Rats; Rats, Sprague-Dawley; Receptors, LHRH; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sex Characteristics; Testis; Weaning; Weight Gain

This study was conducted to define the regulatory mechanisms underlying stress-induced decreases in food intake and weight gain. Rats received a single or 4 daily injections of dexamethasone (0.1 or 1 mg/kg). Food intake and weight gain were recorded, and plasma leptin, brain contents of serotonin (5-hydroxytryptamine; 5-HT), 5-hydroxy-indole-acetic acid (5-HIAA) and the raphe expression of tryptophan hydroxylase (TPH), monoamine oxidase A (MAO-A) and 5-HT reuptake transporter (5-HTT) genes were examined. A single injection of dexamethasone did not acutely affect food intake, but cumulative food intake and weight gain were suppressed dose-dependently by daily injections of dexamethasone. Both a single and repeated injections of dexamethasone elevated plasma leptin in a dose dependent manner. 5-HT contents in the hypothalamus was decreased, but 5-HIAA increased, both by a single and repeated dexamethasone. A single injection of dexamethasone did not affect mRNA expressions of TPH, MAO-A and 5-HTT genes, but repeated dexamethasone increased them in the dorsal raphe nucleus. These results suggest that plasma leptin may play a role in dexamethasone-induced anorexia. Additionally, increased expression of MAO-A and 5-HTT genes by repeated dexamethasone appears to be implicated in decreases of the brain 5-HT contents.

Topics: Animals; Dexamethasone; Dose-Response Relationship, Drug; Eating; Hydroxyindoleacetic Acid; Hypothalamus; Leptin; Male; Monoamine Oxidase; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; RNA, Messenger; Serotonin; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase; Weight Gain

Leptin regulates energy balance and glucose homeostasis, at least in part, via activation of receptors in the arcuate nucleus of the hypothalamus located in proopiomelanocortin (POMC) neurons. Females have greater sensitivity to central leptin than males, suggested by a greater anorectic effect of central leptin administration in females. We hypothesized that the regulation of energy balance and peripheral glucose homeostasis of female rodents would be affected to a greater extent than in males if the action of leptin in POMC neurons were disturbed. Male and female mice lacking leptin receptors only in POMC neurons gained significantly more body weight and accumulated more body fat. However, female mice gained disproportionately more visceral adiposity than males, and this appeared to be largely the result of differences in energy expenditure. When maintained on a high-fat diet (HFD), both male and female mutants had higher levels of insulin following exogenous glucose challenges. Chow- and HFD-fed males but not females had abnormal glucose disappearance curves following insulin administrations. Collectively, these data indicate that the action of leptin in POMC neurons is sexually different to influence the regulation of energy balance, fat distribution, and glucose homeostasis.

Topics: Adiposity; Animals; Blood Glucose; Dietary Fats; Energy Metabolism; Female; Gene Targeting; Homeostasis; Insulin; Leptin; Male; Mice; Mice, Knockout; Neurons; Pro-Opiomelanocortin; Receptors, Leptin; Sex Characteristics; Weight Gain

An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity, hyperleptinemia, insulin resistance, and type 2 diabetes. Although the mechanisms are unclear, this "programming" has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition (UN) during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet. Using this model of maternal UN, we have recently shown that neonatal leptin treatment in females reverses the postnatal sequelae induced by developmental programming. To examine possible gender-related effects of neonatal leptin treatment, the present study investigated the effect of neonatal leptin treatment on the metabolic phenotype of adult male offspring. Leptin treatment (recombinant rat leptin, 2.5 microg/g.d, sc) from postnatal d 3-13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring. Neonatal leptin treatment of male offspring from normally nourished mothers caused an increase in diet-induced weight gain and related metabolic sequelae, including hyperinsulinemia and increased total body adiposity compared with saline-treated controls. This occurred without an increase in caloric intake. These effects were specific to offspring of normal pregnancies and were not observed in offspring of mothers after UN during pregnancy. In the latter, neonatal leptin treatment conferred protection against the development of the programmed phenotype, particularly in those fed the chow diet postnatally. These data further reinforce the importance of leptin in determining long-term energy homeostasis, and suggest that leptin's effects are modulated by gender and both prenatal and postnatal nutritional status.

Topics: Adipose Tissue; Animals; Animals, Newborn; Blood Glucose; Bone Density; C-Peptide; Eating; Female; Insulin; Leptin; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Pregnancy; Rats; Rats, Wistar; Weight Gain

Chronic consumption of high-fat or -carbohydrate diets is associated with the development of obesity; however, it is not well established whether dietary protein plays a role in the development of abnormalities of lipid metabolism that occur during obesity. To determine the effect of different types of protein during diet-induced obesity on hepatic and adipocyte lipid metabolism, rats were fed casein (CAS) or soy (SOY) protein diets with 5% fat or high-fat diets with 25% fat (HF-CAS and HF-SOY) for 180 d. Rats fed soy diets had lower hepatic sterol regulatory element binding protein-1 (SREBP-1) expression and higher SREBP-2 expression than those fed casein diets, leading to less hepatic lipid deposition. On the other hand, long-term HF-SOY consumption prevented hyperleptinemia in comparison with rats fed HF-CAS. Rats fed soy protein diet showed higher adipocyte perilipin mRNA expression and smaller adipocyte area than those fed casein diets, which was associated with a lower body fat content. Furthermore, the lipid droplet area in brown adipose tissue was significantly lower in rats fed soy diets than in those fed casein diets and it was associated with higher uncoupling protein-1 (UCP-1) expression. As a result, rats fed the soy diets gained less weight than those fed the casein diets, in part due to an increase in the thermogenic capacity mediated by UCP-1. These results suggest that the type of protein consumed and the presence of fat in the diet modulate lipid metabolism in adipose tissue and liver.

Topics: Adipocytes; Adipose Tissue; Animals; Body Composition; Carrier Proteins; Caseins; Cholesterol; Cholic Acids; Dietary Fats; Dietary Proteins; Fatty Acids, Nonesterified; Glucagon; Insulin; Leptin; Liver; Male; Perilipin-1; Phosphoproteins; PPAR gamma; Rats; Rats, Sprague-Dawley; RNA, Messenger; Soybean Proteins; Sterol Regulatory Element Binding Protein 1; Sterol Regulatory Element Binding Protein 2; Triglycerides; Weight Gain

Topics: Adipose Tissue; Biomarkers, Tumor; Body Mass Index; Body Weight; Breast Neoplasms; Disease-Free Survival; Estrogens; Exercise; Female; Humans; Inflammation; Insulin; Insulin-Like Growth Factor I; Leptin; Neoplasms; Obesity; Overweight; Recurrence; Risk Assessment; Risk Factors; United Kingdom; Weight Gain

Epidemiological evidence has revealed that undernutrition in utero is closely associated with obesity and related detrimental metabolic sequelae in adulthood. Recently, using a wild-type (wt) mouse model in which offspring were exposed to intrauterine undernutrition (UN offspring), we reported that the premature leptin surge during neonatal growth promotes lifelong changes in energy regulating circuitry in the hypothalamus, thus playing an important role in the development of pronounced obesity on a high-fat diet (HFD) in adulthood. Here, we further evaluate the essential involvement of leptin in the developmental origins of obesity using leptin-deficient ob/ob mice.. We assessed the progression of obesity on an HFD in adult leptin-deficient ob/ob male mice that were exposed to intrauterine undernutrition by maternal food restriction (ob/ob UN offspring) or to leptin treatment during the neonatal period; this treatment is comparable to the premature leptin surge observed in the wt-UN offspring.. On an HFD, the body weight of the male ob/ob UN offspring paralleled that of the ob/ob offspring exposed to normal intrauterine nutrition (ob/ob NN offspring). In contrast, early exposure to leptin in the ob/ob NN offspring during early neonatal growth reproduced the development of pronounced obesity on an HFD in adulthood.. The presence of leptin and associated energy regulation are indispensable in the acceleration of obesity on an HFD caused by undernutrition in utero. The premature leptin surge plays an essential role in the developmental origins of obesity as a programming signal during the early neonatal period.

Topics: Animals; Animals, Newborn; Dietary Fats; Disease Models, Animal; Eating; Female; Hypothalamus; Leptin; Male; Malnutrition; Mice; Mice, Obese; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, Leptin; RNA, Messenger; Weight Gain

Topics: Appetite; Ghrelin; Humans; Hypothalamus; Insulin; Leptin; Magnetic Resonance Imaging; Nicotine; Research; Smoking; Substance Withdrawal Syndrome; Tobacco Use Disorder; Weight Gain

Loss of function mutations in the receptor tyrosine kinase TrkB pathway resulted in hyperphagia and morbid obesity in human and rodents. Conversely, peripheral or central stimulation of TrkB by its natural ligands BDNF or NT4 reduced body weight and food intake in mice, supporting the idea that TrkB is a key anorexigenic signal downstream of the melanocortin-4 receptor (Mc4r) system. Here we show that in non-human primates TrkB agonists were anorexigenic when applied centrally, but surprisingly orexigenic, leading to gain in appetite, body weight, fat deposits and serum leptin levels, when given peripherally. The orexigenic and pro-obesity effects of peripherally administered TrkB agonists appear to be dose dependent, not associated with fluid retention nor with evidence of receptor down regulation. Our findings revealed that TrkB signaling exerts dual control on energy homeostasis in the primates that could be targeted for the treatment of either wasting disorders or obesity.

Topics: Animals; Appetite; Body Weight; Brain-Derived Neurotrophic Factor; Gene Deletion; Leptin; Ligands; Macaca mulatta; Mutation; Obesity; Receptor, Melanocortin, Type 4; Receptor, trkB; Recombinant Proteins; Signal Transduction; Weight Gain

S100B protein is mainly synthesized in glial cells and modulates the balance between cell proliferation and differentiation in neurons and glial cells. However, S100B is not CNS-specific since its production was detected in numerous non-cerebral tissues e.g. adipocytes. In this study we investigated the influence of chronic fasting and subsequent weight gain on serum levels of S100B in patients with anorexia nervosa. We found that nutritional status was an important factor influencing serum levels of S100B.

Topics: Adolescent; Age Factors; Anorexia Nervosa; Biomarkers; Body Composition; Body Mass Index; Chronic Disease; Dietary Proteins; Down-Regulation; Female; Humans; Leptin; Nerve Growth Factors; Nutritional Status; Predictive Value of Tests; Recovery of Function; Reference Values; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Starvation; Weight Gain

Signal transducer and activator of transcription (Stat)-3 signals mediate many of the metabolic effects of the fat cell-derived hormone, leptin. In mice, brain-specific depletion of either the long form of the leptin receptor (Lepr) or Stat3 results in comparable obese phenotypes as does replacement of Lepr with an altered leptin receptor locus that codes for a Lepr unable to interact with Stat3. Among the multiple brain regions containing leptin-sensitive Stat3 sites, cells expressing feeding-related neuropeptides in the arcuate nucleus of the hypothalamus have received much of the focus. To determine the contribution to energy homeostasis of Stat3 expressed in agouti-related protein (Agrp)/neuropeptide Y (Npy) arcuate neurons, Stat3 was deleted specifically from these cells, and several metabolic indices were measured. It was found that deletion of Stat3 from Agrp/Npy neurons resulted in modest weight gain that was accounted for by increased adiposity. Agrp/Stat3-deficient mice also showed hyperleptinemia, and high-fat diet-induced hyperinsulinemia. Stat3 deletion in Agrp/Npy neurons also resulted in altered hypothalamic gene expression indicated by increased Npy mRNA and decreased induction of suppressor of cytokine signaling-3 in response to leptin. Agrp mRNA levels in the fed or fasted state were unaffected. Behaviorally, mice without Stat3 in Agrp/Npy neurons were mildly hyperphagic and hyporesponsive to leptin. We conclude that Stat3 in Agrp/Npy neurons is required for normal energy homeostasis, but Stat3 signaling in other brain areas also contributes to the regulation of energy homeostasis.

Topics: Adiposity; Agouti-Related Protein; Animals; Body Weight; Dietary Fats; Energy Metabolism; Homeostasis; Hypothalamus; Immunohistochemistry; Leptin; Mice; Neurons; Neuropeptide Y; Reverse Transcriptase Polymerase Chain Reaction; STAT3 Transcription Factor; Weight Gain

A reduction in food intake is a prominent feature of many infectious diseases. However, the underlying mechanisms of parasite-induced anorexia in sheep are poorly understood. Here, we tested the hypotheses (a) that the degree of parasite-induced anorexia in lambs is influenced by their growth potential and (b) that nematode infection results in elevated plasma leptin concentration in lambs. The hypotheses were tested with Suffolk x Greyface (S) and Scottish Black-face (B) lambs that are known to differ in their growth potential (S lambs are of greater growth potential than B lambs). During a primary parasite infection, 24 out of 48 lambs per breed were trickle-infected with 7,000 infective Teladorsagia circumcincta larvae per day, 3 d/wk, for a period of 12 wk (experiment I). The lambs were then dewormed, and after a 2-wk interval, half of the 24 lambs per breed that were previously infected were reinfected for another 12 wk with the same parasite and dose as used in the primary infection (experiment II). In both experiments, infected lambs were fed grass pellets for ad libitum intake, whereas noninfected lambs were fed grass pellets for either ad libitum or restricted intakes. The S lambs were more susceptible than B lambs to nematode infection, as judged from the differences in fecal egg counts (P = 0.007). Parasitized lambs of the more susceptible breed (S) showed anorexia [i.e., a decrease in intake of 13% compared with uninfected controls (P = 0.01)], whereas no significant reduction in food intake was observed in lambs of the more resistant breed (B). Reexposure to nematode infection of previously infected animals tended to result in renewed anorexia in S lambs but not in B lambs (P = 0.08) in a similar extent as during primary infection. Plasma leptin concentrations did not differ between ad libitum-fed infected and control lambs but were greater in infected than in noninfected lambs at a similar level of food intake during both the primary (P = 0.02) and the secondary parasitic infection (P = 0.004) in both breeds. The results show that leptin may be involved in the response of lambs to infection but that it is unlikely that leptin alone is responsible for the parasite-induced anorexia in lambs.

Topics: Animals; Eating; Feces; Female; Gastrointestinal Diseases; Genetic Predisposition to Disease; Leptin; Male; Nematode Infections; Parasite Egg Count; Sheep; Sheep Diseases; Time Factors; Weight Gain

Anorexia nervosa (AN) commonly arises during adolescence, leading to interruptions of somatic and psychological development as well as to cortical atrophy and reductions of brain volume. While most brain changes shift towards normal with weight restoration, it is not certain whether they are related to the loss of brain cells, neuropil or merely due to fluid shifts. We measured S100B serum concentrations and psychometric characteristics in 34 patients with acute AN, 19 weight-recovered patients and 35 healthy control women (HCW). Plasma tryptophan and leptin levels were determined as markers for malnutrition and neuroendocrine adaptation to semi-starvation. Peripheral S100B concentrations of acute and former AN patients were not elevated and not statistically different from HCW. BMI, peripheral leptin levels and measures of psychopathology as well as executive cognitive functioning did not correlate with S100B. Plasma tryptophan was positively related to S100B. Our results are in line with our previous findings showing unaltered GFAP and NSE plasma levels in patients with acute AN. Together they do not support hypotheses comprising the degeneration of glial or neuronal cells to explain common signs of brain atrophy in patients with acute AN.

Topics: Adolescent; Adult; Anorexia Nervosa; Case-Control Studies; Female; Humans; Leptin; Nerve Growth Factors; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Thinness; Tryptophan; Weight Gain

To investigate whether there is association between the-2548G/A functional polymorphism in the promoter region of leptin gene and weight gain following antipsychotic agents (APS) acute treatment in schizophrenic patients.. Eight-four Chinese Han untreated schizophrenia patients in 70 nuclear families were recruited. The polymorphism of leptin gene was determined with PCR-RFLP technique. Body weight was measured in the patients on admission the and after 10 weeks treatment with risperidone or chlorpromazine.. There was an average (8.00+/-6.13)% increases in baseline weight after the 10 week treatment. There were significant differences in the distribution of allele frequencies (chi2=4.031, P=0.045) between the patients with weight changed >or=7% and <7% subgroups. Family-based association analysis further confirmed the above significant finding by transmission disequilibrium test but not by quantitative trait transmission disequilibrium test.. The finding confirms that the-2548G/A polymorphism in promoter region of leptin gene is associated with APS-induced weight gain.

Topics: Adolescent; Adult; Antipsychotic Agents; Family Health; Female; Genotype; Humans; Leptin; Male; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Promoter Regions, Genetic; Schizophrenia; Weight Gain

To understand the adaptation to lactation of obese rats, by studying the interplay among the gut hormone cholecystokinin (CCK), the adiposity hormone leptin and the affiliation hormone oxytocin in modulating body mass and fat storage.. Strain differences were examined between Otsuka Long Evans Tokushima Fatty (OLETF) rats lacking expression of functional CCK-1 receptors and Long Evans Tokushima Otsuka (LETO) controls, tested as nulliparous dams, at the 7 and 15th lactation day, at weaning (lactation day 22) or 8 weeks postweaning.. We measured body mass, fat pads (brown, retroperitoneal and inguinal) and inguinal adipocytes. Plasma levels of leptin and oxytocin were determined.. Fat depots of LETO female rats were larger during lactation compared to the levels found in postweaning and nulliparous female rats. LETO female rats gained weight and accumulated fat during pregnancy and lactation, returning to their normal fat levels postweaning. In contrast, OLETF female rats presented lower body weight and fat depots during the lactation period than nulliparous dams, and regained the weight and fat postweaning. Plasma leptin and oxytocin were highly correlated and followed the same pattern. OLETF leptin levels were highly correlated with fat depot and inguinal cell surface. No significant correlation was found for LETO parameters.. Pregnancy and lactation are energy-consuming events, which naturally induce female rats to increase food intake and accumulate fat. When challenged by the demands of rapidly growing preobese OLETF pups, OLETF dams' fat stores are reduced to lean, LETO levels. During lactation, sensitivity of the oxytocinergic neurons descending from the paraventricular nuclei to the nucleus of the solitary tract to CCK is reduced. We theorized that this pathway is not available to OLETF female rats that lack functional CCK-1 receptors to mediate the signal. The current study contributes to the understanding of the female body's adaptation to lactation.

Topics: Adaptation, Physiological; Adipocytes; Adipose Tissue; Animals; Body Weight; Disease Models, Animal; Female; Hypertrophy; Lactation; Leptin; Mutation; Obesity; Oxytocin; Rats; Rats, Inbred OLETF; Receptors, Cholecystokinin; Weaning; Weight Gain

We tested whether diet-induced obesity results from increased energy consumption, is associated with changes in expression of genes involved in leptin signal transduction, and is altered by hyperleptinemia. C57BL/6 mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for up to 15 weeks. HFD mice weighed significantly more than LFD controls by 3 weeks, despite consuming less energy. HFD mice had significantly greater leptin, insulin, and glucose levels than LFD mice, suggesting leptin and insulin resistance. Adiponectin levels declined with age but were unaffected by diet. HFD was associated with altered hypothalamic expression of genes whose products regulate the activity or nuclear translocation of STAT3, an important mediator of leptin actions. Expression of two isoforms of the leptin receptor decreased at 15 weeks in hypothalami of HFD mice in a tissue-specific manner. The type of fat (saturated versus unsaturated) did not influence weight gain on an HFD, but animals on LFD gained significantly more weight and adiposity if the dietary fat consisted mostly of saturated fats; this occurred despite no difference in energy consumption or absorption. Replacement of leptin to leptin-deficient ob/ob mice decreased hypothalamic leptin receptor expression and did not prevent HFD-induced weight gain. It is concluded that (1) increased energy consumption is not required for HFD-induced obesity in C57BL/6 mice, (2) HFD results in weight gain partly by modulating hypothalamic leptin-signaling pathways, (3) saturated fats induce weight gain even when total fat content of the diet is low, and (4) the effects of HFD are manifest in the presence or absence of circulating leptin.

Topics: Adiponectin; Adiposity; Animals; Blood Glucose; Body Composition; Body Weight; Dietary Fats; Energy Intake; Female; Gene Expression; Hypothalamus; Insulin; Intestinal Absorption; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Reverse Transcriptase Polymerase Chain Reaction; STAT3 Transcription Factor; Weight Gain

Feeding and stress neurocircuits are intertwined. Among the neurotransmitters and receptors common to both circuits, the serotonin 2C receptor is particularly intriguing because its distribution is limited to the central nervous system. Hence, deficits in energy balance and stress responses in mice lacking this gene are likely due to defects in central regulation. The phenotype of the serotonin 2C receptor null (KO) mouse is adult-onset hyperphagia, depressed metabolic rate, and disruption in satiety, with a progression to midlife obesity. A provocative feature of this obese model is our recent finding of a childhood component where the KO mouse is heavier at weaning, a distinction that only returns in adulthood. To determine when the KO mouse becomes heavier, longitudinal and cross-sectional timecourse studies followed weight gain and found significantly heavier body weight, higher plasma leptin, and rectal temperature, only in unhandled KO compared to sibling wildtype controls. To map what metabolic compensations cause the KO weight increase, we launched thermal and behavioral studies in 10 day old mice before there was any genotype difference in body weight, corticosterone levels, or the levels leptin during the developmental leptin peak. The heavier KO weanling is, in part, explained by hyperphagia, lower metabolic rate and activity, and behavioral thermogenesis measured at 10 days of age. However, the infant KO mouse is stress-sensitive and growth is impaired with handling. The serotonin 2C receptor has a role in fine-tuning energetic and stress demands even as neurocircuits are developing, and unbalanced compensations in infancy may program responses in adulthood that are "off target" from optimal function.

Topics: Adiponectin; Age Factors; Animals; Animals, Newborn; Appetite Regulation; Body Temperature Regulation; Corticosterone; Cross-Sectional Studies; Feeding Behavior; Female; Hyperphagia; Insulin; Leptin; Longitudinal Studies; Male; Mice; Mice, Knockout; Neuropeptide Y; Phenotype; Receptor, Serotonin, 5-HT2C; Stress, Psychological; Weaning; Weight Gain

Obesity is a world-wide epidemic, and many factors, including stress, have been linked to this growing trend. After social stress (i.e., defeat), subordinate laboratory rats and most laboratory mice become hypophagic and, subsequently, lose body mass; the opposite is true of subordinate Syrian hamsters. After social defeat, Syrian hamsters become hyperphagic and gain body mass compared with nonstressed controls. It is unknown whether this increase in body mass and food intake is limited to subordinate hamsters. In experiment 1, we asked, do dominant hamsters increase food intake, body mass, and adiposity after an agonistic encounter? Subordinate hamsters increased food intake and body mass compared with nonstressed controls. Although there was no difference in food intake or absolute body mass between dominant and nonstressed control animals, cumulative body mass gain was significantly higher in dominant than in nonstressed control animals. Total carcass lipid and white adipose tissue (WAT) (i.e., retroperitoneal and epididymal WAT) masses were significantly increased in subordinate, but not dominant, hamsters compared with nonstressed controls. In experiment 2, we asked, does footshock stress increase food intake, body mass, and adiposity. Hamsters exposed to defeat, but not footshock stress, increased food intake relative to nonstressed controls. In animals exposed to defeat or footshock stress, body mass, as well as mesenteric WAT mass, increased compared with nonstressed controls. Collectively, these data demonstrate that social and nonsocial stressors increase body and lipid mass in male hamsters, suggesting that this species may prove useful for studying the physiology of stress-induced obesity in some humans.

Topics: Adiposity; Agonistic Behavior; Animals; Body Composition; Body Weight; Cricetinae; Dominance-Subordination; Eating; Electroshock; Leptin; Male; Mesocricetus; Stress, Psychological; Testis; Testosterone; Weight Gain

Rats with a genetic predisposition to develop diet-induced obesity (DIO) have a preexisting reduction in central leptin and insulin sensitivity. High-fat diets also reduce sensitivity to leptin, insulin, and melanocortin agonists. We postulated that such reduced sensitivities would be associated with decreased binding to the hypothalamic leptin, insulin, and melanocortin receptors in selectively bred DIO rats and in rats fed a high-energy (HE; 31% fat) diet for 7 wk. On HE diet, DIO rats gained 15% more weight and had 121% heavier fat pads and 70% higher leptin levels than low fat chow-fed DIO rats. Diet-resistant (DR) rats gained no more weight on HE diet but had 48% heavier fat pads and 70% higher leptin levels than chow-fed DR rats. Compared with DR rats, DIO (125)I-leptin binding was 41, 36, and 40% lower in the hypothalamic dorsomedial, arcuate, and dorsomedial portion of the ventromedial nuclei, respectively, and arcuate (125)I-insulin binding was 31% lower independent of diet. In contrast, hypothalamic melanocortin binding did not differ between DIO and DR rats. However, HE diet intake lowered lateral hypothalamic melanocortin-3 and melanocortin-4 receptor and hippocampal insulin binding of both DIO and DR rats and hypothalamic paraventricular nucleus melanocortin-4 receptor binding only in DR rats. Neither genotype nor diet affected substantia nigra or ventral tegmental area binding. These results corroborate our previous findings demonstrating a preexisting decrease in DIO hypothalamic leptin and insulin signaling and demonstrate that HE diet intake reduces hypothalamic melanocortin and hippocampal insulin binding.

Topics: Adipose Tissue; Animals; Arcuate Nucleus of Hypothalamus; Blood Glucose; Dietary Fats; Dorsomedial Hypothalamic Nucleus; Hypothalamus; Insulin; Iodine Radioisotopes; Leptin; Male; Melanocortins; Obesity; Rats; Rats, Mutant Strains; Receptor, Melanocortin, Type 4; Substantia Nigra; Ventral Tegmental Area; Ventromedial Hypothalamic Nucleus; Weight Gain

Leptin is an adipocyte-derived hormone that signals body energy status to the brain by acting on multiple neuronal subgroups in the hypothalamus, including those that express proopiomelanocortin (Pomc) and agouti-related protein (Agrp). Signal transducer and activator of transcription 3 (Stat3) is an important intracellular signaling molecule activated by leptin, and previous studies have shown that mice carrying a mutated leptin receptor that abolished Stat3 binding are grossly obese. To determine the extent to which Stat3 signaling in Pomc neurons was responsible for these effects, we constructed Pomc-specific Stat3 mutants using a Cre recombinase transgene driven by the Pomc promoter. We find that Pomc expression is diminished in the mutant mice, suggesting that Stat3 is required for Pomc transcription. Pomc-specific Stat3 female mutant mice exhibit a 2-fold increase in fat pad mass but only a slight increase in total body weight. Mutant mice remain responsive to leptin-induced hypophagia and are not hypersensitive to a high-fat diet; however, mutant mice fail to mount a normal compensatory refeeding response. These results demonstrate a requirement for Stat3 in transcriptional regulation of Pomc but indicate that this circuit is only one of several components that underlie the neuronal response to leptin and the role of Stat3 in that response.

Topics: Animals; Dietary Fats; Energy Metabolism; Feeding Behavior; Female; Homeostasis; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Phosphorylation; Pro-Opiomelanocortin; RNA, Messenger; STAT3 Transcription Factor; Transcription, Genetic; Weight Gain

Many of olanzapine's (OLZ) actions in humans related to weight regulation can be modelled in female rats (Cooper et al., 2005). Such effects include weight gain, hyperphagia, enhanced visceral adiposity and elevated Levels of insulin and adiponectin. As sex differences have been reported in the effects of antipsychotic drugs, including OLZ, in rats, the current study extended our study in female rats by directly comparing the actions of OLZ in maLes using identical methodology. Individually housed male Han Wistar rats were administered OLZ twice daily (i.p.), at 0, 1, 2, and 4 mg/kg over 21 days. Both differences from, and simiLarities to, the data obtained in females were obtained. Males treated with OLZ showed reduced weight gain, enhanced visceral adiposity and reduced lean muscle mass. There were no accompanying changes in food or water intake. OLZ did not induce changes in plasma levels of insulin, leptin or glucose. Significant elevation of adiponectin was observed. OLZ-treated males displayed elevated prolactin and suppressed testosterone. OLZ's effects in humans can very clearly be most validly modelled in female rats, although the cause(s) of the sex difference in OLZ's actions in rats are not clear. However, the finding that significantly enhanced adiposity is seen in both male and female rats, in other animal species (mice and dogs) and in humans suggests that studies in male rats of OLZ's effects may be of value, by highlighting the consistent ability of OLZ to increase visceral adiposity. It is hypothesized that such adiposity is a key, clinically relevant, common component of OLZ's actions which may be, at Least partially, independent of both OLZinduced weight gain and hyperphagia, and which is induced reliably in male and female rats and other animal species. Possible mechanisms involved in the effects reported are discussed.

Topics: Adiponectin; Adiposity; Animals; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Dose-Response Relationship, Drug; Drinking; Eating; Female; Hyperphagia; Insulin; Leptin; Male; Metabolic Diseases; Olanzapine; Prolactin; Rats; Rats, Wistar; Sex Factors; Testosterone; Weight Gain

To determine circulating levels of adiponectin in preterm infants and examine possible associations with anthropometric measurements, weight gain, and leptin and insulin levels.. Prospective study.. A university hospital neonatal care unit.. 62 preterm (mean (SD) gestational age 32.0 (2.1) weeks) and 15 full-term infants (reference group).. Blood samples taken at discharge (40.9 (14.8) days of life) from the preterm infants and at a comparable postnatal age in full-term infants. All infants were fed the same commercial formula, but in nine preterms the formula contained long-chain polyunsaturated fatty acids (LCPUFAs).. Serum levels of adiponectin, leptin and insulin. Associations of adiponectin levels were tested only in the preterm group.. Serum levels of adiponectin were lower in preterm (40.9 (14.8) microg/ml) than full-term infants (53.1 (16.0) microg/ml, p<0.01). However, after adjustment for body weight, the influence of prematurity on adiponectin levels was no longer significant. In preterm infants, adiponectin levels independently correlated with being born small for gestational age (SGA) (beta=-0.35, p=0.01), weight gain (beta=0.28, p=0.03) and LCPUFA-supplemented formula (beta=0.34, p=0.009). Serum adiponectin levels did not correlate with insulin or leptin levels. However, insulin levels were higher in preterm than in full-term infants after adjustment for body weight.. Adiponectin levels are lower in preterm infants at discharge than full-term infants probably due to decreased adiposity. The levels are influenced by being born SGA, weight gain and, possibly, by dietary LCPUFAs. The importance of these findings in the development of insulin or leptin resistance in children born prematurely needs to be further studied.

Topics: Adiponectin; Anthropometry; Birth Weight; Body Weight; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Insulin; Leptin; Male; Prospective Studies; Weight Gain

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

To investigate the hypothesis that plasma leptin may predict adiposity changes.. A population-based cohort study.. Fleurbaix and Laventie, in the north of France.. In all, 1175 subjects participated, of whom 946 completed measurements at baseline (1999) and follow-up (2001). After excluding 64 subjects obese at baseline, 882 subjects (478 adults, 404 children 8 years and over) were included in the analysis.. We measured plasma leptin concentrations at baseline and various adiposity parameters at baseline and follow-up. Partial correlation coefficients (r(p)) between baseline plasma leptin and each adiposity indicator at follow-up were calculated with adjustment for baseline age, pubertal stage, adiposity and familial correlations between siblings.. Changes in body mass index and percentage body fat were not related to baseline plasma leptin. High baseline plasma leptin predicted an increase (r(p) (P-value)) in the sum of the four skinfolds (0.18 (<0.0001)), the waist circumference (0.16 (0.0003)) and the waist-to-hip ratio (0.29 (<0.0001)) in adults only, and in the hip circumference in adults (0.20 (<0.0001)) and children (0.22 (<0.0001)). After adjustment for a set of four adiposity variables at baseline (percentage body fat, skinfolds, waist and hip circumferences), baseline plasma leptin predicted only changes in the sum of the four skinfolds in adults (0.15 (0.001)), with similar tendency although not significant in children (0.08 (0.13)).. A high leptin relative to baseline fat mass predicts fat mass gain over time, mainly in the subcutaneous location.

Topics: Adult; Body Composition; Body Mass Index; Child; Cohort Studies; Female; Follow-Up Studies; France; Humans; Leptin; Male; Obesity; Predictive Value of Tests; Skinfold Thickness; Subcutaneous Fat; Waist-Hip Ratio; Weight Gain

To compare the incidence and magnitude of weight gain associated with valproic acid (VPA) monotherapy in male and female epilepsy patients and to determine possible gender-specific differences in frequency of carbohydrate craving, body-composition, glucose homeostasis and lipid metabolism.. Epilepsy patients on VPA monotherapy were consecutively recruited at the outpatient clinic of the Department of Neurology, Innsbruck Medical University. Weight gain during VPA-therapy, frequency of carbohydrate craving and physical exercise, sociopsychological problems and family history for diabetes were obtained from all patients. Clinical data also comprised body-impedance analysis, body mass index and waist-to-hip ratio. Morning fasting blood samples were drawn to determine serum leptin, glucose and lipid concentrations, as well as insulin, C-reactive protein and TNF-alpha.. One hundred and six patients (55 women) were enrolled in the study. Significant weight gain was seen during VPA-therapy in both genders (each p<0.001) with women experiencing increment of weight more frequently and more pronounced than did men. Analyses of patients who gained weight during VPA-therapy revealed significantly higher serum leptin concentrations in women than in men (p<0.001). Women also revealed significantly higher high-density lipoprotein-cholesterol and lower triglyceride concentrations than men (p=0.004 and 0.014, respectively). Frequency of carbohydrate craving was 25.8% in women and 14.3% in men. More women tried to lose or control weight through diet than did men (22.6% versus 7.1%). Moreover, weight gain as a sociopsychological problem was more numorous in women than in men.. Women are more prone to gain weight during VPA therapy though higher frequency of diet and sociopsychological burden than men, which might possibly be related to leptin-resitance and a higher frequency of carbohydrate craving.

Topics: Adult; Anticonvulsants; Appetite; Body Mass Index; Dietary Carbohydrates; Epilepsy; Female; Glucose; Homeostasis; Humans; Leptin; Male; Sex Factors; Valproic Acid; Weight Gain

In rats selectively bred to develop diet-induced obesity (DIO) or to be diet-resistant (DR), DIO maternal obesity selectively enhances the development of obesity and insulin resistance in their adult offspring. We postulated that the interaction between genetic predisposition and factors in the maternal environment alter the development of hypothalamic peptide systems involved in energy homeostasis regulation. Maternal obesity in the current studies led to increased body and fat pad weights and higher leptin and insulin levels in postnatal day 16 offspring of both DIO and DR dams. However, by 6 wk of age, most of these intergroup differences disappeared and offspring of obese DIO dams had unexpected increases in arcuate nucleus leptin receptor mRNA, peripheral insulin sensitivity, diet- and leptin-induced brown adipose temperature increase and 24-h anorectic response compared with offspring of lean DIO, but not lean DR dams. On the other hand, while offspring of obese DIO dams did have the highest ventromedial nucleus melanocortin-4 receptor expression, their anorectic and brown adipose thermogenic responses to the melanocortin agonist, Melanotan II (MTII), did not differ from those of offspring of lean DR or DIO dams. Thus, during their rapid growth phase, juvenile offspring of obese DIO dams have alterations in their hypothalamic systems regulating energy homeostasis, which ameliorates their genetic and perinatally determined predisposition toward leptin resistance. Because they later go onto become more obese, it is possible that interventions during this time period might prevent the subsequent development of obesity.

Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Diet; Hypothalamus; Leptin; Neuropeptides; Obesity; Rats; Receptors, Cell Surface; Receptors, Leptin; Time Factors; Up-Regulation; Weight Gain

Absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. We investigated whether administration of leptin to normally nourished rats affects energy balance in their offspring. Leptin (2 mg.kg(-1).day(-1)) was administered from day 14 of pregnancy and throughout lactation. Male and female offspring were fed either on chow or on high-fat diets that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age. Treatment of the dams with leptin prevented diet-induced increases in the rate of weight gain, retroperitoneal fat pad weight, area under the intraperitoneal glucose tolerance curve, and fasting plasma insulin concentration in female offspring. In the male offspring, the diet-induced increase in weight gain was prevented and increased fat pad weight was reduced. Energy intake per rat was higher in response to the obesogenic diet in male offspring of saline-treated but not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring. Energy expenditure at 3 mo of age was higher for a given body weight in female offspring of leptin-treated compared with saline-treated dams when these animals were fed on the obesogenic diet. A similar trend was seen for male rats fed on the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring.

Topics: Animals; Blood Glucose; Body Composition; Diet; Energy Metabolism; Female; Glucose; Insulin; Insulin Resistance; Leptin; Male; Milk; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Sex Characteristics; Time Factors; Weight Gain

Risperidone has a relatively low risk of causing obesity and diabetes mellitus and is a first-line treatment for schizophrenia. The aim of the present study was to investigate glucose and lipid metabolism, and feeding-control parameters in schizophrenia patients treated with long-term risperidone monotherapy. Fifteen patients with paranoid-type schizophrenia who had been treated with risperidone and had Global Assessment of Function (GAF) scores >70 were selected and compared with healthy volunteers (n = 25). Single assessments of psychotic symptoms, side-effects, Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) score, bodyweight, body fat percentage and blood sampling were performed. Fasting blood glucose, insulin, hemoglobin A1c, homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol, triglyceride, high density lipoprotein (HDL)-, low density lipoprotein-cholesterol, adiponectin, prolactin and feeding-control parameters (ghrelin and leptin) were analyzed. The body fat percentage (P = 0.0018), body mass index (BMI) (P = 0.0150), fasting blood glucose (P = 0.0358), triglyceride (P = 0.0377), leptin (P = 0.0243), total ghrelin (P = 0.0067), active ghrelin (P = 0.0241) and prolactin (P < 0.0001) levels of patients treated with risperidone were significantly higher than those of healthy volunteers, while the HDL-cholesterol level (P = 0.0222) was significantly lower. Although the patients had very mild psychiatric symptoms and maintained functionally high levels, the glucose and lipid parameters were significantly impaired compared to healthy volunteers. A high level of plasma ghrelin might increase appetite, leading to exacerbation of metabolic impairment.

Topics: Adiponectin; Adult; Antipsychotic Agents; Body Composition; Body Mass Index; Cholesterol, HDL; Female; Ghrelin; Glucose; Humans; Hypertension; Leptin; Lipid Metabolism; Lipids; Male; Middle Aged; Peptide Hormones; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Weight Gain

The objective of the current investigation was to determine the relationship between polymorphisms of the leptin system (leptin gene and leptin receptor) and olanzapine-induced weight gain in persons with schizophrenia.. Pharmacogenetic association reanalysis of a longitudinal, open label, six week, fixed dose trial of olanzapine response and adverse effects.. Thirty-seven males and females with clinically symptomatic schizophrenia (age, 23-52) meeting DSM-IV criteria.. Baseline and endpoint weight, BMI, olanzapine dose, plasma levels, and psychopathology measures were completed in a prior study. These subjects were subsequently genotyped for the -1548 G/A polymorphism of the leptin gene and the Q223R polymorphism of the leptin receptor. The relationship between alleles at each locus, olanzapine plasma levels, and percent change in body mass index (BMI) from baseline were conducted.. Genotypes and alleles for each locus were not individually associated with olanzapine-induced weight gain in this study population. Changes in BMI from baseline increased significantly in persons with olanzapine plamsa levels >20.6 ng/mL for subjects carrying at least one G allele at both candidate loci compared to those who did not have a G allele at each (P = 0.049).. This study suggests that genetic variability in the leptin gene and leptin receptor may predispose some individuals to excessive weight gain from increased exposure to olanzapine.

Topics: Adult; Alleles; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Female; Genetic Predisposition to Disease; Genotype; Humans; Leptin; Longitudinal Studies; Male; Middle Aged; Olanzapine; Pharmacogenetics; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Receptors, Cell Surface; Receptors, Leptin; Schizophrenia; Weight Gain

n-3 PUFA have shown potential anti-obesity and insulin-sensitising properties. However, the mechanisms involved are not clearly established. The aim of the present study was to assess the effects of EPA administration, one of the n-3 PUFA, on body-weight gain and adiposity in rats fed on a standard or a high-fat (cafeteria) diet. The actions on white adipose tissue lipolysis, apoptosis and on several genes related to obesity and insulin resistance were also studied. Control and cafeteria-induced overweight male Wistar rats were assigned into two subgroups, one of them daily received EPA ethyl ester (1 g/kg) for 5 weeks by oral administration. The high-fat diet induced a very significant increase in both body weight and fat mass. Rats fed with the cafeteria diet and orally treated with EPA showed a marginally lower body-weight gain (P = 0.09), a decrease in food intake (P < 0.01) and an increase in leptin production (P < 0.05). EPA administration reduced retroperitoneal adipose tissue weight (P < 0.05) which could be secondary to the inhibition of the adipogenic transcription factor PPARgamma gene expression (P < 0.001), and also to the increase in apoptosis (P < 0.05) found in rats fed with a control diet. TNFalpha gene expression was significantly increased (P < 0.05) by the cafeteria diet, while EPA treatment was able to prevent (P < 0.01) the rise in this inflammatory cytokine. Adiposity-corrected adiponectin plasma levels were increased by EPA. These actions on both TNFalpha and adiponectin could explain the beneficial effects of EPA on insulin resistance induced by the cafeteria diet.

Topics: Adiponectin; Adipose Tissue; Animals; Apoptosis; Dietary Fats; Dietary Supplements; Eating; Eicosapentaenoic Acid; Gene Expression; Insulin; Insulin Resistance; Leptin; Lipolysis; Male; PPAR gamma; Rats; Rats, Wistar; RNA, Messenger; Tumor Necrosis Factor-alpha; Weight Gain

Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is limited and contradicting.. Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in body mass index, leptin, insulin sensitivity, and additional endocrine parameters.. We conducted a longitudinal controlled study of 38 female adolescent malnourished AN inpatients, with 13 young, lean, healthy women serving as controls. Blood samples were obtained upon admission and thereafter at 1, 3, and 5 months (at target weight).. Changes in body mass index, leptin, adiponectin, insulin sensitivity, and adiponectin multimeric forms were measured.. At admission, leptin levels of AN patients were significantly lower, whereas insulin sensitivity (assessed by homeostasis model assessment-insulin resistance), adiponectin levels, and the ratio of high molecular weight (HMW) adiponectin to total adiponectin were significantly higher compared with controls. During weight recovery, leptin levels and homeostasis model assessment-insulin resistance increased significantly, whereas adiponectin and HMW adiponectin/total adiponectin ratio decreased significantly, to levels similar to controls. An initial increase in adiponectin levels was observed after 1 month of refeeding. There was no correlation between adiponectin and either T(4) or cortisol levels.. Our study demonstrates hyperadiponectinemia, increased adiponectin HMW isoform, and increased insulin sensitivity in adolescent AN female patients and reversal of these findings with weight rehabilitation. We hypothesize that increased adiponectin levels may have a protective role in maintaining energy homeostasis during extreme malnourishment.

Topics: Adiponectin; Adolescent; Adult; Anorexia Nervosa; Blood Glucose; Body Height; Body Mass Index; Body Weight; Female; Hormones; Humans; Insulin Resistance; Isomerism; Leptin; Weight Gain

Hypoglycaemia is common in preterm and intrauterine growth retarded (IUGR) newborns. Although preterm and IUGR infants have limited adipose tissue stores, the role of adipose tissue and the associated adipocytokines in glucose physiology is not known.. We report the case of a premature intrauterine growth retarded infant who had poor weight gain for the first 6 weeks of life and then developed severe hypoinsulinaemic hypoketotic hypoglycaemia.. There was markedly reduced adiposity with low serum leptin and adiponectin levels. Total energy expenditure and body composition measurements showed that body fat as a percentage of weight averaged 7% at 20 weeks and 28% at 28 weeks. At 20 weeks of age, the patient was equivalent to a deficit of >2 SD scores of body fat, but average fatness by 28 weeks. The hypoglycaemia completely resolved when the patient started gaining weight with an increase in fat mass and a concomitant increase in serum leptin and adiponectin level.. Although the precise mechanism of this patient's severe hypoglycaemia is unclear, further studies are required to understand the role of adipose tissue and adipocytokines in glucose homeostasis in preterm and IUGR infants.

Topics: Adiponectin; Adipose Tissue; Blood Glucose; Body Composition; Body Weight; Fetal Growth Retardation; Humans; Hypoglycemia; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Insulin; Leptin; Male; Weight Gain

To investigate mechanisms that mediate the greater food intake induced by a fat-rich diet, the present study tested an acute "preload-to-test meal" paradigm in normal-weight rats. In this paradigm, the rats were given a small high-fat (HF) compared to low-fat (LF) preload and, after an intermeal interval, allowed to consume freely on a subsequent test meal. Modified versions of this paradigm were tested to determine the robustness of the greater caloric intake induced by the HF preload while standardizing the test protocol. A HF preload of 10-15 kcals, compared to an equicaloric LF preload, significantly increased food intake by 40-50% in the subsequent test meal. This effect, a 4-6 kcal increase, was observed with HF preloads equal in energy density and palatability to the LF preloads. It was evident with preloads or test meals that were liquid or solid, preloads that were injected, test meals that had variable fat content, and natural intermeal intervals of 60-120 min. This overeating after a HF preload was invariably associated with a 2- to 3-fold increase in circulating levels of triglycerides (TG), with no change in leptin or insulin. It was also accompanied by increased expression of the orexigenic peptides, galanin in the paraventricular nucleus and orexin in the perifornical lateral hypothalamus. Moreover, if given repeatedly over several days, the HF compared to equicaloric LF preload significantly increased 24-h food intake. These results establish a protocol for studying the phenomenon of increased feeding on a HF diet under controlled conditions and suggest possible underlying mechanisms involving circulating lipids and orexigenic peptides.

Topics: Animals; Body Weight; Brain Chemistry; Diet; Dietary Fats; Eating; Energy Intake; Food Preferences; Galanin; Hyperphagia; Hypothalamus; Insulin; Intracellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptides; Orexins; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Triglycerides; Weight Gain

The aim of this study was to investigate the effects of a post-weaning isocaloric hyper-soybean oil diet on later obesity and explore the underlying mechanisms. In the present study, newborn male Wistar rats were weaned on d 24, divided into CON (control), HC and HSO groups. CON was assigned to AIN-93G diet (a hypercarbohydrate diet, for short HC diet) during the entire experiment. HC and HSO were fed with HC and isocaloric hyper-soybean oil (HSO) diet for 3 wk respectively, fed with HC diet for 2 wk successively, finally administrated high fat diet (HF) for 6 wk to induce obesity. On 3,5,11 wk, the body weight, body fat content, blood glucose, blood lipid, serum insulin and leptin levels and obesity-related gene (CPT-1, FAS, UCP2, UCP3) expression levels in rats were detected. It was shown that body weight, body fat content, blood glucose and blood lipid, serum insulin and leptin levels in HSO were down-regulated on 3 and 5 wk, therefore were significantly reduced on 11 wk vs. HC. The CPT-1, UCP2, UCP3 gene expressions were up-regulated but FAS were down-regulated persistently in HSO. The study indicated that an early isocaloric HSO diet may reduce later obesity risk and reduce blood lipid and glucose abnormalities in adulthood via persistently influencing insulin and leptin sensitivity and permanent regulation of obesity-related gene expressions.

Topics: Animals; Blood Glucose; Dietary Carbohydrates; Down-Regulation; Gene Expression; Insulin; Leptin; Lipids; Male; Obesity; Rats; Rats, Wistar; RNA, Messenger; Soybean Oil; Weaning; Weight Gain

Leptin is the hormone product of the obese gene that is synthesized and predominantly expressed by adipocytes. This study estimated the genetic variation in serum leptin concentration and evaluated the genetic and phenotypic relationships of serum leptin concentration with performance, efficiency of gain, and carcass merit. There were 464 steers with records for serum leptin concentration, performance, and efficiency of gain and 381 steers with records for carcass traits. The analyses included a total of 813 steers, including those without phenotypic records. Phenotypic and genetic parameter estimates were obtained using SAS and ASREML, respectively. Serum leptin concentration was moderately heritable (h2 = 0.34 +/- 0.13) and averaged 13.91 (SD = 5.74) ng/mL. Sire breed differences in serum leptin concentration correlated well with breed differences in body composition. Specifically, the serum leptin concentration was 20% greater in Angus-sired steers compared with Charolais-sired steers (P < 0.001). Consequently, ultrasound backfat (27%), carcass 12th-rib fat (31%), ultrasound marbling (14%), and carcass marbling (15%) were less in Charolais- than Angus-sired steers (P < 0.001). Conversely, carcass LM area (P = 0.05) and carcass lean meat yield (P < 0.001) were greater in Charolais- compared with Angus-sired steers. Steers with greater serum leptin concentration also had greater DMI (P < 0.001), greater residual feed intake (P = 0.04), and partial efficiency of growth (P = 0.01), but did not differ in feed conversion ratio (P > 0.10). Serum leptin concentration was correlated phenotypically with ultrasound backfat (r = 0.41; P < 0.001), carcass 12th-rib fat (r = 0.42; P < 0.001), ultrasound marbling (r = 0.25; P < 0.01), carcass marbling (r = 0.28; P < 0.01), ultrasound LM area (r = -0.19; P < 0.01), carcass LM area (r = -0.17; P < 0.05), lean meat yield (r = -0.38; P < 0.001), and yield grade (r = 0.32; P < 0.001). The corresponding genetic correlations were generally greater than the phenotypic correlations and included ultrasound backfat (r = 0.76 +/- 0.19), carcass 12th-rib fat (r = 0.54 +/- 0.23), ultrasound marbling (r = 0.27 +/- 0.22), carcass marbling (r = 0.76 +/- 0.21), ultrasound LM area (r = -0.71 +/- 0.19), carcass LM area (r = -0.75 +/- 0.20), lean meat yield (r = -0.59 +/- 0.22), and yield grade (r = 0.39 +/- 0.26). Serum leptin concentration can be a valuable tool that can be incorporated into appropriate selection programs to favorably i

Topics: Adipose Tissue; Animal Feed; Animals; Body Composition; Cattle; Crosses, Genetic; Genotype; Leptin; Male; Meat; Muscle, Skeletal; Phenotype; Ultrasonography; Weight Gain

Visceral adipose tissue and skeletal muscle have central roles in determining whole-body insulin sensitivity. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a potential mediator of insulin sensitivity. It can directly modulate the expression of genes that are involved in glucose and lipid metabolism, including GLUT4, lipoprotein lipase (LPL) and adipocytokines (leptin and adiponectin). In this study, we aimed to determine the effects of obesity-associated insulin resistance on mRNA expression of PPARgamma and its target genes. Dogs were studied when they were lean and at the end of an overfeeding period when they had reached a steady obese state. The use of a sensitive, real-time PCR assay allowed a relative quantification of mRNA expression for PPARgamma, LPL, GLUT4, leptin and adiponectin, in adipose tissue and skeletal muscle. In visceral adipose tissue and/or skeletal muscle, mRNA expression of PPARgamma, LPL and GLUT4 were at least 2-fold less in obese and insulin-resistant dogs compared with the same animals when they were lean and insulin-sensitive. The mRNA expression and plasma concentration of leptin was increased, whereas the plasma level and mRNA expression of adiponectin was decreased, by obesity. In adipose tissue, PPARgamma expression was correlated with leptin and adiponectin. These findings, in an original model of obesity induced by a prolonged period of overfeeding, showed that insulin resistance is associated with a decrease in PPARgamma mRNA expression that could dysregulate expression of several genes involved in glucose and lipid metabolism.

Topics: Adiponectin; Animals; Blood Glucose; Dogs; Gene Expression; Glucose Transporter Type 4; Insulin; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipoprotein Lipase; Muscle, Skeletal; Obesity; PPAR gamma; RNA, Messenger; Triglycerides; Tumor Necrosis Factor-alpha; Weight Gain

Zn deficiency reduces food intake and growth rate in rodents. To determine the relationship between Zn deficiency and the regulation of food intake, we evaluated leptin gene expression in epididymal white adipose tissue (eWAT), and hypothalamic corticotropin-releasing hormone (hCRH) and hypothalamic neuropeptide Y (hNPY) of rats Zn-deficient only to show reduced food intake and growth rate but not food intake cycling. Growing male Sprague-Dawley rats (240 g) were randomly assigned to one of four dietary groups: Zn-adequate (ZA; 30 mg/kg diet), Zn-deficient (ZD; 3 mg/kg diet), pair-fed with ZD (PF; 30 mg/kg diet) and Zn-sufficient (ZS; 50 mg/kg diet) (n 8), and were fed for 3 weeks. Food intake and body weight were measured, as were blood mononuclear cells and pancreas Zn levels. eWAT leptin, hCRH and hNPY mRNA levels were determined. Food intake was decreased by about 10 % in ZD and PF rats compared to ZA and ZS rats. Growth and eWAT leptin mRNA levels were unaffected in PF rats but were significantly (P < 0.05) decreased in ZD rats. However, hNPY showed a tendency to increase, and hCRH significantly (P < 0.05) decreased, in both ZD and PF rats. These results suggest that while leptin gene expression may be directly affected by Zn, hNPY and hCRH are likely responding to reduced food intake caused by Zn deficiency.

Topics: Adipose Tissue, White; Animals; Appetite Regulation; Corticotropin-Releasing Hormone; Diet; Epididymis; Gene Expression; Hypothalamus; Leptin; Male; Neuropeptide Y; Rats; Rats, Sprague-Dawley; RNA, Messenger; Weight Gain; Zinc

A high concentration of dietary carbohydrate is suggested to increase the risk of obesity and diabetes mellitus in domestic cats. To evaluate this, food intake, body weight, fat mass and circulating adiposity-related factors were determined in twenty-four sexually mature (9-12 months) cats assigned to four six-cat dietary groups balanced for body weight and sex. The effect of dietary fat in exchange for carbohydrate at 9, 25, 44 and 64 % of metabolisable energy (ME) in a purified diet of constant protein:ME ratio was studied 13 weeks before and 17 weeks after gonadectomy (GX). Body weight did not significantly change among the cats before GX except for an increase of 17 (sem 5) % in cats given the highest-fat diet. Following GX, all groups gained body weight, and body fat mass was positively correlated (r 0.50; P < 0.04) with dietary fat percentage. Post-GX weight gains were much greater for females (+39 (sem 5) %) than males (+10 (sem 4) %). Plasma ghrelin concentration negatively correlated (P < 0.02) with dietary fat percentage and, before GX, was greater (P < 0.05) in females than males. Plasma insulin concentration increased with weight gain induced by high dietary fat. Plasma glucose, TAG and leptin concentrations were not affected by dietary fat percentage, GX or weight gain. These data provide evidence that in cats, high dietary fat, but not carbohydrate, induces weight gain and a congruent increase in insulin, while GX increases sensitivity to weight gain induced by dietary fat.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Composition; Castration; Cat Diseases; Cats; Dietary Carbohydrates; Dietary Fats; Energy Metabolism; Female; Ghrelin; Insulin; Leptin; Male; Obesity; Orchiectomy; Ovariectomy; Peptide Hormones; Sex Factors; Triglycerides; Weight Gain

Excess weight gain during the early postnatal period increases the risk of persistent obesity into adulthood and impacts on the subsequent risk for metabolic and cardiovascular diseases. The current study investigated the long-term effect of early excess weight gain, through reduced nursing litter size, on body weight regulation and its relation to brown adipose tissue (BAT) thermogenesis. Animals raised in a small litter (SL, three pups per litter) were compared with those raised in a normal litter size (NL, eight pups per litter). BAT from young adult NL and SL rats, maintained under either ambient or cold conditions, were used for gene expression, morphological, and functional analysis. Compared with NL, SL rats showed excess weight gain, and adult SL animals had a reduced thermogenic capacity as displayed by lower levels of uncoupling protein 1 (UCP1). When exposed to cold, BAT from SL rats was less active and demonstrated reduced responsiveness to cold. Furthermore, reduction in transcript abundance of several lipid lipases and transcriptional regulators was observed in SL rats either at ambient temperature or under cold conditions. Finally, the expression of sympathetic beta 3-adrenergic receptor and the response to the sympathetic receptor agonist isoproterenol were decreased in SL rats. Overall, these observations provide the first evidence that postnatal excess weight gain results in abnormalities in BAT thermogenesis and sympathetic outflow, which likely increases susceptibility to obesity in adulthood.

Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Humans; Infant; Insulin; Leptin; Lipolysis; Litter Size; Models, Animal; Obesity; Rats; Rats, Sprague-Dawley; Thermogenesis; Weight Gain

Epidemiological and animal studies suggest that the alteration of hormonal and metabolic environment during fetal and neonatal development can contribute to development of metabolic syndrome in adulthood. In this paper, we investigated the impact of maternal high-fat (HF) diet on hypothalamic leptin sensitivity and body weight gain of offspring. Adult Wistar female rats received a HF or a control normal-fat (C) diet for 6 wk before gestation until the end of the suckling period. After weaning, pups received either C or HF diet during 6 wk. Body weight gain and metabolic and endocrine parameters were measured in the eight groups of rats formed according to a postweaning diet, maternal diet, and gender. To evaluate hypothalamic leptin sensitivity in each group, STAT-3 phosphorylation was measured in response to leptin or saline intraperitoneal bolus. Pups exhibited similar body weights at birth, but at weaning, those born to HF dams weighed significantly less (-12%) than those born to C dams. When given the HF diet, males and females born to HF dams exhibited smaller body weight and feed efficiency than those born to C dams, suggesting increased energy expenditure programmed by the maternal HF diet. Thus, maternal HF feeding could be protective against adverse effects of the HF diet as observed in male offspring of control dams: overweight (+17%) with hyperleptinemia and hyperinsulinemia. Furthermore, offspring of HF dams fed either C or HF diet exhibited an alteration in hypothalamic leptin-dependent STAT-3 phosphorylation. We conclude that maternal high-fat diet programs a hypothalamic leptin resistance in offspring, which, however, fails to increase the body weight gain until adulthood.

Topics: Animals; Animals, Suckling; Blotting, Western; Body Weight; Diet; Dietary Fats; Female; Hypothalamus; Leptin; Male; Obesity; Phosphorylation; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; STAT3 Transcription Factor; Weight Gain

The gut hormone peptide YY 3-36 [PYY (3-36)] has been suggested to posses anorexigenic actions in animals and human adults. However, its circulating concentrations and function have not been studied in neonates. Serum concentrations of PYY (3-36) were determined by RIA (RIA) in 62 healthy preterm infants [mean(SD) gestational age, 32.0(2.1) weeks; postnatal age, 40.9(14.8 d)] and 15 healthy fullterm infants of comparable postnatal age and gender. The correlations between PYY (3-36) levels and anthropometric characteristics, food intake, growth rates and circulating concentrations of total PYY, ghrelin, leptin, insulin and adiponectin were examined. Mean (SD) PYY (3-36) concentrations were higher in preterm [543.7(157.6) ng/L) than full term infants [350.9(114.1) ng/L; p < 0.001) and accounted for 48% and 42% of total PYY basal plasma immunoreactivity in preterm and full term infants, respectively. In multiple regression analysis, PYY (3-36) concentrations correlated negatively with the infants' BMI and positively with serum ghrelin concentrations, but not with caloric intake, weight gain or concentrations of any other hormone studied. In conclusion, PYY (3-36) represents almost half of total PYY immunoreactivity in neonates. It's correlations with ghrelin and BMI suggest a role of this peptide in the regulation of energy homeostasis; however, its specific functions and physiologic significance in neonates remain to be elucidated.

Topics: Adiponectin; Adiposity; Body Mass Index; Energy Intake; Energy Metabolism; Female; Gestational Age; Ghrelin; Homeostasis; Humans; Infant, Newborn; Infant, Premature; Insulin; Leptin; Male; Peptide Fragments; Peptide Hormones; Peptide YY; Radioimmunoassay; Weight Gain

The expression of leptin receptor (OB-R) is downregulated by leptin in some cell lines. This study investigated the expressions of leptin receptors at central nerve system and peripheral site in a dietary model of obesity. Rats in the 8 week high-diet and control group were classified based on body weight gain into obese and control groups. Serum leptin and insulin concentrations were measured and gene expressions of short form of leptin receptor (OB-Ra) and long form (OB-Rb) in hypothalamus and liver were detected by RT-PCR. The levels of serum leptin in obese rats were increased compared with control rats (p<0.05). The levels of OB-Ra and OB-Rb gene expressions in both hypothalamus and liver in obese rats were reduced significantly (p<0.01). Serum leptin concentrations of obese rats had a significant negative relationship with both of OB-Ra or OB-Rb gene expression levels in hypothalamus and liver (p<0.01). On the other hand, serum insulin levels had no relationship with OB-Ra or OB-Rb gene expression levels in neither liver nor hypothalamus. Rats with diet-induced obesity have hyperleptinemia and reduced expressions of leptin receptors in hypothalamus and liver. The results suggest that a leptin downregulated OB-R expression is one of leptin resistant mechanisms for maintaining obesity.

Topics: Animals; Body Weight; Gene Expression Regulation; Hypothalamus; Insulin; Leptin; Lipids; Liver; Male; Obesity; Protein Isoforms; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger; Weight Gain

In the present study, the antiobesity effects of Isaria sinclairii (I. sinclairii, a fungus cultured on silkworms) powder were investigated in obese (fa/fa) Zucker rats over 4 mo. Rats were given 5 or 10% (w/w) I. sinclairii powder (I. S.), 10% mulberry leaf powder, or 10% silkworm powder mixed with standard diet; a fifth (control) group was given standard diet alone. Dose-dependent decreases in rate of body weight gain were observed in the IS-treated groups after 2 wk of treatment. Interestingly, weights of abdominal adipose tissues surrounding the epididymides were markedly reduced by I. S., in parallel with an attenuated body weight gain. However, no significant differences were observed versus the control group in terms of urinalysis or ocular or histopathological examinations. In the serum, total cholesterol, triglyceride, bilirubin, and low-density lipoprotein (LDL) were significantly lower in the 10% I. S. group than control after 17 wk of treatment. The mulberry leaf diet (10%) significantly reduced serum bilirubin levels. Obese (fa/fa) Zucker rats displayed markedly elevated serum leptin levels (>24.6%) in the I. S. 5 and 10% groups compared with nontreated controls. Data suggest that I. sinclairii exerts an antiobesity effect in Zucker obese rats.

Topics: Adipose Tissue; Animals; Ascomycota; Body Weight; Cholesterol; Dose-Response Relationship, Drug; Leptin; Male; Morus; Obesity; Plant Leaves; Rats; Rats, Zucker; Triglycerides; Weight Gain

Topics: Animals; Anti-Obesity Agents; Central Nervous System; Cyclohexanes; Energy Metabolism; Feeding Behavior; Humans; Leptin; Obesity; Pyrazoles; Receptors, Leptin; Receptors, Neuropeptide Y; Signal Transduction; Spiro Compounds; Weight Gain

Circulating leptin levels positively correlate with adult BMI and size at birth. Previous studies found gender-specific associations between polymorphisms in the leptin gene and postnatal obesity-related traits or circulating leptin levels. We examined the relationships among leptin gene polymorphisms, size for gestational age, umbilical cord leptin, and gender.. Six single nucleotide polymorphisms (SNPs) were genotyped in the leptin gene in 261 newborns (72 low birth weight Caucasians, 189 randomly-selected African-Americans). In African-Americans, umbilical cord leptin and free testosterone levels were measured. Linear regression was used to identify significant predictors of size for gestational age or cord leptin levels and gender x genotype interaction effects.. There is a significant interaction between gender and genotype at site -2548 (A/G). Among low birth weight Caucasians, the A allele was associated with an increase in female size for gestational age, while the A allele was associated with decreased male birth size. Among African-Americans, the A allele was associated with a decrease in umbilical cord leptin in females and with an increase in cord leptin in males. Cord testosterone levels were not a significant predictor of cord leptin levels either among all African-American newborns or among strata of -2548 genotypes and gender.. In male and female fetuses, site -2548 of the leptin gene may differently affect the expression level of the leptin gene or the rate of fetal growth. This gender-specific effect does not appear to be mediated by the level of free testosterone at delivery.

Topics: Adult; Birth Weight; Black People; Body Mass Index; Body Size; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Leptin; Male; Maternal Age; Parity; Pregnancy; Sex Characteristics; United States; Weight Gain; White People

To observe the antiobesity activity of trans-10,cis-12-conjugated linoleic acid (CLA)-producing lactobacillus in mice.. Lactobacillus plantarum PL62, which can grow in the presence of linoleic acid, was selected and studied. The culture supernatant of Lact. plantarum PL62 contained trans-10,cis-12-conjugated linoleic acid (6.4 microg ml(-1)), and the crude enzyme prepared from washed cells produced trans-10,cis-12 CLA (1395 microg mg(-1) protein). Lact. plantarum PL62 reduced the weights of epididymal, inguinal, mesenteric, and perirenal white adipose tissues and significantly reduced the blood levels of total glucose and body weights of mice (P<0.01).. trans-10,cis-12-CLA-producing Lact. plantarum PL62 can exert the same antiobesity activity as trans-10,cis-12-CLA in mice.. trans-10,cis-12-CLA-producing Lactobacillus can be a replacement for CLA for obesity treatment via the continuous production of trans-10,cis-12-CLA. The results provide a novel opportunity to develop foods with antiobesity activity.

Topics: Animals; Chromatography, Gas; Dietary Fats; Eating; Energy Intake; Feces; Glycerol; Lactobacillus plantarum; Leptin; Linoleic Acids, Conjugated; Lipids; Male; Mice; Mice, Inbred C57BL; Obesity; Organ Size; Probiotics; Weight Gain

Our aim was to study the feeding behavior of healthy term infants in the first week of life and determine whether this was related to cord blood leptin, ghrelin, and insulin. A total of 100 healthy bottle-fed infants were studied by weighing bottles of milk before and after feeds. Leptin, total ghrelin, and insulin concentrations were measured in cord blood. Mean (SD) birth weight was 3.46 (0.43) kg. Mean milk intake increased from 196.7 (83.0) g on d 1 to 585.0 (128.4) g on d 7. Milk intake over the first 6 d was significantly associated with weight gain to d 7. There was no relationship between cord ghrelin or leptin and milk intake or feed frequency. Cord blood insulin was inversely related to the mean daily number of feeds over the first 6 d (r = -0.21, p < 0.05). Birth weight and milk intake are the major determinants of weight gain in the first week of life in healthy bottle-fed infants. Total cord ghrelin and leptin are not directly related to milk intake or feed frequency in the first week of life. Circulating insulin concentrations may have a role in the initiation of feeding behavior.

Topics: Birth Weight; Bottle Feeding; Feeding Behavior; Female; Fetal Blood; Gestational Age; Ghrelin; Humans; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Insulin; Leptin; Male; Time Factors; Weight Gain

Diets that are high in dietary fiber are reported to have substantial health benefits. We sought to compare the metabolic effects of 3 types of dietary fibers -- sugarcane fiber (SCF), psyllium (PSY), and cellulose (CEL) -- on body weight, carbohydrate metabolism, and stomach ghrelin gene expression in a high-fat diet-fed mouse model. Thirty-six male mice (C57BL/6) were randomly divided into 4 groups that consumed high-fat diet alone (HFD) or high-fat diet containing 10% SCF, PSY, and CEL, respectively. After baseline measurements were assessed for body weight, plasma insulin, glucose, leptin, and glucagon-like peptide 1 (GLP-1), animals were treated for 12 weeks. Parameters were reevaluated at the end of study. Whereas there was no difference at the baseline, body weight gains in the PSY and SCF groups were significantly lower than in the CEL group at the end of study. No difference in body weight was observed between the PSY and SCF animals. Body composition analysis demonstrated that fat mass in the SCF group was considerably lower than in the CEL and HFD groups. In addition, fasting plasma glucose and insulin and areas under the curve of intraperitoneal glucose tolerance test were also significantly lower in the SCF and PSY groups than in the CEL and HFD groups. Moreover, fasting plasma concentrations of leptin were significantly lower and GLP-1 level was 2-fold higher in the SCF and PSY mice than in the HFD and CEL mice. Ghrelin messenger RNA levels of stomach in the SCF group were significantly lower than in the CEL and HFD groups as well. These results suggest differences in response to dietary fiber intake in this animal model because high-fat diets incorporating dietary fibers such as SCF and PSY appeared to attenuate weight gain, enhance insulin sensitivity, and modulate leptin and GLP-1 secretion and gastric ghrelin gene expression.

Topics: Animals; Blood Glucose; Carbohydrate Metabolism; Dietary Fats; Dietary Fiber; Eating; Gastric Mucosa; Ghrelin; Glucagon-Like Peptide 1; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Specific Pathogen-Free Organisms; Stomach; Weight Gain

The aim of this study was to evaluate leptin concentration at birth and in early postnatal life in small- and appropriate-for-gestational-age infants and to assess its relationship with infants' anthropometry at birth and some characteristics of maternal pregnancy.. A total of 367 infants born after 32-42 weeks of gestation were enrolled in the study. Umbilical cord blood samples were collected from 80 small- and 287 appropriate-for-gestational-age newborns. Altogether, 166 venous blood samples were taken from these neonates on days 2-6 of life.. Cord leptin levels were significantly lower in small- compared to appropriate-for-gestational-age infants. We observed a positive correlation between cord leptin and birth weight, all neonatal anthropometric parameters, placental weight, and some maternal nutritional factors. In multivariate analysis, cord leptin concentration explained up to 15% of the variation in sum of newborn's skinfold thickness but only 5% of the variation in birth weight. Postnatally, leptin concentration decreased markedly to the similar low levels in both infant groups and remained so during the first postnatal week.. Significantly lower cord leptin concentration in small-for-gestational-age neonates reflects a lower fat mass content compared to appropriate-for-gestational-age infants. However, an abrupt decrease in leptin levels shortly after birth in both groups suggests that placenta could be an important source of leptin in fetal circulation. The impact of low leptin levels at birth in small-for-gestational-age infants on their postnatal appetite and weight gain remains to be elucidated in future studies.

Topics: Age Factors; Birth Weight; Data Interpretation, Statistical; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Leptin; Male; Mothers; Multivariate Analysis; Organ Size; Placenta; Radioimmunoassay; Skinfold Thickness; Weight Gain

Recently, vanadium has been shown to enhance leptin signal transduction in vitro. We hypothesized that chronic oral administration of an organic vanadium complex would enhance both leptin signaling and physiological responsiveness in vivo. Three-month-old F344 x Brown Norway male rats were provided a solution containing escalating doses of vanadyl acetoacetonate (V), peaking at 60 mg/liter elemental vanadium in drinking water on the 11th d of V treatment. Although V treatment tended to suppress weight gain, absolute body weights did not significantly differ between groups after 62 d of treatment. At this point, a permanent cannula was placed into the left lateral ventricle of all animals. The cannula was connected to a sc minipump providing either 5 microg/d leptin or artificial cerebral spinal fluid (ACSF) control solution. This yielded four groups: C-ACSF, C-leptin, V-ACSF, and V-leptin. During the ensuing 26 d, weight gain was similar in C-ACSF and V-ACSF. As expected, leptin caused dramatic weight loss in C-leptin, but leptin-induced weight loss was 43% greater in V-leptin. V enhanced leptin-induced signal transducer and activator of transcription-3 phosphorylation in the hypothalamus, whereas V alone had no effect. V also augmented the leptin-induced increase in brown adipose tissue uncoupling protein-1. The effects of vanadium on responsiveness to a submaximal dose of leptin (0.25 microg/d) were also evaluated, yielding qualitatively similar results. These data demonstrate, for the first time, that chronic V administration enhances the weight-reducing effects of centrally administered leptin in young adult animals, and the mechanism appears to involve enhanced leptin signal transduction.

Topics: Administration, Oral; Animals; Blood Glucose; Glucose Tolerance Test; Injections, Intraventricular; Leptin; Male; Rats; Rats, Inbred BN; Rats, Inbred F344; RNA, Messenger; Vanadium; Weight Gain

To characterize and compare three obesity-prone inbred strains, AKR/J, DBA/2J and C57BL/6J, to three control strains, C3H/HeJ, BALB/cByJ and C57L/J, selected based on their normal eating patterns and moderate weight gain on high-calorie diets.. These six strains were examined at 5 weeks of age while still of normal body weight, and they were maintained for 1 day or 3 weeks on different feeding paradigms with macronutrient diets. Measurements were taken of macronutrient intake, body weight and body fat accrual, circulating hormones and metabolites, and the hypothalamic peptide, galanin.. The three control strains each selected a balanced diet with 50% carbohydrate and 15-25% fat when given a choice of macronutrients, and they had similar, normal range of scores for the measures of body weight, adiposity, the hormones, insulin and leptin, and the metabolites, glucose and triglycerides. When compared to this control baseline, the obesity-prone strains with similar total caloric intake to controls selected a diet with significantly more fat (30-40%) and less carbohydrate (<40%). They also had greater adiposity, with the largest differences detected for the AKR/J and DBA/2J strains. These two obesity-prone strains compared to control strains had elevated levels of insulin and leptin. They also had higher triglyceride levels and increased expression and levels of galanin in the hypothalamic paraventricular nucleus. A very different pattern was detected in the obesity-prone C57BL/6J strain, which exhibited a stronger preference for protein as well as fat, normal levels of insulin, leptin and triglycerides, hyperglycemia relative to all other strains, and a small increase in galanin.. These comparisons to control strains revealed a distinct phenotype in the two obesity-prone strains, AKR/J and DBA/2J, which is very similar to that described in obesity-prone, outbred rats. They also identified a clearly different phenotype in the obesity-prone C57BL/6J strain.

Topics: Adipose Tissue; Animals; Diet; Dietary Carbohydrates; Dietary Fats; Food Preferences; Galanin; Genetic Predisposition to Disease; Insulin; Leptin; Male; Mice; Mice, Inbred Strains; Obesity; Paraventricular Hypothalamic Nucleus; Phenotype; Species Specificity; Triglycerides; Weight Gain

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Biological Clocks; Body Weight; Circadian Rhythm; Corticosterone; Eating; Growth Hormone; Leptin; Male; Prolactin; Rats; Rats, Wistar; Social Isolation; Weight Gain

Heavy burdens of the abomasal nematode, Ostertagia (Telodorsagia) circumcincta, in growing lambs result in a reduction in liveweight gain due largely to a drop in voluntary feed intake. The present study investigated: (1) the role of subdiaphragmatic vagal and non-vagal visceral afferent nerves in mediating a reduction in voluntary feed intake, using subdiaphragmatic vagal deafferentation (vagotomy) either alone or in combination with coeliac-superior mesenteric ganglionectomy (vagotomy and sympathectomy); and (2) the association between appetite, abomasal pH, selected blood values (amidated gastrin (G-17-amide), glycine-extended gastrin (G-17-Gly), pepsinogen and leptin) and worm burden, in sheep experimentally infected with 100,000 O. circumcincta infective larvae per os. Neither vagotomy alone nor vagotomy and sympathectomy in combination adversely affected the establishment or course of development of the parasite burden, when compared with a control group subject to sham surgery. Furthermore, neither surgical procedure prevented the drop in appetite seen 5-10 days post-infection, although combined vagotomy and sympathectomy did reduce voluntary feed intake prior to the start of the study. Ostertagia infection resulted in a significant increase in abomasal pH in all three groups, which was accompanied by an increase in blood G-17-amide and in G-17-Gly, the latter reported for the first time in parasitized ruminants. There were no significant differences in blood leptin, also reported for the first time in parasitized sheep, either between groups or in comparison with pre-infection levels, though weak negative correlations were established between blood leptin and appetite from day 5 to the end of the study in all three groups and a positive correlation with blood G-17-amide in the control group over the same period. These data suggest that neither intact subdiaphragmatic vagal afferent nerves or coeliac-superior mesenteric ganglion fibres, nor changes in circulating gastrin and leptin concentrations play a major role in mediating the hypophagic effects of O. circumcincta in parasitized sheep.

Topics: Abomasum; Afferent Pathways; Animals; Anorexia; Energy Intake; Female; Gastrins; Hydrogen-Ion Concentration; Leptin; Male; Ostertagiasis; Random Allocation; Sheep; Sheep Diseases; Sympathectomy; Time Factors; Vagotomy; Weight Gain

The contribution of the caudal brainstem to adaptation to starvation was tested using chronically maintained decerebrate (CD) and neurologically intact controls. All rats were gavage fed an amount of diet that maintained weight gain in controls. CD rats were subjected to a two-stage surgery to produce a complete transection of the neuroaxis at the mesodiencephalic juncture. One week later, the rats were housed in an indirect calorimeter, and 24 h energy expenditure was measured for 4 d. One half of each of the CD and control groups was then starved for 48 h. Fed CD rats maintained a lower body temperature (35 C), a similar energy expenditure per unit fat-free mass but an elevated respiratory quotient compared with controls. They gained less weight, had 20% less lean tissue, and had 60% more fat than controls. Circulating leptin, adiponectin, and insulin were elevated, glucose was normal, but testosterone was dramatically reduced. Responses to starvation were similar in CD and controls; they reduced energy expenditure, decreased respiratory quotient, indicating lipid utilization, defended body temperature, mobilized fat, decreased serum leptin and insulin, and regulated plasma glucose. These data clearly demonstrate that the isolated caudal brainstem is sufficient to mediate many aspects of the energetic response to starvation. In intact animals, these responses may be refined by a contribution by more rostral brain areas or by communication between fore- and hind-brain. In the absence of communication from the forebrain, the caudal brainstem is inadequate for maintenance of testosterone levels or lean tissue in fed or fasted animals.

Topics: Adiponectin; Adipose Tissue; Animal Feed; Animals; Blood Glucose; Body Composition; Body Temperature; Body Weight; Brain; Energy Intake; Energy Metabolism; Fasting; Food Deprivation; Insulin; Leptin; Lipid Metabolism; Lipids; Male; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Temperature; Testosterone; Time Factors; Weight Gain

To determine if myostatin deficiency attenuates body fat gain with increased dietary fat intake.. Normal and myostatin-deficient mice were fed control (8-10 kcal %fat) and high-fat (HF) (45 kcal %fat) diets for a period of 8 weeks, starting at 2 months of age. Body composition, including percent body fat, lean mass, and fat mass, were measured using DXA. Serum adipokines were measured using a Beadlyte assay.. Two-factor ANOVA revealed significant treatment x genotype interactions for body fat (g), percent body fat, and serum leptin. The HF diet significantly increased body fat, percent body fat, and serum leptin in normal mice but not in myostatin-deficient mice.. Loss of myostatin function not only increases muscle mass in animal models but also attenuates the body fat accumulation that usually accompanies an HF diet.

Topics: Adiposity; Animals; Body Composition; Dietary Fats; Genotype; Leptin; Mice; Mice, Knockout; Models, Animal; Muscle, Skeletal; Myostatin; Transforming Growth Factor beta; Weight Gain

To determine the effect of exercise on weight gain and adiposity in obesity-prone and -resistant rats.. Body weight gain, fat pad weights, food intake, plasma leptin and insulin levels were assessed in outbred male Sprague-Dawley rats, which remained sedentary or were given unrestricted access to running wheels either before or after they developed diet-induced obesity (DIO) or diet-resistance (DR) on a high energy (HE; 31% fat) diet.. When fed a low fat (4.5%) chow diet, rats which would later develop DIO (n=6) after 3 weeks on HE diet ran the same amount as DR rats (n=6). Other rats were first made DIO (n=12) or DR (n=12) after 10 weeks on HE diet and then either kept sedentary or given running wheels for 4 weeks on HE diet. DIO and DR rats ran comparable amounts but only the DIO rats reduced their body weight gain, fat pad relative to body weights and plasma leptin levels significantly, compared to their sedentary controls. Exercise had no effect on food intake in either DIO or DR rats but reduced feed efficiency (weight gain/caloric intake) in both.. Although DIO and DR rats ran similar amounts, the greater reduction in body weight gain and adiposity of exercising DIO rats suggests that they are more sensitive to some metabolic or physiologic system that prevents them from increasing their intake sufficiently to compensate for their net reduction in energy stores.

Topics: Adiposity; Animals; Energy Intake; Insulin; Leptin; Male; Obesity; Physical Exertion; Rats; Rats, Sprague-Dawley; Weight Gain

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

The aim of the study was to characterize the time course of the development of high-fat diet-induced hepatic steatosis and its relation to body fat accretion and changes in plasma lipid profile. Female Sprague-Dawley rats were high-fat fed (HF; 42 %, kJ) for 1, 2, 4, 6, 12 and 16 weeks and compared to standard fed rats (SD). Data obtained from HF rats were further analysed by classifying the animals into obesity-prone and obesity-resistant. In HF rats, liver lipid content increased rapidly by approximately 200 % during the first 2 weeks, decreased almost to baseline levels between weeks 2 and 6, and re-increased by 17 % between weeks 6 and 16 (P<0.05). Body weight, body fat accretion, plasma leptin, NEFA and glycerol concentrations were higher in HF than in SD rats (P<0.05). These higher values were established in 2 weeks and the differences between the groups did not further enlarge from weeks 2 to 16. Obesity-prone rats depicted higher body weight and body fat accretion than obesity-resistant and SD rats. Surprisingly, however, liver lipid content was the same in obesity-prone as in obesity-resistant rats as they were both higher than in SD rats (weeks 2 and 16; P<0.05). Our data support the hypothesis that the liver acts as a systemic buffer, largely increasing its lipid content in the early stage of high-fat feeding. Our results also suggest that the development of non-alcoholic hepatic steatosis is more linked to dietary fat ingestion than to body weight gain.

Topics: 3-Hydroxybutyric Acid; Adipose Tissue; Animals; Diet; Dietary Fats; Energy Intake; Fatty Acids, Nonesterified; Fatty Liver; Female; Glycerol; Leptin; Lipids; Liver; Obesity; Rats; Rats, Sprague-Dawley; Time Factors; Triglycerides; Weight Gain

Fenofibrate, a selective (1)PPAR-alpha activator, is prescribed to treat human dyslipidemia. The aim of this study was to delineate the mechanism of fenofibrate-mediated reductions in adiposity, improvements in insulin sensitivity, and lowering of triglycerides (TG) and free fatty acids (FFA) and to investigate if these favorable changes are related to the inhibition of lipid deposition in the aorta. To test this hypothesis we used male LDLr deficient mice that exhibit the clinical features of metabolic syndrome X when fed a high fat high cholesterol (HF) diet. LDLr deficient mice fed HF diet and simultaneously treated with fenofibrate (100 mg/kg body weight) prevented development of obesity, lowered serum triglycerides and cholesterol, improved insulin sensitivity, and prevented accumulation of lipids in the aorta. Lowering of circulating lipids occurred via down-regulation of lipogenic genes, including fatty acid synthase, acetyl CoA carboxylase and diacyl glycerol acyl transferase-2, concomitant with decreased liver TG and cholesterol, and TG output rate. Fenofibrate also suppressed liver apoCIII mRNA levels and markedly increased lipoprotein lipase mRNA levels, known to enhance serum TG catabolism. In addition, fenofibrate profoundly reduced epididymal fat and mesenteric fat mass to the levels seen in lean mice. The reductions in body weight were associated with elevation of hepatic uncoupling protein 2 (UCP2) mRNA, a concomitant increase in the ketone body formation, and improved insulin sensitivity associated with tumor necrosis factor-alpha reductions and phosphoenol pyruvate carboxykinase down-regulation. These results demonstrate that fenofibrate improves lipid abnormalities partly via inhibition of TG production and partly via clearance of TG-rich apoB particles by elevating LPL and reduced apoCIII. The prevention of obesity development occurred via energy expenditure. Fenofibrate-mediated hypolipidemic effects together with improved insulin sensitivity and loss of adiposity led to the reductions in the aortic lipid deposition by inhibiting early stages of atherosclerosis possibly via vascular cell adhesion molecule-1 (VCAM-1) modulation. These results suggest that potent PPAR-alpha activators may be useful in the treatment of syndrome X.

Topics: Adiposity; Animals; Aorta; Coronary Artery Disease; Diet, Atherogenic; Energy Metabolism; Fenofibrate; Gluconeogenesis; Hypercholesterolemia; Hypertriglyceridemia; Insulin; Insulin Resistance; Leptin; Ligands; Lipid Metabolism; Lipids; Lipogenesis; Liver; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; PPAR alpha; Receptors, LDL; Triglycerides; Weight Gain

Tests were conducted to determine whether weight gain or nutrient intake measures during the first week of exposure to a macronutrient diet can accurately predict an animal's long-term propensity towards obesity. In multiple groups of normal-weight Sprague-Dawley rats (n=35-70/group), daily weight gain during the first 5 days on a high-fat diet (45-60% fat) was found to be strongly, positively correlated (r=+0.71 to r=+0.82) with accumulated body fat in 4 dissected depots after 4-6 weeks on the diet. This measure consistently identified obesity-prone (OP) rats which, relative to the obesity-resistant (OR) rats, were only slightly heavier (+15 g, 4%) and hyperphagic (+9 kcal, 8%) after 5 days but markedly heavier (+70g) with up to 2-fold greater fat mass after several weeks on the diet. Other dietary conditions and measures revealed weaker relationships to ultimate body fat accrual. The OP rats identified by their 5-day weight-gain score exhibited at this early stage clear disturbances characteristic of markedly obese rats. These included elevated leptin, insulin, triglycerides and glucose, along with increased lipoprotein lipase activity (LPL) in adipose tissue and galanin expression in the paraventricular nucleus. Most notable were significant reductions in muscle of LPL activity and ratio of beta-hydroxyacyl-CoA dehydrogenase to citrate synthase activity, indicating a decline in lipid transport and capacity of muscle to metabolize lipids. By occurring early with initial weight gain, these hypothalamic and metabolic disturbances in OP rats, favoring fat storage in adipose tissue over fat oxidation in muscle, may have causal relationships to long-term accumulation of body fat.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Adiposity; Animal Feed; Animals; Body Weight; Citrate (si)-Synthase; Dietary Carbohydrates; Dietary Fats; Energy Intake; Galanin; Insulin; Leptin; Male; Models, Animal; Models, Biological; Muscle, Skeletal; Obesity; Phenotype; Predictive Value of Tests; Rats; Rats, Sprague-Dawley; Triglycerides; Weight Gain

Excessive weight gain during pregnancy increases breast cancer risk in women. To determine whether this may be caused by increased pregnancy leptin levels, leptin receptor (Ob-Rb) mutant (fa/fa) and wild-type (FA/FA) female Zucker rats and Sprague-Dawley rats were fed during pregnancy an obesity-inducing high-fat diet (OID) that increased pregnancy weight gain, or a control diet. Because mutant Zucker rats do not readily become pregnant, their pregnancy was mimicked by exposing the rats to subcutaneous silastic capsules containing 150 microg of estradiol and 30 mg of progesterone for 3 wk. Sprague-Dawley rats underwent normal pregnancy. An assessment of hormone levels on gestation d 17 indicated that an exposure to the OID significantly elevated serum leptin concentration but did not affect those of estradiol or insulin-like growth factor 1 (IGF-1). Insulin and adiponectin levels were higher in the obese than lean Zucker rats, but were not related to pregnancy weight gain. Exposure to the OID during pregnancy increased 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in all genetic backgrounds, including leptin receptor mutant Zucker rats. The results also indicated that obese Zucker rats that underwent mimicked pregnancy developed more palpable tumors and hyperplastic alveolar nodules that lean Zucker rats. Further, mammary epithelial cell proliferation assessed using PCNA staining was elevated in obese Zucker rats as was activation of mitogen-activated protein kinase (MAPK); however, neither of these 2 changes occurred in the context of excessive weight gain during pregnancy. It remains to be determined whether an increase in leptin levels was causally associated with an increase in the dams' mammary tumorigenesis, including in obese Zucker rats with dramatically reduced leptin signaling.

Topics: Adiponectin; Animals; Carcinogens; Cell Division; Diet; Estradiol; Female; Insulin; Insulin-Like Growth Factor I; Leptin; Mammary Neoplasms, Experimental; Mitogen-Activated Protein Kinases; Obesity; Pregnancy; Pregnancy Complications; Progesterone; Rats; Rats, Sprague-Dawley; Rats, Zucker; Risk Factors; Weight Gain

To investigate the association between DNA polymorphisms in the NPY and AGRP genes and body fatness.. The association between the AGRP Ala67Thr or the NPY Leu7Pro polymorphisms and indicators of body fatness (baseline leptin levels, body mass index (BMI) values and prevalence of overweight) are investigated in 582 participants of two large cohorts in The Netherlands (total 18 500 adult men and women), aged 20-40 years whose weight remained relatively constant or whose weight increased substantially (range 5.5-47 kg) during a mean follow-up of 7 years.. No consistent associations were found for the indicators of body fatness for men and women. Among women, BMI values, leptin levels and prevalence of overweight were not statistically different for carriers of the mutant alleles compared to that of the non-carriers. Among men, carriers of the Thr67-allele of the AGRP gene had similar leptin levels, but higher BMI values compared to those with the genotyping Ala67/Ala67: mean adjusted BMI 25.6 kg/m2 (95% CI 24.3-27.0) vs 23.9 kg/m2 (23.6-24.3). Also, the risk of being overweight at baseline tended to be higher for male carriers of the Thr67-allele of the AGRP gene (OR 2.52; 95% CI 0.86-7.4). Furthermore, male carriers of the Pro7-allele of the NPY gene had on average higher leptin levels and BMI values vs non-carriers of this allele: 4.7 microg/l (95% CI 3.7-6.0) and 25.7 kg/m2 (95% CI 24.4-27.0) vs 3.1 microg/l (95% CI 2.9-3.4) and 23.9 kg/m2 (95% CI 23.5-24.3), respectively. These male carriers had also a higher risk on being overweight at baseline (OR 3.3 (95% CI 1.2-8.9)) compared to non-carriers of the Pro7-allele.. The consistent findings among men suggest that the NPY Leu7Pro polymorphism (or another linked marker) might be involved in the development of obesity at younger ages. The findings for the AGRP Ala67Thr were less consistent and need further investigation. Among women, these polymorphisms do not play an important role.

Topics: Adult; Agouti-Related Protein; Anthropometry; Body Mass Index; Cohort Studies; Female; Genotype; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptide Y; Overweight; Polymorphism, Genetic; Weight Gain

We previously showed that neonatal leptin treatment programmes higher body weight and food intake in adult rats. Here we investigate whether leptin treatment during lactation affects the anorectic effect of leptin on adult rats and their hypothalamic leptin receptors (OB-Rb) and whether those changes could have consequences on intermediary metabolism. When the offspring were born, pups were divided into two groups: the Lep group, injected daily with leptin (8 microg/100 g body weight, subcutaneously) for the first 10 d of lactation, and the control group, injected daily with saline. After weaning (day 21), body weight and food intake were monitored until the rats were 150 d old. Food intake was higher in the Lep group (approximately 14 %, P<0.05) from day 133 onwards, and body weight was higher (approximately 10 %, P<0.05) from day 69 onwards, compared with the control group. At 150 d of age, the rats were tested for food intake in response to either leptin (0.5 mg/kg body weight intraperitoneally; groups CL and LepL) or saline (groups CSal and LepSal). The CL group showed a decrease in food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group demonstrated a decrease in OB-Rb expression (-40 %, P<0.05), hyperleptinaemia (+78 %, P<0.05), hyperinsulinaemia (+100 %, P<0.02), hypertriacylglycerolaemia (+17 %, P<0.05) and a higher protein content in the body (+16 %, P<0.05) without changes in fat mass and glycaemia. We conclude that neonatal leptin treatment programmes both hyperleptinaemia and hyperinsulinaemia in adulthood, which leads to leptin resistance by reducing the expression of the hypothalamic leptin receptor.

Topics: Aging; Animals; Animals, Newborn; Biometry; Blood Glucose; Body Composition; Drug Resistance; Eating; Hypothalamus; Insulin; Lactation; Leptin; Male; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, Leptin; Weight Gain

Recent studies in human and animal models of narcolepsy have suggested that obesity in narcolepsy may be due to deficiency of hypocretin signaling, and is also under the influence of environmental factors and the genetic background. In the current study, using two hypocretin/orexin deficient narcoleptic mouse models (i.e. preproorexin knockout (KO) and orexin/ataxin-3 transgenic (TG) mice) with cross-sectional assessments, we have further analyzed factors affecting obesity. We found that both KO and TG narcoleptic mice with mixed genetic backgrounds (N4-5, 93.75-96.88% genetic composition of C57BL/6) tended to be heavier than wild type (WT) mice of 100-200 days old. The body weight of heterozygous mice was intermediate between those of KO and WT mice. Obesity was more prominent in females in both KO and TG narcoleptic mice and was associated with higher serum leptin levels, suggesting a partial leptin resistance. Obesity is less prominent in the congenic TG narcoleptic mice, but is still evident in females. Our results confirmed that hypocretin/orexin ligand deficiency is one of the critical factors for the obese tendency in narcolepsy. However, multiple factors are also likely to affect this phenotype, and a sex difference specific alteration of leptin-hypocretin signaling may be involved.

Topics: Animals; Female; Intracellular Signaling Peptides and Proteins; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Models, Animal; Narcolepsy; Neuropeptides; Obesity; Orexins; Sex Factors; Signal Transduction; Weight Gain

This study aims to establish a model that will allow the comparison of the phenotypic variations between a fat-preferring strain and a macronutrient non-preferring strain of mouse.. Five strains (AKR, A/J, ARC, C57Bl/6 and BALB/c) were fed a two-choice diet (high-fat/low-carbohydrate and low-fat/high-carbohydrate) for 30 days. Following completion of the 30-day feeding period, the brains of the fat-preferring and macronutrient non-preferring mice were removed for the analysis of the expression of the genes - agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC).. Upon completion of the experiment, it was found that the C57Bl/6 strain was the strongest fat preferrer consuming 72% of their calories from the high-fat diet, whereas the BALB/c was found to have no macronutrient preference. Using in situ hybridization techniques, no significant differences in the expression of POMC were found between the two strains. It was, however, showed that the BALB/c mice had a 33.7% higher expression level of AgRP than the C57Bl/6 mice.. The lower expression level of AgRP in the C57Bl/6 mice may be suggestive of a defensive response to their chronic preferential consumption of the high-fat diet. However, the wide variety of neuroregulatory signals involved in macronutrient preference along with the possibility of the occurrence of post-transcriptional effects suggests further biological analyses need to be performed using this model.

Topics: Agouti-Related Protein; Animals; Body Weight; Dietary Carbohydrates; Dietary Fats; Energy Intake; Food Preferences; Gene Expression; In Situ Hybridization; Intercellular Signaling Peptides and Proteins; Leptin; Male; Mice; Mice, Inbred Strains; Phenotype; Pro-Opiomelanocortin; RNA, Messenger; Species Specificity; Weight Gain

11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) catalyzes regeneration of active intracellular glucocorticoids in fat, liver, and discrete brain regions. Although overexpression of 11 beta-HSD1 in adipose tissue causes hyperphagia and the metabolic syndrome, male 11 beta-HSD1 null (11 beta-HSD1-/-) mice resist metabolic disease on high-fat (HF) diet, but also show hyperphagia. This suggests 11 beta-HSD1 may influence the central actions of glucocorticoids on appetite and perhaps energy balance. We show that 11 beta-HSD1-/- mice express lower hypothalamic mRNA levels of the anorexigenic cocaine and amphetamine-regulated transcript and melanocortin-4 receptor, but higher levels of the orexigenic melanin-concentrating hormone mRNAs than controls (C57BL/6J) on a low-fat diet (11% fat). HF (58% fat) diet promoted transient ( approximately 8 wk) hyperphagia and decreased food efficiency in 11 beta-HSD1-/- mice and decreased melanocortin-4 receptor mRNA expression in control but not 11 beta-HSD1-/- mice. 11 beta-HSD1-/- mice showed a HF-mediated up-regulation of the orexigenic agouti-related peptide (AGRP) mRNA in the arcuate nucleus which paralleled the transient HF hyperphagia. Conversely, control mice showed a rapid (48 h) HF-mediated increase in arcuate 11 beta-HSD1 associated with subsequent down-regulation of AGRP. This regulatory pattern was unexpected because glucocorticoids increase AGRP, suggesting an alternate hyperphagic mechanism despite partial colocalization of 11 beta-HSD1 and AGRP in arcuate nucleus cells. One major alternate mechanism governing selective fat ingestion and the AGRP system is endogenous opioids. Treatment of HF-fed mice with the mu opioid agonist DAMGO recapitulated the HF-induced dissociation of arcuate AGRP expression between control and 11 beta-HSD1-/- mice, whereas the opioid antagonist naloxone given with HF induced a rise in arcuate AGRP and blocked HF-diet induction of 11 beta-HSD1. These data suggest that 11 beta-HSD1 in brain plays a role in the adaptive restraint of excess fat intake, in part by increasing inhibitory opioid tone on AGRP expression in the arcuate nucleus.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Corticosterone; Dietary Fats; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enzyme Induction; Female; Gene Expression; Hyperphagia; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Pro-Opiomelanocortin; Proteins; Receptor, Melanocortin, Type 4; Receptors, Opioid, mu; RNA, Messenger; Thyroid Hormones; Weight Gain

Prolactin (PRL), best recognized for its lactogenic activity, is also involved in the regulation of metabolic homeostasis in both mammalian and nonmammalian species. Although several mouse models have been used to study the metabolic functions of PRL, a clear-cut consensus has not emerged given the limited and often conflicting data. To clarify the role of PRL in metabolic homeostasis in males and nonlactating females, we used the PRL-deficient mouse. Our objectives were to compare: 1) weight gain, 2) body composition, 3) serum lipid profile, 4) circulating leptin and adiponectin levels, and 5) glucose tolerance in PRL knockout, heterozygous, and wild-type mice maintained on standard chow, high-fat, or low-fat diets. In addition, we compared the lipolytic actions of PRL using adipose tissue explants from mice, rats, and humans. We are reporting that PRL deficiency does not affect the rate of weight gain, body composition, serum lipids, or adiponectin levels in either sex on any diet. Glucose tolerance was slightly impaired in very young PRL knockout male pups but not in adults or in females at any age. Leptin was elevated in male, but not female, PRL knockout mice maintained on a low-fat diet. PRL did not affect lipolysis in adipose tissue explants from mice but significantly inhibited glycerol release from both rat and human adipose explants in a dose-dependent manner. We conclude that PRL deficiency has negligible gross metabolic effects in mice.

Topics: Adiponectin; Adipose Tissue; Animals; Body Composition; Diet, Fat-Restricted; Dietary Fats; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Leptin; Lipids; Lipolysis; Lymphocytes; Male; Metabolism; Mice; Mice, Knockout; Phenotype; Prolactin; Rats; Reverse Transcriptase Polymerase Chain Reaction; Sex Characteristics; Weight Gain

Topics: Animals; Antipsychotic Agents; Arcuate Nucleus of Hypothalamus; Energy Metabolism; Glucose; Humans; Leptin; Mice; Pro-Opiomelanocortin; Weight Gain

Topics: Circadian Rhythm; Female; Humans; Hypothalamo-Hypophyseal System; Leptin; Male; Motor Activity; Seasonal Affective Disorder; Sex Characteristics; Weight Gain

beta3-Adrenoreceptor agonists can stimulate lipolysis in the white adipose tissue and thermogenesis in the brown adipose tissue. These activities could be useful in the treatment of obesity and the associated metabolic syndrome. The effects of six-week oral administration of the newly synthesized substance B496 (methyl-4-[2-[2-hydroxy-3-(4-ethylcarbamoyl)phenoxyprophyl]amino]etyl)-phenoxyacetate hydrochloride) on serum glucose, triglycerides, total cholesterol, and leptin levels were studied in male Wistar rats fed with a high-fat diet. The animals were divided into a group treated with B496 (5 mg dissolved in 1 litre of water) and a control group. The results indicated a significant reduction in serum glucose levels (-26 %, p<0,01), triacylglyceride levels (-21 %, p<0,05) and leptin levels (-43 %, p<0,01). Further the effect of a single intraperitoneal dose (1 mg/kg) of B496 and BRL-37344 on serum leptin levels in the C57Bl/6J mouse was investigated. Administration of BRL-37344 resulted in a significant decrease in serum leptin levels (-55 %, p<0,001). This reduction was not demonstrated by newly synthesized substance B496.

Topics: Adrenergic beta-Agonists; Animals; Blood Glucose; Cholesterol; Ethanolamines; Leptin; Male; Mice; Mice, Inbred C57BL; Phenoxyacetates; Rats; Rats, Wistar; Receptors, Adrenergic, beta-3; Triglycerides; Weight Gain

To assess the effects of high-fat feeding on white adipose tissue gene expression and liver oxidative stress.. Male Wistar rats were fed on standard pelleted or high-fat diet to produce a diet-induced obesity model. Therefore, body composition, serum biochemical values and liver malondialdehyde (MDA) were determined after 56 days of feeding. Expression (mRNA) values of three genes were also determined by reverse transcriptase-polymerase chain reaction in white adipose tissue.. Animals fed on the high-fat diet showed more body weight, higher fat deposition and total liver weight, and increased energy intake compared with those on the standard-fat diet. Serum fasting measurements (glucose, insulin, leptin) and homeostasis model assessment insulin resistance index were significantly increased by the high-fat diet consumption. As an indicator of oxidative stress, peroxide decomposition in liver was analyzed, showing an increase of MDA concentrations in rats fed on high-fat diet in comparison with control rats. Interestingly, liver MDA levels correlated positively with body weight gain, serum leptin, and homeostasis model assessment. Finally, leptin and glycerol-3-phosphate dehydrogenase mRNA levels, but not fatty acid synthase, were increased by high-fat diet in comparison with the control-fed group.. These results show a link among increased fat depots, insulin resistance, and liver oxidative stress. Thus, liver oxidative stress probably contributes to hepatic disorders and aggravates the metabolic syndrome, which is accompanied by a stimulation of the esterification of fatty acids as measured by glycerol-3-phosphate dehydrogenase in the adipose tissue, providing support to the hypothesis that not only calories count in the induction of weight gain or metabolic syndrome and that other factors such as oxidative stress may be involved.

Topics: Adipose Tissue; Animals; Body Composition; Dietary Fats; Gene Expression; Insulin Resistance; Leptin; Liver; Male; Malondialdehyde; Organ Size; Oxidative Stress; Random Allocation; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Weight Gain

JTP-426467 was identified as a result of screening in search of selective antagonist for peroxisome proliferator-activated receptor gamma (PPARgamma). We examined whether JTP-426467 functioned as a PPARgamma antagonist in vitro and in vivo and investigated physiological effects of JTP-426467.. The effect of JTP-426467 as a PPARgamma antagonist was studied in a cell-based reporter assay and an adipocyte differentiation assay. Target mRNA expression levels were determined by branched DNA (bDNA) assay. To examine the effects as a PPARgamma antagonist in vivo, a competitive study between JTP-426467 and BRL49653 (rosiglitazone), a PPARgamma agonist, was performed using KK-Ay mice. The effects of JTP-426467 alone after administration to KK-Ay mice were also explored. JTP-426467 antagonized PPARgamma activity in a reporter assay system, but not PPARalpha.. JTP-426467 inhibited the expression of hormone-sensitive lipase (HSL) mRNA, an adipocyte-abundant gene, but not PPARgamma itself or cyclophilin mRNA (as constitutive mRNA), and also suppressed triglyceride accumulation in differentiated stromal vascular fraction cells (SVFs). JTP-426467 antagonized PPARgamma agonistic action by BRL49653 in KK-Ay mice on high-fat diet, in terms of plasma glucose, body weight gain and interscapular brown adipose tissue (IBAT) weight. JTP-426467 alone inhibited body weight gain and decreased plasma leptin level in KK-Ay mice.. JTP-426467 acted as a pure and potent PPARgamma antagonist in vitro. Interestingly, JTP-426467 completely antagonized the effects of PPARgamma agonist BRL49653 in an obese diabetic model. JTP-426467 may be a useful tool for the study of PPARgamma in biological and physiological function.

Topics: Adipocytes; Adipogenesis; Animals; Anti-Obesity Agents; Benzoxazoles; Blood Glucose; Cell Differentiation; Cells, Cultured; Dose-Response Relationship, Drug; Gene Expression Regulation; Genes, Reporter; HeLa Cells; Humans; Hypoglycemic Agents; Leptin; Male; Mice; Obesity; PPAR gamma; RNA, Messenger; Rosiglitazone; Thiazolidinediones; Weight Gain

Recently, gastric Helicobacter pylori (H. pylori) colonization has been shown to affect the expression of leptin and ghrelin, hormones that control appetite and satiety. Gastric leptin, produced by chief and parietal cells and released in response to meals, may play a role in weight gain after eradication of H. pylori infection, whereas ghrelin, produced by X/A-like enteroendocrine cells in oxyntic gland, is released during fasting, and suppressed by feeding and leptin. Whether either that H. pylori genes represent microbial contributions to the complement of thrifty genes of humans, or that H. pylori disappearance plays a role in adiposity remains to be determined. Simply, ghrelin-leptin might tango in body weight regulation, gastric inflammation, and gastric motility. In the current review about the possible role of ghrelin in gastric inflammation, we found that high serum albumin condition decreased ghrelin expression, whereas serum albumin deprivation significantly increased ghrelin expression, however, of which regulation was abolished after H. pylori infection. Ghrelin significantly attenuated the inflammatory stimuli imposed after H. pylori, shown with inactivation of phospho-extracellular signal-regulated kinase (p-ERK) and nuclear factor-kappaB (NF-kappaB)-DNA binding activities. Conclusively, besides orexigenic and weight gaining actions of gastric hormone, ghrelin, it likely endows the stomach the protective effect from exogenous damages.

Topics: Amino Acid Sequence; Appetite Stimulants; Gastritis; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Insulin-Like Growth Factor I; Leptin; Mitogen-Activated Protein Kinases; Molecular Sequence Data; Neurosecretory Systems; NF-kappa B; Peptide Hormones; Signal Transduction; Weight Gain

The ketogenic diet (KD) is an efficacious therapy for medically refractory childhood epilepsy that also slows weight gain. We tested the hypothesis that the KD slows weight gain via neurohormones involved in energy homeostasis. We found that juvenile rodents fed a KD had slower weight gain than those fed a standard diet (SD). Rats fed a KD had higher serum leptin levels and lower insulin levels compared with those fed an SD. We investigated the increase in leptin further because this change was the only one consistent with slower weight gain. Although rats fed the SD experienced slower weight gain when calorie restricted, they had serum leptin levels similar to those fed the SD ad libitum. Furthermore, leptin deficient (ob/ob) and leptin receptor deficient (db/db) mice did not show slower weight gain on the KD. All animals on the KD had elevated serum beta-hydroxybutyrate (betaHB) levels. Thus, ketosis is insufficient and a functioning leptin signaling system appears necessary for the KD to slow weight gain. The increase in leptin may contribute to the anticonvulsant effects of the KD.

Topics: Animals; Caloric Restriction; Diet; Ketones; Ketosis; Leptin; Mice; Mice, Knockout; Mice, Obese; Obesity; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, Leptin; Weight Gain

In this study, we tested the hypothesis that insufficiency of leptin restraint in the hypothalamus is responsible for promoting weight gain and adiposity after ovariectomy (ovx). Whether increasing leptin transgene expression can overcome the diminution in leptin restraint was evaluated in ovx rats.. Enhanced leptin or green fluorescent protein (GFP; control) transgene expression was induced by a single intracerebroventricular injection of recombinant adeno-associated viral vector encoding either leptin gene (rAAV-lep) or GFP gene (rAAV-GFP; control) in acutely and chronically ovx rats. Body weight and food intake responses were monitored weekly. White adipose tissue (WAT) mass and serum levels of WAT-derived hormones, leptin, and adiponectin were analyzed at termination of the experiments.. An increase in leptin transgene expression in the hypothalamus initiated soon after ovx blocked hyperphagia and body weight gain and markedly suppressed WAT mass and adipokines, leptin, and adiponectin. Similar suppression of weight gain and adiposity and serum leptin and adiponectin levels after intracerebroventricular rAAV-lep injection in chronically ovx rats were observed concomitant with unchanged daily food intake. These findings are consistent with the hypothesis that in the absence of ovarian steroids, the existent insufficiency of leptin restraint at the hypothalamic level can be overcome with ectopic leptin expression, thereby reinstating central control on weight and adiposity.

Topics: Adenoviridae; Adiponectin; Adiposity; Analysis of Variance; Animals; Eating; Female; Gene Expression; Genetic Therapy; Genetic Vectors; Hypothalamus; Injections, Intraventricular; Ion Channels; Leptin; Mitochondrial Proteins; Ovariectomy; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Uncoupling Protein 1; Weight Gain

Neuropeptide Y (NPY) stimulates feeding and weight gain, but deletion of the NPY gene does not affect food intake and body weight in mice bred on a mixed genetic background. We reasoned that the orexigenic action of NPY would be evident in C57Bl/6J mice susceptible to obesity. NPY deficiency has no significant effect in mice fed a normal rodent diet. However, energy expenditure is elevated during fasting, and hyperphagia and weight gain are blunted during refeeding. Expression of agouti-related peptide (AGRP) in the hypothalamus is increased in NPY knockout (NPYko) than wild-type mice, but unlike wild type there is no further increase in AGRP when NPYko mice are fasted. Moreover, NPYko mice have higher oxygen consumption and uncoupling protein-1 expression in brown adipose tissue during fasting. The failure of an increase in orexigenic peptides and higher thermogenesis may contribute to attenuation of weight gain when NPYko mice are refed. C57Bl/6J mice lacking NPY are also less susceptible to diet-induced obesity (DIO) as a result of reduced feeding and increased energy expenditure. The resistance to DIO in NPYko mice is associated with a reduction in nocturnal feeding and increased expression of anorexigenic hypothalamic peptides. Insulin, leptin, and triglyceride levels increase with adiposity in both wild-type and NPYko mice.

Topics: Aging; Animals; Appetite; Blood Glucose; Body Weight; Corticosterone; Dietary Fats; Eating; Fasting; Female; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Neuropeptide Y; Obesity; Oxygen Consumption; Thyroxine; Weight Gain

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

To evaluate postprandial changes in the leptin concentration of CSF in dogs during development of obesity.. 4 male Beagles.. Weight gain was induced and assessments were made when the dogs were in thin, optimal, and obese body conditions (BCs). The fat area at the level of the L3 vertebra was measured via computed tomography to assess the degree of obesity. Dogs were evaluated in fed and unfed states. Dogs in the fed state received food at 9 AM. Blood and CSF samples were collected at 8 AM, 4 PM, and 10 PM.. Baseline CSF leptin concentrations in the thin, optimal, and obese dogs were 24.3 +/- 2.7 pg/mL, 86.1 +/- 14.7 pg/mL, and 116.2 +/- 47.3 pg/mL, respectively. In the thin BC, CSF leptin concentration transiently increased at 4 PM. In the optimal BC, baseline CSF leptin concentration was maintained until 10 PM. In the obese BC, CSF leptin concentration increased from baseline value at 4 PM and 10 PM. Correlation between CSF leptin concentration and fat area was good at all time points. There was a significant negative correlation between the CSF leptin concentration-to-serum leptin concentration ratio and fat area at 4 PM; this correlation was not significant at 8 AM and 10 PM.. Decreased transport of leptin at the blood-brain barrier may be 1 mechanism of leptin resistance in dogs. However, leptin resistance at the blood-brain barrier may not be important in development of obesity in dogs.

Topics: Animals; Body Composition; Dog Diseases; Dogs; Leptin; Male; Obesity; Postprandial Period; Time Factors; Weight Gain

Soy products are mainly composed of proteins, phytochemicals such as isoflavones, soy lipids, and carbohydrates. It is unclear whether an individual component alone or a combined effect of multiple bioactive compounds contributes to the beneficial properties of soy. We investigated the effect of dietary genistein (the principal soy isoflavone) alone and combined with L-carnitine to evaluate possible synergistic effects on the intentionally induced prediabetic state characterized by insulin resistance and obesity in C57Bl/6J mice fed a high-fat diet (HD). In the HD-alone group, abdominal and back fat relative to total body weight were significantly higher compared with other groups including those fed normal diet (ND). Among the HD groups, final weight gains of the HD plus genistein (HD+G) and HD plus genistein plus L-carnitine (HD+G+C) groups were lower compared with that of the control (HD-alone). Especially in liver, the results showed that genistein with carnitine transcriptionally up-regulated expressions of acyl-coenzyme A synthetase (ACS) and carnitine palmitoyltransferase-I (CPT-I) by approximately 50% and 40%, respectively, compared with genistein alone. However, the up-regulation of CPT-I did not directly reflect the enzyme activity of CPT-I. On the other hand, the effects of genistein and genistein with carnitine on the expressions of ACS and CPT-I in muscle were not significant. Our study suggests that genistein with carnitine exerts anti-obesity effects, probably by modulating peroxisome proliferator-activated receptor-associated genes. However, further work is needed to elucidate the possible mechanisms by which genistein and carnitine intervene.

Topics: Adipose Tissue; Animals; Carnitine; Carnitine O-Palmitoyltransferase; Coenzyme A Ligases; Diet; Dietary Fats; Drug Synergism; Fatty Acid Synthases; Gene Expression Regulation, Enzymologic; Genistein; Glyceraldehyde-3-Phosphate Dehydrogenases; Insulin Resistance; Leptin; Lipids; Liver; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Obesity; Random Allocation; RNA, Messenger; Weight Gain

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

The objective of this study was to investigate the secretion of pancreatic enzymes and antibacterial activity in weaned pigs of three pure breeds, Pietrain, Duroc and Polish synthetic line 990, to look for eventual differences related to the genotype. Six male pigs of each breed, about 24 kg mean body weight, were equipped with chronic pancreatic duct catheters and duodenal cannulas to assess pure pancreatic juice, and jugular vein catheters for blood withdrawal. Pancreatic juice was collected before and after the morning feeding. Protein output and enzyme activities revealed two distinct profiles: strong manifestation of the prandial phase in Pietrain and line 990 pigs, and weak manifestation in Duroc. The antibacterial activity did not follow the enzyme kinetics, and it was the strongest in pancreatic juice from Pietrain pigs. Postprandial insulinaemia was reduced in the order of: line 990>Pietrain>Duroc. A slight (not significant) tendency towards a reduction of leptin after feeding in synthetic line 990 corresponded with elevated secretion of pancreatic enzymes and plasma insulin. The presented results suggest that the prandial secretion of pancreatic juice differs according to genotype, and the differences may be in part related to release of insulin.

Topics: Animals; Escherichia coli; Genotype; Glucagon; Insulin; Leptin; Male; Pancreatic Juice; Proteins; Species Specificity; Swine; Weight Gain

High blood pressure (BP) is a major determinant of cardiovascular events in obesity. The beta2- and beta3-adrenoceptor polymorphisms are associated with obesity and hypertension. In the present study, we examine the relationships of beta2- and beta3-adrenoceptor polymorphisms with further weight gain-induced BP elevation in obese subjects. Changes in BP, body weight, total body fat-mass, waist-to-hip ratio, plasma norepinephrine (NE) and leptin levels, and beta2(Arg16Gly)- and beta3(Trp64Arg)-adrenoceptor polymorphisms were measured periodically over a 5-year period in 55 entry obese (body mass index [BMI]> or =25.0 kg/m(2)) normotensive (BP<140/90 mmHg) men. BP elevation and weight gain were defined as > or =10% increases from entry levels over 5 years in mean BP or BMI. Obese subjects with weight gain, BP elevation or weight gain-induced BP elevation had higher frequencies of the Gly16 allele of Arg16GIy and Arg64 allele of Trp64Arg. Subjects carrying the Gly16 or Arg64 alleles had significantly greater total fat-mass and waist-to-hip ratio at entry and over a 5-year period compared to the subjects who did not carry these polymorphisms. Subjects carrying the Gly16 allele had similar levels of plasma NE, higher levels of plasma leptin and a lower slope of the regression lines between plasma leptin and NE levels. Those carrying the Arg64 allele had higher plasma NE levels at entry and over a 5-year period compared to the subjects without the Arg64 allele, but plasma leptin levels and slopes were similar. The findings demonstrate that the Arg64 allele of the beta3-adrenoceptor polymorphisms relates to weight gain-induced BP elevation accompanying high plasma NE (heightened sympathetic activity) in obese men. The Gly16 allele of the beta2-adrenoceptor polymorphisms links to weight gain-induced BP elevation associated with leptin resistance. beta2- and beta3-adrenoceptor polymorphisms could predict the future BP elevation and further weight gain-induced BP elevation in originally obese subjects.

Topics: Adult; Alleles; Amino Acid Substitution; Blood Pressure; Body Mass Index; Cohort Studies; Humans; Hypertension; Leptin; Male; Norepinephrine; Obesity; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Receptors, Adrenergic, beta-3; Weight Gain

Leptin, the ob gene product, has an important role in the regulation of body weight. Although tamoxifen, a nonsteroidal antiestrogenic agent, is known to have estrogenic effects on fat metabolism, its influence on adipose tissue remains unknown. In the present study, the effect of tamoxifen on the concentration of leptin was investigated in ovariectomized rats treated with tamoxifen or vehicle. The dosage of tamoxifen was extrapolated from the human dosage. Food intake, adipose tissue weight, and plasma insulin were assessed at the end of the experiment.. Tamoxifen-treated rats showed a significant reduction of body weight gain, food intake, adipose tissue weight and leptin concentration (p < 0.001). The plasma insulin level was significantly higher after tamoxifen treatment (p = 0.01) in tamoxifen-treated rats than in control rats. We concluded that tamoxifen reduces food intake in the acute phase and a reduction of adipose tissue gain may result in reduced levels of plasma leptin in ovariectomized rats. Furthermore, rats treated with tamoxifen may be resistant to insulin action.

Topics: Adipose Tissue; Animals; Eating; Estrogen Receptor Modulators; Female; Insulin; Leptin; Ovariectomy; Rats; Rats, Sprague-Dawley; Tamoxifen; Weight Gain

Circulating levels of ghrelin, a stomach peptide that promotes food intake, rise before and fall after meal. We aimed to investigate whether there is an independent contribution of the small bowel to the regulation of ghrelin and appetite. A duodenal-jejunal bypass (DJB) with preservation of normal gastric volume and exposure to nutrients was performed in 12-wk-old obese Zucker ZDF fa/fa rat. Food intake, weight gain, 48-h fasting, and 24-h refeeding levels of total and acylated ghrelin were measured. The DJB was challenged against gastric banding (GB), diet, and a sham operation in matched animals. Normal controls were age-matched Wistar rats, which underwent either DJB or a sham operation. The Zucker obese animals showed a paradoxical increase of acylated ghrelin levels after refeeding (+30% with respect to fasting levels; P = 0.001), an abnormality that was completely reversed only by the DJB (-30%; P = 0.01) but not after GB, diet, or sham operation. In obese rats, the DJB resulted in significantly less food intake and weight gain compared with both GB (P < 0.05) and sham operation (P < 0.01). In sharp contrast, the DJB did not alter food intake and weight gain in normal rats. The DJB does not physically restrict the flow of food but restores meal-induced suppression of acylated ghrelin and significantly reduces food intake in Zucker obese rats. These findings suggest an independent intestinal contribution to the regulation of the dynamic ghrelin response to eating and the possibility that defective signaling from the proximal bowel could be involved in the pathogenesis of obesity/hyperphagia.

Topics: Anastomosis, Roux-en-Y; Animals; Diabetes Mellitus, Type 2; Eating; Ghrelin; Insulin; Intestine, Small; Leptin; Male; Obesity; Peptide Hormones; Rats; Rats, Zucker; RNA, Messenger; Weight Gain

We investigated the ability of Garcinia cambogia extract containing (-)-hydroxycitric acid (HCA) to suppress body fat accumulation in developing male Zucker obese (fa/fa) rats. We also examined histopathologically the safety of its high doses. Diets containing different levels of HCA (0, 10, 51, 102 and 154 mmol/kg diet) were fed to 6-week-old rats for 92 or 93 days. Each diet group was pair-fed to the 154 mmol HCA/kg diet group. Epididymal fat accumulation and histopathological changes in tissues were observed. The highest dose of HCA-containing Garcinia cambogia (154 mmol HCA/kg diet) showed significant suppression of epididymal fat accumulation in developing male Zucker obese rats, compared with the other groups. However, the diets containing 102 mmol HCA/kg diet and higher (778 and 1244 mg HCA/kg BW/d, respectively) caused potent testicular atrophy and toxicity, whereas diets containing 51 mmol HCA/kg diet (389 mg HCA/kg BW/d) or less did not. Accordingly, 51 mmol HCA/kg diet (389 mg HCA/kg BW/d) was deemed to be the no observed adverse effect level (NOAEL).

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; ATP Citrate (pro-S)-Lyase; Citrates; Dose-Response Relationship, Drug; Garcinia cambogia; Leptin; Liver; Male; No-Observed-Adverse-Effect Level; Organ Size; Plant Extracts; Random Allocation; Rats; Rats, Zucker; Testis; Testosterone; Weight Gain

A low-fat diet is hypothesized to be associated with significant weight loss. However, most previous studies have been limited to low-fat, low-calorie restrictive diets. This study evaluated the effect of isocaloric diets given "ad libitum" but different in relative amounts of fat and carbohydrate on body size, energy metabolism, body composition, insulin-like growth factor-1, and leptin serum levels in growing Wistar rats.. Weanling male rats were fed with one of three diets that contained a ratio of carbohydrate to fat of 1:1, 2:1, or 3:1. Food intake, body weight, body length, oxygen consumption, and body composition were measured at ages 21 to 50 d. Serum levels of insulin-like growth factor-1 and leptin were also determined.. Energy intake was similar across groups. The ratio of body weight to body length remained adequate throughout the experimental period. However, groups that received 3:1 and 2:1 showed increased weight and progressive decreases in energy expenditure, body fat composition, and serum level of leptin, but the ratio of insulin-like growth factor-1 to body length was not affected.. Dietary substitution of fat with carbohydrates contributes to weight gain by decreasing energy expenditure and possibly by decreasing leptin secretion.

Topics: Animals; Body Composition; Diet, Fat-Restricted; Dietary Carbohydrates; Dietary Fats; Energy Intake; Energy Metabolism; Leptin; Male; Oxygen Consumption; Rats; Rats, Wistar; Weight Gain

Low birth weight (LBW) as a result of restricted fetal growth increases the risk for later metabolic diseases and adiposity. However the relationship between LBW and postnatal growth and adult body composition has not been fully investigated. We have used sheep to determine the effects of LBW on postnatal growth and body composition at maturity. LBW was induced by twinning and placental embolization. At birth, LBW lambs were 38% lighter than controls (2.8 +/- 0.2 vs 4.4 +/- 0.3 kg, P<0.05), but had caught up in bodyweight by 8 weeks after birth. At approximately 2.3 years, bodyweights were not different between groups, but there were reductions in absolute (-8%) and relative (-17%) brain weights of LBW sheep (P<0.05) compared to controls. X-ray absorptiometry showed that the mature LBW sheep, compared to controls, had greater amounts of lean muscle (38.1 +/- 1.3 vs 35.3 +/- 0.5 kg, P<0.05) and tended to have more body fat (12.2 +/- 1.2 vs 9.6 +/- 0.9 kg; P=0.1); at autopsy abdominal fat mass was greater in LBW sheep (3.06 +/- 0.26 vs 2.20 +/- 0.25 kg, P<0.05). Plasma leptin concentrations were not different between groups. We conclude that, in sheep, LBW is associated with early postnatal catch-up in body weight, but body composition is permanently altered such that, relative to controls, adiposity is increased and brain weight is decreased.

Topics: Absorptiometry, Photon; Adipose Tissue; Animals; Birth Weight; Body Composition; Body Constitution; Body Weight; Brain; Leptin; Organ Size; Sheep; Time Factors; Weight Gain

This study was designed to investigate the longitudinal and dynamic profile of leptin and its relationship with sex hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and testosterone (TTE) in neonatal 'minipuberty'. We also investigated the effects of leptin in the regulation of body weight gain and body mass index (BMI) in the first 3 months of life.. A longitudinal study was carried out in a cohort of 15 male and 15 female term infants during the first 3 months of life. Blood samples were collected in the morning from the infants on the 3rd, 15th, 30th, and 90th days of life. At each sample collection, anthropometric measurements were recorded. Serum leptin, LH, FSH, E2 (girls only) and TTE (boys only) concentrations were analyzed using standard biochemical methods. Association of leptin with weight gain, BMI, and these hormones during infancy was evaluated.. Leptin levels increased significantly between the 3rd and 90th days of life in both boys and girls. BMI of both groups increased significantly from the 3rd to the 90th day. There was no significant difference in the leptin levels and leptin/BMI ratios of the two sexes at different time points. Leptin levels on the 30th and 90th days correlated significantly with BMI in both sexes. LH and FSH levels in both groups were found to be significantly higher on the 15th day of life. No correlation was observed between leptin and LH, FSH, E2 or TTE levels throughout the study.. Leptin levels do not differ between the two sexes during early infancy and possibly there is no role for leptin in the surge of gonadotropins or sex steroids in neonatal minipuberty. The relationship between leptin and BMI could not be seen in the first postnatal days and the transient lack of the regulatory effect of BMI on leptin concentrations might reflect an adaptive resistance in the production of leptin to support catch-up growth after initial physiological weight loss in newborns.

Topics: Anthropometry; Body Mass Index; Estradiol; Female; Gonadotropins; Humans; Infant; Infant, Newborn; Leptin; Longitudinal Studies; Male; Reference Values; Sex Characteristics; Testosterone; Weight Gain

Islet amyloid polypeptide (IAPP) reduces food intake and body weight in laboratory animals. In addition, IAPP appears to regulate nutrient metabolism. In the present studies, we investigated the effect of chronic IAPP treatment on different aspects of energy homeostasis.. IAPP was infused (25 pmol/kg/min) from subcutaneous osmotic pumps for 2-7 days. Rats in 2 saline-infused control groups were fed ad libitum (AF) or pair-fed (PF) against the IAPP-treated rats.. As expected, the IAPP infusion reduced food intake and body weight gain. In addition, the IAPP treatment decreased the epididymal fat pad (vs. PF rats, p < 0.05) and lowered circulating levels of triglycerides (vs. PF rats, p < 0.05), free fatty acids (vs. PF rats, p < 0.05), leptin (vs. both AF and PF rats, p < 0.05) and insulin (vs. AF rats, p < 0.05). In contrast, glucose and protein metabolism in the IAPP-treated rats was largely unchanged, as shown in results regarding serum glucose, glucose transport in skeletal muscle, blood urea nitrogen, and glycogen and protein content in the liver and in skeletal muscle.. In summary, chronic IAPP exposure led to a changed lipid metabolism, which was characterized by decreased adiposity, hypolipidemia and hypoleptinemia, and to unchanged glucose and protein homeostasis. These results were similar to those seen in rodents during chronic exposure to another satiety/adiposity regulator, leptin. In conclusion, chronically administered IAPP plays a role as a satiety and adiposity signal in rats, and helps regulate energy homeostasis.

Topics: Adipose Tissue; Amyloid; Animals; Feeding Behavior; Gene Expression; Homeostasis; Insulin; Ion Channels; Islet Amyloid Polypeptide; Leptin; Membrane Transport Proteins; Mitochondrial Proteins; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Rats, Wistar; Uncoupling Protein 2; Weight Gain

Some novel antipsychotics, including olanzapine, induce weight gain and metabolic abnormalities, which represent the major adverse effects of these drugs. However, the mechanism(s) involved in such effects are unclear.. The aim of this study was to develop, in female rats, a parametric model of olanzapine-induced weight gain and metabolic abnormalities and evaluate it against clinical findings.. Female rats were administered olanzapine b.i.d. at doses of 0, 1, 2 and 4 mg/kg over 20 days, and a wide range of variables were recorded during and after drug administration.. Olanzapine increased both 24 h and total food intake. This was associated with rapid onset weight gain and increased adiposity (assessed by visceral fat pad masses). Insulin, but not glucose, concentrations were elevated, with a significant increase in the HOMA-IR index, indicative of insulin resistance. A nonsignificant trend towards higher levels of leptin was observed. Paradoxically, there was a significant increase in adiponectin. All of these variables showed maximal increases at either 1 or 2 mg/kg and attenuated effects at 4 mg/kg. Prolactin levels were also increased by olanzapine. However, for this variable, there was a clear dose-response curve, with the maximal effect at the highest dose (4 mg/kg).. These data suggest that aspects of olanzapine-induced weight gain and metabolic abnormalities can possibly be modelled in female rats. It is suggested that olanzapine-induced hyperphagia acts as an initial stimulus which leads to weight gain, enhanced visceral adiposity and subsequent insulin resistance, although the latter may be ameliorated by compensatory responses in adiponectin levels. Prolactin elevation appears likely not to be involved in the weight gain, adiposity and metabolic changes seen in this model.

Topics: Adipose Tissue; Animals; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Drinking; Eating; Estradiol; Female; Homeostasis; Hyperinsulinism; Insulin Resistance; Leptin; Metabolic Diseases; Olanzapine; Prolactin; Rats; Rats, Wistar; Statistics as Topic; Weight Gain

In mice, body weight is regulated by adipocyte-derived leptin. TNFalpha is a critical mediator of inflammation-induced cachexia in Crohn's disease (CD). The regulation of leptin by TNFalpha is poorly understood in CD. Pharmacological neutralization of TNFalpha with infliximab offers a unique opportunity to study TNFalpha-mediated regulation of leptin in CD patients.. We prospectively followed up CD patients treated with infliximab (n = 20). Body composition was assessed before and after treatment at 1 and 4 wk. Serum leptin, IL-6, soluble TNF receptor type II, and soluble intercellular antiadhesion molecule-1 levels were measured as well as cholesterol levels and free urinary cortisol. Because methylprednisolone (MP) increases leptin production in vivo, CD patients treated with MP (n = 9) were studied separately as a positive control group.. Infliximab induced clinical remission and a significant decrease in C-reactive protein (P < 0.01) and IL-6 (P < 0.05) levels in all CD patients and increased body weight (P = 0.013) at 4 wk. Leptinemia was significantly increased after infliximab administration at 1 wk (P = 0.014) and 4 wk (P < 0.001). This increase in serum leptin occurred early at 1 wk, when no significant weight and fat mass changes could be observed and was associated with the down-regulation of TNFalpha-regulated mediators, soluble TNF receptor type II (P = 0.015), and soluble intercellular antiadhesion molecule-1 (P = 0.007). Moreover, infliximab increased cholesterol levels at 1 wk (P = 0.001). Twenty-four-hour cortisol secretion was not altered by infliximab. Leptinemia increased at 1 wk after MP administration (P = 0.028).. Infliximab increases leptinemia in CD. This study suggests that TNFalpha exerts major inhibitory actions on leptin production in CD patients.

Topics: Adult; Antibodies, Monoclonal; Biomarkers; Body Mass Index; Crohn Disease; Female; Humans; Infliximab; Interleukin-6; Leptin; Male; Receptors, Leptin; Receptors, Tumor Necrosis Factor, Type II; Regression Analysis; Tumor Necrosis Factor-alpha; Weight Gain

To examine the determinants of adiponectin levels (i) in 23 women with anorexia nervosa (mean BMI 15.0 +/- 1.2) and 43 healthy normal weight females (mean BMI 22.3 +/- 2.3; cross-sectional design) as well as (ii) after six and twelve weeks of weight gain in subgroups of 18 and 11 anorectic patients (mean weight gain 5.8 kg; longitudinal design). Plasma adiponectin and leptin concentrations were measured and their relationships to body composition (fat mass by bioelectrical impedance analysis and anthropometrics), different hormones and metabolic parameters (insulin, ACTH, cortisol, glucose, FFA, lipid profile) were investigated.. In anorectic patients, adiponectin levels were higher (+29 %) and leptin levels were lower (-75 %) than in control subjects. There was a high variance in adiponectin levels in patients ranging from 2.6 to 18 nM. Combining patients and controls, an inverse linear correlation was observed between adiponectin levels and fat mass (r = -0.36, p < 0.05), while a positive exponential relation was found between leptin levels and fat mass (r = 0.82, p < 0.001). In anorectic patients, there were no significant correlations between adiponectin and hormonal or metabolic parameters. Weight gain resulted in increasing leptin (+0.17 +/- 0.12 nM; p < 0.001) and a nonsignificant decrease in adiponectin concentrations (-1.12 +/- 2.51 nM). Changes in leptin levels were mainly explained by a gain in fat mass (r = 0.85, p < 0.001). In contrast, changes in adiponectin levels were closely linked to initial adiponectin levels (r = -0.84, p < 0.001) but not to changes in fat mass or BMI.. Cross-sectionally serum adiponectin concentration followed a linear inverse function with fat mass when patients and controls were combined. Longitudinally gain in fat mass was not associated with changes in adiponectin levels suggesting other yet unidentified influences on adiponectin secretion in anorexia nervosa.

Topics: Adiponectin; Adipose Tissue; Anorexia Nervosa; Anthropometry; Body Composition; Case-Control Studies; Cross-Sectional Studies; Electric Impedance; Female; Hormones; Humans; Leptin; Longitudinal Studies; Weight Gain

Previous research indicates that the neonatal pig does not alter feed intake in response to changes in the energy density of manufactured liquid diets. Also, the limited response of IGF-I to exogenous porcine ST (pST) previously observed in young pigs may be influenced by the source of dietary energy. Our objectives were to 1) determine the effect of a high-fat (HF; 25% fat and 4,639 kcal/kg ME; DM basis) or low-fat (LF; 2% fat and 3,481 kcal/kg ME; DM basis) manufactured liquid diet on pig performance; and 2) determine whether the limited response to exogenous pST in young pigs depends on the source of dietary energy. Two replicates of 60 pigs (n = 120; barrows and gilts distributed evenly), with an initial BW of 4,207 +/- 51 g, were weaned from the sow at 10 d of age and used in a randomized complete block design. Pigs were assigned by BW to one of six pens. Diets were formulated to provide a constant lysine:ME ratio and were fed on a pen basis for a duration of 9 d. On d 5, barrows and gilts within a pen were assigned randomly to receive either 0 or 120 microg of pST.kg BW(-1).d(-1) for 4 d. Pigs gained 336 +/- 9 g/d, which resulted in an ending BW of 7,228 +/- 120 g, regardless of dietary treatment (P > 0.15). Pigs fed the LF diet consumed 17% more DM per pen daily than pigs fed the HF diet (2,777 +/- 67 vs. 2,376 +/- 67 g/d, P < 0.01), but calculated ME intake did not differ between dietary treatments (P > 0.20). The G:F was 24% greater in HF- than in LF-fed pigs (P < 0.01). Plasma urea N concentrations were higher in the HF-fed pigs (11.0 +/- 0.6 mg/dL) than in pigs fed the LF diet (6.2 +/- 0.6 mg/dL; P < 0.05). Treatment with pST increased circulating IGF-I (P < 0.01) and decreased PUN (P < 0.01) concentration 32 and 25%, respectively, regardless of dietary treatment (P > 0.30). Circulating leptin averaged 1.8 +/- 0.1 ng/mL and was not affected by dietary treatment (P > 0.35) or pST (P > 0.40). These results suggest that the ST/IGF axis is responsive in the young pig and the increase in circulating IGF-I and growth is independent of the source of dietary energy. Also, young pigs respond to a lower energy density liquid diet with increased feed intake, without altering growth performance, apparently utilizing a mechanism other than circulating leptin.

Topics: Animal Feed; Animals; Blood Urea Nitrogen; Diet; Dietary Fats; Female; Growth Hormone; Insulin-Like Growth Factor I; Leptin; Male; Random Allocation; Swine; Time Factors; Weaning; Weight Gain

The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus. We found that homozygous Clock mutant mice have a greatly attenuated diurnal feeding rhythm, are hyperphagic and obese, and develop a metabolic syndrome of hyperleptinemia, hyperlipidemia, hepatic steatosis, hyperglycemia, and hypoinsulinemia. Expression of transcripts encoding selected hypothalamic peptides associated with energy balance was attenuated in the Clock mutant mice. These results suggest that the circadian clock gene network plays an important role in mammalian energy balance.

Topics: Adipocytes; Animals; Body Weight; Brain; Circadian Rhythm; CLOCK Proteins; Dietary Fats; Energy Intake; Energy Metabolism; Feeding Behavior; Hepatocytes; Hyperglycemia; Hyperlipidemias; Insulin; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Motor Activity; Mutation; Neuropeptides; Obesity; Trans-Activators; Weight Gain

Topics: Alleles; Antipsychotic Agents; Humans; Leptin; Obesity; Pharmacogenetics; Receptor, Serotonin, 5-HT2C; Risk Factors; Weight Gain

Weight gain, leading to further morbidity and poor treatment adherence, is a common consequence of treatment with antipsychotic drugs. Two recent studies in the same cohort of Chinese Han subjects have shown that polymorphisms of the promoter regions of both the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor and the leptin genes, are associated with antipsychotic-induced weight gain over 10 weeks. We have investigated whether these effects remain true in a Caucasian population and following longer term treatment.. Seventy-three Spanish caucasian patients with a first-episode psychosis and initially drug-naive were genotyped for the 5-HT2C receptor -759C/T and leptin -2548A/G polymorphisms. Body mass index and plasma leptin levels were monitored after 6 weeks, 3 months and 9 months of antipsychotic treatment.. Patients with the -759T variant allele showed significantly less weight gain than those without this allele. This effect held true in the smaller group of patients receiving olanzapine. The -2548 leptin polymorphism was not associated with short-term (6 week and 3 month) weight increases but did show significant association with 9-month antipsychotic-induced weight gain. The 5-HT2C -759 genotype was significantly associated with pre-treatment plasma leptin levels.. These findings confirm the importance of two genetic factors associated with long-term antipsychotic-induced weight increases in schizophrenia, and implicate a role for leptin in the 5-HT receptor-mediated weight regulation.

Topics: Adult; Affective Disorders, Psychotic; Alleles; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Female; Genetic Variation; Genotype; Humans; Leptin; Male; Models, Genetic; Olanzapine; Pharmacogenetics; Polymorphism, Genetic; Promoter Regions, Genetic; Receptor, Serotonin, 5-HT2C; Receptors, Leptin; Schizophrenia; Time Factors; Weight Gain

Leptin resistance is generally considered a consequence of obesity. We postulated that leptin resistance is associated with diminished hypothalamic leptin signalling capacity and that leptin resistance is causal to obesity. We assessed maximal leptin-mediated binding of the transcription factor signal transducer and activator of transcription 3 (STAT3), and the response to high-fat feeding in lean leptin-resistant rats.. Recombinant adeno-associated virus encoding rat leptin cDNA (rAAV-leptin) or control vector were administered by intracerebroventricular injection to lean F344 x BN rats for up to 150 days, and food consumption, body weight, serum leptin and glucose tolerance were measured. Leptin-mediated hypothalamic transcription factor binding was assessed at day 150 following an intracerebroventricular injection of 2 mug leptin. Rats pretreated with either control or rAAV-leptin vector for 94 days were given a high-fat diet, and energy intake, body weight gain and adiposity were examined.. The rAAV-leptin-treated rats initially responded to leptin gene delivery then became leptin-resistant. They displayed persistent submaximal hypothalamic leptin signalling and enhanced insulin sensitivity, yet maximal hypothalamic signalling capacity was decreased by more than 50%. On a high-fat diet, the leptin-resistant rats consumed more energy, gained more weight and accumulated greater visceral fat mass than controls.. The maximal hypothalamic leptin signalling capacity was diminished in leptin-resistant rats receiving central rAAV-leptin gene therapy. Moreover, this leptin-invoked leptin resistance perturbs the regulation of energy homeostasis in response to high fat exposure, producing augmented energy consumption. This, coupled with potential hypersensitivity to insulin, creates a milieu favouring fat deposition. Our data suggest that leptin resistance is both a consequence and cause of obesity.

Topics: Animals; Body Weight; Diet; DNA, Complementary; Feeding Behavior; Glucose Tolerance Test; Injections, Intraventricular; Insulin; Leptin; Male; Obesity; Rats; Rats, Inbred BN; Rats, Inbred F344; Signal Transduction; Weight Gain

Topics: Adipose Tissue; Adult; Antipsychotic Agents; Body Mass Index; Cholesterol; Female; Humans; Insulin; Leptin; Male; Schizophrenia; Weight Gain

The efficacy of central leptin therapy on weight homeostasis through various phases of reproduction, pregnancy outcome and postnatal, prepubertal and pubertal growth of offspring was assessed. Enhanced leptin transgene expression after a single intracerebroventricular injection of recombinant adeno-associated virus vector encoding the leptin gene (rAAV-lep) decreased calorie intake and weight in adult nulliparous female rats. rAAV-lep treated rats conceived normally, displayed unremarkable pregnancy rate, parturition and delivered normal sized litters. Significantly lower weight was maintained through gestation, lactation, and post-lactation periods. The maintenance of a modest weight reduction was accompanied by voluntarily reduced calorie intake, increased thermogenic energy expenditure, decreased adiposity as reflected by drastically reduced leptin levels, and suppressed insulin and insulin-like growth factor 1 levels through lactation and post-lactation in rAAV-lep treated dams. The offspring at birth weighed significantly less than those of controls and this lower weight range was sustained during postnatal, prepubertal, pubertal and adult (3 months old) periods, contemporaneous with metabolic circulating hormones in the normal range. For the first time we show the persistent efficacy of central leptin gene therapy to suppress weight gain through all phases of reproduction, lactation and post-lactation in dams and reveal the potential imprinting link to producing lower weight in the F1 generation.

Topics: Adipose Tissue; Animals; Appetite Regulation; Body Weight; Eating; Female; Gene Expression; Genetic Therapy; Hypothalamus; Insulin; Insulin-Like Growth Factor I; Lactation; Leptin; Male; Obesity; Pregnancy; Rats; Rats, Sprague-Dawley; RNA, Messenger; Weight Gain

The potential management benefits of in vitro embryo production have been offset by an increased incidence of health-related problems in resulting calves [increased birth weight, congenital abnormalities, and peri- and postnatal mortality (large-offspring syndrome)] and of recipient cows (prolonged gestation, dystocia, increased hydroallantois, abortion). The aim of the present research was to determine whether relevant metabolic, endocrine, or hematological traits could be related to the causes of enhanced growth performance of in vitro fertilized calves. Growth performance and feed efficiency as well as hematological, metabolic, and endocrine traits studied in calves derived from in vitro-produced embryos (IVP; n = 11) and in calves derived from artificial insemination (AI; n = 8). Donor cows from which oocytes for in vitro fertilization were obtained had a heterogeneous background, thus excluding genetic maternal influences. On the other hand, semen for in vitro fertilization and for artificial insemination was from the same bull, and recipient cows were held under the same husbandry and feeding conditions as AI cows, thus reducing the variability. Blood samples were collected preprandially on d 1, 2, 3, 4, 7, 14, 28, 56, and 112 of life and every 20 min between 0830 and 1630 h on d 7 and 112 for the evaluation of growth hormone secretory patterns. Gestation of IVP cows was longer than that of AI cows, but birth weights were similar in both groups. Feed intake, average daily gain, and body length during the experimental period, body weight from wk 8 to 16, and gain/feed ratio during the first month of life were higher in IVP than in AI calves. At birth, potassium, 3,5,3'-triiodothyronine, and thyroxine concentrations were lower in IVP than in AI calves. Concentrations of sodium and potassium on d 7, of triglycerides on d 28, and of albumin on d 56 were higher in IVP than in AI calves. In conclusion, IVP calves had higher feed intake and growth rate during the entire growth period and improved feed efficiency in the first month of life than AI calves, but this was not mirrored by consistent changes of hematological, metabolic, or endocrine traits, whose concentrations were in the normal range. Additional work is needed to study IVP calves under field conditions.

Topics: Animals; Animals, Newborn; Blood Gas Analysis; Blood Glucose; Blood Proteins; Cattle; Colostrum; Eating; Electrolytes; Erythrocyte Count; Female; Fertilization in Vitro; Growth Hormone; Health Status; Hematocrit; Hormones; Insemination, Artificial; Insulin-Like Growth Factor II; Leptin; Leukocyte Count; Lipids; Male; Potassium; Serum Albumin, Bovine; Thyroxine; Triiodothyronine; Weight Gain

Palatable food is rich in fat and/or sucrose. In this study we examined the long-term effects of such diets on food intake, body weight, adiposity and circulating levels of the satiety peptide leptin and the hunger peptide ghrelin. The experiments involved rats and mice and lasted 5 weeks. In rats, we examined the effect of diets rich in fat and/or sucrose and in mice the effect of a high fat diet with or without sucrose in the drinking water. Animals fed with the palatable diets had a larger intake of calories, gained more weight and became more adipose than animals fed standard rat chow. Fasted animals are known to have low serum leptin and high serum ghrelin and to display elevated serum leptin and lowered serum ghrelin postprandially. With time, a sucrose-rich diet was found to raise the fasting level of leptin and to lower the fasting level of ghrelin in rats. A fat-rich diet suppressed serum ghrelin without affecting serum leptin; high sucrose and high fat in combination greatly reduced serum ghrelin and raised serum leptin in the fasted state. The mRNA expression of leptin in the rat stomach was up-regulated by sucrose-rich (but not by fat-rich) diets, whereas the expression of ghrelin seemed not to be affected by the palatable diets. Mice responded to sucrose in the drinking water with elevated serum leptin (fasted state) and to all palatable diets with low serum ghrelin. The expression of both leptin and ghrelin mRNA in the stomach was suppressed in fasted mice that had received a high fat diet for 5 weeks. We conclude that the expression of leptin mRNA in stomach and the concentration of leptin in serum were elevated in response to sucrose-rich rather than fat-rich diets, linking leptin with sucrose metabolism. In contrast, the expression of ghrelin and the serum ghrelin concentration were suppressed by all palatable diets, sucrose and fat alike. In view of the increased body weight and adiposity neither elevated leptin nor suppressed ghrelin were able to control/restrain the overeating that is associated with palatable diets.

Topics: Adipose Tissue; Animals; Dietary Carbohydrates; Dietary Fats; Eating; Fasting; Female; Ghrelin; Hyperphagia; Leptin; Mice; Peptide Hormones; Rats; Rats, Sprague-Dawley; RNA, Messenger; Stomach; Weight Gain

To identify early molecular changes in weight gain, using analysis of gene expression changes in adipose tissue of mice fed well-defined humanized (Western) high-fat and low-fat (control) diets during a short (3- to 5-week) time interval.. An adipose-enriched cDNA microarray was constructed and used for the expression analyses of visceral adipose tissues of wildtype young adult C57BL/6J male mice on different diets.. Mice on a high-fat diet had significantly higher body weight (at most, 9.6% greater) and adipose tissue weights compared with mice on a control diet. Gene expression analyses revealed 31 transcripts significantly differentially expressed in visceral adipose tissue between the diet groups. Most of these genes were expressed more on the high-fat diet. They mainly encode proteins involved in cellular structure (e.g., myosin, procollagen, vimentin) and lipid metabolism (e.g., leptin, lipoprotein lipase, carbonic anhydrase 3). This increase in gene expression was accompanied by a decrease in oxidative phosphorylation and carbohydrate metabolism (ATP citrate lyase). Importantly, genes belonging to steroid hormone biosynthesis (3beta-hydroxysteroid dehydrogenase-1, cholesterol side-chain cleavage cytochrome P450, and steroid-11beta-hydroxylase) were all expressed less in mice on a high-fat diet.. A short time period of 3 to 5 weeks of high-fat feeding altered gene expression patterns in visceral adipose tissue in male mice. Gene expression changes indicate initiation of adipose tissue enlargement and the down-regulation of adipose steroid hormone biosynthesis. The latter suggests a mechanism by which initial progression toward weight gain is counteracted.

Topics: Adipose Tissue; Animals; Corticosterone; Dietary Fats; Gene Expression Regulation; Hormones; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Organ Size; Random Allocation; RNA; Steroids; Weight Gain

Reproductive activity of Mongolian gerbils is regulated by photoperiod nevertheless body weight regulation is controlled without ambient photoperiod. Food intake is a major factor affecting rodent reproductive efficiency. Leptin is a hormone secreted by adipose tissue and modulates food intake, energy expenditure and body fat stores. In this study we studied the interaction of photoperiod and food availability on growth, sexual maturation and leptin concentration in the male and female gerbils. Gerbils were gestated and reared in either 14L:10D or 2L:22D. At weaning, gerbils were housed individually and divided into three groups: fed ad libitum, fed 80% of ad libitum or fed 60% of ad libitum. Body weights were recorded at weaning and every week thereafter. After twelve weeks of treatment, animals were sacrificed and testes and uterine weights were determined and blood was collected for leptin measurement. Food restriction reduced body weight and inhibited reproductive development. Absolute paired testis weights were similar in ad lib and 80% of ad lib groups but significantly different compared with the 60% of ad lib group in both photoperiods. Body weights were also directly dependent upon the level of food restriction. Uterine mass was only affected in the 60% of ad lib group in 14L but both food restriction levels significantly affected the uterine weights in 2L. Significant variations were found in leptin profiles. Leptin concentration was highest in ad lib and 80% of ad lib groups and lowest in 60% of ad lib groups. These results suggest that the reproductive activity of Mongolian gerbils is sensitive to food intake and multiple potential environmental cues (e.g., food availability, temperature) can be utilized.

Topics: Animals; Circadian Rhythm; Feeding Behavior; Female; Food Supply; Gerbillinae; Leptin; Male; Photoperiod; Sexual Maturation; Weight Gain

An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity and insulin resistance. Although the mechanisms are unclear, this programming has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet. Reduced locomotor activity and hyperphagia contribute to the increased fat mass. Using this model of maternal undernutrition, we investigated the effects of neonatal leptin treatment on the metabolic phenotype of adult female offspring. Leptin treatment (rec-rat leptin, 2.5 microg/g.d, sc) from postnatal d 3-13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring, and normalized caloric intake, locomotor activity, body weight, fat mass, and fasting plasma glucose, insulin, and leptin concentrations in programmed offspring in adult life in contrast to saline-treated offspring of undernourished mothers who developed all these features on a high-fat diet. Neonatal leptin had no demonstrable effects on the adult offspring of normally fed mothers. This study suggests that developmental metabolic programming is potentially reversible by an intervention late in the phase of developmental plasticity. The complete normalization of the programmed phenotype by neonatal leptin treatment implies that leptin has effects that reverse the prenatal adaptations resulting from relative fetal undernutrition.

Topics: Absorptiometry, Photon; Adipose Tissue; Aging; Animals; Animals, Newborn; Disease Models, Animal; Female; Insulin; Leptin; Malnutrition; Obesity; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Weight Gain

The purpose of this study was to test whether the melanocortin-4 receptor (MC4R) is critical in the development of hypertension associated with obesity and its metabolic disorders. MC4R-deficient homozygous (-/-) and heterozygous (+/-) and wild-type (WT) C57BL/6J mice 17 to 19 weeks old (n=5 to 7 per group) were implanted with telemetry devices for monitoring 24-hour mean arterial pressure (MAP) and heart rate (HR). After 3-day stable control measurements on normal-salt diet (NSD; 0.4% NaCl), mice received a high-salt diet (HSD; 4% NaCl) for 7 days, followed by 3-day recovery on NSD. MC4R (-/-) mice were severely obese compared with MC4R (+/-) and WT mice (body weight 48+/-1.5 versus 31+/-0.6 and 30+/-0.5 g respectively). On NSD, MAP was similar in all groups of mice (MC4R (-/-) 110+/-3 mm Hg; MC4R (+/-) 109+/-2 mm Hg; WT 114+/-2 mm Hg), and HR in MC4R (-/-) was lower than in WT (604+/-5 versus 645+/-9 bpm; P<0.05) but not different from MC4R (+/-) (625+/-13 bpm) mice. HSD did not significantly alter MAP or HR in any of the groups. Epididymal and retroperitoneal fat weights and plasma leptin levels were several-fold greater in MC4R (-/-) compared with MC4R (+/-) and WT mice. Plasma insulin and glucose levels were also significantly greater in MC4R (-/-) than in MC4R (+/-) and WT mice. These data suggest that despite obesity, visceral adiposity, hyperleptinemia, and hyperinsulinemia, MC4R (-/-) mice are neither hypertensive nor salt sensitive, indicating that a functional MC4R may be necessary for the development of hypertension associated with obesity and its metabolic abnormalities.

Topics: Adipose Tissue; Animals; Blood Pressure; Body Size; Dose-Response Relationship, Drug; Drinking; Eating; Heart Rate; Hormones; Hyperinsulinism; Hypertension; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Receptor, Melanocortin, Type 4; Sodium Chloride; Sodium Chloride, Dietary; Viscera; Weight Gain

The large amount of absorbed dietary lipid after feeding a high-fat diet is mainly transported as triacylglycerol (TG)-rich lipoproteins (TRL) in the post-prandial blood and is subsequently distributed to peripheral tissues including adipose and muscle tissues. An in vivo and an in vitro study were conducted to investigate the possible role of post-prandial TRL after high fat feeding in the regulation of obese (ob) gene expression. Adult male Wistar rats were fasted for 48 h and re-fed either a fat-free/high-carbohydrate diet or a high-fat diet for 2, 4, or 8 h and plasma glucose, insulin, TG, and leptin as well as ob mRNA expression in epididymal fat pads were examined. Rats re-fed the high-fat diet had significantly higher plasma TG (p < 0.05) and lower plasma leptin and adipose ob mRNA (p < 0.05) than those fed the fat-free/high-carbohydrate diet; however, plasma glucose and insulin concentrations were not significantly different between the two groups. Plasma lipid analysis found large amount of TRL in rats fed with high-fat diet; however, only very small amount of the TRL was found in rats fed with fat-free/high-carbohydrate diet. We speculated that TRL might involve in regulation of ob gene expression. To further examine the regulation of TRL on ob mRNA expression, differentiated 3T3-L1 adipocytes were treated with TRL collected from rats fed 5 ml soybean oil by gastric intubations. TRL down-regulated ob mRNA not only in a dose and time dependent manner but also in the presence of insulin in 3T3-L1 adipocytes. These results suggest a possible role of TRL in the down-regulation of adipose ob mRNA expression and may account, at least in part, for the previous observations that short-term high fat feeding resulted in lower plasma leptin.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue; Animal Feed; Animals; Blood Glucose; Body Composition; Dietary Fats; Down-Regulation; Epididymis; Insulin; Leptin; Lipids; Lipoproteins; Male; Mice; Muscles; Obesity; Postprandial Period; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Triglycerides; Weight Gain

Positive relationships between circulating leptin concentrations and body fat content have been established in sheep when covering a rather broad range of age and/or body weight. The usefulness of leptin measurements for predicting carcass fat has yet to be evaluated specifically in fattening lambs. We therefore measured plasma leptin concentrations in 56 male lambs half and half Merino Mutton and Blackheaded Mutton. Subcutaneous fat thickness was measured by ultrasound 1 day before the lambs were slaughtered at 35 or 45 kg live weight. Carcass composition was determined by tissue dissection. The coefficients of correlations between leptin and the different amounts in fat depots ranged from 0.40 to 0.56 within the two live weight groups, and from 0.53 to 0.64 when taking the two groups together. Carcass fat percentage was estimated by leptin concentrations with the same accuracy (R2 = 0.34) as with ultrasound fat thickness. The accuracy was higher for leptin in the 35 kg-group whereas the accuracy was higher for ultrasound fat thickness in the 45 kg-group (R2 = 0.26 vs. 0.31). A combination of leptin and ultrasound fat thickness clearly enhanced the precision of estimation in all groups. Further investigations on the influence of factors such as breed, gender, duration of feed withdrawal or photoperiod on the association between leptin and carcass composition are necessary before the suitability of plasma leptin concentration for practical application can be evaluated.

Topics: Adipose Tissue; Aging; Animals; Body Composition; Body Weight; Leptin; Male; Predictive Value of Tests; Sensitivity and Specificity; Sheep; Ultrasonography; Weight Gain

We have used milk progesterone analysis to monitor reproductive function in lactating dairy cows and have then related this reproductive function to a variety of metabolic variables. Monitoring of cows (n = 41) during the period of onset of luteal function (first milk progesterone reading>5 ng/ml) revealed that delayed onset was associated with increased milk yield and greater loss of body weight and body condition but was not related to plasma metabolite or leptin concentrations. Further monitoring of reproductive function in these 41 cows and an additional 33 cows (total n = 74) during the mating period (from weeks 6 to 14 post partum) identified reproductive cycle abnormalities in 29 (39.2% of animals). The occurrence of cycle abnormalities was associated with increased milk yield (P < 0.05), elevated plasma beta hydroxybutyrate (P < 0.05) and reduced plasma leptin (P < 0.01) concentrations as well as a lower (P < 0.05) rate of gain of body weight and condition score but was not associated with plasma urea or glucose concentrations. Furthermore, cows exhibiting cycle abnormalities had a longer (P < 0.01) interval to first service and a smaller percentage had conceived by 100 days post partum (34.5% versus 66.7%; P < 0.01). These results provide further evidence that impaired reproductive function during the post partum period in dairy cows is caused by a poor energy status and not elevated urea concentrations. Reduced plasma leptin concentrations in animals suffering reproductive dysfunction further supports this view.

Topics: 3-Hydroxybutyric Acid; Animals; Blood Glucose; Body Composition; Cattle; Female; Lactation; Leptin; Milk; Postpartum Period; Reproduction; Time Factors; Urea; Weight Gain

Topics: Animals; Animals, Newborn; Diet; Genetic Predisposition to Disease; Humans; Leptin; Obesity; Rats; Rats, Wistar; United States; Weight Gain

Dietary factors promote obesity and obesity-related disorders, such as fatty liver disease. Natural killer T (NKT) cells are components of the innate immune system that regulate proinflammatory (Th-1) and anti-inflammatory (Th-2) immune responses. Previously, we noted that NKT cells are selectively reduced in the fatty livers of obese, leptin-deficient ob/ob mice and demonstrated that this promotes proinflammatory polarization of hepatic cytokine production, exacerbating lipopolysaccharide (LPS) liver injury in these animals. In the current study, we show that hepatic NKT cells are also depleted by diets that induce obesity and fatty livers in wild-type mice, promoting Th-1 polarization of hepatic cytokine production and sensitization to LPS liver injury despite persistent leptin. Adult male C57BL6 mice fed diets containing high amounts of either fat or sucrose, or combined high-fat, high-sucrose, develop increased hepatic NKT cell apoptosis and reduced liver NKT cells. The hepatic lymphocytes are more Th-1 polarized with increased intracellular interferon gamma and tumor necrosis factor alpha. Mice fed high-fat diets also exhibit more liver injury, reflected by 2-fold greater serum alanine aminotransferase (ALT) than control animals after receiving LPS. In conclusion, when otherwise normal mice are fed with high-fat or sucrose diet, they become obese, develop fatty livers, and acquire hepatic innate immune system abnormalities, including increased NKT cell apoptosis. The latter reduces liver NKT cell populations and promotes excessive hepatic production of Th-1 cytokines that promote hepatic inflammation. These diet-induced alterations in the hepatic innate immune system may contribute to obesity-related liver disease.

Topics: Animals; Apoptosis; Dietary Fats; Dietary Proteins; Dietary Sucrose; Fatty Liver; Interferon-gamma; Interleukin-12; Killer Cells, Natural; Leptin; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Th1 Cells; Th2 Cells; Weight Gain

Anemia is prevalent among pregnant adolescents, but few data exist on biochemical indicators of iron status in this group. We hypothesized that among an at-risk population of African-American, pregnant adolescents, the degree of iron depletion and deficiency would be marked, and that iron deficiency anemia would comprise the majority of the observed anemia. To examine this, blood samples were collected from 80 girls (< or =18 y old) attending an inner city maternity clinic, 23 of whom were studied longitudinally in the 2nd and 3rd trimesters depending on contact at the clinic. Sample sizes for the biomarkers varied according to the blood volume available at the time the assays were completed. Descriptive statistics were applied to characterize iron status, and multivariate regression and logistic analyses were used to identify significant determinants of iron status. Depleted iron stores (ferritin < or = 15 microg/L) were indicated for 25% (n = 44) and 61% (n = 59) of adolescents during the 2nd and 3rd trimesters, respectively. Serum folate (39.3 +/- 15.4 nmol/L, n = 60), RBC folate (2378 +/- 971 nmol/L, n = 60), and serum vitamin B-12 concentrations (313 +/- 163 pmol/L, n = 60) were within normal ranges. Adolescents with serum transferrin receptor:serum ferritin ratios (R:F ratio) > 300 during the 2nd trimester were 12.5 times (95% CI 2.83, 55.25) more likely to be classified with iron deficiency anemia during the 3rd trimester (P = 0.0002) than those with lower ratios. Estimates of body iron were lower in those tested after wk 26 of gestation (P < 0.0001), and reserves were depleted in 5.0% vs. 31.3% of the 2nd (n = 40) and 3rd (n = 48) trimester cohorts, respectively. In conclusion, iron-deficiency anemia was prevalent among these pregnant minority adolescents. Targeted screening and interventions to improve diet and compliance with prenatal iron supplementation are warranted for this at-risk group.

Topics: Adolescent; Anemia, Iron-Deficiency; Birth Weight; Black or African American; Body Mass Index; Erythropoietin; Female; Ferritins; Folic Acid; Gestational Age; Hemoglobins; Humans; Iron; Iron Deficiencies; Leptin; Pregnancy; Pregnancy Complications; Pregnancy in Adolescence; Regression Analysis; Transferrin; Vitamin B 12; Weight Gain

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

The expression of 76 sequences, previously isolated as differentially expressed in visceral white adipose tissue (WAT) of female rats, fed with a high-fat diet for 11 days (Lopez et al., Biochem Biophys Res Comm 318: 234-239, 2004), was analyzed in epidydimal WAT of male rats after a feeding period of 65 days with the same diet, using microarray technology. After Northern blot validation of the results, only three genes appeared upregulated (caveolin-2, the alpha-1 chain of haemoglobin and rat mammary tumor-7) and two downregulated (adiponectin and dystroglycan). We have also analyzed caveolin-1 gene expression and found that follows the opposite pattern of caveolin-2, indicating that they are inversely regulated. Our results suggest that if feeding with a high-fat diet is prolonged, many of the initial changes in gene expression, probably aimed to consume the energy surplus and prevent excessive fat deposition, are not maintained, and adaptation to an increased lipid storage is developed.

Topics: Adiponectin; Adipose Tissue; Animals; Caveolin 2; Dietary Fats; Down-Regulation; Dystroglycans; Epididymis; Gene Expression Regulation; Glycated Hemoglobin; Leptin; Male; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis; Protein Biosynthesis; Proteins; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Up-Regulation; Weight Gain

The interaction of dietary protein type and fat level on the body fat-reducing activity of conjugated linoleic acid (CLA) was studied in male rats fed diets containing casein (CAS) or soy protein (SOY) as a protein source with low fat (LF, 6.0% soybean oil) or high fat (HF, 13.0% soybean oil) combinations for 4 weeks. CLA was added at the 1.0% level to all diets. The weight of perirenal adipose tissue tended to be lower in the SOY groups than in the corresponding CAS groups, and the difference between the LF diets was significant. The weight of epididymal adipose tissue showed a similar but insignificant trend. The weight of brown adipose tissue was heaviest on the SOY-HF diet and lowest on two CAS diets, the SOY-LF diet being intermediate. The concentration of serum leptin was lowest on the SOY-LF diet and was significantly lower than that of the corresponding CAS group, but this difference disappeared when the dietary fat level increased. The serum cholesterol-lowering activity of SOY in relation to CAS was reproduced even when CLA was given. Thus the body fat-reducing activity of CLA was most marked when rats were fed the SOY-LF diet. Although the CAS-HF diet increased body fat deposition, the magnitude of the reduction by lowering dietary fat level was more marked than in the case of SOY. These results indicate a complicated interaction of dietary manipulations with the body fat-reducing effect of CLA, but the combination of CLA with the SOY-LF diet appears to be an appropriate approach.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Body Weight; Caseins; Cytokines; Diet; Dietary Fats; Dietary Proteins; Epididymis; Fatty Acids; Leptin; Linoleic Acid; Lipid Metabolism; Lipids; Liver; Male; Organ Size; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Soybean Proteins; Weight Gain

Leptin is thought to be related to vegetative symptoms of depression such as alterations in food intake and weight. Fifty-seven drug-free patients and 26 healthy controls were enrolled in this study. We have found that the serum leptin levels were higher in patients with atypical depressive disorder than in controls, but not in patients with non-atypical depressive disorder, however, body mass index, age, and gender were not significantly different between these groups. Probably, these findings seem to be associated with some features of the atypical depressive disorders such as weight gain, a result of hyperphagia.

Topics: Adult; Body Mass Index; Depressive Disorder; Female; Human Growth Hormone; Humans; Hydrocortisone; Insulin; Leptin; Male; Weight Gain

To investigate whether administration of leptin to rats during pregnancy and lactation affects placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) activity and the susceptibility of their offspring to weight gain and insulin resistance.. Pregnant rats fed on a low-protein diet were administered leptin or saline by subcutaneous minipump from day 14 of gestation and throughout lactation. A further group was fed a normal diet and given saline. After weaning, the offspring of each group were fed on a normal diet until 6 weeks of age and then half of each group was transferred to a high-fat diet until 12 months of age.. Plasma leptin levels were raised two-fold on days 16-18 of pregnancy in the leptin-treated dams, but, despite a constant rate of infusion, at parturition they dipped to control levels before rising again. The activity of placental 11beta-HSD2 was reduced by the low-protein diet; this reduction was prevented by treating the dams with leptin. The male offspring of the saline-treated dams gained more weight and had higher plasma leptin levels on the high fat than the chow diet, but the offspring of the leptin-treated dams did not. Fasting blood glucose and intraperitoneal glucose tolerance at 6 and 12 months of age was unaffected by the high-fat diet, but only the offspring of the leptin-treated dams achieved this control without raised insulin levels.. The rate of leptin clearance appears to increase at parturition. The administration of leptin to rats during late pregnancy and lactation makes their male offspring less susceptible to high-fat-diet-induced weight gain and insulin resistance.

Topics: Animals; Birth Weight; Blood Glucose; Diet, Protein-Restricted; Dietary Fats; Female; Insulin Resistance; Lactation; Leptin; Organ Size; Placenta; Pregnancy; Rats; Rats, Wistar; Weight Gain

Obesity is frequently associated with leptin resistance. The present study investigated whether leptin resistance in rats is present before obesity develops, and thus could underlie obesity induced by 16 wk exposure to a liquid, palatable, high-energy diet (HED). Before HED exposure, male Wistar rats (weighing between 330 and 360 g) received intravenous infusions of 20 microg leptin 2 h before dark (approximately 57 microg/kg rat). Relative to saline infusion, this caused a highly variable effect on food intake (ranging between -94 and +129%), with food intake suppression that appeared negatively correlated with HED-induced increases in body weight gain, caloric intake, adiposity, and plasma leptin levels. In contrast, leptin's thermogenic response was positively correlated to body weight gain linked to weights of viscera, but not to adiposity. Before HED exposure, leptin unexpectedly increased food intake in some rats (fi+, n = 8), whereas others displayed the normal reduction in food intake (fi-, n = 7). HED-exposed fi+ rats had higher plasma leptin levels, retroperitoneal fat pad weight, HED intake, and body weight gain than fi- and chow-fed rats. These parameters were also higher in HED-exposed fi-rats relative to chow rats, except for plasma leptin concentrations. It is concluded that leptin's reduced efficacy to suppress food intake could predict obesity on an HED. An unexpected orexigenic effect of leptin might potentially contribute to this as well.

Topics: Animals; Body Temperature; Body Weight; Diet; Dose-Response Relationship, Drug; Eating; Energy Metabolism; Hormones; Injections, Intravenous; Leptin; Male; Nutritional Status; Obesity; Organ Size; Rats; Rats, Wistar; Weight Gain

The effects of running wheel exercise and caloric restriction on the regulation of body weight, adiposity, and hypothalamic neuropeptide expression were compared in diet-induced obese male rats over 6 wk. Compared with sedentary controls, exercising rats had reduced body weight gain (24%), visceral (4 fat pads; 36%) and carcass (leptin; 35%) adiposity but not insulin levels. Hypothalamic arcuate nucleus (ARC) proopiomelanocortin (POMC) mRNA expression was 25% lower, but ARC neuropeptide Y (NPY), agouti- related peptide, dorsomedial nucleus (DMN) NPY, and paraventricular nucleus (PVN) corticotropin- releasing hormone (CRH) expression was comparable to controls. Sedentary rats calorically restricted to 85% of control body weight reduced their visceral adiposity (24%), leptin (64%), and insulin (21%) levels. ARC NPY (23%) and DMN NPY (60%) were increased, while ARC POMC (40%) and PVN CRH (14%) were decreased. Calorically restricted exercising rats an half as much as ad libitum-fed exercising rats and had less visceral obesity than comparably restricted sedentary rats. When sedentary restricted rats were refed after 4 wk, they increased intake and regained the weight gain and adiposity of sedentary controls. While refed exercising rats and sedentary rats ate comparable amounts, refed exercising rats regained weight and adiposity only to the level of ad libitum-fed exercising rats. Thus exercise lowers the defended level of weight gain and adiposity without a compensatory increase in intake and with a very different profile of hypothalamic neuropeptide expression from calorically restricted rats. This may be due to exercise-related factors other than plasma insulin and leptin.

Topics: Adipose Tissue; Agouti-Related Protein; Animals; Autoradiography; Corticotropin-Releasing Hormone; Diet; Energy Intake; Energy Metabolism; Insulin; Leptin; Male; Motor Activity; Neuropeptide Y; Obesity; Peptide Fragments; Physical Exertion; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger; Weight Gain

Weight gain is a common consequence of antipsychotic drug treatment and can lead to further morbidity.. To assess the effects of antipsychotic drug therapy on abdominal fat deposition, on insulin and leptin secretion, and on circulating glucose and lipids.. Abdominal body fat was determined by magnetic resonance imaging in a group of previously untreated patients with schizophrenia, before and after 10 weeks' antipsychotic drug treatment. Body mass and blood concentrations of glucose, insulin, leptin and lipids were also measured.. Significant increases in both subcutaneous and intra-abdominal fat were identified after antipsychotic drug treatment. A three-fold increase in leptin secretion as well as significant increases in levels of circulating lipids and non-fasting glucose were also identified.. Patients first receiving antipsychotic drugs experience substantial deposition of both subcutaneous and intra-abdominal fat, reflecting a loss of the normal inhibitory control of leptin on body mass. Along with fat deposition, the increase in levels of fasting lipids and in non-fasting glucose may provide early signs of drug-induced progression towards the metabolic syndrome.

Topics: Abdomen; Adipose Tissue; Adult; Antipsychotic Agents; Blood Glucose; Body Constitution; Female; Humans; Insulin; Leptin; Magnetic Resonance Imaging; Male; Schizophrenia; Sex Factors; Treatment Outcome; Weight Gain

Topics: Adiponectin; Adult; C-Reactive Protein; Endothelium, Vascular; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Pre-Eclampsia; Pregnancy; Proteins; Weight Gain

The objective of this study was to determine the relationships among plasma concentrations of leptin, insulin, and IGF-I with dynamic changes in body condition scores (BCS) in heifers. Nineteen Zebu-Brown Swiss crossbred heifers, 24 to 30 mo old, weighing 322 +/- 9 kg, and with an initial BCS of 2.6 +/- 0.11 (range = 1 to 9) were used. Heifers were fed 60% of their maintenance requirements until they reached a BCS of < or = 2. Heifers were then maintained at that level for 25 d, after which they were fed to gain 1 kg of body weight daily until a BCS of 6 was reached. Heifers were weighed weekly and BCS was measured every 2 wk. Plasma samples were collected twice weekly, and leptin and insulin were determined by RIA. An immunoradiometric assay was used to measure IGF-I from one sample every 2 wk. Plasma concentrations of leptin were positively correlated during nutritional restriction (NR) and weight gain (WG) periods with BCS (r = 0.47 for NR, and r = 0.83 for WG; P < 0.01) and body weight (r = 0.40 for NR, and r = 0.78 for WG; P < 0.01). Plasma concentrations of leptin decreased during nutritional restriction (P < 0.01) as BCS decreased. During weight gain, leptin concentration increased at BCS 3 and thereafter for each integer change in the BCS. Regression analysis showed that changes in body weight affect leptin concentrations within a given BCS. There was a decrease in IGF-I as BCS declined (P < 0.01). During weight gain, by contrast, IGF-I increased significantly (P < 0.01) with every unit change in body condition up to BCS of 4 and plateaued thereafter. Insulin concentrations did not change during nutritional restriction when BCS decreased from 3 to 1. However, once the diet was improved, there was a large increase in insulin concentrations in heifers with BCS 1 (P < 0.01). Among heifers of BCS 2 and 3, insulin did not differ and was lower than in heifers of BCS 1 (P < 0.01). Insulin increased (P < 0.01) among heifers at BCS 4 to 6. Leptin was positively correlated (P < 0.01) with both IGF-I (r = 0.34 for NR, and r = 0.36 for WG) and insulin (r = 0.18 for WG). Insulin was correlated with IGF-I (r = 0.60; P < 0.01). During nutritional restriction, insulin did not correlate with leptin (r = -0.05), BCS (r = -0.03), or IGF-I (r = 0.07). It was concluded that leptin serves as a dynamic indicator of body condition in heifers, as well as an indicator of nutritional status.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Body Composition; Body Constitution; Cattle; Female; Insulin; Insulin-Like Growth Factor I; Leptin; Random Allocation; Weight Gain

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

The role for leptin in food intake regulation in the mink, a polytocous seasonal breeder with altricial young, was investigated in pregnant and lactating dams and data were related to quantitative energy metabolism measurements and plasma concentrations of other important metabolic hormones. A total of nine mink dams were measured in consecutive 1-week balance periods, each including a 22 h measurement of heat production by means of indirect calorimetry, and blood was sampled at weekly intervals throughout gestation and during lactation weeks 1-4. Intake of metabolisable energy (ME) was high and energy balance was positive until the first third of true gestation. During mid- and late gestation ME intake decreased (P<0.001) while heat production remained almost constant, resulting in negative energy balance and the loss of body weight. From late gestation until lactation week 4, ME intake increased by 3.5 times, but weight loss continued. Plasma concentrations of leptin were approximately doubled during the last two-thirds of true gestation (P<0.01), demonstrating a clear gestational hyperleptinaemia. Concentrations declined rapidly after parturition and then remained stable. Insulin was independent of leptin, with low concentrations coincident with hyperleptinaemia. Also, concentrations of thyroid hormones declined during gestation, probably reflecting the low food intake. Hyperleptinaemia concomitant with low ME intake, negative energy balance and mobilisation of body reserves suggested an anorexigenic effect of leptin in pregnant mink. This suppression of food intake in late gestation might be permissive for the rapid increase in food intake occurring after parturition.

Topics: Animals; Appetite; Birth Weight; Diet; Eating; Energy Metabolism; Female; Hormones; Lactation; Leptin; Mink; Nitrogen; Oxidation-Reduction; Pregnancy; Pregnancy Outcome; Weight Gain

Thirty-six Angus x Hereford heifers (365 kg) were used to determine effects of dietary lipid supplementation from two sources during the final 32 or 60 d of feeding on serum and adipose tissue leptin concentrations, animal performance, and carcass characteristics. Following an initial feeding period of 56 d, heifers were fed one of three diets in a 3 x 2 factorial arrangement: 1) basal diet, 2) basal diet plus 4% (DM basis) corn oil, or 3) basal diet plus 2% (DM basis) rumen-protected conjugated linoleic acid (a mixture of Ca-salts of palm oil fatty acids with 31% conjugated linoleic acid). Jugular blood samples were collected at 28-d intervals (d 28 to 118) and serum subsequently harvested for leptin quantification via RIA. Real-time ultrasound measurements were collected at 28-d intervals across time on feed. At slaughter, samples were obtained from various adipose depots. Data were analyzed with dietary treatment, length of supplementation, adipose depot (when appropriate), and all two- and three-way (when appropriate) interactions in the repeated measures model. Measures of feedlot performance, including ADG, DMI, and gain:feed did not differ (P > 0.23) with dietary treatment or supplementation length. Heifers supplemented with corn oil tended (P < 0.07) to have higher marbling scores following 32 d of treatment than those supplemented with rumen-protected conjugated linoleic acid, with controls intermediate. Quality grade and hot carcass weight did not differ (P > 0.15) with treatment or length of supplementation. Leptin concentrations were higher (P < 0.05) from d 57 to 118 on feed than the initial period (d 0 to 56) of dietary adaptation when all animals received the basal diet. Circulating leptin concentrations were not affected by dietary treatment. However, leptin concentrations in adipose tissues were greater (P < 0.05) for heifers supplemented with corn oil than either control or rumen-protected conjugated linoleic acid diets, which did not differ. Compared with adipose tissues from rumen-protected conjugated linoleic acid-supplemented animals, tissues from heifers fed corn oil contained 68% greater leptin concentration. Correlations between performance, carcass traits, and serum leptin concentrations were low. Serum leptin concentrations across time on feed were not associated with carcass and performance data, including ADG, DMI, and gain:feed. Based on these data, concentrations of leptin are not related to indices of feedlot performance an

Topics: Adipose Tissue; Animals; Cattle; Dietary Supplements; Eating; Female; Leptin; Linoleic Acids; Linoleic Acids, Conjugated; Meat; Radioimmunoassay; Random Allocation; Rumen; Time Factors; Ultrasonography; Weight Gain

Leptin has been postulated to comprise part of an adipostat, whereby during states of excessive energy storage, elevated levels of the hormone prevent further weight gain by inhibiting appetite. A physiological role for leptin in this regard remains unclear because the presence of excessive food, and therefore the need to restrain overeating under natural conditions, is doubtful. We have previously shown that CRH-deficient (Crh(-/-)) mice have glucocorticoid insufficiency and lack the fasting-induced increase in glucocorticoid, a hormone important in stimulating leptin synthesis and secretion. We hypothesized that these mice might have low circulating leptin. Indeed, Crh(-/-) mice exhibited no diurnal variation of leptin, whereas normal littermates showed a clear rhythm, and their leptin levels were lower than their counterparts. A continuous peripheral CRH infusion to Crh(-/-) mice not only restored corticosterone levels, but it also increased leptin expression to normal. Surprisingly, 36 h of fasting elevated leptin levels in Crh(-/-) mice, rather than falling as in normal mice. This abnormal leptin change during fasting in Crh(-/-) mice was corrected by corticosterone replacement. Furthermore, Crh(-/-) mice lost less body weight during 24 h of fasting and ate less food during refeeding than normal littermates. Taken together, we conclude that glucocorticoid insufficiency in Crh(-/-) mice results in impaired leptin production as well as an abnormal increase in leptin during fasting, and propose that the fast-induced physiological reduction in leptin may play an important role to stimulate food intake during the recovery from fasting.

Topics: Adrenocorticotropic Hormone; Animals; Corticotropin-Releasing Hormone; Eating; Fasting; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Weight Gain

Chronic attenuation of hyperinsulinemia by diazoxide (DZ), a K-adenosine triphosphate (ATP) channel opener and an inhibitor of glucose-mediated insulin secretion, improved glucose tolerance and lipid profile and decreased the rate of weight gain in obese Zucker rats. To determine whether suppression of hyperinsulinemia alters daily food consumption, rate of weight gain, glucose tolerance, and lipid profile, we compared the effects of NN414, a potent and SUR1/Kir6.2 selective K(atp)() channel opener, with DZ in obese and lean Zucker rats. DZ (150 mg/kg/d), low-dose (LDNN414: 10 mg/kg/d), high-dose (HDNN414: 30 mg/kg/d), and vehicle (C) were administered to 7-week-old obese and lean female Zucker rats for a period of 6 weeks. Each animal underwent an intraperitoneal glucose tolerance test (IPGTT) at the end of study period. While NN414 treatment did not affect food intake and rate of weight gain in any of the strains, DZ treatment reduced food intake (P <.001) and rate of weight gain (P <.001) in obese rats. The fasting plasma insulin levels and area under the curve (AUC) insulin response to IPGTT were significantly attenuated in LDNN414 (P <.05), HDNN414 (P <.01), and DZ (P <.01) obese and lean rats compared with their controls. This was accompanied by a significant reduction in AUC glucose only in LDNN414 (P <.05), HDNN414 (P <.01), and DZ (P <.01) obese rats compared with controls. While hemoglobin A(1c) (HbA(1c)) was not affected in LDNN414 obese rats, it was higher in HDNN414 obese animals (P <.001), LD-, HDNN414 (P <.001), and DZ (P <.005) lean rats compared with their respective controls. DZ obese rats showed lower HbA(1c) levels than C obese rats (P <.02). The plasma free fatty acid (FFA) levels were only decreased in HDNN414 (P <.05) and DZ (P <.002) obese rats, whereas plasma triglyceride (TG) levels were decreased in LDNN414 (P <.05), HDNN414 (P <.001), and DZ (P <.001) obese rats compared with controls. Finally, plasma leptin level was only decreased in DZ obese rats compared with controls (P <.001). The new SUR1/Kir6.2 selective K(atp)() channel opener, NN414, reduced hyperinsulinemia in a dose-dependent manner without a significant effect on food consumption and rate of weight gain. NN414-induced beta-cell rest in obese rats was associated with a significant improvement in glucose responsiveness, suggesting an increase in insulin sensitivity after its withdrawal. There was an overall deterioration in glycemic control at the high dose as measur

Topics: Animals; Area Under Curve; Blood Glucose; Bridged Bicyclo Compounds, Heterocyclic; Cyclic S-Oxides; Eating; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Glycated Hemoglobin; Hyperinsulinism; Hypoglycemic Agents; Insulin; Islets of Langerhans; Leptin; Potassium Channels, Inwardly Rectifying; Rats; Rats, Zucker; Triglycerides; Weight Gain

To study the role of adiponectin, a novel adipocyte-specific secreted protein, on the pathophysiology of eating disorders, circulating levels of fasting adiponectin, leptin, insulin, and glucose were measured in 31 female patients with anorexia nervosa (AN) and in 11 with bulimia nervosa. Hormone levels were compared with 16 age-matched, normal body weight controls, six healthy constitutionally thin subjects, and nine obese subjects. Moreover, changes in levels were reevaluated after nutritional treatment and weight gain in 13 patients with AN. Serum adiponectin concentrations in AN and bulimia nervosa were significantly lower than those in normal-weight controls. These results were unexpected because the levels were high in constitutionally thin subjects and low in obese subjects, which provide a negative correlation with body mass index (BMI) and body fat mass. In contrast, serum leptin levels correlated very well with BMI and fat mass among all the patients and controls. The insulin resistance was significantly low in AN and high in obese subjects. The concentrations of adiponectin after weight recovery increased to the normal level despite a relatively small increase in BMI. These findings suggest that abnormal feeding behavior in the patients with eating disorders may reduce circulating adiponectin level, and weight recovery can restore it.

Topics: Adiponectin; Adipose Tissue; Adult; Anorexia Nervosa; Body Composition; Body Mass Index; Bulimia; Case-Control Studies; Female; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Middle Aged; Nutrition Therapy; Obesity; Osmolar Concentration; Proteins; Thinness; Weight Gain

Ghrelin, a 28 amino-acid peptide secreted primarily from the stomach has been identified as the endogenous ligand for the growth hormone secretagogue receptor. Ghrelin is suppressed in the postprandial state and has been linked to both type II diabetes and obesity.. To investigate the effects of a period of overfeeding with high-fat dietary supplements on plasma ghrelin levels in nonobese men.. Six healthy males (21-34 y; BMI 21-24 kg/m(2)) underwent the dietary intervention after completing diet and exercise diaries for 7 days. For 3 further weeks subjects followed their own diet diary supplemented with 125 ml single cream and 50 g roasted peanuts (88 g fat, 15 g Protein, 8 g carbohydrate) every day. Oral fat tolerance tests (OFTT) were undertaken at baseline, 7, 14 and 21 days of fat supplementation. The diet was increased in energy by 3.9 MJ/day and from a mean of 29-45% energy intake from fat with a small weight gain noted each week (P=0.009).. Ghrelin concentrations were significantly reduced during the baseline OFTT. The postprandial ghrelin response (AUC) was significantly reduced following 2 weeks of dietary supplementation (P=0.005) increasing the suppression of plasma ghrelin by 18% despite only a 3% increase in body weight. Plasma triacylglycerol (P=0.009) and leptin (P=0.035) concentrations were also elevated and postprandial pancreatic polypeptide levels decreased (P=0.038) following dietary-supplementation.. These results suggest that the metabolic profile associated with obesity, including a reduction in plasma ghrelin levels, may be related to recent dietary energy intake and precedes the development of significant adiposity.

Topics: Adult; Analysis of Variance; Body Weight; Dietary Fats; Eating; Fatty Acids, Nonesterified; Gastric Emptying; Ghrelin; Humans; Leptin; Male; Peptide Hormones; Postprandial Period; Triglycerides; Weight Gain

Leptin and peroxisome proliferator-activated receptors are two important adipose tissue factors involved in energy metabolism regulation. It has been shown that PPARgamma agonists decrease leptin levels. However, the effects of PPARalpha agonists on leptin have not been investigated much. The aim of this study was to compare the effects of a PPARgamma agonist rosiglitazone (RSG) and PPARalpha agonist gemfibrozil (G) on body weight and serum insulin and leptin levels in diet-induced obese rats. Male Wistar rats were divided into six groups according to diet and drug therapy. After four weeks, serum glucose, triglyceride, insulin and leptin levels were significantly decreased in the high-fat-fed and RSG-treated groups compared to the group fed a high-fat diet only (162 +/- 19 vs. 207 +/- 34 mg/dl, 58 +/- 20 vs. 112 +/- 23 mg/dl, 3.1 +/- 1.0 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.5 vs. 3.6 +/- 1.6 ng/ml, respectively). However, these parameters were not statistically different in RSG animals treated with a standard diet compared to the standard diet group. The high fat+RSG group gained much more weight compared to high-fat and high-fat+G groups (p > 0.05). Additionally, serum glucose, insulin and leptin levels were significantly decreased in the high-fat-fed and G-treated group compared to high-fat group (149 +/- 19 vs. 207 +/- 34 mg/dl, 57 +/- 16 vs. 112 +/- 23 mg/dl, 4.3 +/- 2.1 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.4 vs. 3.6 +/- 1.6 ng/ml, respectively). These results suggest that PPARalpha agonists may decrease serum glucose, insulin and leptin levels as PPARgamma agonists do in diet-induced obese rats.

Topics: Adipose Tissue; Animals; Dietary Fats; Energy Metabolism; Gemfibrozil; Hypoglycemic Agents; Hypolipidemic Agents; Insulin; Leptin; Male; Obesity; PPAR alpha; PPAR gamma; Rats; Rats, Wistar; Rosiglitazone; Thiazolidinediones; Weight Gain

The present study examined whether blockade of melanocortin receptors subtypes 3 and 4 (MC3/4-R) inhibits chronic cardiovascular and dietary responses to leptin infusion. A cannula was placed in the lateral ventricle of male Sprague-Dawley rats for chronic intracerebroventricular (ICV) infusion via osmotic minipump, and arterial and venous catheters were implanted for measurement of mean arterial pressure (MAP) and heart rate (HR) 24 h/d and IV infusions. After a 5-day control period, rats received (1) 0.9% saline vehicle ICV for 12 days plus leptin (1 microg/kg per minute IV, n=5) during the final 7 days; (2) MC3/4-R antagonist SHU-9119 (1 nmol/h ICV) for 12 days plus leptin (1 microg/kg per minute IV, n=6) during the final 7 days; and (3) SHU-9119 (1 nmol/h ICV, n=8) for 12 days. Leptin infusion in vehicle-treated rats caused a small increase in MAP (5+/-1 mm Hg) despite reduced food intake (23+/-1 to 10+/-1 g/d) and decreased body weight (-6%+/-1%). SHU-9119 infusion completely prevented the cardiovascular and dietary actions of leptin, leading to increased food intake (23+/-1 to 49+/-4 g/d) and body weight (+30%+/-2%), markedly decreased HR (-77+/-9 bpm), and caused a decrease in MAP (-6+/-1 mm Hg). Similar results were observed when SHU-9119 was infused alone in vehicle-treated rats. Leptin decreased plasma insulin to 30% of control values, an effect that was also abolished by SHU-9119 treatment, which caused a 5-fold increase in plasma insulin concentration. Thus, MC3/4-R antagonism completely blocked the chronic cardiovascular, satiety, and metabolic effects of leptin, suggesting that the hypothalamic melanocortin system plays an important role in mediating these actions of leptin.

Topics: Animals; Blood Pressure; Diuresis; Eating; Heart Rate; Hemodynamics; Hypothalamus; Infusion Pumps, Implantable; Insulin; Kidney; Leptin; Male; Melanocyte-Stimulating Hormones; Natriuresis; Rats; Rats, Sprague-Dawley; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Renin; Satiety Response; Weight Gain

In this study, we measured the ghrelin, leptin, and insulin variations in lean and obese Zucker fa/fa rats during the acute phase of body weight gain. At 2 months of age, plasma insulin and leptin concentrations in fa/fa rats were, respectively, 470% and 3700% higher than in lean rats (p <0.0001). Plasma ghrelin was significantly lower (-24.6%; p <0.02) than in lean rats. At 6 months of age, ghrelin increased in both genotypes but the difference was no more significant. The inverse correlations existing between ghrelin and either body weight (BW), insulin or leptin at 2 months of age were no more observable in 6-month-old rats. At 6 months of age, the lean rats had the same body weight as the 2-month-old obese rats. In these body weight-matched rats, ghrelin was not correlated with BW but it remained negatively correlated with insulin and leptin. At the same body weight, obese rats had a much lower plasma ghrelin than lean rats (717+/-42 vs. 1754+/-83 pg/ml; p <0.0001). These data indicate that body composition rather than body weight is the primary factor for the down-regulation of the ghrelin system. This down-regulation constitutes a mechanism of defense of the organism against the development of obesity at least during the first part of life.

Topics: Animals; Body Weight; Eating; Ghrelin; Homozygote; Insulin; Leptin; Longitudinal Studies; Peptide Hormones; Radioimmunoassay; Rats; Rats, Zucker; Regression Analysis; Weight Gain

The effect of ethanol drinking on some hormonal and metabolic changes in the rat and on lipolysis in isolated adipocytes was tested. Male growing Wistar rats divided into two groups were used in the experiment. Ten percent ethanol solution as the only drinking fluid for 2 weeks depressed body weight gain. The diminution of blood insulin with simultaneous increase in leptin concentration found in these rats suggest that the physiological regulation of leptin secretion is disturbed by ethanol. Liver triglycerides content was substantially augmented due to ethanol ingestion. Adipocytes were isolated from both groups of rats by collagenase digestion and the lipolytic activity of these cells was compared. Isolated cells (10(6)/ml) were incubated for 90 min in Krebs-Ringer buffer (pH 7.4, 37 degrees C) containing 3 mm glucose and different lipolytic modulators: adrenaline (1 microm), insulin (1 nm), dibutyryl-cAMP (1 mm) and DPCPX (a selective antagonist of adenosine A1 receptor, 1 microM). To determine basal lipolysis cells were incubated without lipolytic agents. Lipolysis was determined by the amount of glycerol released from cells to the incubation medium. Basal and adrenaline-induced lipolysis was depressed in adipocytes of ethanol-drinking rats. The antilipolytic activity of insulin was the same in both groups of isolated cells. Lipolysis induced by dibutyryl-cAMP was only slightly reduced due to ethanol consumption, whereas triglycerides breakdown evoked by adenosine A1 receptor antagonism was unchanged. Results obtained in vitro indicate that subchronic ethanol drinking attenuates basal and stimulated lipolysis in adipocytes, however, the antilipolytic effect of insulin and the adenosine pathway are unchanged.

Topics: Adenosine A1 Receptor Antagonists; Adipocytes; Adipose Tissue; Alcohol Drinking; Animals; Bucladesine; Epinephrine; Ethanol; Insulin; Leptin; Lipolysis; Liver; Male; Random Allocation; Rats; Rats, Wistar; Weight Gain; Xanthines

The present study sought to determine the effects of kindled seizures generated from the left and right amygdala upon weight gain in rat. Seventy-five female Sprague-Dawley rats were implanted with electrodes in basal amygdala of the left and right hemispheres. A kindling paradigm was employed in which electrical stimulation was applied once per day for 30 days after Stage 5 seizures. An electrode was implanted into the basal amygdala of the control rats but no stimulation was applied. All rats were weighed daily during the course of the experiment and changes in weight during this period were recorded for all rats. The results demonstrated that kindling from either the left or right amygdala induced significant increases in weight gain relative to the control rats. However, kindling from the left basal amygdala induced increases in body weight that were four times greater than control rats and two times greater than the rats kindled from the right side of the basal amygdala. Likewise, serum leptin levels, which were highly correlated with weight gain, also showed significantly greater increases in left amygdaloid kindled rats relative to rats kindled from the right amygdala and control rats. These findings demonstrate that basal amygdaloid kindling induces significant increases in weight gain and that the magnitude of these effects is linked to the dominance of the left hemisphere.

Topics: Amygdala; Analysis of Variance; Animals; Dominance, Cerebral; Electric Stimulation; Energy Metabolism; Female; Kindling, Neurologic; Leptin; Rats; Rats, Sprague-Dawley; Seizures; Weight Gain

Lower ghrelin levels have been related to slower growth in small for gestational age infants, and infants with higher cord leptin levels have been reported to gain weight more slowly from birth to 2 yr. This study investigated whether cord blood ghrelin and leptin levels are related to weight gain up to 12 wk of age. One hundred infants were weighed at birth and at 12 wk, and cord blood was assayed for ghrelin and leptin. The mean (+/-sd) birth weight was 3.458 (0.433) kg (median, 3.390; range, 2.510-4.615 kg). The mean (+/-sd) leptin level was 10.1 (6.7) ng/ml (median, 8.4; range, 1.6-36.7 ng/ml), and that of ghrelin was 760.9 (282.9) pg/ml (median, 770; range, 210-1670 pg/ml). Higher birth weight was associated with slower weight gain. Leptin was correlated with birth weight, but ghrelin was not, and leptin and ghrelin levels were not significantly correlated with one another. With birth weight as a control variable, ghrelin was significantly associated with slow weight gain (chi(2) = 7.20 with 1 df; P < 0.01), although leptin was not (chi(2) = 1.59 with 1 df; P > 0.1). In conclusion, lower cord ghrelin levels are associated with slower weight gain from birth to 3 months of age.

Topics: Aging; Birth Weight; Female; Fetal Blood; Ghrelin; Humans; Infant, Newborn; Leptin; Male; Peptide Hormones; Weight Gain

The objectives were to determine relative ADG, ADFI, behavior, and endocrine responses in weaned pigs receiving exogenous ghrelin. Twenty-four barrows weaned at 18 d of age (d 0 of the experiment) were catheterized via the jugular vein, weighed, and assigned to either a ghrelin (n = 12) or saline (control; n = 12) infusion group. Initial pig BW did not differ between treatments (7.87+/-0.39 vs. 7.92+/-0.35 kg for ghrelin and control treatments, respectively). Pig BW and feed intakes were measured once daily throughout the experiment. Starting on d 1, the ghrelin pigs were intravenously infused three times daily for 5 d with 2 microg/kg BW of human ghrelin, and the control pigs were similarly infused with saline. Activity observations and blood samples were taken at -15, 0, 15, 30, 60, 90, 120, 240, and 480 min relative to the first infusion and then three times daily (0800, 1600, and 2400) for 8 d. Weight gain during the 5-d infusion period was greater by the ghrelin than by control pigs (0.57+/-0.10 vs. 0.21+/-0.13 kg, respectively; P < 0.04); however, there was no increase in feed intake. During two behavioral observation periods, more pigs in the ghrelin treatment were observed eating compared with control pigs (P < 0.05). The initial infusion of exogenous ghrelin increased serum ghrelin, GH, insulin, and cortisol concentrations (P < 0.05). Endogenous serum ghrelin increased from d 1 to 8 of the experiment in control animals (P < 0.05). Serum IGF-I initially fell in both treatment groups from d 1 to 2 (P < 0.05) but then increased from d 5 to 8 (P < 0.05). Peripheral concentrations of glucose in the ghrelin pigs were greater on d 2, 3, 7, and 8 than on d 1 (P < or = 0.05). In both treatment groups, peripheral concentrations of leptin increased from d 7 to 8, and cortisol decreased from d 1 to 5 of the experiment. These observations provide evidence that ghrelin may positively influence weight gain and concomitantly increase GH, insulin, and cortisol secretion in weaned pigs.

Topics: Animals; Behavior, Animal; Eating; Ghrelin; Growth Hormone; Hydrocortisone; Infusions, Intravenous; Insulin; Leptin; Male; Peptide Hormones; Random Allocation; Swine; Weaning; Weight Gain

To assess the role of endogenous peptides involved in stress responsivity in the development of diet-induced obesity (DIO), selectively bred DIO and diet-resistant (DR) male were weaned onto a low fat (4.5%) chow diet at 3 weeks of age and then fed either chow or a 31% fat by energy content (high energy (HE)) diet for 9 days beginning at 4 weeks of age. Regardless of diet, DIO rats gained more weight than DR rats but did not show the selective DIO weight gain trait characteristic of older DIO rats fed HE diet. At this early age, both DR and DIO rats on HE diet ate more and had higher leptin levels but gained less body weight and had lower feed efficiency (body weight gain (g)/food intake (kcal)) than their chow-fed controls. HE diet also prevented the decline in 24h urine corticosterone levels from the third to fifth week observed in chow-fed rats. Terminally, DIO rats had lower hippocampal glucocorticoid receptor (GR) and amygdalar central nucleus corticotrophin-releasing hormone (CRH) mRNA than DR rats, regardless of their diets. Taken together with prior studies in these rats, there appears to be a critical period between 3 and 5 weeks of age when DIO and DR rats are not phenotypically different and hypothalamo-pituitary-adrenal (HPA) function is rapidly changing. The reduced expression of brain GR and CRH expression at the end of this period might contribute to the propensity of DIO rats to become obese selectively on HE diet after 5 weeks of age.

Topics: Age Factors; Analysis of Variance; Animals; Body Weight; Brain Chemistry; Corticotropin-Releasing Hormone; Dietary Fats; Eating; Gene Expression Regulation; In Situ Hybridization; Leptin; Male; Obesity; Oligoribonucleotides, Antisense; Rats; Receptors, Glucocorticoid; RNA, Complementary; RNA, Messenger; Time Factors; Weight Gain

We investigated the effect of daily intracerebroventricular (ICV) leptin administration (neonatal age 2-7 days) on hypothalamic neuropeptides (neuropeptide Y, alpha-melanocyte-stimulating hormone) that regulate food intake, body weight (BW) gain, and the metabolic/hormonal profile in suckling (8 and 21 days) and adult rat (35, 60, 90, and 120 days). ICV leptin (0.16 mug.g BW(-1).dose(-1); n = 70) led to a postnatal decline in BW (P = 0.0002) that persisted only in the adult females (P = 0.002). The postnatal decline in BW due to leptin was associated with a decline in food intake (P = 0.01) and hypothalamic leptin receptor (P = 0.008) and neuropeptide Y (P = 0.008) immunoreactivities and an increase in alpha-melanocyte-stimulating hormone (P = 0.008) immunoreactivity. In addition, hyperinsulinemia (P = 0.01) with hypocorticosteronemia (P = 0.007) occurred during the postnatal period with hypercorticosteronemia (P = 0.007) and hypoleptinemia (P = 0.008) and an increase in leutinizing hormone (P = 0.01) in the adult male and female progeny. Persistent hyperinsulinemia (P = 0.015) with hyperglycemia (P = 0.008) and glucose intolerance (P = 0.001) were observed only in the adult female. We conclude that postnatal leptin administration alters the adult female phenotype and speculate that this may relate to retention of leptin sensitivity resulting in a lipoatrophic state.

Topics: Animals; Animals, Newborn; Blood Glucose; Dose-Response Relationship, Drug; Drug Administration Schedule; Eating; Female; Glucose; Glucose Tolerance Test; Hormones; Hypothalamus; Injections, Intraventricular; Leptin; Male; Neuropeptides; Osmolar Concentration; Phenotype; Rats; Rats, Sprague-Dawley; Weight Gain

Although circulating leptin and insulin concentration is linked to intrauterine growth, fetal development and birth weight in full-term infants, there has been no enquiry into the influence of cord blood insulin and leptin for catch-up growth in preterm infants. The study evaluated the association of cord blood leptin with growth and weight gain of 96 premature babies during 6 months (corrected age). The temporal changes of anthropometric indexes over this period were calculated by repeated random regression (PROC MIXED) using SAS. Cord blood leptin was negatively associated with the rate of change in BMI (p=0.01) and length (p<0.001), from birth until 64 postnatal weeks. Insulin was positively associated with the change rate in BMI (p=0.03); however, this disappeared when adjusted for birth weight. For the first time, the association between lower leptin levels with greater catch up growth is shown for both BMI and length among preterm children. In conclusion, leptin levels at birth, but not insulin levels, predict growth rates.

Topics: Body Height; Body Mass Index; Female; Fetal Blood; Follow-Up Studies; Humans; Infant, Newborn; Infant, Premature; Insulin; Leptin; Male; Weight Gain

Growth differentiation factor 3 (GDF-3) is structurally a bone morphogenetic protein/growth differentiation factor subfamily member of the TGF-beta superfamily. GDF-3 exhibits highest level of expression in white fat tissue in mice and is greatly induced by high fat diet if fat metabolic pathway is blocked. To identify its biological function, GDF-3 was overexpressed in mice by adenovirus mediated gene transfer. Mice transduced with GDF-3 displayed profound weight gain when fed with high fat diet. The phenotypes included greatly expanded adipose tissue mass, increased body adiposity, highly hypertrophic adipocytes, hepatic steatosis, and elevated plasma leptin. GDF-3 stimulated peroxisome proliferator activated receptor expression in adipocytes, a master nuclear receptor that controls adipogenesis. However, GDF-3 was not involved in blood glucose homeostasis or insulin resistance, a condition associated with obesity. In contrast, similar phenotypes were not observed in GDF-3 mice fed with normal chow, indicating that GDF-3 is only active under high lipid load. Thus, GDF-3 is a new non-diabetic adipogenic factor tightly coupled with fat metabolism.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue; Animals; Base Sequence; Blood Glucose; Cell Size; Cells, Cultured; Cytokines; Dietary Fats; DNA; Fatty Liver; Gene Expression; Growth Differentiation Factor 3; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Mice; Mice, Inbred C57BL; Receptors, Cytoplasmic and Nuclear; Transcription Factors; Transduction, Genetic; Weight Gain

Topics: Adiponectin; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Leptin; Weight Gain

Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARalpha target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARalpha target genes encoding peroxisomal enzymes involved in fatty acid beta-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARalpha activation, but not to differences in leptin production, between female OVX and Sham mice.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Dietary Fats; Eating; Fatty Acids; Female; Fenofibrate; Gene Expression Regulation; Hypolipidemic Agents; Leptin; Liver; Mice; Mice, Inbred C57BL; Ovariectomy; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Transcription Factors; Weight Gain

Bodyweight is an important prognostic indicator in children with cystic fibrosis (CF), but the relationships between body composition and clinical outcomes are less clear. We have investigated the role of leptin (a potential satiety factor) and changes in body composition, height and weight with respect to age and clinical outcome.. 143 children (77 boys) with CF and a median age (range) of 5.99 (2.27-17.98) y were followed with annual measurements of height, weight, skinfolds, forced expiratory volume (FEV1), Shwachman score assessment and fasting blood sample. Our control group comprised 40 children (20 boys, 20 girls) aged 8.6-10.2 y at recruitment who were participating in a longitudinal study of growth and puberty.. SD scores for height, weight and BMI decreased with age; fat and fat-free mass was lower in both sexes compared to controls. Shwachman score decreased with age in both sexes and was related to fat-free mass in girls, and to both fat-free and fat mass in boys. FEV1 decreased with age only in boys and was related to fat-free mass. Leptin levels by age and by fat mass were higher in CF children compared to controls.. Despite improvements in management, contemporary children with CF still gain less body fat and fat-free mass and are shorter than controls. The higher leptin levels we observed may be due to stimulatory effects of inflammatory cytokines and we postulate that they may contribute to the anorexia, poor weight gain and growth of these children.

Topics: Adolescent; Body Composition; Body Height; Body Mass Index; Case-Control Studies; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Leptin; Longitudinal Studies; Male; Prognosis; Weight Gain

To isolate and characterize a region on mouse chromosome 2 harboring quantitative trait loci with large influences on growth and fatness.. A congenic line [M16i.B6-(D2Mit306-D2Mit52); MB2] was created using the polygenic obese M16i selection line as the recipient for an approximately 38-centimorgan region from C57BL/6J. Males and females from M16i and MB2 were compared for body weight, body composition, feed consumption, and additional traits at 6, 15, and 24 weeks. Interactions of genotype and environment (low and high dietary fat) were investigated. Males (8 weeks) were evaluated for fatty acid profiles in liver and for transcriptional profiles in liver and adipose.. Consequences of replacing M16i alleles with C57BL/6J alleles in MB2 were maximized at 15 weeks. MB2 mice were up to 15% lighter than M16i at this age, with no differences in feed consumption. As a percentage of body weight, MB2 had dramatically less epididymal (males) or perimetrial (females) fat (1.17% vs. 2.79% pooled across sex) and lower total lipids (16.1% vs. 23.3%) than M16i. Decreased adiposity in MB2 was not dependent on gender or diet. MB2 mice also had significant decreases in levels of leptin, insulin, and glucose, decreased de novo synthesis of hepatic fatty acid, and transcriptional changes for many genes both within, and external to, the congenic region.. Results confirm the presence and large effects of mouse chromosome 2 quantitative trait loci and further define their phenotypic consequences related to energy balance. The MB2 congenic line is a powerful resource for eventual identification of pathways and mutations within genes regulating predisposition to growth and obesity.

Topics: Adipose Tissue; Alleles; Animals; Body Composition; Chromosome Mapping; Chromosomes, Mammalian; Diglycerides; Eating; Fatty Acids; Female; Insulin; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Phenotype; Quantitative Trait Loci; Triglycerides; Weight Gain

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

This study aimed to evaluate the consequences on food intake and body weight (BW) of leptin administration in rats receiving a choice between the three macronutrients. Two studies were performed: during the first, rats received an acute intraperitoneal (IP) leptin administration (1 mg/kg) twice (at 8 and 14 weeks of age), at the beginning of the nocturnal cycle, while during the second, they received a chronic leptin infusion (osmotic minipump, 7 days). The total 24-h food intake after acute leptin injections was reduced by 14% and 17%, respectively. Body weight gain (BWG) after leptin injections was about half that seen on control days. Chronic leptin infusion reduced total intake, affecting mainly protein (P). Fat intake increased slightly since day 2 and became significant on the fourth day. After the leptin infusion, carbohydrate (CHO) eaters (>35% carbohydrate/total energy) significantly reduced the carbohydrate proportion in their total energy intake. There was no difference concerning macronutrient selection by fat eaters (Hfat). Leptin infusion reduced the number of mixed meals on the first day. In addition, the thermogenesis of brown adipose tissue (BAT) was higher in leptin than in control (C) rats. Consequently, leptin injections reduced food intake and BWG and increased thermogenesis, thus acting on the two terms of the energy balance. Moreover, leptin has different effects on macronutrient preferences, dependent upon age (tests 1 and 2) and the type (acute or chronic) of injection. High leptinemia level related to age or to minipump infusion lead to leptin resistance as found in old or obese subjects. It could explain our results.

Topics: Adipose Tissue, Brown; Animals; Body Composition; Diet; Dietary Carbohydrates; Drug Implants; Energy Metabolism; Food Preferences; Hormones; Injections, Intraperitoneal; Leptin; Male; Rats; Rats, Wistar; Weight Gain

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

Adiponectin, a novel adipocytokine with insulin sensitizing properties, is inversely related to obesity and insulin resistance in adults. We recently reported large variations in weight gain and insulin sensitivity during the first year in infants born small for gestational age (SGA) or appropriate for gestational age (AGA). We now determined whether adiponectin levels were related to postnatal growth and insulin sensitivity in a prospective cohort followed from birth to two years old (n = 85) (55 female/30 male, 65 SGA/20 AGA). Serum adiponectin levels at one year and two years were higher compared to reported levels in adults and older children, and decreased from one year (21.6 +/- 0.6 microg/ml) to two years (15.7 +/- 0.7 microg/ml) (p < 0.05). At two years adiponectin levels were lower in females (15.3 +/- 0.4 microg/ml) than males (16.4 +/- 0.6 microg/ml) (p < 0.05), but no gender difference was seen in leptin or insulin levels. No differences in adiponectin levels were seen between SGA and AGA infants at one or two years. However, in SGA infants changes in adiponectin between one to two years old were inversely related to weight gain (r = -0.310, p < 0.05). Changes in leptin levels between one to two years were positively related to weight gain in both SGA and AGA infants (r = 0.450 and r = 0.500 respectively, both p < 0.05). Adiponectin levels were unrelated to insulin levels at one or two years, nor to change in insulin levels between one to two years. In multiple regression analysis, adiponectin levels were related only to postnatal age; omitting age from the model, the determinants of higher adiponectin levels were male gender (p = 0.03), lower postnatal body weight (p < 0.001), and higher birth weight SD score (p = 0.004). In conclusion, fall in serum adiponectin levels during the first two years of life were related to increasing age and greater weight gain SGA infants, but were unrelated to insulin sensitivity.

Topics: Adiponectin; Cohort Studies; Female; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Male; Prospective Studies; Weight Gain

Diet-induced obesity is the primary determinant of the current epidemic of diabetes. We have explored the role of genetics in this phenomenon, using C57Bl/6 (B6), 129S6/SvEvTac (129), and intercross (B6 x 129)F2 mice on a low- or high-fat diet. Over an 18-week period, B6 and F2 mice gained more weight, had higher levels of insulin and leptin, and showed greater glucose intolerance than 129 mice, despite lower food intake. By contrast, metabolic rate and diet-induced thermogenesis were significantly higher in the 129 mice. Genome-wide scans identified several quantitative trait loci, including a quantitative trait locus that was linked with hyperinsulinemia/insulin resistance on chromosome 14 in a region similar to that seen in mice with genetically induced insulin resistance. Microarray analysis indicated significant changes in expression levels between B6 and 129 mice in the identified chromosomal area of Wnt5a and protein kinase Cdelta (PKCdelta). Thus, caloric efficiency, i.e., the "thrifty gene," is a dominant-acting genetic determinant of diet-induced obesity in mice and can be linked to a locus on chromosome 14, including genes linked to adipose development and insulin sensitivity.

Topics: Animals; Crosses, Genetic; Diet, Fat-Restricted; Dietary Fats; Energy Metabolism; Insulin; Insulin Resistance; Leptin; Mice; Mice, Inbred C57BL; Obesity; Weight Gain

Blood pressure (BP) and heart rate (HR) responses to stress are significant predictors of cardiovascular morbidity and mortality. Because obesity is a major risk factor for cardiovascular disease, we examined whether diet-induced obesity alters the BP and HR responses to stress and whether these alterations are associated with augmented cardiovascular morbidity in the rat.. Adult male spontaneously hypertensive rats were fed either a normal diet or high-fat diet (HFD) for 12 weeks. At weeks 0 and 12, body weight was measured, and BP and HR were recorded by radiotelemetry throughout three consecutive day and night periods and in response to 30-minute immobilization stress. At the end of the 12-week intervention, the rats were sacrificed, and their organs and sera were collected.. With the intervention, HFD rats showed a significantly greater increase in body weight (as expected) and circulating leptin and free fatty acid levels compared with normal diet rats. In addition, they showed similar increases in BP and HR elevations during stress but significantly slower BP and HR decreases after stress. These HFD-induced delays in stress recovery were associated with BP and HR elevations during the night (behaviorally active) period and with augmentations in cardiac mass.. The results of this study indicate that, in spontaneously hypertensive rats, dietary obesity delays cardiovascular recovery from stress, and, in parallel, it promotes the development of nocturnal hypertension as well as cardiac hypertrophy. This suggests that dietary obesity may significantly potentiate the impact of daily stressful experiences on the cardiovascular system.

Topics: Animals; Cardiovascular System; Dietary Fats; Fatty Acids, Nonesterified; Glucose Tolerance Test; Hypertension; Kidney; Leptin; Lipids; Male; Myocardium; Obesity; Organ Size; Rats; Rats, Inbred SHR; Restraint, Physical; Stress, Physiological; Time Factors; Weight Gain

Anorexia nervosa (AN) is a state of leptin and gonadotropin deficiency. Leptin levels are decreased in normal weight women with hypothalamic amenorrhea and leptin may be a sensitive marker of overall nutritional status. The aim of the study is to provide additional information on plasma leptin levels and on gonadotropin responses after clomiphene testing in patients with AN who recovered weight but were still amenorrheic. We evaluated 17 patients with AN, female age 20+/-1.2 yr who reached goal weight [body mass index (BMI) 14.9+/-0.5 to 19.3+/-0.4 kg/m2]. At diagnosis serum leptin levels were 2.2+/-0.1 microg/l while after behavioural therapy and hypercaloric diet for 6-12 months serum leptin levels rose to 6.4+/-1.4 microg/l significantly lower compared with those in the control (no.=10, age 28+/-6.2 yr, BMI 21.1+/-0.3 kg/m2, leptin 9.3+/-0.7 pg/l; p<0.05). None of the patients resumed spontaneous menstrual cycles after weight gain. They were tested with a 10-day administration of clomiphene citrate. All had a significant rise in LH secretion (from 1.7+/-0.3 IU/l to 8.3+/-0.9 IU/l, p<0.01) and serum estradiol levels (from 19.0+/-5.4 to 937.7+/-241.2 pg/ml, p<0.03). Nine out of 17 patients menstruated after clomiphene. Serum leptin levels were not different in those who menstruated from those who did not (6.4+/-1.4 to 6.8+/-1.4 microg/l, p>0.05). Body compositon was studied in 12 additional carefully matched patients with AN who recovered weight. Six of them resumed spontaneous menstrual cycles. Neither BMI, body fat, nor leptin appeared as significant determinants of menstrual status. In conclusion, relative hypoleptinemia persists, independent of fat mass, in weight recovered patients with AN. A normal response to clomiphene in weight-recovered yet still amenorrhoeic patients with AN, offers reassurance that the axis is intact and that the problem lies in the hypothalamus. It is reasonable to believe that nutritional disturbances, fat intake and persisting psychological factors still affect plasma leptin levels and reproductive functions in weight-recovered patients with amenorrhea.

Topics: Adolescent; Adult; Amenorrhea; Anorexia Nervosa; Body Mass Index; Body Weight; Case-Control Studies; Clomiphene; Estrogen Antagonists; Female; Gonadotropins; Humans; Hypothalamus; Leptin; Nutritional Status; Weight Gain

Topics: Antidepressive Agents; Antipsychotic Agents; Humans; Leptin; Mental Disorders; Prognosis; Psychotropic Drugs; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Weight Gain

Isoforms of the thyroid hormone receptor (TR)alpha and TRbeta genes mediate thyroid hormone action. How TR isoforms modulate tissue-specific thyroid hormone (TH) action remains largely unknown. The steroid receptor coactivator-1 (SRC-1) is among a group of transcriptional coactivator proteins that bind to TRs, along with other members of the nuclear receptor superfamily, and modulate the activity of genes regulated by TH. Mice deficient in SRC-1 possess decreased tissue responsiveness to TH and many steroid hormones; however, it is not known whether or not SRC-1-mediated activation of TH-regulated gene transcription in peripheral tissues, such as heart and liver, is TR isoform specific. We have generated mice deficient in TRalpha and SRC-1, as well as in TRbeta and SRC-1, and investigated thyroid function tests and effects of TH deprivation and TH treatment compared with wild-type (WT) mice or those deficient in either TR or SRC-1 alone. The data show that 1) in the absence of TRalpha or TRbeta, SRC-1 is important for normal growth; 2) SRC-1 modulates TRalpha and TRbeta effects on heart rate; 3) two new TRbeta-dependent markers of TH action in the liver have been identified, osteopontin (upregulated) and glutathione S-transferase (downregulated); and 4) SRC-1 may mediate the hypersensitivity to TH seen in liver of TRalpha-deficient mice.

Topics: Animals; Energy Metabolism; Gene Expression; Genotype; Heart Rate; Histone Acetyltransferases; Leptin; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Receptor Coactivator 1; Oligonucleotide Array Sequence Analysis; Receptors, Thyroid Hormone; Response Elements; Reverse Transcriptase Polymerase Chain Reaction; Thyroid Gland; Thyroid Hormone Receptors alpha; Thyroid Hormone Receptors beta; Thyroid Hormones; Thyrotropin; Thyroxine; Transcription Factors; Triiodothyronine; Weight Gain

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Haloperidol; Humans; Leptin; Male; Olanzapine; Pirenzepine; Quetiapine Fumarate; Schizophrenia; Triglycerides; Weight Gain

In this study, we examined the effect of dietary conjugated linoleic acid (CLA) on body fat levels in Sprague-Dawley rats.. Rats were fed AIN-93G type diets containing 4%, 7%, and 10% fats with or without 1.5% CLA.. Three weeks after the onset of the experimental period, the weights of perirenal white adipose tissue were lower in CLA-fed rats. The weights of epididymal white adipose tissue also were lower in CLA-fed rats than in control rats, but this effect disappeared with increased dietary fat level. Serum leptin levels tended to be lower in the CLA group, especially the low-fat diet group, than in the control group. There were significant positive correlations between serum leptin level and weights of perirenal and epididymal white adipose tissues in control groups, but these correlations were weaker in the CLA groups. Serum tumor necrosis factor-alpha levels also tended to be lower in CLA-fed rats, and this tendency was most remarkable in the rats fed 7% fat diets.. In conclusion, dietary CLA, especially the low-fat diet, reduced body fat without hepatic injury to Sprague-Dawley rats.

Topics: Adipose Tissue; Animals; Body Composition; Dietary Fats; Dose-Response Relationship, Drug; Leptin; Linoleic Acid; Liver; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Weight Gain

When animals are allowed free access to food following an extended period of food restriction, body weight is steadily restored to the pre-food restriction level, ie to a specific body weight 'set-point'. We tested the proposition that leptin is used as a signal by the brain to regulate body weight 'set-point'. To this end, we determined whether long-term leptin infusion in rats would prevent the normal weight regain after food restriction.. Male Sprague-Dawley rats received leptin (leptin-treated) or saline (vehicle-treated) by intravenous infusion. After a 2 week run-in period, food intake was adjusted to 50% of each individual's normal intake for 12 days. Two days prior to the return of unlimited access to food, one group of animals received continuous leptin infusion at 3 micro g/h for the next 14 days. Blood samples taken from the tail vein were used to determine leptin concentrations. A third group of animals that did not undergo food restriction but received saline infusion served as control. As leptin acts in the brain to modulate neuropeptide Y (NPY) levels, hypothalamic NPY content was measured at the end of the study.. Food restriction to 50% normal intake for 12 days induced a 20% weight loss and significant reductions in plasma leptin compared with non-restricted control rats (0.5+/-0.1 vs 2.6+/-0.4 ng/ml, P<0.05). Intravenous infusion of leptin increased leptin concentrations four-fold compared with vehicle-treated animals (9.5+/-1.3 vs 2.2+/-0.4 ng/ml, P<0.05). The infusion of leptin attenuated the increase in daily food intake after free access to food was resumed (P<0.05 at 4, 6 and 8 days). Despite this, both groups of previously restricted rats had regained the same amount of weight after 12 days of ad libitum feeding. No difference was noted in NPY levels measured in the arcuate nucleus and the paraventricular nucleus, in line with the similar amounts of food eaten by all rats at the end of the experiment.. Increasing plasma leptin concentrations just prior to the end of a period of food restriction reduced subsequent food intake, but did not appear to exert a major influence on the body weight 'set-point', as leptin did not prevent weight regain. The results of the present study suggest that leptin may be of little value in maintaining weight loss in individuals who have lost weight through dieting. Further research is required to understand the role of leptin in the regulation of energy balance.

Topics: Animals; Drinking; Eating; Food Deprivation; Hypothalamus; Leptin; Male; Neuropeptide Y; Rats; Rats, Sprague-Dawley; Weight Gain

Neuropeptide Y (NPY) is a strong orexigenic neurotransmitter also known to modulate several neuroendocrine axes. alpha-Melanocyte-stimulating hormone (MSH) is an essential anorectic neuropeptide, acting on hypothalamic MC3/4 receptor subtypes. When given as an intracerebroventricular bolus injection, Melanotan-II (MT-II), a non selective MC receptor agonist, inhibits feeding, suppresses the NPY orexigenic action, and reduces basal insulinaemia. We evaluated the effects of a 7-day central infusion of MT-II (15 nmol/day) given either alone or in association with NPY (5 nmol/day) in male Sprague-Dawley rats. MT-II produced almost full anorexia for 1-2 days but then feeding gradually returned to normal despite continued MT-II infusion. When coinfused with NPY, MT-II also produced the same initial anorectic episode but then maintained feeding to upper normal levels, thus cancelling the hyperphagia driven by NPY. Whereas NPY infusion produced a doubling of fat pad weight, MT-II reduced adiposity by a factor of two compared to pair-fed rats, and vastly curtailed the NPY-driven increase in fat pad weight. MT-II infusion also significantly curtailed the NPY-induced rise in insulin and leptin secretions. NPY infusion significantly inhibited hypothalamic pro-opiomelanocortin mRNA expression, most likely cancelling the alpha-MSH anorectic activity. As expected from previous studies, chronic NPY infusion strongly inhibited both the gonadotropic and somatotropic axes, and coinfusion of MT-II did not reverse these NPY-driven effects, in sharp contrast with that seen for the metabolic data. MT-II infusion alone had little effect on these axes. In conclusion, chronic MT-II infusion generated a severe but transient reduction in feeding, suggesting an escape phenomenon, and clearly reduced fat pad size. When coinfused with NPY, MT-II was able to cancel most of the NPY effects on feeding, but not those on the neuroendocrine axes. It appears therefore that, as expected, NPY and alpha-MSH closely interact in the control of feeding, whereas the neural pathways by which NPY affects growth and reproduction are distinct and not sensitive to MC peptide modulation.

Topics: Adipocytes; Adipose Tissue; alpha-MSH; Animals; Carrier Proteins; Drinking; Drug Interactions; Eating; Gene Expression; Gonadal Steroid Hormones; Growth Hormone-Releasing Hormone; Hypothalamus; Insulin; Insulin-Like Growth Factor I; Intracellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptide Y; Neuropeptides; Obesity; Orexins; Peptides, Cyclic; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Weight Gain

Concentrations of leptin in serum and milk were assessed in gilts fed diets during gestation that differed in energy level. Beginning at day 45 and continuing throughout pregnancy, gilts received either a high-energy (6882 kcal metabolizable energy (ME) per day) or low-energy (5221 kcal ME per day) diet (n = 9 per group). All gilts had ad libitum access to a standard lactation diet throughout a 21 day lactation. During gestation, gilts consuming the high-energy diet gained more body weight (P < 0.01) and backfat thickness (P = 0.03) than gilts fed the low-energy diet; however, serum concentrations of leptin remained similar between groups (P = 0.35). Within 24 h after farrowing, gilts fed the high-energy diet had greater levels of leptin in serum and milk than gilts that consumed the low-energy diet during gestation (P < 0.07); Across treatments, backfat thickness and leptin levels in serum were positively correlated (r(2) = 0.51; P = 0.03). At weaning, backfat thickness (P < 0.07), but not body weights or serum and milk levels of leptin (P > 0.1), were greater for gilts fed the high-energy, versus the low-energy, diet during gestation. Gilts that were fed the low-energy diet during gestation consumed more feed during week 2 of lactation (P = 0.06). Our results suggest that altering the level of energy in the diets of gestating swine can influence circulating and milk concentrations of leptin, as well as feed consumption, during lactation.

Topics: Adipose Tissue; Animals; Body Composition; Body Constitution; Diet, Reducing; Energy Intake; Female; Lactation; Leptin; Milk; Pregnancy; Pregnancy, Animal; Swine; Weight Gain

We describe a model of energy homeostasis to better understand neuronal pathways that control energy balance and their regulation by hormonal signals such as insulin and leptin. Catabolic neuronal pathways are those that both reduce food intake and increase energy expenditure (e.g., melanocortin neurons in the hypothalamic arcuate nucleus) and are stimulated by input from insulin and leptin. We propose that in the basal state, catabolic effectors are activated in response to physiological concentrations of leptin and insulin, and that this activation is essential to prevent excessive weight gain. In contrast, anabolic pathways (e.g., neurons containing neuropeptide Y) are those that stimulate food intake and decrease energy expenditure and are strongly inhibited by these same basal concentrations of insulin and leptin. In the basal state, therefore, catabolic effector pathways are activated while anabolic effector pathways are largely inhibited. The response to weight loss includes both activation of anabolic and inhibition of catabolic pathways and is, thus, inherently more vigorous than the response to weight gain (stimulation of already-activated catabolic pathways and inhibition of already-suppressed anabolic pathways). Teleological, molecular, physiological, and clinical aspects of this hypothesis are presented, along with a discussion of currently available supporting evidence.

Topics: Adipose Tissue; Animals; Energy Metabolism; Feedback; Feeding Behavior; Homeostasis; Humans; Insulin; Leptin; Models, Biological; Pro-Opiomelanocortin; Weight Gain

Long-term treatment with glucocorticoids induces weight gain and increased risk to develop obesity-related metabolic complications. The underlying mechanisms are not fully understood. Glucocorticoid therapy has previously been associated with increased levels of circulating leptin. In this study the eating behaviour was therefore studied in relation to leptin levels before and after short-term prednisolone treatment.. Within-subject design.. Twelve healthy postmenopausal women with a mean body mass index (BMI) of 28.9 kg m-2 (+/-0.8 SEM) volunteered after recruitment by an advertisement in the local paper.. The subjects received 25 mg prednisolone daily for 7 days.. Fasting serum samples were obtained before, during and after treatment for determination of leptin and insulin, glucose and fractionated lipoproteins in plasma. The microstructure of the eating behaviour was registered with a universal eating monitor, VIKTOR. Appetite was estimated by visual analogue rating scales and food intake by a 48-h recall.. Serum leptin increased after 2 and 7 days of glucocorticoid administration (P < 0.01), and the food intake measured by VIKTOR after 7 days of treatment (P < 0.05). No statistically significant changes were however, found in the 48-h food- recall or in the subjective appetite registrations. Insulin levels were borderline elevated (P = 0.062) after treatment, but no significant changes of fasting glucose were seen. High density lipoprotein cholesterol (HDL) increased (P < 0.05), whilst low density lipoprotein cholesterol (LDL) decreased (P < 0.05).. Food intake was elevated after glucocorticoid administration as observed with an objective, quantitative method, in spite of increased levels of circulating leptin.

Topics: Body Mass Index; Fasting; Feeding Behavior; Female; Glucocorticoids; Humans; Leptin; Middle Aged; Postmenopause; Prednisolone; Risk Factors; Weight Gain

To investigate whether dietary fatty acid (FA) composition and energy restriction (ER) interactively influence obese (ob) gene expression, rats consumed diets containing beef tallow, safflower, or fish oil ad libitum (AL) or at 60% AL intake. Circulating leptin concentrations were higher (P < 0.0001) after AL feeding, but were not influenced by dietary fat. ER decreased (P < 0.0001) weight gain and visceral adipose weight, which were positively correlated (r = 0.40 P < 0.001, r = 0.58 P < 0.0001) with circulating leptin levels. Visceral adipose ob mRNA levels were greater in animals fed unsaturated fats, particularly safflower oil, which had the highest ob mRNA levels. Circulating leptin levels did not parallel ob mRNA levels, except for the greater abundance detected in AL adipose in comparison to ER animals. In addition, visceral FA profiles reflected dietary fat source and were influenced by an interaction of dietary fat and energy. These data demonstrate that dietary fat, particularly from a plant or marine source, and ER interactively influence ob mRNA levels; however, alterations in ob mRNA do not confer changes in circulating leptin, with the exception of ER, which is a key determinant. Thus, dietary intake is an important regulator of leptin production; however, the significance of these modest changes in diet-induced obese animals requires further study.

Topics: Adipose Tissue; Animals; Dietary Fats; Energy Intake; Fats; Fatty Acids; Fish Oils; Gene Expression Regulation; Insulin; Leptin; Male; Rats; Rats, Sprague-Dawley; RNA, Messenger; Safflower Oil; Weight Gain

The mechanism underlying the gender-based difference in circulating leptin levels (females>males) is still uncertain, because the difference persists even after adjustment for fat mass and sex steroid concentrations. In this study, we tested the possibility that the neonatal sex steroid milieu, which is critical for the sexual differentiation of the brain, may permanently affect leptin secretion in rats of both sexes. Male rats were neonatally castrated (NC), and females were neonatally androgenized (NA) by testosterone (T). Two subsets of the NC males were given T on postnatal day 1 or 29. Appropriate controls for all these groups were prepared. The animals were sacrificed on postnatal day 57, and at this age, the percent body fat was similar among all the male and female groups. NC males had a two-fold, significantly higher level of leptin than intact males. This hyperleptinemia induced by NC was prevented by T when it was given neonatally, but not on the day 29. By contrast, NA for females was without effect on leptin titers in later life. These results suggest that neonatal T in male rats may, at least in part, mediate the sex-related difference in leptin secretion that becomes apparent in later life. However, as intact females still had significantly higher leptin titers than NC males, it is very likely that additional factors may also be responsible for the sexually dimorphic leptin secretion in rats.

Topics: Adipose Tissue; Aging; Animals; Animals, Newborn; Female; Gonads; Leptin; Male; Orchiectomy; Rats; Rats, Wistar; Sex Characteristics; Steroids; Testosterone; Weight Gain

Previous studies suggest a possible link between leptin and hepatic inflammation; however, the role of leptin on liver disease remains unclear. The purpose of the present study was to evaluate the effect of leptin on tissue lipid peroxidation and the antioxidant status in experimental hepatotoxicity. Administering ethanol (6.32 g/kg body weight) to 4-week-old healthy mice for 45 days resulted in significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lowered activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione related enzymes such as glutathione peroxidase (GPx) and glutathione S-transferase (GST) as compared with those of the control mice. subsequent to the experimental induction of hepatotoxicity (i.e. after the initial period of 30 days) exogenous leptin was simultaneously administered (230 microg/kg body weight) every alternate day for 15 days along with the daily dose of alcohol. Leptin administration to control and alcohol-treated mice significantly reduced the weight gain, significantly elevated the liver and kidney levels of TBARS and CD, and significantly lowered the levels of enzymic and non-enzymic antioxidants as compared with the untreated control and alcohol supplemented mice. It is postulated that the increase in systemic leptin levels enhance the oxidative stress, and lower the antioxidant defence, leading to augmented hepatic inflammation in alcoholic liver disease.

Topics: Analysis of Variance; Animals; Brain; Catalase; Ethanol; Glutathione; Kidney; Leptin; Lipid Peroxidation; Liver; Liver Diseases, Alcoholic; Male; Mice; Oxidative Stress; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Weight Gain

The objective of this study was to evaluate the relationship between serum concentrations of the hormone leptin with growth and carcass traits insix distinct breeds of pigs entered into the 2000 National Barrow Show Sire Progeny Test. Breeds evaluated were Berkshire (n = 131), Chester White (n = 33), Duroc (n = 40), Landrace (n = 23), Poland China (n = 26), and Yorkshire (n = 41). Serum samples were collected and assayed for concentrations of leptin at entry into test (On-Test Leptin) at 34 +/- 6.7 kg of live weight and again 24 h prior to harvest (Off-Test Leptin) at 111 +/- 3.1 kg of live weight. Carcass measurements taken included hot carcass weight, carcass length, backfat, longissimus muscle area (LMA), longissimus pH, Hunter L-value, chemically determined intramuscular fat (IMF), and subjective color, marbling, and firmness scores. Average daily gain, IMF percentages, and water-holding capacity (WHC) were also determined. On-Test Leptin concentrations were not different (P > 0.10) between swine breeds; however, Off-Test Leptin concentrations did differ (P < 0.001) across genotype. Berkshire had the greatest Off-Test Leptin concentrations (6.58 +/- 0.43 ng/mL), and Duroc and Yorkshire had the lowest (3.49 and 3.96 +/- 0.68 ng/mL; respectively). In addition, Off-Test Leptin concentrations were correlated with average daily gain (r = 0.29; P < 0.001), last-rib fat thickness (r = 0.48; P < 0.001), 10th rib backfat (r = 0.52; P < 0.001), LMA (r = -0.33; P < 0.001), percent fat-free carcass lean (r = -0.51; P < 0.001), and WHC (r = 0.15; P < 0.05). Off-Test Leptin concentrations also differed by gender, with barrows having greater (P < 0.001) serum concentrations of leptin than gilts (6.55 +/- 0.48 vs 3.35 +/- 0.44). Differences exist between breeds of pigs in a manner consistent with breed-specific traits for growth, leanness, and quality; thus, leptin may serve as a useful marker for selection or identification of specific growth and carcass traits.

Topics: Adipose Tissue; Animals; Biomarkers; Body Composition; Female; Genotype; Leptin; Male; Meat; Sex Factors; Swine; Weight Gain

The present study was designed to define how dietary fat type regulates body adiposity in dietary obesity-susceptible (DOS) Sprague-Dawley (SD) rats. Eighty-three SD rats received a purified diet containing 50 g maize oil (MO)/kg for 3 weeks and then thirty-nine of the rats, designated as the DOS rats, were allotted to diets containing 160 g MO (DOS-MO), beef tallow (DOS-BT) or fish oil (DOS-FO)/kg for 9 weeks. As a result of the experiment, the DOS-FO rats had significantly (P<0.05) reduced weight gain and abdominal and epididymal fat-pad mass than the DOS-MO and DOS-BT rats. Serum leptin level was also significantly (P<0.05) lower in the DOS-FO rats; however, hypothalamic leptin receptor (a and b) mRNA and neuropeptide Y expressions were not altered by dietary fat sources. A lower acetyl-CoA carboxylase mRNA expression in the liver was observed in the DOS-FO group, whereas hepatic peroxisome proliferator-activated receptor-gamma mRNA and protein expressions were markedly elevated in the DOS-FO group compared with those in the other groups. We did not observe differences in acetyl-CoA carboxylase and peroxisome proliferator-activated receptor-gamma expressions in epididymal fat of the DOS rats consuming MO, BT or FO. It is concluded from our present observations that dietary fat type, especially that rich in FO, plays a potential role in down-regulation of adiposity by altering hepatic lipogenic genes, rather than feeding behaviour, in the DOS-SD rats.

Topics: Acetyl-CoA Carboxylase; Adipose Tissue; Animals; Cattle; Corn Oil; Dietary Fats; Disease Susceptibility; Eating; Fish Oils; Gene Expression Regulation; Leptin; Liver; Male; Neuropeptide Y; Obesity; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Receptors, Leptin; Transcription Factors; Weight Gain

Topics: Body Mass Index; Female; Humans; Indians, North American; Leptin; Male; Weight Gain

To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain.. From two large prospective cohorts in The Netherlands (n = 17,500), we compared the baseline leptin of 259 subjects who had gained an average of 12.6 kg (range 5.5 to 33 kg) with 277 subjects who kept stable weight (range -2.6 to 3.1 kg) after a mean follow-up of 6.8 years. Three polymorphisms in the LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) were determined.. Weight gainers had significantly higher baseline leptin levels than those who kept stable weight (odds ratio = 1.27, 95% confidence interval 1.1 to 1.5, per SD increase in log(e)-transformed leptin). Weight gainers with the Arg109 or the Arg223 alleles had higher leptin levels compared with the noncarriers of these alleles. Only among men, the association between leptin and weight gain tended to be stronger among those with an Arg223 allele compared with those without this mutation.. Relatively high leptin levels predict weight gain, suggesting that leptin resistance plays a role in the development of obesity in the general population. Higher leptin levels for those with a Lys109Arg or Gln223Arg mutation (or a linked other marker) may imply that these subjects have a modified functional leptin receptor. However, the role of these mutations on weight gain is limited.

Topics: Adult; Alleles; Arginine; Body Mass Index; Female; Glutamine; Humans; Leptin; Lysine; Male; Netherlands; Odds Ratio; Polymorphism, Genetic; Prospective Studies; Receptors, Cell Surface; Receptors, Leptin; Sex Characteristics; Weight Gain

The adipocyte hormone leptin plays an important part in the reproductive function and in energy homeostasis. Only single studies have addressed the relationship between leptin and the hypothalamus-pituitary-gonadal axis (HPG) in anorexia nervosa (AN). In the present study 18 female adolescents with AN were investigated during weight gain. Leptin, LH, FSH, fT3, BMI and body composition were measured in the 1(st), 3(rd), 7(th) and 11(th) week of inpatient treatment. 18 eumenorrheic age- and gender-matched controls were examined once during the early follicular phase of their menstrual cycle. Our results demonstrate a critical leptin level of 1.2 ng/ml for an increase of FSH and confirmed a leptin threshold level of 1.85 ng/ml for LH. It may be concluded that leptin represents a metabolic gate to gonadotropin secretion. Once this is exceeded other biological mechanisms seem to be important for the complete recovery of the reproductive function and the resumption of menses.

Topics: Adolescent; Analysis of Variance; Anorexia Nervosa; Body Mass Index; Female; Gonadotropins; Humans; Leptin; Reproduction; Statistics, Nonparametric; Weight Gain

Topics: Adipose Tissue; Antipsychotic Agents; Clozapine; Humans; Leptin; Weight Gain

Bitter melon (BM) is known for its hypoglycemic effect but its effect on rats fed a hyperinsulinemic high fat diet has not been examined. In a dose-response (0.375, 0.75 and 1.5%) study, oral glucose tolerance was improved in rats fed a high fat (HF; 30%) diet supplemented with freeze-dried BM juice at a dose of 0.75% or higher (P < 0.05). At the highest dose, BM-supplemented rats had lower energy efficiency (P < 0.05) and tended (P = 0.10) to have less visceral fat mass. In a subsequent experiment, rats habitually fed a HF diet either continued to consume the diet or were switched to a HF+BM, low fat (LF; 7%) or LF+BM diet for 7 wk. BM was added at 0.75%. Final body weight and visceral fat mass of the two last-mentioned groups were similar to those of rats fed a LF diet for the entire duration. Rats switched to the HF+BM diet gained less weight and had less visceral fat than those fed the HF diet (P < 0.05). The addition of BM did not change apparent fat absorption. BM supplementation to the HF diet improved insulin resistance, lowered serum insulin and leptin but raised serum free fatty acid concentration (P < 0.05). This study reveals for the first time that BM reduces adiposity in rats fed a HF diet. BM appears to have multiple influences on glucose and lipid metabolism that strongly counteract the untoward effects of a high fat diet.

Topics: Adipose Tissue; Animals; Dietary Fats; Energy Intake; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Insulin; Leptin; Male; Momordica; Organ Size; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Weight Gain

To assess the leptin responses to a 4-day energy-restricted diet in men with different weight history; high retrospective weight gain was expected to be associated with a small decline in leptin.. Changes in fasting leptin and insulin were measured during a 4-day controlled intervention, in which men with high retrospective weight gain and men who had stable weight consumed 35% of their estimated energy needs.. A total of 44 healthy men (age: 31-52 y, BMI: 22.7-39.8 kg/m(2)) were recruited from a cohort study: 22 men who had gained weight (weight change >1 kg/y) and 22 men whose weight had remained stable (weight change +/-0.3 kg/y) between the first (1987-1991) and the second measurement (1993-1997) of the cohort study. The intervention study was carried out in 2001.. After intervention, changes in fasting leptin levels were similar for both groups of retrospective weight gain: -2.2 microlU/ml (95% CI: -2.8; -1.7) and -2.4 microlU/ml (95% CI: -3.2; -1.7) respectively (P=0.69). Proportional changes in fasting leptin levels were different: -43.3% (95% CI: -47.8; -38.4) in the participants whose weight had remained stable (n=22) and -35.2% (95% CI: -42.4; -27.1) in those who had gained weight (n=22)(P<0.05). Analyses in a subgroup of men (n=18), in which the contrast in weight history was more pronounced than in the total group, did not show this difference. A higher proportional decrease in insulin levels was seen in men whose weight remained stable than in those who had gained weight: -35.4% (95% CI: -46.9; -21.3) and -12.8% (95% CI: -28.1; 5.7), respectively. The proportional decrease in leptin was positively associated with the proportional decrease in insulin (r=0.52; P<0.05). The decrease in leptin was positively associated with preintervention body weight (r=0.36; P<0.05), BMI (r=0.44; P<0.05), and waist-circumference (r=0.46; P<0.05).. Although we found that the 4-day energy restriction had a smaller effect on the decrease in leptin in men with retrospective weight gain, our study does not show convincing evidence that men who gained weight are less leptin responsive to changes in energy balance than those who were weight stable.

Topics: Adult; Blood Glucose; Body Weight; Cohort Studies; Diet, Reducing; Energy Metabolism; Fasting; Humans; Insulin; Leptin; Male; Middle Aged; Retrospective Studies; Weight Gain

Previous studies suggest a possible link between leptin and hepatic inflammation; however the role of leptin in liver diseases remains unclear. The purpose of the present study was to evaluate the effect of leptin on plasma and tissue lipids in experimental hepatotoxicity. Administering ethanol (6.32 g/kg body weight) to 4-week-old healthy mice for 45 days resulted in significantly elevated levels of plasma and tissue phospholipids, triglycerides and free fatty acids as compared with those of the control animals. Subsequent to the experimental induction of hepatotoxicity (i.e., the initial period of 30 days) exogenous leptin was simultaneously administered (230 microg/kg body weight) every alternate day for 15 days along with the daily dose of alcohol. Leptin administration to control and alcohol-treated mice reduced the weight gain and significantly lowered the levels of plasma and tissue lipids as compared with the untreated control and alcohol supplemented mice. It is postulated that the increase in systemic leptin levels lower the plasma and tissue lipids of alcohol-treated mice, which operates independently of changes in food intake, body weight and the size of the fat stores.

Topics: Animals; Fatty Acids, Nonesterified; Hypolipidemic Agents; Leptin; Lipid Metabolism; Lipids; Liver Diseases, Alcoholic; Male; Mice; Phospholipids; Triglycerides; Weight Gain

Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain.. The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002.. Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups.. Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Dibenzothiazepines; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Leptin; Male; Obesity; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome; Triglycerides; Weight Gain

Gonadectomy predisposes domestic cats to undesired body weight gain and obesity. The disturbance responsible for this disregulation of energy balance has not been clearly identified. Energy intake and expenditure, body composition and plasma concentrations of leptin, insulin, glucose and triacylglycerol were determined during a 36-wk period in adult male (2-5 y) gonadectomized (n = 8) and intact (n = 8) normal cats and gonadectomized (n = 8) and intact (n = 8) lipoprotein lipase (LPL)-deficient cats. Cats were housed individually in temperature- and light-controlled rooms and continuously provided a commercial dry-type diet. In normal and LPL-deficient cats, body weight increased (P < 0.05) after gonadectomy by 27 to 29%, mostly as a result of fat accretion. There was a rapid increase (P < 0.05) in food intake of approximately 12% after gonadectomy of normal and LPL-deficient cats. The metabolic rate (kJ.kg(-1).d(-1)), determined in normal intact (319 +/- 20, n = 5) and gonadectomized (332 +/- 36, n = 5) cats, did not differ after gonadectomy. After gonadectomy, plasma concentrations of glucose and triacylglycerol did not change, whereas plasma insulin and leptin concentrations increased (P < 0.05), but not coincidentally with body weight gain. A stair-step increase in energy intake, and not decreased energy expenditure, appears to drive the weight gain associated with gonadectomy. Body fat mass appears to increase until the energy intake supports no further expansion. Adiposity signaling through insulin or leptin does not appear to mediate the energy intake effect. LPL deficiency did not preclude development of the overweight body condition. Therefore, gonadectomy-induced weight gain in cats is not a result of changed adipose LPL activity, as previously suggested.

Topics: Animals; Blood Glucose; Body Composition; Body Weight; Cats; Eating; Energy Metabolism; Insulin; Leptin; Lipoprotein Lipase; Male; Orchiectomy; Osmolar Concentration; Triglycerides; Weight Gain

Similar to leptin, ciliary neurotrophic factor (CNTF) suppresses appetite and selectively reduces body fat in leptin-deficient ob/ob mice. To assess the relative importance of specific regions of the hypothalamus in mediating these effects, we administered a CNTF analogue (CNTFAx15) or leptin to mice made obese by administration of gold thioglucose (GTG), which destroys a well-defined portion of the medial basal hypothalamus. CNTFAx15 treatment reduced appetite and body weight in obese GTG-lesioned C57BL/6 mice, whereas leptin failed to effect similar changes regardless of whether treatment was initiated before or after the lesioned mice had become obese. Because leptin does not reduce food intake or body weight in most forms of obesity (a condition termed 'leptin resistance'), we also investigated the actions of leptin in GTG-lesioned leptin-deficient (ob/ob) mice. By contrast to C57BL/6 mice, leptin treatment reduced food intake and body weight in GTG-lesioned ob/ob mice, although the effect was attenuated. To further compare the neural substrates mediating the anorectic actions of leptin and CNTF, we determined the patterns of neurone activation induced by these proteins in the hypothalamus of intact and GTG-lesioned mice by staining for phosphorylated signal transducer and activator of transcription 3 (pSTAT3). CNTFAx15 stimulated robust pSTAT3 signalling in neurones of the medial arcuate nucleus in both intact and lesioned C57BL/6 and ob/ob mice. Leptin administration stimulated pSTAT3 signalling in only a few neurones of the medial arcuate nucleus in intact or lesioned C57BL/6 mice, but elicited a robust response in intact or lesioned ob/ob mice. By contrast to CNTFAx15, leptin treatment also resulted in prominent activation of STAT3 in several areas of the hypothalamus outside the medial arcuate nucleus. This leptin-induced pSTAT3 signal was at least as prominent in intact and GTG-lesioned C57BL/6 mice as it was in ob/ob mice, and thus was not correlated with appetite suppression or weight loss. These results indicate that the medial arcuate nucleus is a key mediator of appetite suppression and weight loss produced by CNTF and leptin, whereas GTG-vulnerable regions play a role only in leptin-induced weight loss. Other regions of hypothalamus in which pSTAT3 signal is induced by leptin may regulate energy metabolism through mechanisms other than appetite reduction.

Topics: Animals; Appetite; Arcuate Nucleus of Hypothalamus; Aurothioglucose; Body Weight; Ciliary Neurotrophic Factor; DNA-Binding Proteins; Drug Resistance; Eating; Hypothalamus; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Neurons; Obesity; Phosphorylation; Signal Transduction; STAT3 Transcription Factor; Trans-Activators; Weight Gain

Ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R), is an appetite stimulatory signal from the stomach with structural resemblance to motilin. We examined the effects of the gastric peptide ghrelin and GHS-R antagonists on energy balance and glycaemic control in mice.. Body weight, fat mass, glucose, insulin, and gene expression of leptin, adiponectin, and resistin in white adipose tissue (WAT) were measured after repeated administrations of ghrelin under a high fat diet. Gastric ghrelin gene expression was assessed by northern blot analysis. Energy intake and gastric emptying were measured after administration of GHS-R antagonists. Repeated administration of GHS-R antagonist was continued for six days in ob/ob obese mice.. Ghrelin induced remarkable adiposity and worsened glycaemic control under a high fat diet. Pair feeding inhibited this effect. Ghrelin elevated leptin mRNA expression and reduced resistin mRNA expression. Gastric ghrelin mRNA expression during fasting was increased by a high fat diet. GHS-R antagonists decreased energy intake in lean mice, in mice with diet induced obesity, and in ob/ob obese mice; it also reduced the rate of gastric emptying. Repeated administration of GHS-R antagonist decreased body weight gain and improved glycaemic control in ob/ob obese mice.. Ghrelin appears to be closely related to excess weight gain, adiposity, and insulin resistance, particularly under a high fat diet and in the dynamic stage. Gastric peptide ghrelin and GHS-R may be promising therapeutic targets not only for anorexia-cachexia but also for obesity and type 2 diabetes, which are becoming increasingly prevalent worldwide.

Topics: Adiponectin; Adipose Tissue; Animals; Blotting, Northern; Dietary Fats; Eating; Energy Metabolism; Gastric Emptying; Gene Expression; Ghrelin; Glucose; Hormones, Ectopic; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Nerve Growth Factor; Peptide Hormones; Proteins; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Ghrelin; Resistin; RNA, Messenger; Weight Gain

Demographic, psychopathological and hormonal parameters of 22 women with previous anorexia nervosa (AN) presently recovered, in a state of stabilized nutritional normalization for 3 months to 2 years but with persistent amenorrhoea, and of 20 psychophysically healthy age- and sex-matched normally menstruating controls were studied. Body mass index (BMI) values did not differ in patients and controls. Psychological examination, monitored by Eating Disorder Inventory 1, Bulimic Investigation Test Edinburgh, Yale-Brown-Cornell Eating Disorder Scale, and Tridimensional Personality Questionnaire rating scales, showed the persistence of some of the psychopathological symptoms of AN. Hormonal examinations included basal plasma concentrations of follicle stimulating hormone, luteotropic hormone, estrogens (E), progesterone, thyrotropic hormone, FT(3), FT(4) (immunoradiometric assays), leptin (LEP) (enzymatic-linked-immunosorbent assay) and 24 h urinary free cortisol (immunoradiometric assay). Hormone values were the same in patients and controls, except for E and LEP levels, which were significantly lower in patients than in controls. The concentrations of the two hormones were not correlated with the BMI of the patients, but LEP values were correlated negatively with the difference between the present BMI and the preanorexic one. The values of both hormones correlated negatively with some of the psychopathological aspects typical of AN, in particular with high 'body dissatisfaction', 'ineffectiveness', and 'interpersonal distrust' and with low 'interoceptive awareness'.

Topics: Adult; Amenorrhea; Anorexia Nervosa; Body Mass Index; Estrogens; Female; Humans; Hydrocortisone; Leptin; Personality Disorders; Personality Inventory; Progesterone; Recovery of Function; Recurrence; Thyrotropin-Releasing Hormone; Weight Gain

The extent to which childhood GHD affects adult fracture risk is unclear. We measured femoral strength in adult transgenic growth-retarded rats as a model of GHD. Long-term, moderate GHD was accompanied by endocrine and morphometric changes consistent with a significant reduction in femoral strength.. Childhood growth hormone deficiency (GHD) is associated with osteopenia, but little is known about its effects on subsequent adult bone strength and fracture risk.. We have therefore measured femoral strength (failure load measured by three-point bending) in a new model of moderate GHD, the transgenic growth-retarded (Tgr) rat at 15, 22-23, and 52 weeks of age, and have quantified potential morphological and endocrine determinants of bone strength.. Skeletal growth retardation in Tgr rats was accompanied by a sustained reduction in the anterior-posterior diameter of the femoral cortex, whereas mid-diaphyseal cortical wall thicknesses were largely unaltered. Total femoral strength was significantly impaired in Tgr rats (p < 0.01), and this impairment was more pronounced in males than females. Compromised bone strength in Tgr rats could not be accounted for by the reduction in mechanical load (body weight) and was not caused by impairment of the material properties of the calcified tissue (ultimate tensile stress), despite marked reductions in femoral mineral density (areal bone mineral density; p < 0.001). Microcomputerized tomographical analysis revealed significant modification of the architecture of trabecular bone in Tgr rats, with reductions in the number and thickness of trabeculae (p < 0.05) and in the degree of anisotropy (p < 0.01). The marked reduction in plasma insulin-like growth factor-1 in Tgr rats was accompanied by the development of high circulating leptin levels (p < 0.01).. These results show that the changes in endocrinology and bone morphology associated with long-term moderate GHD in Tgr rats are accompanied by changes consistent with a significant reduction in the threshold for femoral fracture.

Topics: Age Factors; Animals; Animals, Genetically Modified; Biomechanical Phenomena; Bone Density; Bone Development; Calcification, Physiologic; Compressive Strength; Dwarfism; Female; Femur; Growth Hormone; Insulin-Like Growth Factor I; Leptin; Male; Rats; Sex Characteristics; Weight Gain

To characterize the meal patterns of free feeding Sprague-Dawley rats that become obese or resist obesity when chronically fed a high-fat diet.. Male Sprague-Dawley rats (N = 120) were weaned onto a high-fat diet, and body weight was monitored for 19 weeks. Rats from the upper [diet-induced obese (DIO)] and lower [diet-resistant (DR)] deciles for body-weight gain were selected for study. A cohort of chow-fed (CF) rats weight-matched to the DR group was also studied. Food intake was continuously monitored for 7 consecutive days using a BioDAQ food intake monitoring system.. DIO rats were obese, hyperphagic, hyperleptinemic, hyperinsulinemic, hyperglycemic, and hypertriglyceridemic relative to the DR and CF rats. The hyperphagia of DIOs was caused by an increase in meal size, not number. CF rats ate more calories than DR rats; however, this was because of an increase in meal number, not size. When expressed as a function of lean mass, CF and DR rats consumed the same amount of calories. The intermeal intervals of DIO and DR rats were similar; both were longer than CF rats. The nocturnal satiety ratio of DIO rats was significantly lower than DR and CF rats. The proportion of calories eaten during the nocturnal period did not differ among groups.. The hyperphagia of a Sprague-Dawley rat model of chronic diet-induced obesity is caused by an increase in meal size, not number. These results are an important step toward understanding the mechanisms underlying differences in feeding behavior of DIO and DR rats.

Topics: Animals; Body Composition; Circadian Rhythm; Diet; Eating; Energy Intake; Food; Genetic Predisposition to Disease; Hyperglycemia; Hyperinsulinism; Hyperphagia; Hypertriglyceridemia; Insulin; Leptin; Male; Obesity; Rats; Rats, Sprague-Dawley; Satiation; Weight Gain

Leptin is secreted during pregnancy by the placenta and by the maternal and fetal adipose tissues. The leptin levels mainly reflect the amount of fat stored and thus are indicative of the energy balance, i.e., small-for-gestational-age (SGA) neonates represent the negative metabolic balance of in utero starved babies. We chose to compare maternal and umbilical cord leptin levels in pregnancies complicated by asymmetrical SGA versus those with appropriate-for-gestational-age (AGA) neonates as well as a model of multifetal growth concordant gestations in order to establish through the 'leptin link' the relative contributions of mother, fetus, and placenta to fetal weight. We found that the maternal leptin levels at delivery correlated poorly with the maternal weight gain/body mass index and with neonatal birth weight. Furthermore, the umbilical cord leptin levels correlated well with neonatal and placental weights in the AGA group but not in the SGA group. As in AGA singleton pregnancies, in multifetal uncomplicated pregnancies, the umbilical cord leptin levels correlated well with the birth weight of individuals, regardless of the status of the twin or triplet in the set. Thus, we speculated that in SGA neonates the birth weight represents the lean body weight and the low adipose tissue content (as opposed to the AGA neonates who have a substantial adipose tissue content) and, therefore, reflects mainly the basic placental contribution.

Topics: Adipose Tissue; Birth Weight; Body Mass Index; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Leptin; Organ Size; Placenta; Pregnancy; Weight Gain

We previously demonstrated that daily melatonin administration to middle-aged rats to restore youthful plasma melatonin levels also decreased body weight, visceral fat, plasma leptin, and plasma insulin to more youthful levels, without detectable changes in consumption of chow diet. We now evaluate: (a) whether melatonin alters consumption of a more precisely quantifiable liquid diet similar in high-fat content to the typical American diet; (b) differences between melatonin-induced endocrine responses in the fasted vs fed state; and (c) time course of these responses. Ten-month-old male Sprague- Dawley rats received liquid diet containing either 0.2 micro g/mL melatonin (MELATONIN) or vehicle (CONTROL) (n = 14/treatment); the diet was available throughout each night, but was removed for the final 10 h of each daytime. MELATONIN rats gained 4% body weight during the first 2 wk and then stabilized, whereas CONTROL rats continued to gain for an additional week, achieving 8% gain (p < 0.05 vs MELATONIN). During the first 3 wk, afternoon tail-blood leptin, but not insulin, levels decreased in melatonin-treated rats (p < 0.05 vs CONTROL). After 8 wk, half of the rats were killed at the midpoint of the dark period (NIGHT; fed) and half at the end of the light period (DAYTIME; fasted). NIGHT but not DAYTIME plasma leptin levels were decreased in MELATONIN rats, whereas DAYTIME but not NIGHT plasma insulin levels were decreased (p < 0.05 vs CONTROL). Melatonin treatment did not alter cumulative food consumption. Thus, melatonin decreased weight gain in response to high-fat diet, decreased plasma leptin levels within 3 wk-before decreasing plasma insulin-and exerted these metabolic effects independent of total food consumption.

Topics: Age Factors; Animals; Circadian Rhythm; Dietary Fats; Eating; Fasting; Insulin; Leptin; Male; Melatonin; Rats; Rats, Sprague-Dawley; Weight Gain

It has been reported that hypertension and obesity often coexist with hyperuricemia. To clarify the relations between serum uric acid, plasma norepinephrine, and insulin or leptin levels in subjects with weight gain-induced blood pressure elevation, we conducted the present longitudinal study. In 433 young, nonobese, normotensive men, body mass index, blood pressure, and levels of serum uric acid, fasting plasma norepinephrine, insulin, and leptin were measured every year for 5 years. Subjects were stratified by significant weight gain and/or blood pressure elevation (>10% in body mass index or mean blood pressure) for 5 years. At entry, blood pressure, uric acid, and norepinephrine values in subjects with blood pressure elevation were greater than in those without it, although body mass index, insulin, and leptin were similar. At entry, body mass index, blood pressure, uric acid, and norepinephrine in subjects with weight gain were greater than in those without weight gain. The increases in body mass index, mean blood pressure, uric acid, norepinephrine, insulin, and leptin for 5 years were greater in subjects with blood pressure elevation and/or weight gain than in subjects without, and those increases were greatest in subjects with weight gain whose blood pressure was elevated. By multiple regression analysis, basal mean blood pressure, norepinephrine, and uric acid were significant determinant factors of changes in mean blood pressure over 5 years, and basal body mass index, norepinephrine, and uric acid were significant determinant factors of changes in body mass index. These results demonstrate that serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation.

Topics: Adult; Blood Pressure; Demography; Humans; Insulin; Leptin; Longitudinal Studies; Male; Norepinephrine; Prospective Studies; Uric Acid; Weight Gain

Melatonin is involved in the regulation of seasonal obesity in various species, including some rodents. This involvement has been demonstrated in nonphotoperiodic rodents like rats, but only in models of enhanced body weight such as genetically obese or middle-aged rats. The aim of this investigation was to determine the effects of melatonin on body weight and metabolic parameters in a model closer to that observed in Western populations, i.e. Sprague Dawley rats fed a high-fat diet. They were treated for 3 wk with melatonin (30 mg/kg) 4 h after lights-on [Zeitgeber time (ZT) 4] or 1 h before lights-out (ZT11). Given at ZT11, melatonin decreased body weight gain and feed efficiency by half. Melatonin had no effect on plasma insulin level, but it decreased plasma glucose (13%), leptin (28%), and triglyceride (28%) levels. Furthermore, in pinealectomized high-fat diet rats, body weight gain and feed efficiency were increased 4 wk after surgery. Adipose tissue weight, insulinemia, and glycemia had a tendency to increase. Treatment with melatonin prevented in part these changes. These data demonstrate that melatonin may act as a regulator of body weight in a model of obesity and may prevent some of the side effects on glucose homeostasis such as decreased insulin sensitivity.

Topics: Adipose Tissue; Animals; Blood Glucose; Dietary Fats; Eating; Insulin; Leptin; Male; Melatonin; Obesity; Pineal Gland; Rats; Rats, Sprague-Dawley; Triglycerides; Weight Gain

Many adult diseases, including type 2 diabetes, hypertension and cardiovascular disease, are related to low birth weight. The mechanistic basis of this relationship is not known. To investigate the role of fetal undernutrition, we used a rat model of maternal protein restriction in which dams were fed a diet containing 80 g protein/kg (v. 200 g/kg in the control group) throughout gestation and lactation. Offspring were born smaller than controls and in adulthood developed diabetes, hyperinsulinaemia and tissue insulin resistance. To determine possible mechanisms of fetal programming, circulating levels of several hormones were measured in maternal plasma at gestational days 14, 17 and 21 and fetal plasma at gestational day 21. Several differences were noted at day 14, when glucose concentrations in maternal and feto-placental blood were raised significantly (P=0.04 and P=0.0001 respectively); insulin levels in the low-protein (LP) dams were raised (P=0.04), prolactin levels were raised (P=0.047) and progesterone levels were reduced (P=0.02). Circulating 17beta-oestradiol in the LP dams was raised by 35 % over those of the controls from day 17 to day 21 (P=0.008). A significant decrease in maternal leptin levels (P=0.004) was observed at gestation on day 21. Neither oestradiol nor leptin levels were altered in the fetal circulation at day 21. Maternal and fetal corticosterone levels were comparable with control levels, suggesting that they do not initiate the programming effects in this model. Our present results suggest that maternal protein restriction imposes changes in maternal levels of glucose, insulin, prolactin, progesterone, oestradiol and leptin; these changes could influence the programming of eventual adult disease in the developing fetus.

Topics: Animals; Blood Glucose; Body Weight; Corticosterone; Diet, Protein-Restricted; Disease Models, Animal; Eating; Estradiol; Fatty Acids, Nonesterified; Female; Fetal Growth Retardation; Insulin; Leptin; Organ Size; Placenta; Pregnancy; Progesterone; Prolactin; Rats; Rats, Wistar; Triglycerides; Weight Gain

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 determine if adult female rats adapt to lower and higher dietary energy density.. Study 1 compared high-fat (56%), high-energy density (HD) (21.6 kJ/g) and high-fat (56%), low-energy density (LD) (16.0 kJ/g) diets before surgery (two groups, 2 weeks, n = 16) and after surgery [ovariectomy (O) Sham (S); 2 x 2 factorial, n = 8; 6 weeks]. The second study (no surgery) compared high-fat (60.0%), high-energy (22.0 kJ/g) and low-fat (10.0%), low-energy (15.1 kJ/g) diets (n = 8).. In study 1, food intake was similar for the first 2 weeks, but rats on the LD diet consumed less energy, gained less weight, and had lower nonfasted serum leptin (all p < 0.0001) than rats on the HD diet. After surgery, rats on the LD and HD diets had similar weight gain, but rats on the LD diet consumed more food (p < 0.0001) and less energy (p < 0.009). O rats consumed more food and gained more weight (p < 0.0001) than S rats. Results from study 2 were similar to those from study 1.. The results demonstrated that O and S surgery rats and rats with no surgery adjust their food intake to defend a level of energy intake. This defense only occurred after a 2-week adaptation period. The major differences in final body weights and abdominal fat resulted from the initial 2 weeks before adaptation to energy density. Rats fed higher-energy diets seemed to "settle" at a higher level of adiposity, and rats fed lower-energy diets consumed more food to increase energy consumption.

Topics: Adaptation, Physiological; Animals; Dietary Carbohydrates; Dietary Fats; Eating; Energy Intake; Feces; Female; Leptin; Nitrogen; Ovariectomy; Random Allocation; Rats; Rats, Sprague-Dawley; Urinalysis; Weight Gain

Exposure to stress may cause either an increase or a decrease in food intake. Behavioral and physiological responses to stress, including alterations in feeding behavior, are sexually dimorphic. This study aimed to evaluate the interaction between estradiol levels and chronic variate stress on the intake of sweet food and on serum levels of leptin, a hormone secreted by the adipose cells with a role in the regulation of body weight. Adult female Wistar rats were used. After ovariectomy, the animals received estradiol replacement (or oil) subcutaneously. Rats were then divided in controls and stressed (submitted to 30 days of variate stress). Consumption of sweet food and of serum leptin was measured. Although animals receiving estradiol replacement presented smaller weight gain, they showed an increased consumption of sweet food. Chronic variate stress decreased sweet food intake at 30, but not at 20, days of treatment. Estradiol replacement in the stressed group prevented both the reduction observed in sweet food intake and the increase in leptin levels. These results suggest that there is an interaction between chronic stress and estradiol replacement in feeding behavior concerning sweet food consumption, and this interaction may be related to altered leptin levels.

Topics: Animals; Body Weight; Chronic Disease; Estradiol; Estrogen Replacement Therapy; Feeding Behavior; Female; Food Preferences; Leptin; Ovariectomy; Rats; Rats, Wistar; Stress, Psychological; Weight Gain

Long-term food restriction (85%, 70% and 50% of ad libitum energy intake for one month) induced a substantial fall in serum leptin concentration and leptin mRNA levels in epididymal white adipose tissue in rats. Surprisingly, this suppression was not reversed by refeeding ad libitum for 48 h. The reduction in serum leptin concentration and leptin mRNA level did not strictly correlate with reduction in fat or body mass. Unlike serum leptin concentration and epididymal adipose tissue leptin mRNA levels, fatty acid synthase activity, fatty acid synthase protein abundance and fatty acid synthase mRNA levels increased significantly in white adipose tissue after refeeding rats subjected to food restriction. The increase in serum insulin concentration was observed in all groups on different degrees of food restriction and refed ad libitum for 48 h compared to controls. A decrease in serum insulin concentration was found in the rats not refed before sacrifice. Long-term food restriction did not significantly affect serum glucose concentrations in either refed or non-refed rats. The data reported in this paper indicate that there is no rapid rebound in serum leptin concentration or leptin gene expression in contrast to the increase in serum insulin concentration and fatty acid gene expression in white adipose tissue of rats refed ad libitum after one month's food restriction.

Topics: Adipose Tissue; Animals; Blotting, Western; Fasting; Fatty Acid Synthases; Fatty Acids; Food Deprivation; Gene Expression; Insulin; Leptin; Male; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Weight Gain

To elucidate the role of leptin on maxillo-facial morphological growth using hereditary obesity model ob/ob mice, and to examine the presence of the leptin receptor gene expression in the mouse condylar head cartilage.. Leptin was intraperitoneally administered once a day in 10 C57BL/6J (lean) and 10 C57BL/6J-ob (ob/ob) mice (leptin administration group), and phosphate-buffered saline (PBS) in 10 lean and 10 ob/ob mice (PBS administration group), between the fifth and 11th week after birth. The amount of fat, the body amount without fat, the rate of body fat, and the width of the condylar cervical area were measured during the 11th week, and roentgenographic cephalometric analysis was performed at the fifth, eighth, and 11th week. Furthermore, the condylar head cartilage in C57BL/6J mice was stereoscopically excised to extract total RNA, and RT-PCR method was performed regarding the leptin receptor gene.. The body fat amount in ob/ob mice with leptin production insufficiency was greater than that in lean mice, and significant differences were noted in every measurement item regarding maxillo-facial morphology. Recovery of bone length was noted in ob/ob mice by administering leptin. Furthermore, the expression of the leptin receptor gene in the condylar head cartilage was confirmed.. Exogenous leptin administration leads to significant increases in craniofacial dimensions; and leptin receptors are expressed in mandibular condylar cartilage. These results indicate an important role for leptin in craniofacial growth and morphology. We speculate that leptin's direct peripheral effect on bone and cartilage is closely involved in this role.

Topics: Adipose Tissue; Animals; Body Mass Index; Cartilage; Cephalometry; Gene Expression Regulation; Leptin; Male; Mandible; Mandibular Condyle; Maxillofacial Development; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Obese; Nasal Bone; Obesity; Occipital Bone; Receptors, Cell Surface; Receptors, Cytokine; Receptors, Leptin; Skull; Weight Gain

To investigate the effect of a high-energy (HE) diet on caloric intake, body weight, and related parameters in outbred male Sprague-Dawley (SD) rats.. Twenty-eight SD rats were fed either chow (C) for 19 weeks or HE diet for 14 weeks and then C for 5 weeks. Blood hormones and metabolites were assayed, and expression of uncoupling protein-1 and hypothalamic energy-balance-related genes were determined by Northern blotting and in situ hybridization, respectively.. HE rats gained body weight more rapidly than C animals with a range of weight gains, but there was no evidence that weight gain was bimodally distributed. Caloric intake was transiently elevated after introduction of the HE diet. Transfer of HE rats back to C resulted in a drop in caloric intake, but a stable body weight. In terminal analysis, two of four dissected adipose tissue depots were heavier in rats that had previously been fed HE diet. Blood leptin, insulin, glucose, and nonesterified fatty acids were not different between the groups. Uncoupling protein-1 mRNA was elevated in interscapular brown adipose tissue from HE rats. There was a trend for agouti-related peptide mRNA in the hypothalamic arcuate nucleus to be higher in HE rats.. Contrary to other studies of the SD rat on HE diet, body weight and other measured parameters were normally distributed. There was no segregation into two distinct populations on the basis of susceptibility to diet-induced obesity. This characteristic may be dependent on the breeding colony from which animals were sourced.

Topics: Adipose Tissue; Adipose Tissue, Brown; Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Blood Glucose; Carrier Proteins; Energy Intake; Fatty Acids, Nonesterified; Insulin; Intercellular Signaling Peptides and Proteins; Ion Channels; Leptin; Male; Membrane Proteins; Mitochondrial Proteins; Organ Size; Proteins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Uncoupling Protein 1; Weight Gain

To investigate the role of the monounsaturated n-9 fatty acids (MUFA) in the lipolytic activity of adipocytes, a study was carried out in which an increase in MUFA was produced in the tissues by two different methods; by the dietary enrichment of oleic acid or by producing an essential fatty acid deficiency syndrome. For this, forty-five male Sprague-Dawley rats were fed with a normal-energy diet and were subdivided into three groups. The diets varied in the type of dietary fat; palmitic acid, olive oil, or soyabean oil+palmitic acid. At the end of the study measurements were taken of weight, plasma leptin, tissue concentration of fatty acids, fat-cell size in the epididymal and the omental adipose tissues, adipocyte lipolytic activity of both tissues after stimulation with adrenaline, and the capacity of insulin to inhibit lipolysis. The baseline and adrenaline-stimulated lipolytic activity were greater and the anti-lipolytic capacity of insulin lower in the animals undergoing an increase in MUFA in the tissues (palmitic-acid and olive-oil diets). The area under the curve of glycerol, used as an indicator of lipolytic activity, was positively correlated with the concentration of MUFA and negatively with polyunsaturated fatty acids in the adipose tissues. It is concluded that an increase in tissue MUFA, however obtained, induces an increase in lipolytic activity.

Topics: Adipocytes; Adipose Tissue; Animals; Body Weight; Cells, Cultured; Diet; Dietary Fats, Unsaturated; Dose-Response Relationship, Drug; Epinephrine; Fatty Acids, Monounsaturated; Insulin; Leptin; Linear Models; Lipolysis; Male; Oleic Acid; Rats; Rats, Sprague-Dawley; Weight Gain

To investigate whether the -2548G/A functional polymorphism in promoter region of leptin gene influencing weight gain following antipsychotic agents (APS) acute treatment in schizophrenic patients.. 128 Chinese Han untreated patients with schizophrenia (male 61, female 67) with an age and gender matched health controls (n = 38) were recruited. The polymorphism of leptin gene was determined with PCR-RFLP technique. MRI determined abdominal body fat in 22 controls and 30 patients on admission and after 10 weeks treatment with risperidone or chlorpromazine. Body mass index (BMI) was measured on admission and every week subsequently (for patients).. There were average increases in (6.2 +/- 5.7)% of baseline weight and in (38.5 +/- 42)% of baseline abdominal subcutaneous fat (SUB) and in (40.0 +/- 41.2)% of baseline intra-abdominal fat (IAF) 10 weeks after treatment. There were no significant differences in the distribution of allele and genotypes either between the patients and controls or between gender groups. It was found significantly increased weight gain in the patient with the -2548AA genotype (chi(2) = 7.529, df = 1, P = 0.006; OR = 1.941; 95% CI: 1.175 - 3.207); The genotypes had no influence on the baseline weight indicators both in patients and controls. However, as compared with the patients with G allele, the patients with AA genotype had significant increase in BMI (P = 0.003) and SUB (P = 0.009).. The finding identify that the -2548G/A polymorphism in promoter region of leptin gene associated with APS-induced weight gain and abdominal fat deposition and distribution. -2548AA may be a genetic risk factor for the development of weight gain and body fat deposition in Chinese Han schizophrenic patients during APS acute treatment.

Topics: Adipose Tissue; Adolescent; Adult; Antipsychotic Agents; Female; Genotype; Humans; Leptin; Male; Middle Aged; Polymorphism, Genetic; Promoter Regions, Genetic; Weight Gain

Zinc deficiency in animals causes impaired growth and anorexia, and the mechanisms for these symptoms of zinc deficiency are not yet clear. We investigated whether circulating leptin levels and gene expression would be dysregulated under zinc deficiency and what would be the implications for appetite in rats. In study 1, 24 Sprague-Dawley rats were provided consecutively with three different dietary zinc intake levels: Zn-adequate (30 mg/kg of diet), Zn-depleted (1 mg/kg of diet), and Zn-replete (50 mg/kg of diet), for 1, 2, and 2 weeks, respectively. At the end of each dietary period, one-third of the rats were killed. In study 2, rats were assigned to one of the four Zn diet groups: Zn-adequate (30 mg/kg of diet), pair-fed (30 mg/kg of diet), Zn-deficient (1 mg/kg of diet), or Zn-sufficient (50 mg/kg of diet), and were fed for 4 weeks. Tissue Zn and serum leptin were measured, and leptin gene expression in adipose tissues (inguinal and abdominal) was determined by reverse transcription-polymerase chain reaction and northern blotting. Blood subfractions as plasma, red blood cells, and mononuclear cells and liver Zn level were decreased during the Zn-depletion period (P <.05). Serum leptin showed a tendency to increase during the Zn-depletion period and decreased back to the level of the Zn-repletion period. Leptin mRNA levels in inguinal adipocytes also increased during the Zn-depletion (P <.05) and Zn-deficient periods, which is consistent with the change in serum leptin. However, the decrease in leptin mRNA in abdominal adipocytes was not consistent with the increase in inguinal leptin levels and the change in serum leptin. Increased leptin levels in linguinal adipocytes is consistent with the expected physiological change of a decrease in appetite under Zn deficiency. However, before coming to any firm conclusion, further studies on adipose tissue-specific leptin expression, including the appetite-related neuropeptides, are necessary for clarifying the cause of lower appetite in zinc deficiency.

Topics: Adipocytes; Animals; Appetite; Eating; Energy Intake; Gene Expression Regulation; Leptin; Male; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Weight Gain; Zinc

Intracerebroventricular administration of recombinant adeno-associated virus (rAAV) encoding the rat leptin gene (rAAV-lep) to 24-d-old female and male rats suppressed postpubertal weight gain for extended periods by decreasing food consumption and adiposity, as reflected by lowered serum leptin, insulin, and FFA. Serum ghrelin levels were increased in young but not older rats. Central rAAV-lep therapy also increased energy expenditure through nonshivering thermogenesis in younger rats as shown by expression of uncoupling protein mRNA in brown adipose tissue. The sustained decrease in appetite seemingly resulted from attenuation of appetite-stimulating neuropeptide Y and enhancement of appetite-inhibiting melanocortin signalings in the hypothalamus. Neither the onset of pubertal sexual maturation nor reproductive cyclicity in adult female rats was affected by the sustained reduction in energy consumption and weight gain. These findings demonstrate that central leptin gene therapy in prepubertal rats is a novel therapy to control postpubertal weight gain, adiposity, and hyperinsulinemia for extended periods.

Topics: Adipose Tissue, Brown; Animals; Appetite; Carrier Proteins; Dependovirus; Energy Intake; Estrous Cycle; Female; Gene Expression; Genetic Therapy; Ghrelin; Growth; Hyperinsulinism; Hypothalamus; Injections, Intraventricular; Insulin; Ion Channels; Leptin; Male; Membrane Proteins; Mitochondrial Proteins; Neuropeptides; Obesity; Peptide Hormones; Rats; Rats, Sprague-Dawley; RNA, Messenger; Uncoupling Protein 1; Vagina; Weight Gain

Weight gain is a widely reported side effect of clozapine, but no predictive factor has been identified so far. We investigated whether pretreatment values of circulating leptin or its early changes during clozapine administration could predict the long-term weight gain induced by the drug. Body weight and plasma levels of leptin were prospectively measured in 22 patients (13 men and 9 women) with drug-resistant schizophrenia undergoing a long-term treatment with clozapine. At the end of the second week of clozapine administration, circulating leptin increased much more than weight gain, and this increase was inversely correlated to body weight increase observed after 6 and 8 months of treatment. These findings suggest that early changes in leptin secretion may predict long-term weight gain in the course of clozapine administration.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Clozapine; Female; Humans; Leptin; Male; Middle Aged; Prospective Studies; Schizophrenia; Statistics, Nonparametric; Weight Gain

The aim of this work was to study the evolution of rat food choice in relation to their age and metabolic parameters. Eighty Wistar rats were studied from birth to 13 weeks of age. At weaning, six litters were fed on a macronutrient self-selecting diet and four on a standard diet. In self-selecting males, protein intake was maximal at Week 7 of age and then plateaued (Week 13), whereas in females, protein consumption peaked at Week 7 and then steadily decreased. Females showed a strong and early preference for fat, which increased continuously with age. Males and females ingested their total energy intake during the dark period (respectively, 79% and 70%). Simple meals (composed of one item) were mainly ingested during the light phase, while mixed meals (at least two items) were ingested during the night. In males, most mixed meals began with carbohydrate bouts and finished with proteins, while in females no particular choice was observed at the beginning of meals, but most of them ended with protein bouts. Body weights of either male and female self-selecting or control fed rats were not significantly different at the end of the experiment. Differences between dietary groups in body fat mass were not observed with the exception of higher subcutaneous fat found in self-selecting rats. Moreover, insulinemia was lower in both male and female self-selecting rats. The high-protein, high-fat diet chosen by the self-selecting rats could be linked to a prevention of the age-related insulin resistance.

Topics: Adipose Tissue; Aging; Animals; Blood Proteins; Body Composition; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Female; Food Preferences; Insulin; Leptin; Liver; Male; Proteins; Rats; Rats, Wistar; Sex Characteristics; Weaning; Weight Gain

In this study, we evaluated the anti-obesity effects of selective beta3 adrenergic receptor agonist (ARa) and/or a diet in oophorectomized (OVX) treatment in obese rats. Ten-week-old female Sprague-Dawley rats were divided into 4 groups: (1) OVX; (2) OVX treated with beta3 ARa, BRL 35 135; (3) sham-operated controls (sham group); (4) sham-treated with beta3 ARa (sham+ARa group). These four groups were divided into two groups, one on ad libitum diet, and the other on a diet of limited chow. The effects of beta3 ARa on body weight, intraabdominal fat weight, adipocyte volume, serum lipid content, and serum leptin were measured after 4 weeks had been completed. On both the ad libitum and the limited diet, ARa significantly reduced the ratio of intraabdominal fat and body weight (IAF ratio) regardless whether in the OVX or sham group, although ARa had no influence on weight gain. On the ad libitum diet, the serum leptin was significantly increased after OVX, and significantly reduced after ARa administration. ARa significantly reduced the volume of intraabdominal adipocytes. We conclude that ARa reduces intraabdominal fat without reducing body weight in oophorectomized rats. The serum parameter affected differently to rats on the ad libitum diet and on the limited diet.

Topics: Adipocytes; Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Agonists; Animals; Anti-Obesity Agents; Cell Size; Cholesterol; Diet; Eating; Estrogens; Fatty Acids, Nonesterified; Female; Leptin; Ovariectomy; Rats; Rats, Sprague-Dawley; Triglycerides; Weight Gain

The role of leptin in neonatal growth and bone metabolism has been investigated, but not simultaneously. The objectives of this study were to determine if leptin relates to bone mass during rapid growth; if consumption of maternal milk is related to elevated circulating concentrations of leptin resulting in higher fat mass; and if glucocorticoids result in higher fat mass and reduced bone mass due to elevated leptin. Thirty-two piglets were randomized to either a suckling or milk substitute plus either dexamethasone (DEX) or placebo injection for 15 days beginning at 5 days of age. Milk and blood samples were obtained at baseline, and after 15 days, blood was sampled again for measurement of leptin and bone biochemistry. Weight at baseline plus weight and length after 15 days were recorded, followed by measurement of whole body bone mineral content, bone area, and fat mass using dual energy x-ray absorptiometry. At baseline, plasma leptin was elevated in suckled piglets. Piglets that suckled had elevated fat mass as did those who received DEX. However, DEX resulted in suppressed weight and length, bone mass, and bone metabolism. Leptin was similar among groups after the 15 days. After accounting for body size and treatment effects, piglet plasma leptin was predictive of bone and fat mass. Leptin circulating early postnatally is linked to body composition, specifically fat and bone mass. Elevations in fat mass and reductions in bone mass observed after 15 days of DEX treatment are not related to leptin metabolism. Both human and porcine neonates share similar characteristics with respect to relationships of leptin with fat and bone mass.

Topics: Adipose Tissue; Animal Feed; Animals; Body Composition; Body Weight; Bone and Bones; Bone Density; Dexamethasone; Leptin; Male; Milk; Minerals; Models, Animal; Organ Size; Random Allocation; Species Specificity; Swine; Weight Gain

Childhood obesity is an emerging health problem. This study assesses the effects of three levels of dietary fat (10%, 32%, and 45% measured by kilocalories) on weight gain, body composition, energy metabolism, and comorbidity factors in rats from weaning through maturation.. The role of dietary fat on the susceptibility to obesity was assessed by feeding diets containing three levels of dietary fat to rats from weaning through 7 months of age. Body composition was analyzed by DXA after 6 and 12 weeks of dietary treatment. Energy metabolism was measured by indirect calorimetry.. Energy intake, weight gain, fat mass, and plasma glucose, cholesterol, triglyceride, free fatty acid, leptin, and insulin levels increased dose-dependently with increased dietary fat. No difference in absolute lean mass among the three groups was observed. Therefore, the differences in weight gain are accounted for primarily by increased fat accretion. Compared with rats that were relatively resistant to obesity when on a 45% fat diet, diet-induced obesity-prone rats were in positive energy balance and had an elevated respiratory quotient, indicating a switch in energy substrate use from fat to carbohydrate, which promotes body-fat accretion.. Our data support the hypothesis that administration of increasing amount of dietary fat to very young rats enhances susceptibility to diet-induced obesity and its comorbidities.

Topics: Adipose Tissue; Aging; Animals; Blood Glucose; Body Composition; Cholesterol; Dietary Fats; Energy Intake; Energy Metabolism; Fatty Acids, Nonesterified; Insulin; Leptin; Male; Obesity; Rats; Rats, Sprague-Dawley; Triglycerides; Weaning; Weight Gain

Leptin is bound in human blood by a high affinity binding protein, which appears to be identical with the soluble leptin receptor (sOB-R). Using a ligand-mediated immunofunctional assay for the determination of serum sOB-R, we investigated its course during childhood, puberty, and adolescence in a large cohort of 581 healthy children and adolescents and a small group of 13 patients with anorexia nervosa. In the first years of life, sOB-R is detectable in remarkably high concentrations. Thereafter, a continuous decline of sOB-R levels was found. Consequently, correlation analyses demonstrated significant inverse relationships (P < 0.001) of sOB-R with age, IGF-I levels, pubertal stage, auxological and body composition parameters, as well as with leptin concentrations. Multiple regression analysis revealed that height, IGF-I, and age (only in girls) were independent predictors of sOB-R levels; these variables account for approximately 65% and 48% of the variation of sOB-R levels in boys and girls, respectively. The courses of age-dependent median values for the free leptin index (FLI, ratio between leptin and sOB-R levels) and for leptin levels were parallel in both genders. Correlation analyses demonstrated that in particular parameters of growth and sexual maturation are more closely related to the FLI than to leptin alone; this closer relationship is more pronounced among boys. Weight gains of patients with anorexia nervosa resulted in a significant increase in leptin and IGF-I levels (P < 0.01), whereas the median of sOB-R values decreased (P < 0.01). sOB-R and IGF-I levels were again significantly correlated (r = -0.55, P < 0.01). These findings suggest that high levels of sOB-R in emaciation may reflect an up-regulation of the sOB-R to suppress leptin action during energy deficiency. Furthermore, determinations of sOB-R and FLI are additional valuable tools to investigate the leptin axis during growth and sexual maturation.

Topics: Adolescent; Adult; Aging; Anorexia Nervosa; Body Composition; Body Height; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Insulin-Like Growth Factor I; Leptin; Male; Puberty; Receptors, Cell Surface; Receptors, Leptin; Reference Values; Regression Analysis; Solubility; Weight Gain

1. Risperidone is an atypical antipsychotic drug that possesses 5-hydroxytryptamine 5-HT2 receptor antagonism combined with milder dopamine D2 receptor antagonism. 2. Excessive bodyweight gain is one of the side-effects of antipsychotics. Risperidone treatment causes a greater increase in the body mass of patients than treatment with conventional antipsychotics, such as haloperidol. Therefore, the present study was undertaken in order to address the aetiology of the risperidone-induced bodyweight change in rats by examining the expression of leptin, an appetite-regulating hormone produced in white adipose tissue (WAT), and uncoupling protein (UCP)-1, a substance promoting energy expenditure in the brown adipose tissues (BAT). 3. Eight-week-old male rats were injected subcutaneously with risperidone (0.005, 0.05 or 0.5 mg/kg) twice daily for 21 days. Both bodyweight and food intake were monitored daily. On day 21, rats were decapitated and their serum leptin and prolactin concentrations were measured. Expression levels of leptin, Ucp1 and beta3-adrenoceptor (beta3-AR) genes in WAT and BAT were quantified using real-time polymerase chain reaction amplification. 4. Injection of 0.005 mg/kg risperidone into rats increased food intake and the rate of bodyweight gain, as well as the augmentation of leptin gene expression in WAT. Injection of 0.05 mg/kg risperidone increased food intake and leptin gene expression in WAT, but the rate of bodyweight gain was not affected. Injection of 0.5 mg/kg risperidone caused a reduction in bodyweight gain, as well as enhanced Ucp1 gene expression in BAT and serum prolactin concentrations. The serum leptin concentration and beta3-AR gene expression in WAT and BAT were not affected by injection of 0.5 mg/kg risperidone. 5. Although the changes in food intake observed in risperidone-injected rats were rationalized neither by serum leptin nor prolactin concentrations, the reduction in the rate of bodyweight gain following injection of 0.5 mg/kg can be explained, in part, by increased energy expenditure, as revealed by the remarkable increase in the UCP-1 mRNA expression level in BAT. The role of leptin in risperidone-induced alterations in bodyweight gain remain to be clarified.

Topics: Adipose Tissue; Animals; Antipsychotic Agents; Dose-Response Relationship, Drug; Eating; Leptin; Male; Rats; Rats, Sprague-Dawley; Risperidone; Weight Gain

To identify the specific hypothalamic sites in which leptin acts to decrease energy intake and/or increase energy expenditure, recombinant adeno-associated virus vector-encoding leptin was microinjected bilaterally into one of four hypothalamic sites in female rats. Leptin transgene expression in the ventromedial nucleus and paraventricular nucleus induced comparable decreases in daily food intake (FI; 18-20%) and body weight (BW; 26-29%), accompanied by drastic reductions in serum leptin (81-97%), insulin (92-93%), free fatty acids (35-36%), and normoglycemia. Leptin transgene expression in the arcuate nucleus (ARC) decreased BW gain (21%) and FI (11%) to a lesser range, but the metabolic hormones were suppressed to the same extent. Leptin transgene expression in the medial preoptic area (MPOA) decreased BW and metabolic hormones without decreasing FI. Finally, leptin transgene expression in all four sites augmented serum ghrelin and thermogenic energy expenditure, as shown by uncoupling protein-1 mRNA expression in brown adipose tissue. Proopiomelanocortin gene expression in the ARC was up-regulated by leptin expression in all four sites, but neuropeptide Y gene expression in the ARC was suppressed by leptin transgene expression in the ARC but not in the MPOA. Thus, whereas leptin expression in the paraventricular nucleus, ventromedial nucleus, or ARC suppresses adiposity and insulin by decreasing energy intake and increasing energy expenditure, in the MPOA it suppresses these variables by increasing energy expenditure alone.

Topics: Adipose Tissue, Brown; Animals; Appetite; Arcuate Nucleus of Hypothalamus; Blood Glucose; Carrier Proteins; Energy Intake; Energy Metabolism; Fatty Acids, Nonesterified; Female; Gene Expression; Ghrelin; Green Fluorescent Proteins; Hypothalamus; In Situ Hybridization; Insulin; Ion Channels; Leptin; Luminescent Proteins; Membrane Proteins; Microinjections; Mitochondrial Proteins; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Peptide Hormones; Preoptic Area; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transfection; Uncoupling Protein 1; Ventromedial Hypothalamic Nucleus; Weight Gain

This study was designed to investigate whether dietary fat and genetic background might differentially alter the expression of hypothalamic genes involved in food intake.. Three-month-old Osborne-Mendel (OM) and S5B/Pl rats were fed either a high-fat or a low-fat diet for 14 days. mRNA for neuropeptide Y (NPY), corticotrophin-releasing hormone, NPY Y-1 receptor and Y-5 receptor, and serotonin 2c (5-HT2c) receptors were measured using Northern blotting or ribonuclease protection assays.. OM rats showed an increased expression of NPY and corticotrophin-releasing hormone compared with S5B/Pl rats. The expression of NPY-Y1 and -Y5 receptor mRNA was significantly higher in the hypothalamus of OM rats compared with S5B/Pl rats. The expression of 5HT-2c receptor mRNA was significantly reduced in both strains of rats eating a high-fat diet when compared with the animals eating the low-fat diet.. These data suggest that over activity of the NPY system may contribute to the development of obesity in OM rats and that expression of the 5HT-2c receptor gene may be modulated by dietary fat.

Topics: Animals; Corticosterone; Corticotropin-Releasing Hormone; Dietary Fats; Eating; Gene Expression; Hypothalamus; Insulin; Leptin; Male; Neuropeptide Y; Obesity; Organ Size; Rats; Receptor, Serotonin, 5-HT2C; Receptors, Neuropeptide Y; Receptors, Serotonin; RNA, Messenger; Species Specificity; Weight Gain

Leptin regulates food intake in adult mammals by stimulating hypothalamic anorexigenic pathways and inhibiting orexigenic ones. In developing rodents, fat stores are low, yet circulating leptin levels are high and do not appear to regulate food intake. We determined whether two appetite-related neuropeptides [neuropeptide Y (NPY) and proopiomelanocortin (POMC)] and food intake behavior are sensitive to leptin [3 mg/kg body weight (BW), ip] in neonates. We measured the effects of 1) acute leptin administration (3 mg/kg BW, ip, 3 h before testing) on food intake on postnatal day (PND) 5, 8, and 10; and 2) chronic leptin treatment (3 mg/kg BW, ip, daily PND3-PND10) on BW gain and fat pads weight on PND10. In addition to hypothalamic POMC and NPY expression, we determined the expression of suppressor of cytokine signaling-3, all subtypes of leptin receptors, and corticotropin-releasing factor receptor-2 mRNA in PND10 pups receiving either an acute (PND10) or a chronic (PND 3-10) leptin (3 mg/kg BW, ip) or vehicle treatment. Brains were removed 30 or 120 min after the last injection. Acute leptin administration did not affect food intake at any age tested. Chronic leptin treatment did not change BW but decreased fat pad weight significantly. In the arcuate nucleus (ARC), acute leptin increased SOCS-3 and POMC mRNA levels, but decreased NPY mRNA levels in the rostral part of ARC. Chronic leptin down-regulated all subtypes of leptin receptors mRNA and decreased NPY mRNA levels in the caudal ARC but had no further effect on POMC expression. Chronic leptin increased corticotropin-releasing factor receptor-2 mRNA levels in the ventromedial hypothalamus. We conclude that despite adult-like effects of leptin on POMC, NPY, and CRFR-2 expression in neonates, leptin does not regulate food intake during early development.

Topics: Adipose Tissue; Animals; Animals, Newborn; Appetite; Arcuate Nucleus of Hypothalamus; Eating; Gene Expression Regulation; Hypothalamus; Hypothalamus, Middle; Leptin; Neuropeptide Y; Neuropeptides; Organ Size; Pro-Opiomelanocortin; Proteins; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, Corticotropin-Releasing Hormone; Receptors, Leptin; Repressor Proteins; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Transcription Factors; Weight Gain