leptin and Malnutrition

Malnutrition occurs when nutrient intake is too low for any reason and occurs regardless of gender or age. Therefore, besides loss of eating or digestive functionality due to illness, malnutrition can occur when a healthy individual undergoes an extreme diet and biases their nutrition, or when athletes exerts more energy than they can replenish through food. It has recently been reported that in Japan, the mortality rate of leaner individuals is equal to or higher than that of obese people. It is important to understand what homeostatic maintenance mechanism is behind this when the body is under hypotrophic conditions. Such mechanisms are generally endocranially controlled. We address this fundamental concern in this paper by focusing on peptide hormones. We introduce a mechanism for survival in a malnourished state via the regulation of food intake and temperature. Additionally, we will discuss the latest findings and future prospects for research on changes in the endocrine environment associated with malnutrition associated with exercise. We also review changes in next-generation endocrine environments when caused by malnutrition brought on by dieting.

Topics: Body Temperature; Diet, Reducing; Energy Intake; Energy Metabolism; Epigenesis, Genetic; Exercise; Feeding Behavior; Female; Ghrelin; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Leptin; Malnutrition; Neuropeptide Y; Peptide Hormones; Peptide YY; Pregnancy; Prenatal Exposure Delayed Effects; Sports; Thermogenesis

Maternal and perinatal undernutrition affects the lung development of litters and it may produce long-lasting alterations in respiratory health. This can be demonstrated using animal models and epidemiological studies. During pregnancy, maternal diet controls lung development by direct and indirect mechanisms. For sure, food intake and caloric restriction directly influence the whole body maturation and the lung. In addition, the maternal food intake during pregnancy controls mother, placenta, and fetal endocrine systems that regulate nutrient uptake and distribution to the fetus and pulmonary tissue development. There are several hormones involved in metabolic regulations, which may play an essential role in lung development during pregnancy. This review focuses on the effect of metabolic hormones in lung development and in how undernutrition alters the hormonal environment during pregnancy to disrupt normal lung maturation. We explore the role of GLP-1, ghrelin, and leptin, and also retinoids and cholecalciferol as hormones synthetized from diet precursors. Finally, we also address how metabolic hormones altered during pregnancy may affect lung pathophysiology in the adulthood.

Topics: Animals; Cholecalciferol; Female; Fetal Development; Fetal Growth Retardation; Ghrelin; Glucagon-Like Peptide 1; Hormones; Humans; Leptin; Lung; Malnutrition; Maternal Nutritional Physiological Phenomena; Pregnancy; Retinoids; Tretinoin

Multiple sclerosis (MS) is a multifactorial, inflammatory, and neurodegenerative disease of the central nervous system, where environmental factors interact with genetic susceptibility. The role of diet on MS has not been comprehensively elucidated; therefore, through an extensive search of relevant literature, this review reports the most significant evidence regarding nutrition as a possible co-factor influencing the inflammatory cascade by acting on both its molecular pathways and gut microbiota. Since nutritional status and dietary habits in MS patients have not been extensively reported, the lack of a scientific-based consensus on dietary recommendation in MS could encourage many patients to experiment alternative dietetic regimens, increasing the risk of malnutrition. This work investigates the health implications of an unbalanced diet in MS, and collects recent findings on nutrients of great interest among MS patients and physicians. The aim of this review is to elucidate the role of an accurate nutritional counseling in MS to move toward a multidisciplinary management of the disease and to encourage future studies demonstrating the role of a healthy diet on the onset and course of MS.

Topics: Animals; Antioxidants; Body Composition; Complementary Therapies; Diet; Disease Models, Animal; Dysbiosis; Fatty Acids; Fatty Acids, Unsaturated; Humans; Inflammation; Leptin; Lipopolysaccharides; Malnutrition; Micronutrients; Multiple Sclerosis; Nutritional Status; Obesity; Osteoporosis; Randomized Controlled Trials as Topic; Recommended Dietary Allowances; Risk Factors; Vitamin D

The exact mechanisms linking metabolic and neuroendocrine adaptations to undernutrition and the pathophysiology of anorexia nervosa (AN) are not fully understood. AN is a psychiatric disorder of complex etiology characterized by extreme starvation while the disease is progressing into a chronic state. Metabolic and endocrine alterations associated to this disorder are part of a powerful response to maintain whole body energy homeostasis. But these modifications may also contribute to associated neuropsychiatric symptoms (reward abnormalities, anxiety, depression) and thus participate to sustain the disease. The current review presents data with both a clinical and basic research point of view on the role of nutritional and energy sensors with neuroendocrine actions in the pathophysiology of the disease, as they modulate metabolic responses, reproductive functions, stress responses as well as physical activity. While clinical data present a full description of changes occurring in AN, animal models that integrate either spontaneous genetic mutations or experimentally-induced food restriction with hyperactivity and/or social stress recapitulate the main metabolic and endocrine alterations of AN and provide mechanistic information between undernutrition state and symptoms of the disease. Further progress on the central and peripheral mechanism involved in the pathophysiology of eating disorders partly relies on the development and/or refinement of existing animal models to include recently identified genetic traits and better mimic the complex and multifactorial dimensions of the disease.

Topics: Adaptation, Physiological; Animals; Anorexia Nervosa; Ghrelin; Glucocorticoids; Humans; Leptin; Malnutrition

Topics: Adaptive Immunity; Animals; Autoimmune Diseases; Communicable Diseases; Humans; Immunity, Innate; Immunologic Deficiency Syndromes; Leptin; Malnutrition

T cells are highly influenced by nutrient uptake from their environment, and changes in overall nutritional status, such as malnutrition or obesity, can result in altered T-cell metabolism and behavior. In states of severe malnutrition or starvation, T-cell survival, proliferation, and inflammatory cytokine production are all decreased, as is T-cell glucose uptake and metabolism. The altered T-cell function and metabolism seen in malnutrition is associated with altered adipokine levels, most particularly decreased leptin. Circulating leptin levels are low in malnutrition, and leptin has been shown to be a key link between nutrition and immunity. The current view is that leptin signaling is required to upregulate activated T-cell glucose metabolism and thereby fuel T-cell activation. In the setting of obesity, T cells have been found to have a key role in promoting the recruitment of inflammatory macrophages to adipose depots along with the production of inflammatory cytokines that promote the development of insulin resistance leading to diabetes. Deletion of T cells, key T-cell transcription factors, or pro-inflammatory T-cell cytokines prevents insulin resistance in obesity and underscores the importance of T cells in obesity-associated inflammation and metabolic disease. Altogether, T cells have a critical role in nutritional immunometabolism.

Topics: Animals; Cytokines; Food; Glucose; Humans; Inflammation; Insulin Resistance; Leptin; Lymphocyte Activation; Malnutrition; Nutritional Status; Obesity; Signal Transduction; T-Lymphocytes

Malnutrition is considered a leading cause of growth attenuation in children. When food is replenished, spontaneous catch-up (CU) growth usually occurs, bringing the child back to its original growth trajectory. However, in some cases, the CU growth is not complete, leading to a permanent growth deficit. This review summarizes our current knowledge regarding the mechanism regulating nutrition and growth, including systemic factors, such as insulin, growth hormone, insulin- like growth factor-1, vitamin D, fibroblast growth factor-21, etc., and local mechanisms, including autophagy, as well as regulators of transcription, protein synthesis, miRNAs and epigenetics. Studying the molecular mechanisms regulating CU growth may lead to the establishment of better nutritional and therapeutic regimens for more effective CU growth in children with malnutrition and growth abnormalities. It will be fascinating to follow this research in the coming years and to translate the knowledge gained to clinical benefit.

Topics: Autophagy; Child; Epigenomics; Fibroblast Growth Factors; Glucocorticoids; Growth Disorders; Growth Hormone; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Infant; Insulin; Insulin-Like Growth Factor I; Leptin; Malnutrition; MicroRNAs; Nutritional Status; Thyroid Hormones; TOR Serine-Threonine Kinases; Vitamin D

Suboptimal maternal nutrition exerts lasting impacts on obesity risk in offspring, but the direction of the effect is determined by the timing of exposure. While maternal undernutrition in early pregnancy is associated with increased body mass index, in later pregnancy it can be protective. The importance of the timing of maternal undernutrition is also observed in rodents, however, many of the processes that occur in the last trimester of human gestation are delayed to the postnatal period. Neonatal leptin administration exerts lasting impacts on susceptibility to obesity in rodents. Although leptin can influence the formation of hypothalamic circuits involved in homeostatic control of feeding during the postnatal period, these effects are too late to account for its ability to reverse adverse metabolic programming due to early gestational exposure to maternal undernutrition. This review presents an alternative framework for understanding the effects of neonatal leptin through influences on developing thermoregulatory circuits.

Topics: Adult; Female; Humans; Leptin; Malnutrition; Maternal Nutritional Physiological Phenomena; Obesity; Pregnancy; Prenatal Exposure Delayed Effects

Anemia, dyslipidemia, malnutrition, together with mineral and bone disorders are common complications in patients with chronic kidney disease (CKD). All are associated with increased risk of mortality. Leptin is a small peptide hormone that is mainly but not exclusively produced in adipose tissue. It is also secreted by normal human osteoblasts, subchondral osteoblasts, placental syncytiotrophoblasts, and the gastric epithelium. Leptin binds to its receptors in the hypothalamus to regulate bone metabolism and food intake. Leptin also has several other important metabolic effects on peripheral tissues, including the liver, skeletal muscle, and bone marrow. Leptin is cleared principally by the kidney. Not surprisingly, serum leptin appears to increase concurrently with declines in the glomerular filtration rate in patients with CKD. A growing body of evidence suggests that leptin might be closely related to hematopoiesis, nutrition, and bone metabolism in CKD patients. Results are conflicting regarding leptin in patients with CKD, in whom both beneficial and detrimental effects on uremia outcome are found. This review elucidates the discovery of leptin and its receptors, changes in serum or plasma leptin levels, the functions of leptin, relationships between leptin and the complications mentioned above, and pharmaceutical interventions in serum leptin levels in patients with CKD.

Topics: Anemia; Bone and Bones; Bone Diseases, Metabolic; Dyslipidemias; Hematopoiesis; Humans; Leptin; Malnutrition; Nutritional Status; Receptors, Leptin; Renal Insufficiency, Chronic

Malnutrition, marked by variant nutrient deficiencies, is considered a leading cause of stunted growth worldwide. In developing countries, malnutrition is caused mainly by food shortage and infectious diseases. Malnutrition may also be found in the developed world, where it is due mostly to prematurity, chronic diseases, and anorexia nervosa. In most cases, when food consumption is corrected, spontaneous catch-up (CU) growth occurs. However, CU growth is not always complete, leading to growth deficits. Therefore, it is important to understand the mechanisms that govern this process. Using a rat model of food restriction followed by refeeding, we established a nutrition-induced CU growth model. Levels of leptin and insulin-like growth factor-1 were found to significantly decrease when food was restricted and to increase already 1 day after refeeding. Gene expression analysis of the growth plate revealed that food restriction specifically affects transcription factors such as the hypoxia inducible factor-1 and its downstream targets on the one hand, and global gene expression, indicating epigenetic regulation, on the other. Food restriction also reduced the level of several microRNAs, including the chondrocyte-specific miR-140, which led to an increase in its target, SIRT1, a class III histone deacetylase. These findings may explain the global changes in gene expression observed under nutritional manipulation. We suggest that multiple levels of regulation, including transcription factors, epigenetic mechanisms, and microRNAs respond to nutritional cues and offer a possible explanation for some of the effects of food restriction on epiphyseal growth plate growth. The means whereby these components sense changes in nutritional status are still unknown. Deciphering the role of epigenetic regulation in growth may pave the way for the development of new treatments for children with growth disorders.

Topics: Animals; Developed Countries; Developing Countries; Epigenesis, Genetic; Growth Plate; Humans; Insulin-Like Growth Factor I; Leptin; Malnutrition; Micronutrients; MicroRNAs; Nutritional Status; Rats; Sirolimus

Ghrelin is an orexigenic hormone with additional effects on the regulation of inflammation and the cardiovascular system. It may play an important role in the pathogenesis of cachexia/protein-energy wasting (PEW), inflammation and cardiovascular complications in chronic kidney disease (CKD). There are three circulating gene products of ghrelin, namely, acyl ghrelin, des-acyl ghrelin and obestatin, each with individual distinct functions. Perturbations of these circulating ghrelin proteins impact the overall milieu of CKD. Leptin is an anorexigenic hormone which is secreted from the adipocytes and interacts with ghrelin and other appetite-regulating hormones. Leptin also plays a role in regulating inflammation and the cardiovascular system. Indeed, ghrelin and leptin may play yin-and-yang roles in CKD pathophysiology. Clinical trials involving the use of the mimetics or antagonists of these hormones are limited to short-term phase I/II studies. Further understanding of their interactions in CKD pathophysiology is needed for potential large-scale clinical trials, which may impact the quality of life and survival of patients with CKD.

Topics: Animals; Appetite Regulation; Body Weight; Cardiovascular Diseases; Disease Progression; Ghrelin; Humans; Inflammation; Kidney; Leptin; Malnutrition; Prognosis; Renal Insufficiency, Chronic; Signal Transduction

Anorexia is a common complication in patients with chronic kidney disease (CKD) and is associated with the development of malnutrition and an increased risk of mortality. Several compounds are linked to anorexia in these patients; however, the mechanisms are unknown. Zinc (Zn) deficiency is associated with decreased food intake and has been observed in CKD patients. In addition, leptin is an anorexigenic peptide, and patients with CKD present generally high levels of this hormone. Studies have suggested an association between Zn and leptin status in human and rats; however, the results are inconsistent. Some claimed that Zn supplementation does not change leptin release or that there is no significant relationship between Zn and leptin. Others have reported that Zn might be a mediator of leptin production. CKD patients have hyperleptinemia and hypozincemia, but the relationship between Zn deficiency and leptin levels in CKD patients has been poorly understood until now. The aim of this review is to integrate knowledge on leptin and Zn actions to provide a cohesive clinical perspective regarding their interactions in CKD patients.

Topics: Animals; Anorexia; Eating; Humans; Kidney Failure, Chronic; Leptin; Malnutrition; Rats; Zinc

In patients with chronic obstructive pulmonary disease (COPD), malnutrition and limited physical activity are very common and contribute to disease prognosis, whereas a balance between caloric intake and exercise allows body weight stability and muscle mass preservation. The goal of this review is to analyze the implications of chronic hypoxia on three key elements involved in energy homeostasis and its role in COPD cachexia. The first one is energy intake. Body weight loss, often observed in patients with COPD, is related to lack of appetite. Inflammatory cytokines are known to be involved in anorexia and to be correlated to arterial partial pressure of oxygen. Recent studies in animals have investigated the role of hypoxia in peptides involved in food consumption such as leptin, ghrelin, and adenosine monophosphate activated protein kinase. The second element is muscle function, which is strongly related to energy use. In COPD, muscle atrophy and muscle fiber shift to the glycolytic type might be an adaptation to chronic hypoxia to preserve the muscle from oxidative stress. Muscle atrophy could be the result of a marked activation of the ubiquitin-proteasome pathway as found in muscle of patients with COPD. Hypoxia, via hypoxia inducible factor-1, is implicated in mitochondrial biogenesis and autophagy. Third, hormonal control of energy balance seems to be affected in patients with COPD. Insulin resistance has been described in this group of patients as well as a sort of "growth hormone resistance." Hypoxia, by hypoxia inducible factor-1, accelerates the degradation of tri-iodothyronine and thyroxine, decreasing cellular oxygen consumption, suggesting an adaptive mechanism rather than a primary cause of COPD cachexia. COPD rehabilitation aimed at maintaining function and quality of life needs to address body weight stabilization and, in particular, muscle mass preservation.

Topics: Anorexia; Appetite; Cachexia; Cytokines; Energy Intake; Energy Metabolism; Exercise; Ghrelin; Human Growth Hormone; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Leptin; Malnutrition; Muscular Atrophy; Nutritional Status; Oxygen; Pulmonary Disease, Chronic Obstructive

The goal of this review is to shed light on the role of maternal malnutrition in inducing epigenetic changes in gene expression, leading to alterations in fetal growth and development, and to altered postnatal phenotype and the development of metabolic disease. We present evidence supporting the concept that both maternal undernutrition and overnutrition can induce the same cadre of fetal organ and tissue abnormalities and lead to the same postnatal metabolic changes in the resulting offspring. Furthermore, we present evidence that in both overnourished and undernourished ovine pregnancies, fetuses experience a period of nutrient restriction as a result of alterations in placental delivery of maternal nutrients into the fetal compartment. We argue that this bout of reduced fetal nutrition in undernourished and overnourished pregnancies leads to the development of a thrifty phenotype in which the fetus attempts to alter the function of its tissues and organs to maximise its chances of survival in a postnatal environment that is deficient in nutrients. Importantly, we present evidence to support the concept that these phenotypic changes in offspring quality resulting from maternal malnutrition are transmitted to subsequent generations, independent of their maternal nutritional inputs.

Topics: Animals; Epigenesis, Genetic; Female; Fetal Development; Gene Expression Regulation, Developmental; Humans; Leptin; Malnutrition; Maternal Nutritional Physiological Phenomena; Models, Animal; Overnutrition; Phenotype; Pregnancy; Sheep

Topics: Animals; Comorbidity; Diabetes Mellitus; Global Health; HIV Infections; Humans; Infections; Leptin; Malaria; Malnutrition; Measles; Obesity; Protein-Energy Malnutrition; Risk Factors; T-Lymphocytes; Tuberculosis

Recent epidemiology demonstrates higher rate of obesity and metabolic syndrome in offspring with undernutrition in utero. IUGR babies with intrauterine undernutrition grow rapidly to catch up with normal growth course. Leptin is an adipocyte derived satiety factor that regulates food intake and energy expenditure. We demonstrated in mice model with maternal food restriction during pregnancy that premature leptin surge during neonatal catch up growth of the offspring lead them to impaired leptin sensitivity and obesity in adulthood.

Topics: Animals; Disease Models, Animal; Eating; Energy Intake; Female; Fetal Growth Retardation; Humans; Leptin; Malnutrition; Metabolic Syndrome; Obesity; Pregnancy; Pregnancy Complications

Anorexia nervosa (AN), a condition of severe undernutrition, is associated with low bone mineral density (BMD) in adults and adolescents. Whereas adult women with AN have an uncoupling of bone turnover markers with increased bone resorption and decreased bone formation markers, adolescents with AN have decreased bone turnover overall. Possible contributors to low BMD in AN include hypoestrogenism and hypoandrogenism, undernutrition with decreased lean body mass, and hypercortisolemia. IGF-I, a known bone trophic factor, is reduced despite elevated growth hormone (GH) levels, leading to an acquired GH resistant state. Elevated ghrelin and peptide YY levels may also contribute to impaired bone metabolism. Weight recovery is associated with recovery of BMD but this is often partial, and long-term and sustained weight recovery may be necessary before significant improvements are observed. Anti-resorptive therapies have been studied in AN with conflicting results. Oral estrogen does not increase BMD or prevent bone loss in AN. The combination of bone anabolic and anti-resorptive therapy (rhIGF-I with oral estrogen), however, did result in a significant increase in BMD in a study of adult women with AN. A better understanding of the pathophysiology of low BMD in AN, and development of effective therapeutic strategies is critical. This is particularly so for adolescents, who are in the process of accruing peak bone mass, and in whom a failure to attain peak bone mass may occur in AN in addition to loss of established bone.

Topics: Androgens; Anorexia Nervosa; Bone Density Conservation Agents; Calcium; Diphosphonates; Eating; Estrogen Replacement Therapy; Ghrelin; Humans; Hypogonadism; Insulin-Like Growth Factor I; Leptin; Malnutrition; Motor Activity; Osteoporosis; Peptide Hormones; Peptide YY; Recombinant Proteins; Vitamin D

Malnutrition is defined as abnormalities caused by an inadequate diet, but this term is often used inappropriately to describe the syndrome of loss of body weight with muscle mass being replaced by fatty tissue and declining serum proteins present in adults and children with chronic kidney disease (CKD). This syndrome is more accurately described as cachexia, and manifests as growth failure in children with CKD. Cachexia is common and is an important risk factor for poor quality of life and increased mortality and morbidity in both adults and children with CKD. Anorexia, acidosis and inflammation are important causes of cachexia, but the underlying molecular mechanism is not well understood. Dietary intake is often poor and resting metabolic rate is increased in CKD. The energy cost of growth is increased in experimental CKD. Circulating concentrations of cytokines, such as leptin, tumor necrosis factor-alpha and interleukins 1 and 6 are increased in patients with CKD and correlate with the degree of cachexia in these individuals. We hypothesize that cytokines signal through orexigenic neuropetides such as agouti-related peptide and neuropeptide Y (NPY), and anorexigenic neuropetides such as proopiomelanocortin and alpha-melanocyte-stimulating hormone in the arcuate nucleus in the hypothalamus. This signaling system also involves the NPY receptor and the melanocortin receptors and controls appetite and metabolic rate in health and disease. Furthermore, the first order neurons of this system are located outside the blood-brain barrier and can therefore sense the circulating levels of cytokines, as well as long-term satiety hormones such as leptin and insulin and short-term satiety hormones such as ghrelin and peptide (P) YY. There is experimental evidence that this hypothalamic neuropeptide signaling system may have an important role in the pathogenesis of cachexia in CKD. Understanding the molecular mechanism of cachexia in CKD may lead to novel therapeutic strategies.

Topics: Cachexia; Child; Chronic Disease; Cytokines; Ghrelin; Humans; Kidney Diseases; Kidney Failure, Chronic; Leptin; Malnutrition; Peptide Hormones

Topics: Carnitine; Cytokines; Dialysis; Energy Intake; Humans; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Malnutrition; Nutrition Therapy

Intra-uterine growth retardation (IUGR), caused by maternal undernutrition or placental insufficiency, is usually associated with disproportionately large reductions in the growth of some fetal organs and tissues (thymus, liver, spleen, thyroid) and impaired cellular development of other tissues (small intestine, secondary wool follicles, skeletal muscle). Growth of other tissues, most notably brain, is relatively unimpaired. In our restudy of postnatal consequences of IUGR in the offspring of prolific ewes, growth-retarded newborn lambs tended to be hypoglycaemic and showed sluggish postnatal engagement of the growth hormone (GH)-insulin-like growth factor (IGF) system. When artificially reared in an optimum environment, low birth weight lambs grew at rates similar to those of normal lambs. However, low birth weight lambs were fatter at any given weight, apparently related to their high energy intakes, especially soon after birth, had low maintenance energy requirements, and limited capacity for bone and muscle growth. These growth characteristics were accompanied by higher plasma concentrations of GH and leptin, and lower concentrations of insulin-like growth factor I (IGF-I) during the first 2 weeks of postnatal life, and higher concentrations of insulin during subsequent growth up to 20 kg body weight. Emerging evidence indicates that in sheep, as in rodents, fetal programming of postnatal cardiovascular and metabolic dysfunctions is associated with IUGR and may be mediated partly by overexposure of the fetus to cortisol. Similar postnatal responses can be elicited by maternal undernutrition or cortisol treatment in early to mid-pregnancy without changing the growth of the fetus or placenta.

Topics: Animals; Animals, Newborn; Female; Fetal Growth Retardation; Growth Disorders; Growth Hormone; Hydrocortisone; Insulin; Insulin-Like Growth Factor I; Leptin; Malnutrition; Maternal Nutritional Physiological Phenomena; Placental Insufficiency; Pregnancy; Sheep; Sheep Diseases

To evaluate leptin and adiponectin as markers of undernutrition in cancer patients, and compare their performances with those of other biomarkers.. This was a prospective and observational study of 132 patients with various types of cancer. Following the recommended professional criteria, we diagnosed undernutrition at the time of blood sampling for the biological analysis of leptin, adiponectin, paraoxonase (hydrolysis rate of three substrates: paraoxon (PON), phenylacetate (ARE) and thiolactone (LAC)), and the calculation of the Prognostic Inflammatory and Nutritional Index (PINI). Patients were monitored for one year to establish the mortality rate of the group. Relationships between biological variables and undernutrition were evaluated using univariate and multivariate logistic regression models. The Kaplan Meier method was used to analyse survival curves. Hazard ratios for death were calculated according to the quartiles of each biological variable.. In the case of undernutrition, a decrease was observed in levels of leptin and in the lactonase activity (LAC) of paraoxonase, while adiponectin levels increased. Besides PINI, leptin was the only parameter that was independently related to undernutrition. While no relation was found between survival and leptin or adiponectin levels, evidence was found that PINI, LAC and ARE were associated with survival, even in multivariate analysis.. Leptin and PINI are good markers of installed undernutrition, and PINI and ARE or LAC are reliable markers of the risk of death in patients suffering from cancer.

Topics: Adiponectin; Aged; Biomarkers, Tumor; Disease-Free Survival; Female; Humans; Leptin; Male; Malnutrition; Middle Aged; Neoplasms; Nutritional Status; Prospective Studies; Survival Rate

Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m(2). Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD.

Topics: Adolescent; Adult; Aged; Anemia; Bone Diseases; Female; Humans; Leptin; Male; Malnutrition; Middle Aged; Parathyroidectomy; Renal Insufficiency, Chronic

Refeeding syndrome (RS) is a potentially fatal condition that can occur following the re-introduction of nutrition after a period of starvation. Hypophosphataemia following the reintroduction of nutrition is often the only reliable biochemical marker of RS. Refeeding index (RI) generated from baseline insulin-like growth factor-1 (IGF-1) and leptin has been proposed as a useful biochemical marker for the identification of patients at risk of developing refeeding hypophosphataemia (RH).. A prospective study included 52 patients referred for parenteral nutrition (PN). The sensitivity and specificity of IGF-1 measured using a sensitive assay was compared to the RI in predicting the development of RH (a ≥ 30% drop in PO4 during the first 36-h of PN administration). Leptin and IGF-1 were analysed on baseline samples using a quantitative enzyme-linked immunoassay. Daily blood samples were collected from all patients for routine biochemistry for the full duration of PN administration.. High sensitivity IGF-1 measurement alone was comparable with the RI, using receiver-operating characteristic (ROC) curve analysis, with areas under the curve being 0.79 and 0.80, respectively, and superior to leptin alone (0.72) for predicting ≥ 30% drop in PO4. The cut-off value for IGF-1 that gave best sensitivity (91% [95% CI 75-98%]) and specificity (65% [95% CI 41-85%]) was 63.7 µg/L, with a likelihood ratio of 2.59.. Baseline IGF-1 is an objective, sensitive and specific biochemical marker in identifying patients who are at high risk of developing RH prior to PN administration and therefore may have a role in clinical practice.

Topics: Adult; Area Under Curve; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypophosphatemia; Insulin-Like Growth Factor I; Leptin; Male; Malnutrition; Middle Aged; Parenteral Nutrition; Prognosis; Prospective Studies; Refeeding Syndrome; ROC Curve

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

Despite malnutrition being a major problem in hospitalized elderly patients, there is a lack of studies focusing on the comparative value of biological parameters for monitoring renutrition. The aim of this study was to determine which biological parameter(s) could best monitor successful renutrition in hospitalized malnourished elderly patients.. The objective of the study was to explore the impact of a 6-week renutrition process on anthropometric and biological parameters in elderly patients and to define the biological parameters associated with weight regain.. A total of 72 hospitalized malnourished elderly patients admitted to a hospital-based geriatric rehabilitation unit.. Patients were evaluated at admission and at 6 weeks for anthropometric measurements of weight, sum of the four subcutaneous skinfold thicknesses, calf circumference and biological serum parameters including albumin, transthyretin, leptin, IGF-1, IGFBP-1 and IGFBP-3. Renutrition was considered successful if a patient gained at least 5% of body weight over 6 weeks.. Leptin was the only biological parameter that increased at 6 weeks in successful renutrition. Leptin variations were not influenced by C-reactive protein variations, in contrast to transthyretin which can be modified by the inflammatory states frequently encountered in geriatric patients.. Serum leptin is a more appropriate parameter than transthyretin for monitoring renutrition.

Topics: Aged, 80 and over; Biomarkers; Body Weight; Female; Food; Geriatric Assessment; Hospitalization; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Malnutrition; Monitoring, Physiologic; Nutrition Assessment; Nutritional Status; Prealbumin; Serum Albumin; Skinfold Thickness; Time Factors; Treatment Outcome

Malnutrition is a prominent feature of tuberculosis. Little is known about the role of the appetite-related hormones, ghrelin and leptin, in malnutrition in tuberculosis. This study was undertaken to determine whether ghrelin and leptin contribute to malnutrition in active pulmonary tuberculosis.. Nutritional parameters and plasma levels of ghrelin, leptin, and inflammatory cytokines were measured before treatment and after clinical improvement following anti-tuberculosis chemotherapy in 23 tuberculosis subjects and 23 healthy controls prospectively. Patients were divided into well-nourished (n=15) and malnourished (n=8) groups.. Ghrelin but not leptin levels were significantly lower in the malnourished tuberculosis group than in the well-nourished tuberculosis group [44.0 (43.0-54.0) vs. 122 (108-158)pg/mL; p<0.05]. Malnutrition score was negatively correlated to ghrelin (rho=-0.76, p<0.01) but not to leptin levels. TNF-alpha and IL-6 levels were significantly higher in the malnourished tuberculosis group than in the well-nourished tuberculosis group and controls. Plasma levels of ghrelin tended to decrease as inflammatory cytokines increased before treatment.. Decreased plasma ghrelin levels, in addition to increased plasma inflammatory cytokine levels, may be associated with malnutrition in active pulmonary tuberculosis.

Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Biomarkers; C-Reactive Protein; Female; Ghrelin; Humans; Inflammation Mediators; Interleukin-6; Leptin; Male; Malnutrition; Middle Aged; Mycobacterium tuberculosis; Nutrition Assessment; Nutritional Status; Severity of Illness Index; Sputum; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha; Young Adult

Fetal growth improves in pregnant women who take daily maternal multiple micronutrients [United Nations International Multiple Micronutrient Preparation (UNIMMAP)] rather than iron and folic acid (IFA) alone.. Our objective was to test whether such an effect was mediated by changes in concentrations of cord hormones.. In a double-blind, controlled trial carried out in Burkina Faso, we randomly assigned 1426 pregnant women to receive UNIMMAP or IFA supplements. We measured concentrations of insulin-like growth factor I (IGF-I), leptin, insulin, free thyroxine, and cortisol in cord serum in a subsample of 294 live single newborns. We performed mediation analysis with an Aroian test.. UNIMMAP supplementation had no significant effect on cord hormone concentrations. However, UNIMMAP supplementation significantly affected concentrations of IGF-I (+30%; 95% CI: 8%, 52%; P = 0.009) and leptin in male newborns. In these infants, 51.1% (P = 0.08) of the effect of UNIMMAP supplementation on birth weight was mediated through IGF-I, whereas for female newborns, this proportion was negligible. UNIMMAP supplementation also increased cortisol concentrations by 36% (P = 0.009) in cord blood in primiparae (P for interaction = 0.02). Growth-retarded infants had 41.2% lower IGF-I (P < 0.0001) and 27.3% lower leptin (P = 0.04) than did infants with normal growth. Offspring of primiparae had reduced IGF-I and insulin concentrations, and their cortisol concentrations were 25% higher (P = 0.05). Male newborns had lower concentrations of IGF-I, leptin, and insulin than did female newborns.. UNIMMAP supplementation had sex-specific effects on cord IGF-I and leptin concentrations that were of unclear clinical significance. Other pathways may have been involved in the action of UNIMMAP on fetal growth. The specific hormonal pattern in primiparae could be related to constrained fetal growth. Confirmatory studies are warranted. This trial was registered at clinicaltrials.gov as NCT00642408.

Topics: Adult; Burkina Faso; Dietary Supplements; Female; Fetal Blood; Fetal Growth Retardation; Hormones; Humans; Hydrocortisone; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Malnutrition; Micronutrients; Multivariate Analysis; Pregnancy; Sex Factors; Thyroxine; Young Adult

The objective of the present study is to demonstrate the effect of nucleotide intake and intensive nutritional support on the concentration of insulin-like growth factor I (IGF-I) and other hormonal biomarkers in severely malnourished children. Twenty-six severely malnourished children < 48 months of age received formula without lactose via enteral feeding for 2 weeks and ad libitum for an additional 2 weeks. Anthropometrical measurements were performed and serum concentrations of IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3), leptin, soluble leptin receptor (sOB-R), as well as the estimated molar excess of sOB-R over leptin were obtained. Two groups were formed. One group received formula with nucleotides (NT+; n 13) and the other without nucleotides (NT-; n 13). A control group was included (n 13). Parametric and non-parametric tests as well as ANOVA models were used. Nutritional recovery, nucleotides intake, type of malnutrition, age and the interaction between gender and malnutrition influenced the concentration of IGF-I (P < 0.001). Nutritional recovery, nucleotides intake, gender and type of malnutrition had an effect on IGFBP-3 (P < 0.001). Nutritional recovery had a significant effect on serum leptin (P = 0.001). Age and nutritional recovery had an effect on sOB-R (P < 0.001); all variables included affected the molar excess of sOB-R over leptin (P < 0.001). In conclusion, nucleotide intake and nutritional recovery had a notable effect on IGF-I, IGFBP-3 and other hormonal biomarkers. This outcome could stimulate the catch-up growth of severely malnourished infants and toddlers during the nutritional recovery period.

Topics: Anthropometry; Biomarkers; Child, Preschool; Enteral Nutrition; Female; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Malnutrition; Nucleotides

To evaluate the effects of a high-fat diet during post-weaning growth on intermediate metabolism and retroperitoneal adipose tissue, in adult male rats exposed to adequate or deficient zinc intake during prenatal and postnatal life.. Female Wistar rats were fed low- or control-zinc diets from pregnancy to offspring weaning. Male offspring born from control mothers were fed either control or high-fat, control-zinc diets for 60 days. Male offspring born from zinc deficient mothers were fed either low-zinc or high-fat, low-zinc diets for 60 days. At 74 days of life, oral glucose tolerance test was performed. In 81-day-old offspring, blood pressure, lipid profile, plasmatic lipid peroxidation and serum adiponectin level were determined. In retroperitoneal adipose tissue, we evaluated oxidative stress, morphology and adipocytokines mRNA expression. Low-zinc diet induced adipocytes hypertrophy, increased oxidative stress, and decreased adiponectin mRNA expression in adipose tissue. Low-zinc diet increased systolic blood pressure, triglyceridemia, plasmatic lipid peroxidation and glycemia at 3 h after glucose overload. Animals fed high-fat or high-fat, low-zinc diets showed adipocytes hypertrophy, decreased adiponectin mRNA expression, and increased leptin mRNA expression and oxidative stress in adipose tissue. They also exhibited decreased serum adiponectin levels, increased triglyceridemia, plasmatic lipid peroxidation and area under the oral glucose tolerance curve. High-fat, low-zinc diet induced greater alterations in adipocyte hypertrophy, leptin mRNA expression and glucose tolerance test than high-fat diet.. Zinc deficiency since early stages of intrauterine life could increase susceptibility to metabolic alterations induced by high-fat diets during postnatal life.

Topics: Adipocytes; Adiponectin; Animals; Diet, High-Fat; Female; Hypertrophy; Leptin; Male; Malnutrition; Pregnancy; Rats; Rats, Wistar; RNA, Messenger; Zinc

Herein, we assessed milk hormones, the biochemical composition of milk, and its association with neonatal body weight gain and metabolic homeostasis in weaned rats whose mothers were undernourished in the last third of pregnancy. From the 14th day of pregnancy until delivery, undernourished mothers had their food restricted by 50% (FR50), whereas control mothers were fed ad libitum. The litter size was adjusted to eight pups, and rats were weaned at 22 days old. Milk and blood from mothers, as well as blood and tissues from pups, were collected for further analyses. At birth, FR50 pups were smaller than control pups, and they exhibited hyperphagia and rapid catch-up growth during the suckling period. On day 12, the milk from FR50 mothers had higher energy content, glucose, total cholesterol, triglycerides, and acylated ghrelin but lower leptin and corticosterone levels. Interestingly, FR50 mothers were hypoglycemic and hyperleptinemic at the end of the nursing period. Weaned FR50 pups had an obese phenotype and exhibited insulin resistance, which was associated with hyperglycemia and hypertriglyceridemia; they also had high blood levels of total cholesterol, leptin, and acylated ghrelin. In addition, the protein expression of growth hormone secretagogue receptor (GHSR) in the hypothalamus was increased by almost 4-fold in FR50 pups. In summary, maternal calorie restriction during the last third of pregnancy disrupts energy and metabolic hormones in milk, induces pup hyperleptinemia and hyperghrelinemia, and upregulates their hypothalamic GHSR, thus suggesting that the hypothalamic neuroendocrine circuitry may be working to address the early onset of obesity.

Topics: Animals; Body Weight; Cholesterol; Female; Ghrelin; Leptin; Malnutrition; Milk; Obesity; Pregnancy; Rats; Rats, Wistar

Hemodialyzed patients with poor erythropoietin response tend to have low volume of visceral adipose tissue and score high on malnutrition-inflammation score. This study investigates in-depth the role of leptin and chosen cytokines in the development of malnutrition-inflammation syndrome (MIS) and erythropoietin resistance.. Eighty-one hemodialyzed patients with erythropoietin-treated anemia were enrolled in the study. Their body composition was measured. Erythropoietin resistance index was calculated. Blood samples for leptin, IL-6, IL-18, TNF-alpha, and IL-1-alpha serum levels were drawn.. Leptin showed negative correlation with erythropoietin resistance index (ERI), whilst IL-6 showed the opposite. IL-6 seemed to be linked more to HD parameters and vintage, while TNF-alpha and leptin were more dependent on body composition. IL-18 and IL-1-alpha did not affect nutritional parameters nor ERI.. Modulation of adipokine- and cytokine-related signaling is a promising target in tempering malnutrition in hemodialyzed, and thus achieving better outcomes in anemia treatment. Large clinical studies that target the inflammatory response in hemodialysis, especially regarding IL-6, TNF-alpha, and leptin, would be of great worth.

Topics: Anemia; Erythropoietin; Humans; Inflammation; Interleukin-1; Interleukin-18; Interleukin-6; Kidney Failure, Chronic; Leptin; Malnutrition; Renal Dialysis; Tumor Necrosis Factor-alpha

Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.. The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome were determined in 52 undernourished SEEM participants and 42 North American controls and patients with celiac disease.. After accounting for growth at study entry, circulating insulin-like growth factor-1 (IGF-1) and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxification genes and induction of antimicrobial response genes were EED-specific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal coexpression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z < -2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization.. Children with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention. ClinicalTrials.gov, Number: NCT03588013. (https://clinicaltrials.gov/ct2/show/NCT03588013).

Topics: Biomarkers; Case-Control Studies; Celiac Disease; Cell Proliferation; Child Development; Child, Preschool; Creatinine; DNA Methylation; Epigenome; Female; Ferritins; Genomics; Growth Disorders; Humans; Infant; Infant, Newborn; Insulin-Like Growth Factor I; Intestinal Diseases; Intestinal Mucosa; Leptin; Lipid Metabolism; Lymphocyte Activation; Lymphocytes; Male; Malnutrition; Oxidative Stress; Pakistan; Transcriptome

In much of the developing world, severe malnutrition is the most prevalent cause of immunodeficiency and affects up to 50% of the population in some impoverished communities. As yet, we do not know how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will behave in populations with immunodeficiency caused by malnourishment. Interestingly, researchers are now speculating that, in some instances, a defective cellular immune system could paradoxically be a protective factor against severe disease in certain patients contracting SARS-CoV and SARS-CoV-2. This could be linked to the absence of T-cell activation. Based on available information presented here, it is plausible that the hyperimmune response, and subsequent cytokine storm often associated with severe coronavirus disease 2019 (COVID-19), could be "counteracted" by the defective immune response seen in individuals with malnutrition-induced leptin deficiency. In this paper, we proposed a theory that although those with malnutrition-linked leptin deficiency are at risk of SARS-CoV-2 infection, they are at lower risk of developing severe COVID-19.

Topics: Antibody Formation; Body Mass Index; COVID-19; COVID-19 Vaccines; Cytokine Release Syndrome; Developing Countries; Disease Susceptibility; Humans; Immunity, Cellular; Immunogenicity, Vaccine; Immunologic Deficiency Syndromes; Leptin; Lymphocyte Activation; Malnutrition; Models, Biological; Obesity; Protein-Energy Malnutrition; Risk; SARS-CoV-2; Severity of Illness Index; T-Lymphocytes

Advanced cancers are associated with a chronic inflammation, especially high interleukin-6 (IL-6) and with various levels of adipokines (leptin and adiponectin), while ghrelin counteracts the anorexigenic effect of leptin in cancer-induced anorexia-cachexia syndrome. We aimed to understand how IL-6, adipokines and ghrelin plasma levels could be influenced by cancer on the one hand, and by age, frailty, and nutritional status in old cancer patients on the other hand. Ninety-nine patients aged 79[76-83] years old were included. Sixty-six percent had advanced stages of cancer, and 34% had cachexia. Fifty percent were at risk of malnutrition, and 10% had overt malnutrition. None of the variables studied was significantly correlated with the advanced stage, or cachexia. In multiple regression, the only parameter significantly and positively associated with age was adiponectin (p = 0.008). Despite a high prevalence of frailty in our study, we did not find any independent association of frailty (assessed by G8) with IL-6, leptin, adiponectin, or ghrelin in multivariate analysis. We observed that a low albumin level was independently associated with a higher level of IL-6 (p < 0.0001), but not with the MNA score. However, leptin showed a positive correlation with BMI (p < 0.0001), confirming the persistence of a relationship between leptin and adiposity, even in older cancer patients. Finally, high IL-6 level was associated with a higher mortality rate (p = 0.027). In conclusion, IL-6, leptin, adiponectin, and ghrelin are not associated with advanced stages of cancer or cancer-induced cachexia in older subjects with cancer, but they are significantly correlated with anthropometric factors and body composition.

Topics: Adipokines; Adiponectin; Adiposity; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cachexia; Female; Frailty; Ghrelin; Humans; Inflammation; Interleukin-6; Leptin; Male; Malnutrition; Neoplasms; Nutritional Status; Tumor Necrosis Factor-alpha

Leptin is an adipokine secreted from adipocytes that mediate lipid metabolism and inflammation. This cross-sectional study investigated the relationship between serum leptin level and nutrition status evaluated by malnutrition-inflammation score (MIS) among patients undergoing hemodialysis (HD).. This study included 100 patients on HD. Nutritional status was based on MIS (malnutrition ≥7 points). Body composition, biochemistry data, and serum leptin level were evaluated.. Of 100 subjects, 33 (33.0%) were categorized as having malnutrition. Compared with subjects in the well-nourished group, those in the malnutrition group had on average an older age, longer HD duration, and lower height, weight, body mass index, waist circumference, body fat mass, serum triglyceride level, and creatinine level. Serum leptin levels were also significantly lower in the malnutrition group (P < 0.001), whereas C-reactive protein (CRP) levels were higher (P = 0.002). Multivariable linear regression analysis revealed that HD duration (β = 2.06, P = 0.009), serum leptin level (β = -5.16, P < 0.001), CRP level (β = 3.33, P < 0.001), and albumin level (β = -1.95, P = 0.008) were factors independently associated with MIS. The discriminative power of serum leptin level to predict malnutrition was 0.834 (95% confidence interval: 0.747-0.901, P < 0.001).. Low serum leptin level was associated with malnutrition, and serum leptin level may be a valuable marker for nutrition assessment in patients undergoing HD.

Topics: Aged; Cross-Sectional Studies; Female; Humans; Inflammation; Leptin; Male; Malnutrition; Middle Aged; Renal Dialysis

Changes in the nutritional supply during the perinatal period can lead to metabolic disturbances and obesity in adulthood.. The divergent litter size model was used to investigate the hypothalamic sensitivity to leptin and ghrelin as well as the mechanisms involved in the disruption of food intake and energy expenditure.. On postnatal day 3 (P3), male Wistar rats were divided into 3 groups: small litter (SL - 3 pups), normal litter (NL - 10 pups), and large litter (LL - 16 pups). Animals at P60 were intraperitoneally treated with leptin (500 µg/Kg), ghrelin (40 µg/Kg), or vehicle (0.9% NaCl) at 5 pm and the following parameters were assessed: food intake and body weight; immunostaining of p-STAT-3 in the hypothalamus; Western Blotting analysis of p-AMPKα and UCP2 in the mediobasal hypothalamus (MBH), and UCP1 in the interscapular brown adipose tissue (BAT); or heat production, VO. SL rats had earlier leptin and ghrelin surges, while LL rats had no variations. At P60, after leptin treatment, LL rats showed hypophagia and increased p-STAT-3 expression in the arcuate nucleus, but SL rats had no response. After ghrelin treatment, LL rats did not have the orexigenic response or AMPKα phosphorylation in the MBH, while SL animals, unexpectedly, decreased body weight gain, without changes in food intake, and increased metabolic parameters and UCP1 expression in the BAT.. Changes in the nutritional supply at early stages of life modify leptin and ghrelin responsiveness in adulthood, programming metabolic and central mechanisms, which contribute to overweight and obesity in adulthood.

Topics: Aging; Animals; Arcuate Nucleus of Hypothalamus; Body Weight; Eating; Energy Metabolism; Female; Ghrelin; Hyperphagia; Hypothalamus; Leptin; Litter Size; Male; Malnutrition; Obesity; Pregnancy; Rats; Rats, Wistar; STAT3 Transcription Factor

Hypothalamic neurons including proopiomelanocortin (POMC)-producing neurons regulate body weights. The non-motile primary cilium is a critical sensory organelle on the cell surface. An association between ciliary defects and obesity has been suggested, but the underlying mechanisms are not fully understood. Here we show that inhibition of ciliogenesis in POMC-expressing developing hypothalamic neurons, by depleting ciliogenic genes IFT88 and KIF3A, leads to adulthood obesity in mice. In contrast, adult-onset ciliary dysgenesis in POMC neurons causes no significant change in adiposity. In developing POMC neurons, abnormal cilia formation disrupts axonal projections through impaired lysosomal protein degradation. Notably, maternal nutrition and postnatal leptin surge have a profound impact on ciliogenesis in the hypothalamus of neonatal mice; through these effects they critically modulate the organization of hypothalamic feeding circuits. Our findings reveal a mechanism of early life programming of adult adiposity, which is mediated by primary cilia in developing hypothalamic neurons.

Topics: Adiposity; Animals; Animals, Newborn; Arcuate Nucleus of Hypothalamus; Axons; Cilia; Energy Metabolism; Female; Glucose; Hypothalamus; Leptin; Lysosomes; Malnutrition; Mice, Inbred C57BL; Microtubule-Associated Proteins; Neurogenesis; Obesity; Organogenesis; Pro-Opiomelanocortin; Proteolysis

Prenatal undernutrition affects various physiological functions, such as metabolic and reproductive functions, after birth, and such changes are associated with the pathogeneses of certain diseases. It has been hypothesized that these changes are predictive adaptive responses that help individuals to endure similar conditions in the postnatal period. Thus, we evaluated the effects of prenatal undernutrition on the responses of the body weight (BW) regulation system and reproductive functions to fasting in the pre-pubertal period in male rats. Prenatally normally nourished and undernourished rats exhibited similar reductions in BW and visceral fat after 48 h fasting in the pre-pubertal period. Furthermore, these two groups displayed similar fasting-induced patterns of change in their hypothalamic levels of appetite regulatory factors; i.e., neuropeptide Y and pro-opiomelanocortin. These results indicate that prenatal undernutrition had no marked effects on BW regulation in male rats. On the other hand, serum luteinizing hormone and testosterone levels were decreased by 48 h fasting in the prenatally normally nourished rats, whereas the levels of these hormones did not change in the prenatally undernourished rats. However, the hypothalamic mRNA level of kisspeptin 1 (Kiss1), which is a positive regulator of gonadotropin-releasing hormone/gonadotropins, was reduced by fasting in both groups. These results indicate that prenatal undernutrition might attenuate fasting-induced reproductive dysfunction in the postnatal period; however, these changes might not be induced by alterations in the hypothalamic Kiss1 system. Further studies are needed to clarify the mechanisms involved in these changes in reproductive function.

Topics: Animals; Animals, Newborn; Body Weight; Disorders of Sex Development; Fasting; Female; Gene Expression Regulation, Developmental; Kisspeptins; Leptin; Luteinizing Hormone; Male; Malnutrition; Neuropeptide Y; Organ Size; Pregnancy; Pregnancy Complications; Pro-Opiomelanocortin; Rats; Rats, Wistar; Receptors, Leptin; Testis; Testosterone

Prenatal undernutrition and postnatal overnutrition increase the risk of some peripheral and central metabolic disorders in adulthood. We speculated that disturbances of appetite/metabolic regulatory factors might already have been established in the early stages of life and contribute to obesity later in life. The effects of a high-fat diet on the levels of peripheral and central appetite/metabolic regulatory factors were compared between the offspring of normally nourished dams and those of undernourished dams in the peri-pubertal period. In the offspring of the normally nourished dams (control), the consumption of the high-fat diet resulted in lower hypothalamic mRNA levels of orexigenic factors (neuropeptide Y (NPY) and prepro-orexin (pporexin)), whereas no such changes were seen in the offspring of the undernourished dams (subjected to intrauterine growth restriction). These results indicate that in high-energy conditions either the adaptive response does not function properly or has not been established in the offspring of undernourished dams. Because NPY and pporexin are negatively regulated by leptin, these findings suggest that in the intrauterine growth restriction group, the leptin resistance of hypothalamic functions, which is usually caused by diet-induced obesity in adulthood, had already been established in the peri-pubertal period.

Topics: Animals; Appetite Regulation; Diet, High-Fat; Female; Fetal Development; Fetal Growth Retardation; Gene Expression Regulation, Developmental; Hypothalamus; Intra-Abdominal Fat; Lactation; Leptin; Malnutrition; Maternal Nutritional Physiological Phenomena; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Obesity; Orexins; Protein Precursors; Rats, Sprague-Dawley; Weaning

Protein malnutrition, the most deleterious cause of malnutrition in developing countries, has been considered a primary risk factor for the development of clinical visceral leishmaniasis (VL). Protein malnutrition and infection with Leishmania infantum leads to lymphoid tissue disorganization, including changes in cellularity and lymphocyte subpopulations in the thymus and spleen. Here we report that protein malnutrition modifies thymic chemotactic factors by diminishing the CCL5, CXCL12, IGF1, CXCL9 and CXCL10 protein levels in infected animals. Nevertheless, T cells preserve their migratory capability, as they were able to migrate ex vivo in response to chemotactic stimuli, indicating that malnutrition may compromise the thymic microenvironment and alter in vivo thymocyte migration. Decrease in chemotactic factors protein levels was accompanied by an early increase in the parasite load of the spleen. These results suggest that the precondition of malnutrition is affecting the cell-mediated immune response to L. infantum by altering T cell migration and interfering with the capacity of protein-deprived animals to control parasite spreading and proliferation. Our data provide evidence for a disturbance of T lymphocyte migration involving both central and peripheral T-cells, which likely contribute to the pathophysiology of VL that occurs in malnourished individuals.

Topics: Animals; Apoptosis; Atrophy; Body Weight; Cell Movement; Chemotaxis; Cytokines; Insulin-Like Growth Factor I; Leishmania infantum; Leishmaniasis, Visceral; Leptin; Ligands; Macrophages; Malnutrition; Mice, Inbred BALB C; Parasite Load; Parasites; Receptors, CXCR3; Spleen; T-Lymphocytes; Thymocytes; Thymus Gland

Alterations in the early life environment, including maternal undernutrition (UN) during pregnancy, can lead to increased risk of metabolic and cardiovascular disorders in offspring. Leptin treatment of neonates born to UN rats reverses the programmed metabolic phenotype, but the possible benefits of this treatment on bone tissue have not been defined. We describe for the first time the effects of neonatal leptin treatment on bone in adult offspring following maternal UN. Offspring from either UN or ad libitum-fed (AD) rats were treated with either saline or leptin (2.5 µg/ g.d on postnatal days (D)3-13) and were fed either a chow or high fat (HF) diet from weaning until study completion at D170. Analysis of micro-tomographic data of the left femur showed highly significant effects of UN on cortical and trabecular bone tissue indices, contributing to inferior microstructure and bone strength, almost all of which were reversed by early leptin life treatment. The HF fat diet negatively affected trabecular bone tissue, but the effects of only trabecular separation and number were reversed by leptin treatment. The negative effects of maternal UN on skeletal health in adult offspring might be prevented or attenuated by various interventions including leptin. Establishment of a minimal efficacious leptin dose warrants further study.

Topics: Animals; Body Composition; Body Weight; Bone and Bones; Female; Leptin; Malnutrition; Maternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Rats

A poor early life nutrition environment is well established to result in a range of cardiometabolic disorders in offspring in later life. These effects can be exacerbated via exposure to an obesogenic dietary environment. To date, the effect of maternal diet and/or a post-natal obesogenic nutritional environment on key characteristics related to lens growth and oxidative stress has not been undertaken. The present study, therefore, examined the characteristics and oxidative status of the lens.. Using a model of moderate maternal under-nutrition, rat dams were fed either a control diet (100% ad libitum, CON) or undernourished throughout pregnancy (50% of ad libitum intake, UN) and offspring fed either a control (5% fat, C) or high fat (30% fat, HF) diet post-weaning, resulting in four nutritional groups; CON-C, CON-HF, UN-C, and UN-HF. Offspring lenses were extracted at 160 days of age, weighed, imaged under dark and bright field microscopy, and then dissected into cortical and core fractions for biochemical analyses of oxidative stress markers.. Our findings reveal that lenses from all groups were transparent. However, gender specific changes were evident at the biochemical level with increased oxidative stress detected in the cortex and core of female but not male UN-C lenses, and in the cortex of male but not female CON-HF lenses. The greatest increase in oxidative stress was detected in the UN-HF group in the cortex and core regions of the lens and for both genders.. These findings show that oxidative stress is exacerbated in the lens as a result of a combination of altered pre-natal and post-natal diet. This demonstrates a novel interaction between the two developmental windows and warrants further investigations toward devising appropriate nutritional strategies for minimizing oxidative stress in the lens.

Topics: Adiposity; Animals; Ascorbic Acid; Biomarkers; Blood Glucose; Body Weight; Diet, High-Fat; Female; Glutathione; Insulin; Lens Diseases; Lens, Crystalline; Leptin; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Obesity; Oxidative Stress; Pregnancy; Rats; Rats, Sprague-Dawley; Vitamin E

The major goal of animal production is to obtain abundant and healthy meat for consumers. Maternal food restriction (MFR) is often applied in farms to reduce production costs. However, the suitability of MFR in livestock animals is questionable, as this management may compromise maternal fitness due to a severe negative energetic balance and can induce Intrauterine Growth Restriction (IUGR) and prenatal programming in the offspring. Here, we sought to determine, using pregnant rabbits, the consequences of MFR on maternal endocrine and metabolic status and conceptus development. Pregnant dams were distributed into three groups: CONTROL (ad libitum feeding throughout the entire pregnancy; mean pregnancy length being around 31 days), UNDERFED (50% MFR during the entire pregnancy) and EARLY-UNDERFED (50% MFR only during the preimplantation period, Days 0-7). Maternal leptin concentrations and glycemic and lipid profiles were determined throughout pregnancy, whilst conceptus development was assessed ex-vivo at Day 28. Placental parameters were determined by macroscopic and histological evaluations and apoptotic assessments (TUNEL and Caspase-3). The main results of the study showed that, despite MFR altered maternal plasma lipid concentration (P<0.05), there were no effects on maternal bodyweight, plasma leptin concentration or glycemic profile. Fetal crown-rump lengths were reduced in both undernourished groups (P<0.001), but a significant reduction in fetal weight was only observed in the UNDERFED group (P<0.001). Growth in both undernourished groups was asymmetrical, with reduced liver weight (P<0.001) and significantly increased brain: fetal weight-ratio (P<0.001) and brain: liver weight-ratio (P<0.001) when compared to the CONTROL group. A significant reduction in placental weight was only observed in the UNDERFED group (P<0.001), despite both undernourished groups showing higher apoptotic rates at decidua and labyrinth zone (P<0.05) than the CONTROL group. Thus, these groups evidenced signs of placental degeneration, necrosis and stromal collapse. In summary, MFR may encourage the mother to make strategic decisions to safeguard her metabolic status and fitness at the expense of growth reduction in the litter, resulting in enhanced apoptotic and pathological processes at placental level and IUGR.

Topics: Animals; Apoptosis; Blastocyst; Blood Glucose; Body Weight; Crown-Rump Length; Disease Models, Animal; Female; Fetal Growth Retardation; Fetal Weight; Fetus; Leptin; Lipid Metabolism; Malnutrition; Placenta; Pregnancy; Pregnancy Complications; Pregnancy, Animal; Rabbits

Based on the Developmental Origin of Health and Disease concept, maternal undernutrition has been shown to sensitize adult offspring to metabolic pathologies such as obesity. Using a model of maternal 70% food restriction in pregnant female rats throughout gestation (called FR30), we previously reported that obesity-prone adult male rat offspring displayed hyperleptinemia with modifications in leptin and leptin receptor messenger RNA (mRNA) levels in white adipose tissue (WAT). Apelin is a member of the adipokine family that regulates various aspects of energy metabolism and WAT functionality. We investigated whether apelin and its receptor APJ could be a target of maternal undernutrition. Adult male rat offspring from FR30 dams showed increased plasma apelin levels and apelin gene expression in WAT. Post-weaning high-fat diet led to marked increase in APJ mRNA and protein levels in offspring's WAT. We demonstrate that maternal undernutrition and post-weaning diet have long-term consequences on the apelinergic system of adult male rat offspring.

Topics: Adipose Tissue; Animals; Apelin; Apelin Receptors; Body Weight; Energy Metabolism; Female; Leptin; Male; Malnutrition; Pregnancy; Rats

Recent studies suggest that nutritional status during developmental periods is associated with subsequent development of metabolic abnormalities. In this study, we examined whether malnutrition by fasting for 3 days during the suckling-weaning transient period induces subsequent development of metabolic abnormalities in rats.. Male Sprague-Dawley rats were fasted for 3 days during the suckling-weaning transient period. They are subsequently fed a high-fat, high-sucrose (HF) or low-fat, high-starch (LF) diet for 14 weeks from 17 weeks of age, and the liver and blood samples were collected for measuring mRNA and protein levels of metabolic genes and blood concentrations of glucose and insulin, respectively.. Fasting for 3 days during the suckling-weaning transient period induced impaired glucose tolerance in rats fed the LF diet in adulthood. Liver triglycerides in rats fed the HF diet in adulthood increased to 140 % in rats fasted for 3 days during the suckling-weaning transient period compared with those non-fasted. Furthermore, liver expression of FBP1 and ACCα genes in adult rats fed the LF diet increased to 125 and 145 %, respectively, in rats fasted for 3 days during the suckling-weaning transient period compared to non-fasted rats. PEPCK1 protein expression levels in rats fed the LF diet were higher in rats fasted for 3 days during the suckling-weaning transient period than in non-fasted rats.. Fasting for 3 days in rats during the suckling-weaning transient period enhances metabolic abnormalities in animals fed a HF or LF diet in adulthood by confounding metabolism of lipid and sugar in the liver.

Topics: Adiponectin; Animal Nutritional Physiological Phenomena; Animals; Animals, Suckling; Blood Glucose; Body Weight; Diet, High-Fat; Dietary Fats; Disease Models, Animal; DNA-Binding Proteins; Fasting; Fatty Acids, Nonesterified; Gluconeogenesis; Glucose Intolerance; Insulin; Leptin; Lipogenesis; Liver; Male; Malnutrition; Metabolic Diseases; Organ Size; Rats; Rats, Sprague-Dawley; RNA, Messenger; Triglycerides; Weaning

Fetal growth retardation, which affects short- and long-term fetal brain development, is associated with metabolic, hematological, and thermal disturbances, which can increase the risk of metabolic syndrome later in life. Orexigenic and anorexigenic factors regulate food intake and energy expenditure. We studied how the expression of these factors was affected by food deprivation (FD) in middle-aged female rats that had been subjected to prenatal undernutrition. Eight pregnant rats were divided into two groups, the normal nutrition (NN) (n=4) group and the undernutrition (UN) (n=4) group, which received 50% (approximately 11 g) of the daily food intake of the normal nutrition rats from day 13 of pregnancy to delivery. The pups from these dams were defined as the maternal NN (mNN) and maternal UN (mUN) groups, respectively. After weaning, all of the pups were housed and allowed ad libitum access to food and water. At the age of 6 months, both groups of pups were sub-divided into three groups. One group was allowed to consume normal amounts of food (Fed), and the other two groups were subjected to 24h or 48 h FD (n=7-8 per group). The rats' serum leptin levels and hypothalamic mRNA expression levels of various orexigenic or anorexigenic factors were measured. In both the mNN and mUN rats, the serum leptin levels of the 24h and 48 h FD groups tended to be lower than those of the Fed group, and the serum leptin levels of the 24h FD mUN rats and the Fed mUN rats differed significantly. The hypothalamic neuropeptide Y (NPY) mRNA expression levels of the 24h and 48 h FD groups were significantly higher in the mUN rats than in the mNN rats. In addition, among the mUN rats the hypothalamic NPY mRNA expression levels of the 48 h FD group were significantly higher than those of the Fed group. In both the mNN and mUN rats, prepro-orexin mRNA expression was lower in the 48 h FD group than in the corresponding Fed group. Among the mUN rats, the 48 h FD group exhibited significantly lower hypothalamic proopiomelanocortin (POMC) mRNA expression than the Fed group, and a similar tendency was seen among the mNN rats. Among the mNN rats, the 24h FD group displayed significantly higher hypothalamic leptin receptor (OBRb) mRNA levels than the Fed group. However, no such differences were seen among the mUN rats. As a result, the hypothalamic OBRb mRNA expression levels of the mUN rats in the 24h and 48 h FD groups were lower than those of the corresponding mNN rat groups. Thes

Topics: Analysis of Variance; Animals; Body Weight; Female; Food Deprivation; Gene Expression Regulation; Hypothalamus; Leptin; Malnutrition; Neuropeptide Y; Pregnancy; Prenatal Nutritional Physiological Phenomena; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Receptors, Leptin; RNA, Messenger; Time Factors

Leptin is a regulatory hormone with multiple roles in the immune system. We favor the concept that leptin signaling 'licenses' various immune cells to engage in immune responses and/or to differentiate. Leptin is an inflammatory molecule that is capable of activating both adaptive and innate immunity. It can also 'enhance' immune functions, including inflammatory cytokine production in macrophages, granulocyte chemotaxis, and increased Th17 proliferation. Leptin can also 'inhibit' cells; CD4(+) T cells are inhibited from differentiating into regulatory T cells in the presence of elevated leptin, while NK cells can exhibit impaired cytotoxicity under the same circumstances. Consequently, understanding the effect of leptin signaling is important to appreciate various aspects of immune dysregulation observed in malnutrition, obesity, and autoimmunity.

Topics: Autoimmunity; Cell Differentiation; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation; Humans; Immunity, Innate; Killer Cells, Natural; Leptin; Malnutrition; Nuclear Receptor Subfamily 1, Group F, Member 3; Obesity; Receptors, Leptin; Signal Transduction; T-Lymphocytes, Regulatory; Th17 Cells

Previously we reported that prenatal undernutrition (UN) leads to a dysregulation of appetite suppression through alterations in hypothalamic neuropeptide gene expression. In the current study, we expand our observations and investigate neuroendocrine transcriptional responses and central leptin sensitivity within the arcuate nucleus of rats exposed to prenatal UN or a postnatal high-fat diet (HF). Pregnant Wistar rats were fed a standard chow diet either ad libitum (AD) or at 30 % of AD intake throughout gestation (UN) resulting in either control or intrauterine growth-restricted female offspring. At weaning, AD offspring were fed either a chow (C) or a HF (30 % fat wt/wt) diet ad libitum for the remainder of the study, whereas UN offspring were fed a chow diet only. At ~142 days, AD and UN offspring received either recombinant rat leptin (L) or saline (S) subcutaneously for 14 days. Prenatal UN had a significant effect on hypothalamic NPY (P < 0.0001), AgRP (P < 0.01) and ObRb (P < 0.02) mRNA expression compared to AD chow-fed offspring. A postnatal HF diet had a significant effect on AgRP mRNA expression (P < 0.001), compared to AD chow-fed offspring, but no effect on NPY and ObRb expression. Leptin treatment, in both UN and HF offspring, was ineffective in reducing NPY and AgRP mRNA expression, and had no effect on ObRb expression. These findings suggest that prenatal UN and a postnatal HF diet lead to differential neuroendocrine gene expression in the hypothalamic arcuate nuclei and reduced sensitivity to leptin's anorexigenic effects.

Topics: Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Diet, High-Fat; Female; Gene Expression; Leptin; Male; Malnutrition; Neuropeptide Y; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar

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

Upon activation, T cells require energy for growth, proliferation, and function. Effector T (Teff) cells, such as Th1 and Th17 cells, utilize high levels of glycolytic metabolism to fuel proliferation and function. In contrast, Treg cells require oxidative metabolism to fuel suppressive function. It remains unknown how Teff/Treg-cell metabolism is altered when nutrients are limited and leptin levels are low. We therefore examined the role of malnutrition and associated hypoleptinemia on Teff versus Treg cells. We found that both malnutrition-associated hypoleptinemia and T cell-specific leptin receptor knockout suppressed Teff-cell number, function, and glucose metabolism, but did not alter Treg-cell metabolism or suppressive function. Using the autoimmune mouse model EAE, we confirmed that fasting-induced hypoleptinemia altered Teff-cell, but not Treg-cell, glucose metabolism, and function in vivo, leading to decreased disease severity. To explore potential mechanisms, we examined HIF-1α, a key regulator of Th17 differentiation and Teff-cell glucose metabolism, and found HIF-1α expression was decreased in T cell-specific leptin receptor knockout Th17 cells, and in Teff cells from fasted EAE mice, but was unchanged in Treg cells. Altogether, these data demonstrate a selective, cell-intrinsic requirement for leptin to upregulate glucose metabolism and maintain function in Teff, but not Treg cells.

Topics: Animals; Cell Differentiation; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Glycolysis; Hypoxia-Inducible Factor 1, alpha Subunit; Leptin; Malnutrition; Mice; Mice, Inbred C57BL; Mice, Knockout; T-Lymphocytes, Regulatory; Th17 Cells

There is an ever increasing body of evidence that demonstrates that paternal over-nutrition prior to conception programs impaired metabolic health in offspring. Here we examined whether paternal under-nutrition can also program impaired health in offspring and if any detrimental health outcomes in offspring could be prevented by micronutrient supplementation (vitamins and antioxidants). We discovered that restricting the food intake of male rodents reduced their body weight, fertility, increased sperm oxidative DNA lesions and reduced global sperm methylation. Under-nourished males then sired offspring with reduced postnatal weight and growth but somewhat paradoxically increased adiposity and dyslipidaemia, despite being fed standard chow. Paternal vitamin/antioxidant food fortification during under-nutrition not only normalised founder oxidative sperm DNA lesions but also prevented early growth restriction, fat accumulation and dyslipidaemia in offspring. This demonstrates that paternal under-nutrition reduces postnatal growth but increases the risk of obesity and metabolic disease in the next generation and that micronutrient supplementation during this period of under-nutrition is capable of restoring offspring metabolic health.

Topics: Adiposity; Animals; Antioxidants; Body Composition; Embryonic Development; Female; Food, Fortified; Founder Effect; Infertility, Male; Insulin; Leptin; Lipids; Male; Malnutrition; Metabolic Syndrome; Mice, Inbred C57BL; Paternal Inheritance; Reactive Oxygen Species; Sperm Count; Sperm Motility

Malnutrition is a leading cause of morbidity and mortality in cirrhosis. There is no consensus as to the optimal approach for identifying malnutrition in end-stage liver disease. The aim of this study was to measure biochemical, serologic, hormonal, radiographic, and anthropometric features in a cohort of hospitalized cirrhotic patients to characterize biomarkers for identification of malnutrition.. In this prospective observational cohort study, 52 hospitalized cirrhotic patients were classified as malnourished (42.3%) or nourished (57.7%) based on mid-arm muscle circumference < 23 cm and dominant handgrip strength < 30 kg. Anthropometric measurements were obtained. Appetite was assessed using the Simplified Nutrition Appetite Questionnaire (SNAQ) score. Fasting levels of serum adipokines, cytokines, and hormones were determined using Luminex assays. Logistic regression analysis was used to determine features independently associated with malnutrition.. Subjects with and without malnutrition differed in several key features of metabolic phenotype including wet and dry BMI, skeletal muscle index, visceral fat index and HOMA-IR. Serum leptin levels were lower and INR was higher in malnourished subjects. Serum leptin was significantly correlated with HOMA-IR, wet and dry BMI, mid-arm muscle circumference, skeletal muscle index, and visceral fat index. Logistic regression analysis revealed that INR and log-transformed leptin were independently associated with malnutrition.. Low serum leptin and elevated INR are associated with malnutrition in hospitalized patients with end-stage liver disease.

Topics: Adipokines; Biomarkers; Cytokines; Female; Hormones; Humans; International Normalized Ratio; Leptin; Liver Cirrhosis; Male; Malnutrition; Middle Aged; Prospective Studies

We have reported that maternal overnutrition/obesity (OB) in sheep resulting from feeding 150% of National Research Council (NRC) requirements throughout gestation leads to maternal hyperglycemia and hyperinsulinemia. Further, newborn lambs born to OB vs control-fed (CON, 100% of NRC) ewes exhibited greater adiposity, increased blood cortisol, insulin and glucose and the elimination of the postnatal leptin spike seen in lambs born to CON ewes. This early postnatal leptin peak is necessary for the development of hypothalamic circuits, which program appetite in later life. This study evaluated the multigenerational impact of OB on insulin:glucose dynamics of mature female F1 offspring fed only to requirements throughout gestation and on their lambs (F2 generation).. Adult F1 female offspring born to OB (n=10) or CON (n=7) ewes were utilized. All F1 ewes were subjected to a glucose tolerance test at midgestation and late gestation. Jugular blood was obtained from F2 lambs at birth (day 1) through postnatal day 11, and plasma glucose, insulin, cortisol and leptin concentrations were determined. Dual-energy X-ray absorptiometry was utilized to determine bone mineral density, bone mineral content, lean tissue mass and fat tissue mass.. Fasted blood glucose and insulin concentrations were greater (P<0.05) in OBF1 than CONF1 ewes at midgestation and late gestation. Further, after glucose infusion, both glucose and insulin concentrations remained higher in OBF1 ewes (P<0.05) than CONF1 ewes, demonstrating greater insulin resistance. Blood concentrations of glucose, insulin and cortisol and adiposity were higher (P<0.01) in OBF2 lambs than CONF2 lambs at birth. Importantly, OBF2 lambs failed to exhibit the early postnatal leptin peak exhibited by CONF2 lambs.. These data suggest that these OBF2 lambs are predisposed to exhibit the same metabolic alterations as their mothers, suggesting a multigenerational programming effect.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Blood Glucose; Female; Glucose Tolerance Test; Leptin; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Obesity; Overnutrition; Pregnancy; Prenatal Exposure Delayed Effects; Sheep

Topics: Animals; Cardiovascular System; Female; Heart Diseases; Lactation; Leptin; Malnutrition; Models, Theoretical; Nutritional Status; Rats

This study examined the effects of food restriction during rabbit pregnancy on hormones and metabolites involved in energy homeostasis and metabolic programming. Pregnant does were assigned to four groups: the control group was fed a standard ration while the others received a restricted amount of food (30% restriction) during early (0-9 days), mid (9-18 days), and late (19-28 days) pregnancy. The pregnancy induced a coordinated range of adaptations to fulfil energy requirements of both mother and foetus, such as hyperleptinaemia and hyperinsulinaemia, reduced insulin sensitivity, increased cortisol and non-esterified fatty acid. Food restriction altered leptin, insulin, T3, non-esterified fatty acids and glucose concentrations depending on the gestational phase in which it was applied. Collectively, present data confirm that the endocrinology of pregnancy and the adaptive responses to energy deficit make the rabbit an ideal model for studying nutritional-related disorders and foetal programming of metabolic disease.

Topics: Animal Nutritional Physiological Phenomena; Animals; Diet; Energy Metabolism; Fatty Acids, Nonesterified; Female; Fetus; Glucose; Homeostasis; Hormones; Insulin; Insulin Resistance; Leptin; Malnutrition; Models, Animal; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Rabbits

Prenatal undernutrition and postnatal overnutrition increase the risk of some metabolic disorders in adulthood, and hypothalamic leptin resistance makes an important contribution to these effects. Leptin plays important roles in the maintenance of reproductive function, and its actions might be partially mediated by kisspeptin, which is a potent positive regulator of gonadotropin-releasing hormone. In this study, the effects of prenatal undernutrition and postnatal overnutrition on reproductive parameters and sexual maturation during the peripubertal period were evaluated. Rats subjected to prenatal undernutrition (IUGR) and fed a postnatal high-fat diet (HFD) (n = 7) exhibited 40% higher serum leptin levels and 30% lower hypothalamic Kiss1 (the gene encoding kisspeptin) mRNA levels than those subjected to prenatal undernutrition (IUGR) and fed a normal diet (n = 7). No such HFD-induced postnatal alterations were observed in the rats fed a normal diet during the prenatal period (control) (n = 7 per group). Although the consumption of the HFD did not affect the serum luteinizing hormone levels or body weight of the IUGR or control rats, it did promote vaginal opening in both groups (evaluated in 14 rats per group). These findings indicate that hypothalamic leptin resistance might occur in IUGR-HFD rats, but these changes do not influence downstream effectors of the reproductive endocrinological system. They also suggest that the relationships between nutritional conditions, body weight, reproductive factors, and sexual maturation are complex.

Topics: Animals; Animals, Newborn; Body Weight; Female; Gonadotropin-Releasing Hormone; Hypothalamus; Kisspeptins; Leptin; Male; Malnutrition; Neuropeptides; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Receptors, Neuropeptide; RNA, Messenger

Predisposition to offspring metabolic dysfunction due to poor maternal nutrition differs with the developmental stage at exposure. Post-weaning nutrition also influences offspring phenotype in either adverse or beneficial ways. We studied a well-established rat maternal protein-restriction model to determine whether post-weaning dietary intervention improves adverse outcomes produced by a deficient maternal nutritional environment in pregnancy. Pregnant rats were fed a controlled diet (C, 20% casein) during pregnancy and lactation (CC) or were fed a restricted diet (R, 10% casein isocaloric diet) during pregnancy and C diet during lactation (RC). After weaning, the offspring were fed the C diet. At postnatal day (PND) 70 (young adulthood), female offspring either continued with the C diet (CCC and RCC) or were fed commercial Chow Purina 5001 (I) to further divide the animals into dietary intervention groups CCI and RCI. Another group of mothers and offspring were fed I throughout (III). Offspring food intake was averaged between PND 95-110 and 235-250 and carcass and liver compositions were measured at PND 25 and 250. Leptin (PND 110 and 250) and serum glucose, triglycerides and cholesterol (PND 250) levels were measured. Statistical analysis was carried out using ANOVA. At PND 25, body and liver weights were similar between groups; however, CCC and RCC carcass protein:fat ratios were lower compared with III diet. At PND 110 and 250, offspring CCC and RCC had higher body weight, food intake and serum leptin compared with CCI and RCI. CCI had lower carcass fat and increased protein compared with CCC and improved fasting glucose and triglycerides. Adult dietary intervention partially overcomes adverse effects of programming. Further studies are needed to determine the mechanisms involved.

Topics: Animals; Body Weight; Diet; Diet Therapy; Dietary Proteins; Female; Lactation; Leptin; Liver; Male; Malnutrition; Pregnancy; Prenatal Nutritional Physiological Phenomena; Random Allocation; Rats, Wistar

Although prenatal undernutrition affects the development of metabolic, physiological, and reproductive functions, it remains unclear whether it also affects physiological responses to undernutrition in adulthood. Therefore, in this study we examined whether prenatal undernutrition alters the sensitivity of the hypothalamic-pituitary-gonadal (HPG) axis to fasting in adult male rats. The offspring of ad libitum fed dams (control) and ∼50% food-restricted (during the late gestational period) dams (IUGR) were sub-divided into ad libitum fed (fed) and 48 h food deprivation (FD) groups at 10 weeks of age. In each group, the serum levels of luteinizing hormone (LH), testosterone, and leptin and the hypothalamic mRNA expression levels of gonadotropin-releasing hormone (GnRH) regulatory factors were measured. The serum LH and testosterone levels of the IUGR-fed rats were significantly or tend to be higher than those of the control-fed rats, respectively. The serum LH levels of the IUGR-FD rats were lower than those of the IUGR-fed rats. Similarly, the serum testosterone levels of the IUGR-FD rats tended to be lower than those of the IUGR-fed rats. On the other hand, the serum LH and testosterone levels of the control-fed and control-FD rats did not differ. The serum leptin levels of the IUGR fed rats were higher than those of the control-fed rats. The serum leptin levels of the control-FD and IUGR-FD rats were lower than those of the control-fed and IUGR-fed rats, respectively. The hypothalamic neuropeptide Y (NPY) mRNA levels of the IUGR-FD rats were higher than those of the IUGR-fed rats. Similarly, hypothalamic NPY mRNA levels of control-FD rats were higher than those of the control-fed rats. The hypothalamic kisspeptin, kisspeptin receptor, RFamide-related peptide, GPR147, and OBRb mRNA levels of control fed rats did not differ between control-fed and IUGR-fed rats. Their mRNA levels of the fed and FD rats did not differ in the control or IUGR groups. These results suggested that prenatal undernutrition increased the basal LH and testosterone production, whereas they are easily reduced by food deprivation in male rats. Changes of serum leptin level, but not of hypothalamic reproductive related factors, might be involved in these alterations. However, the precise mechanisms responsible for these effects remain unclear.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Brain-Derived Neurotrophic Factor; Exploratory Behavior; Female; Food Deprivation; Gene Expression Regulation, Developmental; Leptin; Luteinizing Hormone; Male; Malnutrition; Microtubule-Associated Proteins; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Receptor, trkB; Testosterone

Millions of the world's children suffer from malnutrition, which predisposes to death from diarrhea and a variety of infectious diseases. Mortality rates among infants and toddlers remain staggeringly high, in part because the pathogenesis of acute malnutrition and its complications remains poorly understood.. We used metabolomic analysis to characterize the metabolic status of Ugandan children with severe acute malnutrition (SAM) and to delineate changes in hormones, metabolites, growth factors, and cytokines during nutritional therapy. We hypothesized that hormonal and metabolic factors measured at presentation would associate with, or predict, subsequent mortality during treatment.. This was a prospective cohort study of 75 severely malnourished children 6 months to 5 years of age treated as inpatients with F-75 and F-100 and supplemental micronutrients; after discharge, they received ready-to-use therapeutic food (RUTF). This increased the mean weight-for-height z-score (WHZ) from -4.27 to -1.75 SD. Blood samples were obtained at presentation, after 2 weeks of inpatient therapy, and after 4 to 10 weeks of RUTF. Plasma samples were analyzed by tandem mass spectrometry and microassays.. At presentation there were high levels of nonesterified fatty acids (NEFA), ketones, and even-chain acylcarnitines, indicating active lipolysis and fatty acid oxidation. In contrast, albumin, amino acids, and C3 carnitine, a by-product of branched-chain amino acids, were low. Levels of insulin, insulin-like growth factor 1 (IGF-1), adiponectin, and leptin were low, while levels of ghrelin, growth hormone, cortisol, interleukin 6 (IL-6), peptide YY (PYY), and glucagon-like peptide 1 (GLP-1) were high. The metabolic and hormonal changes were reversed by formula feeding and RUTF. Biomarkers associated with mortality included HIV, WHZ, and mid-upper-arm circumference (MUAC); the biochemical factor associated most strongly with mortality was low leptin, a marker of adipose reserve and modulator of immune function.. Low leptin predicts mortality in edematous and nonedematous-patients with SAM. Leptin assays might be used to identify malnourished children at highest risk for death.

Topics: Acute Disease; Biomarkers; Child Nutrition Disorders; Child, Preschool; Cohort Studies; Cytokines; Hormones; Humans; Infant; Infant Nutrition Disorders; Intercellular Signaling Peptides and Proteins; Leptin; Malnutrition; Metabolome; Metabolomics; Nutrition Therapy; Prospective Studies; Uganda

Human studies have suggested that early undernutrition increases the risk of obesity, thereby explaining the increase in overweight among individuals from developing countries who have been undernourished as children. However, this conclusion is controversial, given that other studies do not concur. This study sought to determine whether rehabilitation after undernutrition increases the risk of obesity and metabolic disorders. We employed a published experimental food-restriction model. Wistar female rats subjected to severe food restriction since fetal stage and controls were transferred to a moderately high-fat diet (cafeteria) provided at 70 days of life to 6.5 months. Another group of undernourished rats were rehabilitated with chow. The energy intake of undernourished animals transferred to cafeteria formula exceeded that of the controls under this regime and was probably driven by hypothalamic disorders in insulin and leptin signal transduction. The cafeteria diet resulted in greater relative increases in both fat and lean body mass in the undernourished rats when compared with controls, enabling the former group to completely catch up in length and body mass index. White adipose tissues of undernourished rats transferred to the high-lipid regime developed a browning which, probably, contributed to avoid the obesigenic effect observed in controls. Nevertheless, the restricted group rehabilitated with cafeteria formula had greater accretion of visceral than subcutaneous fat, showed increased signs of macrophage infiltration and inflammation in visceral pad, dyslipidemia, and ectopic fat accumulation. The data indicate that early long-term undernutrition is associated with increased susceptibility to the harmful effects of nutritional rehabilitation, without causing obesity.

Topics: Adipose Tissue, White; Adiposity; Animals; Diet, High-Fat; Energy Intake; Female; Hyperphagia; Hypothalamus; Insulin Resistance; Leptin; Liver; Male; Malnutrition; Muscle, Skeletal; Neuropeptide Y; Obesity; Oxidation-Reduction; Pregnancy; Prenatal Exposure Delayed Effects; Pro-Opiomelanocortin; Rats, Wistar; Risk Factors

Adverse nutritional effects on developing foetal hypothalamic appetitive pathways may contribute to programmed hyperphagia and obesity in intra-uterine growth-restricted, low birth weight offspring. In the present study, for the first time, hypothalamic gene expression for primary orexigenic and anorexigenic genes was examined in late gestation ovine foetuses (130 days; term=145 days) whose mothers were undernourished (UN) or well-nourished (C) throughout pregnancy, or transferred from UN to C on day 90 (UN-C). Pregnancies resulted from singleton embryo transfer into adolescent growing ewes. Body weight, carcass fat content and perirenal adipose tissue (PAT) mass were all lower for UN (n=9) than C (n=7) and intermediate for UN-C foetuses (n=6), with no effect of sex. PAT leptin gene expression (by the reverse transcriptase-polymerase chain reaction) was lower in UN than C and UN-C groups, and lower in males than females. Gene expression (by in situ hybridisation with radiolabelled riboprobes) in the arcuate nucleus was greater in UN than C foetuses for neuropeptide Y (NPY), agouti-related peptide (AGRP) and leptin receptor (OBRb) but not different for pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript. Gene expression in UN-C foetuses was intermediate for NPY and AGRP and not different from C foetuses for OBRb. Gene expression for NPY, AGRP and OBRb correlated negatively with foetal carcass fat content and with PAT leptin gene expression across all groups. Males had greater mRNA expression for AGRP than females, with NPY and OBRb showing similar trends. Therefore, maternal undernutrition throughout pregnancy increased orexigenic gene expression in the late gestation foetal hypothalamus, and expression levels were largely normalised by improved maternal nutrition in the last third of pregnancy. These findings may have implications for avoiding or correcting prenatal programming of postnatal hyperphagia and obesity.

Topics: Adiposity; Animals; Female; Gene Expression Regulation, Developmental; Hypothalamus; Leptin; Malnutrition; Sheep

Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha-Macroglobulins; Biomarkers; Blood Protein Electrophoresis; Body Mass Index; Child; Child, Preschool; Comorbidity; Disease Progression; Disease Susceptibility; Electrophoresis, Polyacrylamide Gel; Ethnicity; Female; Follow-Up Studies; Haptoglobins; Humans; Immunocompromised Host; India; Infant; Interferon-gamma Release Tests; Latent Tuberculosis; Leptin; Male; Malnutrition; Middle Aged; Prospective Studies; Proteome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transferrin; Tuberculin Test; Tuberculosis; Young Adult

Undernutrition during brain development causes long lasting alterations in different neurotransmitter systems that may alter responses to psychoactive drugs. Despite the recognized effects of early undernutrition on the cholinergic system, no evidence that demonstrates the influence of this insult on nicotine susceptibility has been reported. We investigated the effects of protein/calorie restriction during lactation on the susceptibility to nicotine in adolescent mice. Dams were randomly assigned to one of the following groups: Control (C, 20 litters)--free access to standard laboratory diet (23% protein); Protein Restricted (PR, 12 litters)--free access to a isoenergetic, 8% protein diet; Calorie Restricted (CR, 12 litters)--access to standard laboratory diet in restricted quantities (mean ingestion of PR: pair-fed group). Undernutrition extended from postnatal day 2 (PN2) to weaning (PN21). At PN30, animals either received an i.p. injection of nicotine (0.5mg/Kg) or saline and were immediately placed in open field (OF). After the OF, adrenal glands and serum were collected for the analyses of stress-related endocrine parameters and leptin concentration. PR and CR offspring showed less body mass gain and visceral fat mass. PR offspring presented reduced serum leptin concentration. In the OF, nicotine increased locomotor activity of C and PR, but not of CR. CR and PR offspring showed decreased adrenal catecholamine content, which was not dependent on nicotine exposure. Our results indicate that early undernutrition interferes with nicotine-elicited locomotor effects in adolescent mice and suggest that endocrine parameters alterations in malnourished animals do not influence the behavioral response to nicotine.

Topics: Adrenal Medulla; Animals; Animals, Newborn; Body Mass Index; Caloric Restriction; Catecholamines; Diet, Protein-Restricted; Disease Models, Animal; Eating; Exploratory Behavior; Fats; Female; Hormones; Lactation; Leptin; Locomotion; Male; Malnutrition; Mice; Nicotine; Nicotinic Agonists

Undernutrition causes a reduction of body-fat mass and a decrease in the circulating concentration of leptin which impairs the production of proinflammatory cytokines and increases the incidence of infectious diseases. The main objective of this study was to determine whether leptin deficiency is a risk factor for ventilator-associated pneumonia (VAP).. This prospective observational case-control study was conducted in a university ICU during a 2-year period. Patients with VAP (cases) were matched (1:1) to patients without VAP (controls) according to all the following criteria: age, gender, SAPS II, and duration of ICU stay before VAP occurrence. In all patients leptin, C-reactive protein (CRP) and procalcitonin (PCT) were measured at ICU admission, and twice a week. In addition, in cases, leptin, CRP and PCT were also measured on the day of VAP diagnosis.. Eighty-six cases were matched with 86 controls. No significant difference was found in leptin and PCT levels between cases and controls. CRP level was significantly higher on the day of VAP in cases compared with controls (99 vs. 48 mg/L, P=0.001). Combination of CRP-leptin (CRP ≥78 mg/L and leptin ≥6.2 ng/mL on the day of VAP) was significantly (P=0.009) associated with VAP in univariate analysis. Multivariate analysis identified the combination of CRP-leptin (OR [95% CI] 3.08 [1.18-8.04], P=0.003), LOD score (1.27 [1.08-1.48], P=0.003), neuromuscular-blockers use (6.6 [2.03-21.7], P=0.002), and reintubation (3.3 [1.14-9.6], P=0.027) as independent risk factors for VAP.. In our study, leptin level was not associated with VAP occurrence. Further studies are needed to confirm our results, and to define the exact inflammatory role of leptin, and its interest as a biomarker in ICU patients.

Topics: Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Hypoalbuminemia; Infection Control; Intensive Care Units; Leptin; Male; Malnutrition; Middle Aged; Pneumonia, Ventilator-Associated; Prospective Studies; Protein Precursors; Risk Factors; Sensitivity and Specificity; Ventilator Weaning

Adipokine levels may have a role in the diagnostic and prognostic evaluation of malnutrition. The aim of the present study was to evaluate the correlation between malnutrition score and leptin, other biological markers, and body mass index (BMI) in the diagnosis of malnutrition in the elderly.. In this cross-sectional observational study, we enrolled subjects over 70 years. Exclusion criteria were diabetes mellitus, obvious thyroid disorders, significant edema, renal dysfunction, chronic liver disease, symptomatic cardiovascular diseases, and malignity. Patients' demographic and medical data were recorded and anthropometric measurements were performed. Laboratory parameters including leptin, IGF-1, IGFBP-3, IL-6, TNF-α were measured. We defined malnutrition according to mini nutritional assessment (MNA) scale. Patients were divided into four groups according to BMI quartiles.. Average age of the patients was 81.9 ± 4.8 years, 68.2 % female and 31.8 % male. According to their MNA scores, 103 (66.9 %) were well nourished, 33 (21.4 %) were under malnutrition risk and 18 (11.7 %) were malnourished. MNA total and screening scores were positively correlated with albumin, BMI, high-density lipoprotein cholesterol and estimated glomerular filtration rate. Serum leptin levels (ng/ml) were 18.9 ± 22.6, 22.3 ± 21.9, 51.9 ± 85.5, and 61.7 ± 56.1 in BMI groups 1-4, respectively. BMI was positively correlated with leptin and triglyceride levels. Leptin levels were similar among nutritional state groups. Neither BMI nor MNA scores had any significant correlation with adiponectin, ghrelin, IGF-1, or IGFBP-3.. Adipokine levels do not seem to give relevant information in nutritional state assessment.

Topics: Adipokines; Aged; Aged, 80 and over; Aging; Body Mass Index; Cross-Sectional Studies; Cytokines; Female; Humans; Leptin; Lipids; Male; Malnutrition; Nutrition Assessment; Risk Factors

Perinatal nutrient restriction exerts profound influences on brain development. Animals that suffer undernutrition during lactation also display impaired weight gain. Feeding behavior is mainly modulated by neural and hormonal inputs to the hypothalamus. The arcuate-paraventricular neuropeptidergic Y pathway has a prominent role in appetite regulation. The aim of this work was to study the effects of protein undernutrition during lactation on this hypothalamic pathway. We used rats from 5 to 60 postnatal (P) days whose dams were fed a 0% protein diet (PFG) or a normoprotein diet (CG) from P1 to P10. To reproduce the same amount of calorie ingested by the PFG we used an underfed group (UFG). Immunohistochemistry was performed to assess neuropeptide Y (NPY) distribution in the arcuate, periventricular and paraventricular nuclei. Our results showed a NPY immunostaining peak at P10 in all nuclei in CG animals. In UFG animals this peak was observed by P15, while, in the PFG animals only by P20. Our results suggest that the neuropeptidergic arcuate-paraventricular pathway suffered a delay in NPY distribution in undernourished animals, particularly those fed a 0% protein diet, reflecting an effect on this pathway maturation that could explain previously reported alterations on feeding behavior in these animals.

Topics: Adipose Tissue; Analysis of Variance; Animals; Animals, Newborn; Arcuate Nucleus of Hypothalamus; Body Mass Index; Eating; Female; Gene Expression Regulation, Developmental; Leptin; Malnutrition; Neural Pathways; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Pregnancy; Rats; Rats, Wistar

The hypothalamus plays a crucial role in body weight homeostasis through an intricate network of neuronal circuits that are under the precise regulation of peripheral hormones and central transmitters. Although deregulated function of such circuits might be a major contributing factor in obesity, the molecular mechanisms responsible for the hypothalamic control of energy balance remain partially unknown. MicroRNAs (miRNAs) have been recognized as key regulators of different biological processes, including insulin sensitivity and glucose metabolism. However, the roles of miRNA pathways in the control of metabolism have been mostly addressed in peripheral tissues, whereas the potential deregulation of miRNA expression in the hypothalamus in conditions of metabolic distress remains as yet unexplored. In this work, we used high-throughput screening to define to what extent the hypothalamic profiles of miRNA expression are perturbed in two extreme conditions of nutritional stress in male rats, namely chronic caloric restriction and high-fat diet-induced obesity. Our analyses allowed the identification of sets of miRNAs, including let-7a, mir-9*, mir-30e, mir-132, mir-145, mir-200a, and mir-218, whose expression patterns in the hypothalamus were jointly altered by caloric restriction and/or a high-fat diet. The predicted targets of these miRNAs include several elements of key inflammatory and metabolic pathways, including insulin and leptin. Our study is the first to disclose the impact of nutritional challenges on the hypothalamic miRNA expression profiles. These data will help to characterize the molecular miRNA signature of the hypothalamus in extreme metabolic conditions and pave the way for targeted mechanistic analyses of the involvement of deregulated central miRNAs pathways in the pathogenesis of obesity and related disorders.

Topics: Aging; Animals; Appetite Depressants; Body Composition; Caloric Restriction; Computational Biology; Diet, High-Fat; Gene Expression Profiling; Gene Expression Regulation, Developmental; Hypothalamus; Leptin; Male; Malnutrition; MicroRNAs; Models, Biological; Neurons; Obesity; Rats; Rats, Wistar; Weaning

Dengue virus (DENV) infections range from asymptomatic or mild illness to a severe and potentially life threatening disease, dengue hemorrhagic fever (DHF). DHF occurs in primary DENV infections during early infancy. A prospective clinical study of DENV infections during infancy was conducted in San Pablo, Philippines. We found that infants who developed DHF with a primary DENV infection had higher WHO weight-for-age z scores before and at the time of infection compared to infants with primary DENV infections who did not develop DHF. In addition, TLR 7/8-stimulated tumor necrosis factor-α (TNF-α) production from myeloid-derived cells was higher among well-nourished infants. Leptin augmented TLR 7/8-mediated TNF-α production in monocytes and decreased intracellular cAMP levels. Circulating leptin levels were elevated during early infancy and correlated with WHO weight-for-age z scores. Our data support a plausible hypothesis as to why well-nourished infants are at risk for developing DHF with their first DENV infection.

Topics: Adiposity; Adult; Cyclic AMP; Humans; Infant; Intracellular Space; Leptin; Male; Malnutrition; Models, Statistical; Monocytes; Risk; Severe Dengue; Toll-Like Receptor 7; Toll-Like Receptor 8; Tumor Necrosis Factor-alpha

Undernutrition exposure during the perinatal period reduces the growth kinetic of the offspring and sensitizes it to the development of chronic adult metabolic diseases both in animals and in humans. Previous studies have demonstrated that a 50% maternal food restriction performed during the last week of gestation and during lactation has both short- and long-term consequences in the male rat offspring. Pups from undernourished mothers present a decreased intrauterine (IUGR) and extrauterine growth restriction. This is associated with a drastic reduction in their leptin plasma levels during lactation, and exhibit programming of their stress neuroendocrine systems (corticotroph axis and sympatho-adrenal system) in adulthood. In this study, we report that perinatally undernourished 6-month-old adult animals demonstrated increased leptinemia (at PND200), blood pressure (at PND180), food intake (from PND28 to PND168), locomotor activity (PND187) and altered regulation of glycemia (PND193). Cross-fostering experiments indicate that these alterations were prevented in IUGR offspring nursed by control mothers during lactation. Interestingly, the nutritional status of mothers during lactation (ad libitum feeding v. undernutrition) dictates the leptin plasma levels in pups, consistent with decreased leptin concentration in the milk of mothers subjected to perinatal undernutrition. As it has been reported that postnatal leptin levels in rodent neonates may have long-term metabolic consequences, restoration of plasma leptin levels in pups during lactation may contribute to the beneficial effects of cross-fostering IUGR offspring to control mothers. Collectively, our data suggest that modification of milk components may offer new therapeutic perspectives to prevent the programming of adult diseases in offspring from perinatally undernourished mothers.

Topics: Aldosterone; Animals; Animals, Newborn; Atrial Natriuretic Factor; Blood Pressure; Body Composition; Female; Glucose; Heart Rate; Lactation; Leptin; Male; Malnutrition; Pregnancy; Prenatal Nutritional Physiological Phenomena; Rats, Wistar; Time Factors; Vasopressins

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

Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity.

Topics: Adiposity; Analysis of Variance; Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Drug Resistance; Female; Fetal Development; Inheritance Patterns; Leptin; Lipids; Liver Diseases; Male; Malnutrition; Metabolic Syndrome; Obesity; Overnutrition; Swine; Time Factors; Weaning

Increasing evidence suggests that alterations in early nutrition programme physiological changes in adulthood. In the present study, we determined the effects of undernutrition during gestation and lactation on the programming of thyroid function in adult rat offspring. Perinatal undernutrition was achieved by a 40% food restriction in female Wistar rats from the mating day to weaning. On postpartum day 21, the offspring of the control and food-restricted dams were weaned and given free access to a commercial diet until adulthood. The results showed that undernourished rats exhibited decreased 3,5,3'-triiodothyronine (T3) levels but had normal thyroxine (T4) and thyrotropin (TSH) levels at weaning; on day 90, these rats displayed a significant flip, exhibiting normalised T3 (total and free) and total T4 levels, but low free T4 and persistently higher TSH levels, which were maintained even on postnatal day 140. This profile was accompanied by a scarce fat depot, a lower RMR and an exacerbated sympathetic brown adipose tissue (BAT) tone (deiodinase type 2 expression) in basal conditions. Moreover, when a functional challenge (cold exposure) was applied, the restricted group exhibited partial changes in TSH (29 v. 100%) and T4 (non-response v. 17%) levels, a significant decrease in leptin levels (75 v. 32%) and the maintenance of a sympathetic BAT over-response (higher noradrenaline levels) in comparison with the control group. The findings of the present study suggest that undernutrition during the perinatal period produces permanent changes in the hypothalamus-pituitary-thyroid axis with consequent low body weight and decreased RMR and facultative thermogenesis. We hypothesise that these changes predispose individuals to exhibiting adult subclinical hypothyroidism.

Topics: Adipose Tissue, Brown; Animals; Basal Metabolism; Body Weight; Cold Temperature; Female; Humans; Hypothyroidism; Infant Nutritional Physiological Phenomena; Infant, Newborn; Lactation; Leptin; Malnutrition; Norepinephrine; Pregnancy; Prenatal Exposure Delayed Effects; Prenatal Nutritional Physiological Phenomena; Rats; Rats, Wistar; Thermogenesis; Thyroid Gland; Thyroid Hormones

The present study aimed to determine, in a swine model of leptin resistance, the effects of type and timing of maternal malnutrition on growth patterns, adiposity and metabolic features of the progeny when exposed to an obesogenic diet during their juvenile development and possible concomitant effects of the offspring sex. Thus, four groups were considered. A CONTROL group involved pigs born from sows fed with a diet fulfilling their daily maintenance requirements for pregnancy. The treated groups involved the progeny of females fed with the same diet but fulfilling either 160% or 50% of pregnancy requirements during the entire gestation (OVERFED and UNDERFED, respectively) or 100% of requirements until Day 35 of pregnancy and 50% of such amount from Day 36 onwards (LATE-UNDERFED). OVERFED and UNDERFED offspring were more prone to higher corpulence and fat deposition from early postnatal stages, during breast-feeding; adiposity increased significantly when exposed to obesogenic diets, especially in females. The effects of sex were even more remarkable in LATE-UNDERFED offspring, which had similar corpulence to CONTROL piglets; however, females showed a clear predisposition to obesity. Furthermore, the three groups of pigs with maternal malnutrition showed evidences of metabolic syndrome and, in the case of individuals born from OVERFED sows, even of insulin resistance and the prodrome of type-2 diabetes. These findings support the main role of early nutritional programming in the current rise of obesity and associated diseases in ethnics with leptin resistance.

Topics: Adiposity; Animals; Animals, Newborn; Body Weight; Diet; Female; Insulin Resistance; Lactation; Leptin; Male; Malnutrition; Metabolic Diseases; Obesity; Overnutrition; Pregnancy; Prenatal Exposure Delayed Effects; Swine

Poor nutrition during the perinatal period is associated with an increased risk for metabolic syndrome in adulthood. Taurine (TAU) regulates β-cell function and glucose homeo-stasis. Here, we assessed the effects of TAU supplementation upon adiposity and glucose control in malnourished mice fed a high-fat diet (HFD).. Weaned male C57BL/6J mice were fed a control (14% protein - C) or a protein-restricted (6% protein - R) diet for 6 weeks. Afterwards, mice received or not an HFD for 8 weeks (CH and RH). Half of the HFDmice were supplemented with 5% TAU after weaning (CHT and RHT). Protein restriction led to typical malnutrition features. HFD increased body weight, adiposity, and led to hyperleptinemia, hyperphagia, glucose intolerance, and higher liver glucose output in RH and CH groups. Fasted R mice showed higher plasma adiponectin levels and increased phosphorylation of the AMP-activated protein kinase (p-AMPK) in the liver. These parameters were reduced in RH mice and increased p-AMPK persisted in RHT. TAU prevented obesity and improved glucose tolerance only in CHT, but liver glucose control was ameliorated in both supplemented groups. Better CHT liver glucose control was linked to increased Akt (thymoma viral proto-oncogene/protein kinase B) phosphorylation.. Malnourished mice fed an HFD developed obesity, glucose intolerance, and increased liver glucose output. TAU preserved only normal liver glucose control in RHT mice, an effect associated with increased liver p-AMPK content.

Topics: Adiponectin; Adiposity; Amino Acids; AMP-Activated Protein Kinases; Animals; Blood Glucose; Body Weight; Diet, High-Fat; Dietary Supplements; Glucose Intolerance; Leptin; Liver; Male; Malnutrition; Mice; Mice, Inbred C57BL; Phosphorylation; Proto-Oncogene Proteins c-akt; Taurine

It is well established that altered maternal nutrition may induce long-term metabolic consequences in offspring. However, the effects of maternal undernutrition during different developmental windows on sex-specific growth and metabolism in offspring are not well defined. We investigated the effect of moderate maternal undernutrition during pregnancy and/or lactation on postnatal growth and metabolic outcomes in offspring. Wistar rats were randomly assigned to one of four groups: (1) control (CONT) dams fed a standard diet throughout pregnancy and lactation; (2) dams undernourished to 50 % of CONT during pregnancy (UNP); (3) dams fed at 50 % of CONT throughout lactation (UNL); (4) dams fed at 50 % of CONT throughout pregnancy and lactation (UNPL). UNP and UNPL offspring were lighter at birth compared to CONT and UNL. UNL and UNPL offspring were growth restricted at weaning and remained smaller into adulthood. UNP males and females developed increased adiposity and hyperleptinaemia in adulthood compared to all other groups. Adiposity in UNL and UNPL males was similar to CONT offspring. In UNL and UNPL females, adiposity was lower than for CONT females. Markers of bone mass, lipid metabolism and hepatic function were altered in UNP offspring but were similar in UNL and UNPL offspring compared to CONT. Lack of catch-up growth during lactation in offspring of undernourished mothers prevented development of adiposity and related metabolic disorders in later life. These data highlight that the timing and duration of undernutrition during critical windows of development exert differential effects on postnatal outcomes in a sex-specific manner.

Topics: Adipogenesis; Adiposity; Animals; Body Weights and Measures; Bone Development; Female; Fetal Development; Fetal Growth Retardation; Lactation; Leptin; Lipids; Liver; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Pregnancy; Random Allocation; Rats; Rats, Wistar; Sex Characteristics

The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aim to compare the markers of appetite and malnutrition, and their relation with inflammation in HD patients with and without previous kidney transplantation.. Fifty-six patients with failed renal allografts at least 3 months on dialysis (31 men, 25 women; mean age, 46 ± 9 years) and 77 HD patients who never underwent a transplant (43 men, 34 women; mean age, 50 ± 15 years) were included in the study. The appetite and diet assessment tool (ADAT) was used to determine the self reported appetite of patients. Serum concentrations of ghrelin, leptin, insulin like growth factor 1 (IGF-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were measured. Associations among these variables were analyzed.. There were no significant differences considering age, gender or duration of renal replacement therapy between the 2 groups. The scores from Appetite and Diet Assessment Tool were significantly higher in the failed-transplant group. Serum ghrelin levels were significantly higher and serum albumin levels were significantly lower in the failed-transplant group. Serum leptin levels were similar between 2 groups. In addition, hs-CRP, IL-6, and TNF-α levels, which were used as inflammatory parameters, were significantly higher in the failed-transplant group.. Elevated serum ghrelin levels and inflammation may cause diminished appetite and malnutrition in patients with failed renal allografts, and higher levels of this hormone seem to be associated with inflammation caused by retained failed allografts.

Topics: Adult; Appetite; Biomarkers; C-Reactive Protein; Female; Ghrelin; Humans; Inflammation; Insulin-Like Growth Factor I; Interleukin-6; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Malnutrition; Middle Aged; Nutritional Status; Renal Dialysis; Transplantation, Homologous; Treatment Failure; Tumor Necrosis Factor-alpha

Long-term metabolic effects induced by early nutritional changes are suspected to differ between males and females, but few studies have analyzed both sexes simultaneously. We analyzed the consequences of neonatal nutritional changes on body weight (BW) and the adult response to a sucrose-enriched diet in both male and female rats. Litter size was manipulated at birth to induce over- and undernutrition (4 pups: L4; 12 pups: L12; 20 pups: L20). From 50 to 65 days of age, half of each group received a 33% sucrose solution instead of water. Serum leptin, insulin, and ghrelin levels were analyzed at day 65. At weaning, rats from L4 weighed more and those from L20 weighed less than controls (L12). Body weight was greater in L4 rats throughout the study and increased further compared with controls in adult life. L20 males ate less and gained less weight throughout the study, but L20 females had a significant catch-up in BW. Sucrose intake increased total energy consumption in all groups, but not BW gain, with L4 males and L4 and L20 females reducing weight gain. Yet, sucrose intake increased serum leptin levels, with this increase being significant in L4 and L20 males. Our results suggest that females are more capable than males of recuperating and maintaining a normal BW after reduced neonatal nutrition. Furthermore, increased sucrose intake does not increase BW, but could alter body composition as reflected by leptin levels, with the percentage of calories consumed in the form of sucrose being affected by sex and neonatal nutrition.

Topics: Animals; Animals, Newborn; Body Weight; Dietary Carbohydrates; Energy Intake; Female; Ghrelin; Insulin; Leptin; Male; Malnutrition; Nutritional Status; Overnutrition; Rats; Sex Factors; Sucrose

Maternal undernutrition during gestation can condition offspring adult health, with the periconceptional period pointed out as a key period. The aim of this study was to evaluate the effects of maternal periconceptional undernutrition on pregnancy and offspring growth performance in sheep. 52 Merinos d'Arles ewes were fed to requirements (control group, C), whereas 64 ewes received 50% of their dietary needs from -15 to +30 days post-conception (restricted group, R). Thereafter, both groups were fed according to needs. Maternal body weight (BW), body condition score (BCS) and Non Esterified Fatty Acids (NEFA), progesterone, leptin and cortisol plasma concentrations were monitored weekly during the restriction period and the following month, then monthly until weaning. Lambs were weighed weekly until weaning at 22 kg BW, then monthly. Plasma leptin was monitored monthly in lambs. The BW, BCS, and leptin concentrations were significantly decreased, whereas NEFA and cortisol concentrations were increased in R dams. Maximum progesterone concentration was higher in R ewes that had a high (10-25%) vs. low (0-10%) BW loss during restriction (27.9 ± 2.59 vs. 20.8 ± 2.00 ng/mL, P < 0.05). Overall, gestation was significantly longer in the R group (151.0 ± 0.3 vs. 149.4 ± 0.4 days, P < 0.001). There was no difference between groups for pregnancy rates, prolificacy, birth weight and lamb mortality, but the proportion of male lambs was significantly higher in the R group, only for singletons (16/26 vs. 9/26, P < 0.05). Lamb growth was not significantly modified by treatment. Leptin concentrations at birth were significantly lower in R vs. C males (6.15 ± 0.13 ng/mL vs. 7.42 ± 0.36 ng/mL, P < 0.05), whereas in females, leptin concentrations were significantly higher in R vs. C lambs at 4 mo of age (7.31 ± 0.27 ng/mL vs. 6.41 ± 0.29 ng/mL, P < 0.05). These results indicate that maternal periconceptional undernutrition in a hardy breed does not significantly affect lamb birth weight and growth rates, in contrast to previous reports in other breeds, suggesting that caution must be taken when extrapolating programming data between breeds and breeding conditions.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Birth Weight; Fatty Acids, Nonesterified; Female; Hydrocortisone; Leptin; Malnutrition; Pregnancy; Pregnancy Complications; Pregnancy Rate; Prenatal Exposure Delayed Effects; Progesterone; Reproduction; Sheep; Sheep Diseases

Our pilot study evaluates the impact of environmental factors, such as nutrition and smoking status, on epigenetic patterns in a disease-associated gene.. We measured the effects of malnutrition and cigarette smoking on proopiomelanocortin (POMC) promoter-specific DNA methylation in female patients with and without anorexia nervosa (AN). POMC and its derived peptides (alpha melanocyte stimulating hormone and adrenocorticotropic hormone) are implicated in stress and feeding response. Promoter-specific DNA methylation of the POMC gene was determined in peripheral blood mononuclear cells of 54 healthy female control subjects, 40 underweight patients with AN, and 21 weight-restored patients with AN using bisulfite sequencing. Malnutrition was characterized by plasma leptin.. POMC promoter-specific DNA methylation was not affected by diagnosis or nutritional status but significantly negatively associated with cigarette smoking.. Although malnutrition may be expected to reduce DNA methylation through its effects on one-carbon metabolism, our negative results are in line with several in vitro and clinical studies that did not show a direct relation between gene-specific DNA methylation and folate levels. In contrast, smoking has been repeatedly reported to alter DNA methylation of specific genes and should be controlled for in future epigenetic studies.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Case-Control Studies; CpG Islands; DNA Methylation; Epigenesis, Genetic; Female; Humans; Leptin; Malnutrition; Pilot Projects; Pro-Opiomelanocortin; Promoter Regions, Genetic; Smoking

Decompressing the portal hypertension by inserting a transjugular intrahepatic porto-systemic shunt (TIPS) in undernourished liver cirrhosis patients results in gains in body weight. It is important to understand whether this reflects an advantageous or unfavourable shift in nutrition status. This to some extent can be judged from the changes in the patients' adipokine patterns. We, therefore, examined the circulating levels of the most important adipokines before and after the TIPS procedure.. Twenty-five liver cirrhosis patients were examined before TIPS insertion and followed for six months after the procedure. Their body composition was determined by the bioimpedance technique. The serum concentrations of adiponectin, retinol binding protein 4 (RBP4), and leptin were measured.. The TIPS procedure induced a 12% increase in body cell mass (P = 0.03) but did not change the body fat mass. At six months, serum adiponectin was increased by 60% (mean ± SD, 10.7 ± 6.1 vs. 16.9 ± 8.9 mg/L; P = 0.001), serum RBP4 was decreased by 45% (28.6 ± 20.0 vs. 16.3 ± 9.6 mg/L; P = 0.01), and the leptin levels remained unchanged.. The TIPS-related tissue build up was accompanied by increased adiponectin and decreased RBP4. Such changes are associated with an anabolic condition where the adipose tissue possesses residual capacity for energy storage. TIPS, therefore, can be considered to be nutritionally beneficial to cirrhosis patients.

Topics: Adipokines; Adiponectin; Adipose Tissue; Adult; Aged; Body Composition; Electric Impedance; Female; Humans; Hypertension, Portal; Leptin; Liver Cirrhosis; Male; Malnutrition; Middle Aged; Nutritional Status; Portasystemic Shunt, Transjugular Intrahepatic; Retinol-Binding Proteins, Plasma

Considerable epidemiological, experimental and clinical data have amassed showing that the risk of developing disease in later life is dependent upon early life conditions. In particular, altered maternal nutrition, including undernutrition and overnutrition, can lead to metabolic disorders in offspring characterised by obesity and leptin resistance. The adipokine leptin has received significant interest as a potential programming factor; alterations in the profile of leptin in early life are associated with altered susceptibility to obesity and metabolic disorders in adulthood. Maintenance of a critical leptin level during early development facilitates the normal maturation of tissues and signalling pathways involved in metabolic homeostasis. A period of relative hypo- or hyperleptinemia during this window of development will induce some of the metabolic adaptations which underlie developmental programming. However, it remains unclear whether leptin alone is a critical factor for the programming of obesity. At least in animal experimental studies, developmental programming is potentially reversible by manipulating the concentration of circulating leptin during a critical window of developmental plasticity and offers an exciting new approach for therapeutic intervention.

Topics: Animals; Child Development; Epigenesis, Genetic; Female; Humans; Infant; Insulin Resistance; Leptin; Malnutrition; Maternal Nutritional Physiological Phenomena; Metabolic Diseases; Obesity; Overnutrition; Pregnancy; Prenatal Exposure Delayed Effects

Several studies have demonstrated that maternal undernutrition or overnutrition during pregnancy can have negative consequences for the health of children born to these pregnancies, but the physiological mechanisms by which this occurs are not completely understood. During periods of food restriction, concentrations of leptin decline, whereas leptin is elevated in obesity, suggesting that it may play a role in the response to altered nutrition during pregnancy. This study compares placental development and global placental gene expression profiles at Day 11.5 in pregnant control mice, mice that were undernourished, and mice that were undernourished but given leptin. Placentas from mothers exposed to food restriction preserved the placental labyrinth zone at the expense of the junctional zone, an effect abrogated in the restricted plus leptin group, which had a significant decrease in the labyrinth zone area compared with controls. Similarly, there were more significant differences in gene expression between placentas from control and restricted plus leptin mothers (1128 differentially expressed genes) than between placentas of control and restricted mothers (281 differentially expressed genes). We conclude that the presence of high concentrations of circulating leptin during food restriction disrupts the normal adaptive response of the placenta to reduced energy availability.

Topics: Animal Nutritional Physiological Phenomena; Animals; Female; Fetal Weight; Food Deprivation; Gestational Age; Leptin; Malnutrition; Maternal Nutritional Physiological Phenomena; Mice; Microarray Analysis; Organ Size; Placenta; Pregnancy; Pregnancy Complications; Transcriptome

Poor fetal growth, also known as intrauterine growth restriction (IUGR), is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX) or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN). Physiological (glucose and insulin tolerance), morphometric (automated tissue image analysis) and transcriptomic (quantitative PCR) approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.

Topics: Adipose Tissue; Analysis of Variance; Animals; Blood Glucose; Blotting, Western; Body Weights and Measures; C-Peptide; Corticosterone; Dexamethasone; DNA Primers; Female; Fetal Growth Retardation; Gene Expression Profiling; Insulin; Insulin Resistance; Islets of Langerhans; Leptin; Malnutrition; Pregnancy; Prenatal Exposure Delayed Effects; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction

The association between nutritional status, antioxidant human paraoxonase-1 (PON1) activity and low grade inflammation in hemodialized (HD) patients with chronic kidney disease (CKD) is unclear. The aim of this study was to determine PON1 paraoxonase and lactonase activities, ADMA, adiponectin and leptin concentrations, and to clarify the relationship between paraoxonase activity and a set of cardiovascular risk factors in malnourished, normal weight and obese HD patients; 114 HD patients with end-stage renal failure were enrolled.. Leptin levels were significantly higher and PON1 paraoxonase activities were significantly lower in obese patients compared to the other groups. Plasma adiponectin concentration was significantly lower in obese subjects compared to malnourished patients. Paraoxonase activity was negatively correlated with CRP level in HD and malnourished patients. Furthermore, we found significant inverse correlation between paraoxonase activity and BMI in the whole patient group. In multiple regression analysis, PON1 lactonase activity, CRP level and leptin concentration proved to be independent predictors of paraoxonase activity.. Despite the previous findings of reverse epidemiology for the mortality rate of HD patients, further studies are needed to clarify the effects of nutritional state on atherosclerosis in obese and malnourished patients with end-stage renal failure.

Topics: Adiponectin; Aged; Aryldialkylphosphatase; Atherosclerosis; Biomarkers; C-Reactive Protein; Comorbidity; Humans; Kidney Failure, Chronic; Leptin; Malnutrition; Middle Aged; Nutritional Status; Obesity; Regression Analysis; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors

A dynamical model describing the glucose-insulin physiological system was applied to an experiment on the administration of the adipokine leptin between neonatal days 3 and 13 to rats whose dams were subject to different levels of nutrition during gestation. The effect of leptin treatment on the glucose-insulin equilibrium point and on the levels of other associated metabolites showed a significant change in direction that depended on the level of prenatal nutrition. Leptin has been shown to affect two factors that affect the equilibrium levels of glucose and insulin, gluconeogenesis and insulin sensitivity. Each effect is described by a parameter in the dynamical model. Mathematical analysis shows that changes in these parameters in the manner promoted by leptin would indeed increase or decrease the glucose-insulin equilibria depending on their initial equilibrium levels which might be induced by the level of prenatal nutrition. This analysis explains the results of the leptin experiment in the context of the dynamics of the glucocorticoid system. It also proposes a physiological mechanism for the expression of plasticity in the organism based on the status of the glucose and insulin equilibria.

Topics: Algorithms; Animals; Animals, Newborn; Blood Glucose; Female; Gluconeogenesis; Insulin; Insulin Resistance; Insulin-Secreting Cells; Leptin; Malnutrition; Maternal Nutritional Physiological Phenomena; Models, Biological; Pregnancy; Prenatal Exposure Delayed Effects; Rats

A low birth-weight (LBW) offspring exhibits reduced hypothalamic neural satiety pathways and dysregulated signaling leading to programmed hyperphagia and adult obesity. Hypothalamic appetite circuits develop during early life, under the influence of neurotrophic hormones (leptin and insulin). Notably, LBW newborns have reduced plasma leptin and insulin levels. As neurons and glia arise from neuronal progenitor cells (NPC), we postulated that a programmed impairment of NPCs may contribute to reduced hypothalamic neural pathway development in a LBW offspring. Control dams received ad libitum food, whereas study dams were 50% food-restricted from pregnancy day 10 to 21 (LBW). At day 1 of age, hypothalamic NPCs were cultured as neurospheres (NS) and treated with leptin/insulin. We analyzed in vitro NPC proliferation and differentiation into neurons/astrocytes, expression of signal molecules promoting proliferation (activated Notch1 and its downstream target, Hes1) and in vivo NPC proliferation and migration. LBW offspring had impaired in vivo evidence of NPC division and migration, and reduced in vitro evidence of proliferation and differentiation to neurons and astrocytes, under basal and stimulated conditions. The reduced Notch1 and Hes1 expression in LBW neurosphere, under both basal and stimulated conditions, suggests a reduced progenitor cell population or reduced cell density within the neurosphere.

Topics: Animals; Animals, Newborn; Blotting, Western; Cell Differentiation; Cell Movement; Cell Proliferation; Cells, Cultured; Female; Hypothalamus; Insulin; Leptin; Malnutrition; Nerve Growth Factors; Neural Stem Cells; Neurogenesis; Pregnancy; Prenatal Nutritional Physiological Phenomena; Rats; Rats, Sprague-Dawley; Receptors, Notch; Signal Transduction

Maternal malnutrition during lactation programmes for overweight and central leptin resistance in adulthood. The inhibition of lactation by maternal treatment with bromocriptine (a prolactin inhibitor) programmes for obesity, hyperleptinaemia and leptin resistance. Here, we evaluated the short- and long-term effects of early weaning (EW) on body-weight regulation, leptin signalling, and hormone and lipid profiles in rats offspring. Lactating rats were separated into two groups: EW--dams were wrapped with a bandage to interrupt the lactation in the last 3 d of lactation; control--dams whose pups had free access to milk during all lactation (21 d). Data were significant at P < 0·05. At weaning, EW pups presented lower body weight (-10%), length (-4%), visceral fat (-40%), total fat (-30%), serum leptin (-73%), glycaemia (-10%), serum insulin (-20%) and insulin resistance index (IRI; -30 %), but higher total body protein content (+40%). At 180 d, EW offspring showed hyperphagia, higher length (+3%), body weight (+8%), visceral and total fat (+36 and 84%), serum TAG (+96%), glycaemia (+15%), leptinaemia (+185%) and IRI (+29%); however, they showed lower total protein content (-23%), leptin:body fat ratio (41%), prolactinaemia (-38%) and adiponectinaemia (-59%). Despite unchanged leptin receptor (OB-R) and signal transducer and activator of transcription 3 (STAT3), they displayed lower hypothalamic janus tyrosine kinase 2, phosphorylated STAT3 and a higher suppressor of cytokine signalling 3 levels, suggesting a central leptin resistance. Adult rats that were early weaned displayed higher adiposity, insulin resistance and dyslipidaemia, which are related to metabolic syndrome development. Our model reinforces the idea that neonatal malnutrition caused by shortening of the lactation period is important for metabolic programming of future diseases.

Topics: Aging; Animals; Blood Glucose; Body Composition; Body Size; Body Weight; Eating; Female; Genes, Homeobox; Hypothalamus; Lactation; Leptin; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Rats; Signal Transduction; Time Factors; Weaning

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

Several studies have shown that maternal undernutrition leading to low birth weight predisposes offspring to the development of metabolic pathologies such as obesity. Using a model of prenatal maternal 70% food restriction diet (FR30) in rat, we evaluated whether postweaning high-fat (HF) diet would amplify the phenotype observed under standard diet. We investigated biological parameters as well as gene expression profile focusing on white adipose tissues (WAT) of adult offspring. FR30 procedure does not worsen the metabolic syndrome features induced by HF diet. However, FR30HF rats displayed catch-up growth to match the body weight of adult control HF animals, suggesting an increase of adiposity while showing hyperleptinemia and a blunted increase of corticosterone. Using quantitative RT-PCR array, we demonstrated that FR30HF rats exhibited leptin and Ob-Rb as well as many peptide precursor and receptor gene expression variations in WAT. We also showed that the expression of genes involved in adipogenesis was modified in FR30HF animals in a depot-specific manner. We observed an opposite variation of STAT3 phosphorylation levels, suggesting that leptin sensitivity is modified in WAT adult FR30 offspring. We demonstrated that 11β-HSD1, 11β-HSD2, GR, and MR genes are coexpressed in WAT and that FR30 procedure modifies gene expression levels, especially under HF diet. In particular, level variation of 11β-HSD2, whose protein expression was detected by Western blotting, may represent a novel mechanism that may affect WAT glucocorticoid sensitivity. Data suggest that maternal undernutrition differently programs the adult offspring WAT gene expression profile that may predispose for altered fat deposition.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; 11-beta-Hydroxysteroid Dehydrogenase Type 2; Adipose Tissue; Adiposity; Animals; Body Weight; Dietary Fats; Female; Gene Expression; Leptin; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Obesity; Phosphorylation; Rats; Rats, Wistar; STAT3 Transcription Factor

Overnutrition as well as undernutrition is a serious problem in hospitalized patients, especially in infants. Routine laboratory tests detecting disturbances in energy balance are not specific or accurate. The aim of this study was to evaluate adiponectin and leptin as markers of short-time energy malnutrition.. Forty-five infants fed orally and parenterally were included in the study. Plasma glucose, leptin and adiponectin were measured in a fasting state and postprandially (1 h after the meal), after a minimum of 24 h of total parenteral nutrition (TPN) and after a minimum of 8 h of intravenous infusion of glucose and crystalloids.. Postprandial glucose levels in children fed orally was similar to that observed in children who received intravenous infusion of glucose. The TPN children had slightly higher glucose concentration in contrast to leptin levels which were significantly lower in this group (1.08 mg/mL +/- 0.43) as compared to the others (p < 0.05 in both cases). The mean postprandial levels of the adiponectin in orally fed children were significantly higher (10.7 microg/mL +/- 2.4) than in children with TPN (5.8 microg/mL +/- 2.4; p < 0.001) and in children hydrated intravenously (3.3 microg/mL +/- 2.3; p < 0.001). The concentration of adiponectin correlated significantly with calorie intake.. Oral meal does not affect the plasma concentrations of leptin and adiponectin in infants. Adiponectin is a good short-time marker of energy malnutrition in infants.

Topics: Adiponectin; Adipose Tissue; Biomarkers; Blood Glucose; Energy Metabolism; Female; Humans; Infant; Infant Formula; Infant Nutrition Disorders; Leptin; Male; Malnutrition; Parenteral Nutrition, Total; Peptides

Food-restricted animals present metabolic adaptations that facilitate food-seeking behavior and decelerate energy utilization by reducing the hypothalamus-pituitary-thyroid (HPT) axis function. Stress by dehydration induces an anorexic behavior in rats, loss of weight and reduced food intake when compared to ad libitum fed animals, however these alterations are accompanied by HPT axis changes such as increased serum thyrotropin levels and enhanced expression of thyrotropin-releasing hormone (TRH) in the paraventricular nucleus of the hypothalamus, which is considered as anorexigenic peptide. In contrast, a pair-fed group conformed by forced-food-restricted animals (FFR) (eating the exact same amount of food as dehydration-induced anorexic rats--DIA rats) present decreased TRH mRNA levels. NPY synthesis in the arcuate nucleus and orexin-expressing neurons from the lateral hypothalamic area (LHA) are activated during food restriction. These brain structures project into PVN, suggesting that NPY and orexins are possible factors involved in TRHergic neuron activation in DIA rats. Leptin signaling is another likely factor to be involved in TRH differential expression. Therefore, to gain more insight into the regulation of the feeding behavior in the experimental models, we analyzed Y1, Y5, Ox1-R and Ob-R(b) mRNA levels in PVN and prepro-orexin in LHA, since their signaling to the PVN might be altering TRH synthesis and feeding in DIA animals. Prepro-orexinergic cells were activated in FFR animals; Ox1-R and Y1 expression was reduced in FFR vs. controls or DIA group. Compensatory changes in PVN receptor expression of some feeding-related peptides in anorexic rats may alter TRHergic neural response to energy demands.

Topics: Animals; Anorexia; Dehydration; Feeding Behavior; Gene Expression Regulation; Hypothalamo-Hypophyseal System; Intracellular Signaling Peptides and Proteins; Leptin; Male; Malnutrition; Neurons; Neuropeptide Y; Neuropeptides; Orexin Receptors; Orexins; Paraventricular Hypothalamic Nucleus; Pituitary-Adrenal System; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Receptors, Neuropeptide Y; Signal Transduction; Thyrotropin; Thyrotropin-Releasing Hormone

Serotonin (5-HT) pathways play an important role in the pathophysiology of anorexia nervosa (AN). In this study, we investigated functional characteristics of the platelet 5-HT transporter and platelet 5-HT content in AN patients at various stages of their illness in comparison to healthy control woman (HCW) controlling for the 5-HTTLPR deletion/insertion polymorphism and other confounding variables. Fasting blood samples of 58 acutely underweight AN patients (acAN, BMI = 15.2 ± 1.4), 26 AN patients of the initial acAN sample after short-term/partial weight restoration (BMI = 17.3 ± 0.9), 36 weight-recovered AN patients (recAN, BMI = 20.7 ± 2.2) and 58 HCW (BMI = 21.6 ± 2.0) were assessed for kinetic characteristics of platelet 5-HT uptake (V (max), K (m)) and platelet 5-HT content. Plasma leptin served as an indicator of malnutrition. Mean V (max) and K (m) values were significantly higher in recAN subjects in comparison to HCW (2.05 ± 0.62 vs. 1.66 ± 0.40 nmol 5-HT/10(9) platelets min and 432 ± 215 vs. 315 ± 136 nmol, respectively) but there were no differences in platelet 5-HT content (464.8 ± 210.6 vs. 472.0 ± 162.2 ng 5-HT/10(9) platelets). 5-HT parameters in acAN patients and HCW were similar. 5-HTTLPR variants were not related to 5-HT platelet variables. In the longitudinal part of the study we found significantly increased 5-HT content but unchanged 5-HT uptake in AN patients after short-term/partial weight restoration. Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Changes in platelet 5-HT transporter activity were related to the stage of the illness but not to 5-HTTLPR genotype. Increased V (max) and K (m) in recovered AN patients might mirror adaptive modulations of the 5-HT system.

Topics: Adolescent; Adult; Anorexia Nervosa; Biomarkers; Blood Platelets; Feeding Behavior; Female; Genome-Wide Association Study; Humans; INDEL Mutation; Leptin; Malnutrition; Polymorphism, Genetic; Serotonin; Serotonin Plasma Membrane Transport Proteins; Severity of Illness Index; Thinness; Young Adult

The aim of this study was to investigate the serum concentration of adipokines, such as leptin, adiponectin, and resistin, and assess its relation to nutritional and inflammatory parameters in both overweight and normal weight patients on maintenance hemodialysis.. A total of 36 hemodialysis patients (27 M, 9 F; mean age 55.3 +/- 12 yr.) were examined and 23 additional healthy volunteers were recruited as the control group. The concentrations of leptin, leptin receptor, adiponectin, resistin, IL-6, TNFa and CRP were measured by ELISA. Assessment of nutritional status was determined by the levels of albumin, BMI, percentage of body fat (%F), lean body mass (LBM), and Subjective Global Assessment Score (SGA).. According to the SGA 7-points score and the albumin level, 20 patients were of good nutritional status (6-7 points), while 16 patients were mildly malnourished (4-5 points). The concentrations of CRP, resistin, adiponectin, and TNFa were statistically higher in hemodialysis patients than in the control group (p pound 0.05). The adiponectin level was inversely correlated with %F (R Spearman=-0.3; p pound 0.05). The level of leptin was positively correlated with %F as well as with BMI and SGA scores (R Spearman=0.4; p pound 0.05). Although there was no significant difference in the nutritional status between the nonoverweight (BMI 18.5-24.99) and overweight (BMI (3)25.0) groups of patients, in the nonoverweight group there were 12 patients (54.5%) with signs of mild malnutrition compared to 4 malnourished patients (28.5%) in the overweight group. Nonoverweight patients presented significantly lower leptin concentration (12.7 vs 27.8 ug/l) and higher adiponectin level (38.9 vs 32.5 ng/ml) when compared to overweight patients. The levels of IL-6 and TNFa were higher in the nonoverweight group of patients. Overweight patients also had shorter durations of stay in the hemodialysis program (30.5 vs. 87.6 months).. The results of our study indicate that lean hemodialysis patients are more prone to malnutrition and inflammation. The increased levels of leptin and decreased levels of adiponectin in the overweight hemodialysis patients support the idea of a reverse epidemiology phenomenon in this group of patients.

Topics: Adipokines; Adiponectin; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Malnutrition; Middle Aged; Nutritional Status; Overweight; Renal Dialysis; Resistin

Proopiomelanocortin (POMC) and its derived peptides, in particular alpha-MSH, have been shown to play a crucial role in the regulation of hunger, satiety and energy homeostasis. Studies in patients with anorexia nervosa (AN) suggest an abnormal expression of appetite-regulating hormones. Hormone expression levels may be modulated by epigenetic mechanisms, which were recently shown to be implicated in the pathophysiology of eating disorders. We hypothesised that POMC promoter specific DNA methylation and gene expression will be affected by malnutrition and therefore differ in AN patients at distinct stages of the disorder. Promoter specific DNA methylation of the POMC gene and expression of POMC mRNA variants were determined in peripheral blood mononuclear cells (PBMC) of 30 healthy control women (HCW), 31 underweight (acAN) and 30 weight-recovered patients with AN (recAN). Malnutrition was characterized by plasma leptin. Expression of the functionally relevant long POMC mRNA transcript was significantly correlated with leptin levels and higher in acAN compared to recAN and HCW. Expression of the truncated form and mean promoter DNA methylation was similar in all three subgroups. Methylation of single CpG residues in the E2F binding site was inversely related to POMC expression. Our preliminary data on pattern of POMC regulation suggests an association with the underweight state rather than with persisting trait markers of AN. In contrast to POMC expression in the central nervous system, peripheral POMC mRNA expression decreased with malnutrition and hypoleptinemia. This may represent a counterregulatory mechanism as part of the crosstalk between the immune and neuroendocrine systems.

Topics: Adolescent; Adult; alpha-MSH; Anorexia Nervosa; Body Mass Index; Body Weight; Disease-Free Survival; DNA Methylation; Female; Gene Expression; Humans; Leptin; Leukocytes, Mononuclear; Malnutrition; Pro-Opiomelanocortin; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thinness; Young Adult

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

Several studies indicate that maternal undernutrition sensitizes the offspring to the development of metabolic disorders, such as obesity. Using a model of perinatal maternal 50% food-restricted diet (FR50), we recently reported that rat neonates from undernourished mothers exhibit decreased leptin plasma levels associated with alterations of hypothalamic proopiomelanocortin system. The present study aimed at examining the consequences of FR50 on the brain-adipose axis in male rat neonates. Using quantitative RT-PCR array containing 84 obesity-related genes, we demonstrated that most of the genes involved in energy metabolism regulation are expressed in rat gonadal white adipose tissue (WAT) and are sensitive to maternal perinatal undernutrition (MPU). In contrast, hypothalamic gene expression was not substantially affected by MPU. Gene expression of uncoupling protein 1 (UCP1), a marker of brown adipocytes, showed an almost 400-fold stimulation in postnatal day 21 (PND21) FR50 animals, suggesting that their gonadal WAT possesses a brown-like phenotype. This was confirmed by histological and immunoshistochemical procedures, which demonstrated that PND21 FR50 gonadal adipocytes are multilocular, resembling those present in interscapular brown adipose tissue, and exhibit an overexpression of UCP1 and neuropeptide Y (NPY) at the protein level. Control animals contained almost exclusively "classical" unilocular white adipocytes that did not show high UCP1 and NPY labeling. After weaning, FR50 animals exhibited a transient hyperphagia that was associated with the disappearance of brown-like fat pads in PND30 WAT. Our results demonstrate that MPU delays the maturation of gonadal WAT during critical developmental time windows, suggesting that it could have long-term consequences on body weight regulation in the offspring.

Topics: Adipocytes; Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Animals, Newborn; Body Weight; Energy Metabolism; Gene Expression; Hypothalamus; Leptin; Male; Malnutrition; Neuropeptide Y; Obesity; Phenotype; Pro-Opiomelanocortin; Proteins; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Weaning

Anthropometric and classical biologic markers of malnutrition, such as serum albumin, are limited because they are influenced by nonnutritional factors. We propose that a biologic parameter that both predicts nutritional status and is unaffected by nonnutritional factors would facilitate the diagnosis of malnutrition in the elderly. This cross-sectional study included 179 randomized elderly patients. Nutritional status was assessed by the Mini-Nutritional Assessment (MNA) instrument; other end points included anthropometric measures and biologic parameters. Subjects were divided into 3 groups based on MNA-defined nutritional status, and end point means were compared using 2-way analyses of variance adjusted by sex. Correlations between the most accurate biologic marker in predicting malnutrition and other biologic and clinical variables were assessed using Pearson correlation test. Multiple linear regressions were then performed to relate the best biomarker of malnutrition to specific parameters. Finally, leptin levels that predict malnutrition were determined using receiver operating characteristic curve cutoff values. The well-nourished group had significantly higher leptin (P = .001), weight, body mass index, mid-arm circumference, and calf circumference (all, P < .001) compared with the malnourished group and the at risk of malnutrition group. Serum leptin was the optimal biomarker of MNA-defined malnutrition and had significant positive correlations with weight (P = .003) and with all anthropometric values (all P < .001), but no significant correlation with C-reactive protein. Sex, weight, and triglyceride were the best predictors of serum leptin (all P < .001). The optimal cutoff value of serum leptin to detect malnutrition was 4.3 ng/mL in men and 25.7 ng/mL in women. Serum leptin may be a good predictor of nutritional status in elderly patients.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anthropometry; Biomarkers; Body Weights and Measures; Cross-Sectional Studies; Female; Humans; Leptin; Male; Malnutrition; Nutrition Assessment; Nutritional Status; Reference Values; ROC Curve; Sex Factors; Triglycerides

Adipokines such as leptin and adiponectin are adipocyte-specific secretory proteins that play important roles in the metabolic regulation of body weight, insulin resistance and cardiovascular complications. The relationship between the malnutrition-inflammation complex syndrome and high levels of some adipokines in peritoneal dialysis (PD) patients is still unclear. An association between high body mass index (BMI) and improved survival in PD patients has also been proposed. The purpose of this study was to investigate the levels of plasma adipokines and inflammation and oxidative stress markers in overweight and normal weight PD patients.. Thirty PD patients (12 M, 18 F; mean age 57.3 ± 16.6 years) were examined and 23 healthy volunteers were included as a control group. The levels of high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α, interleukin-6, leptin, the leptin receptor, adiponectin, malondialdehyde/4-hydroxynonenal, oxidized low-density lipoprotein, carbonyl groups and asymmetric dimethylarginine (ADMA) were measured in both groups. The nutritional status of each patient was determined by albumin levels, BMI, percentage of body fat (%F), lean body mass (LBM) and the Subjective Global Assessment (SGA) score. The adequacy of dialysis was estimated by weekly Kt/V measurements.. According to the seven-point SGA scores and the albumin levels, the nutrition status of 15 patients was good (6-7 points), while 15 patients were mildly malnourished (3-5 points). The concentrations of hsCRP, leptin and adiponectin were statistically higher in the PD group than in the control group (p < 0.05). Markers of oxidative stress and inflammation were also higher in the PD group. The adiponectin level was inversely correlated with %F and BMI (Spearman's R = -0.3, p ≤ 0.05) and positively correlated with hsCRP level (R = -0.4). The level of leptin was positively correlated with %F, BMI and LBM (R = 0.4, p ≤ 0.05). Patients with normal BMI values had lower leptin concentrations (50.2 vs 242.8 μg/l) and higher adiponectin levels (30.0 vs 20.3 μg/ml) than overweight patients. The statistical analysis indicated that there were no differences in oxidative stress, inflammation and ADMA concentration between the lean and overweight PD patients.. The nutritional status of lean and overweight patients was comparable. Signs of malnutrition were detected in both groups. The severity of chronic inflammation and oxidative stress were not related to BMI in PD patients.

Topics: Adiponectin; Adult; Aged; Aldehydes; Arginine; Biomarkers; Body Mass Index; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Endothelium; Female; Humans; Inflammation; Interleukin-6; Leptin; Lipoproteins, LDL; Male; Malnutrition; Malondialdehyde; Middle Aged; Nutritional Status; Oxidative Stress; Peritoneal Dialysis; Risk Factors; Tumor Necrosis Factor-alpha

Birth weight in humans has been inversely associated with adult disease risk. Results of animal studies have varied depending on species, strain, and treatment.. We compared birth weight and adult health in offspring following 50% maternal undernutrition on gestation days (GD) 1-15 (UN1-15) or GD 10-21 (UN10-21) in Sprague Dawley and Wistar rats. Offspring from food-deprived dams were weighed and cross-fostered to control dams. Litters were weighed during lactation and initiating at weaning males were fed either control or a high-fat diet. Young and mature adult offspring were evaluated for obesity, blood pressure (BP), insulin response to oral glucose, and serum lipids. Nephron endowment, renal glucocorticoid receptor, and renin-aldosterone-angiotensin system components were measured.. The UN10-21 groups had birth weights lower than controls and transient catch up growth by weaning. Neither strain demonstrated obesity or dyslipidemia following prenatal undernutrition, but long-term body weight deficits occurred in the UN groups of both strains. High-fat diet fed offspring gained more weight than control offspring without an effect of prenatal nutrition. Sprague Dawley were slightly more susceptible than Wistar rats to altered insulin response and increased BP following gestational undernutrition. Nephron endowment in Sprague Dawley but not Wistar offspring was lower in the UN10-21 groups. Glucocorticoid and renin-aldosterone-angiotensin system pathways were not altered.. The most consistent effect of maternal undernutrition was elevated BP in offspring. Long-term health effects occurred with undernutrition during either window, but the UN10-21 period resulted in lower birth weight and more severe adult health effects.

Topics: Animals; Animals, Newborn; Birth Weight; Body Weight; Female; Insulin; Leptin; Lipids; Male; Malnutrition; Pregnancy; Prenatal Exposure Delayed Effects; Prenatal Nutritional Physiological Phenomena; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Weaning

To investigate the effect of Shenshuai Yangzhen Capsule (SYC) on hypothalamic leptin-neuropeptide Y (NPY) and proopiomelanocortin (POMC) axes in chronic renal failure (CRF) rats with malnutrition (MN).. Forty-two male SD rats of SPF grade were established into CRF-MN model by 5/6 nephrectomy and 4% casein diet, the happening time of MN in them was recorded. Rats successfully modeled were randomized into three groups, 11 rats in Group A treated with SYC, 11 in group B treated with composite alpha-keto acid and 12 in Group C was untreated. Besides, a normal control group was set up with 8 healthy rats. After being treated for 4 weeks, the renal function related indices, including serum creatinine (Scr), blood urea nitrogen (BUN), 24 hour urine protein (24 h Upro), albumin (ALB), haemoglobin (Hb) insulin like growth factor-1 (IGF-1), total cholesterol (TC) and triglyeride (TG) were measured, and body weight, food intake in rats were observed dynamically, blood leptin and NPY level in rats were determined by radioimmunoassay; mRNA expressions of OB-Rb, NPY and POMC in hypothalamus were detected with RT-PCR.. CRF rats revealed MN at the end of 10th week after modeling. Compared with Group C, the condition of MN in Group A was significantly improved, showing increase of food intake and body weight (P < 0.05), marked improvement of renal function (P < 0.05), decrease of LP and NPY levels in plasma (P < 0.05), as well as up-regulated NPY mRNA expression and down-regulated mRNA expressions of OB-Rb and POMC in hypothalamus (P < 0.01).. SYC can improve the malnutrition condition in rats with CRF, which is possibly by way of depressing OB-Rb and POMC mRNA expression and upgrading NPY mRNA expression in hypothalamus.

Topics: Animals; Drugs, Chinese Herbal; Hypothalamus; Kidney Failure, Chronic; Leptin; Male; Malnutrition; Neuropeptide Y; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; RNA, Messenger

Numerous studies have reported a strong relationship between plasma leptin concentration and percentage of body fat, fat mass, and body mass index (BMI) in obese and non-obese children. The objective of the present study was to assess the usefulness of serum leptin concentration in disclosing prepubertal malnutrition.. Leptin concentrations in serum were determined and anthropometric parameters were measured in 149 children (3-6 and 7-10 years old). The Cole index of nutritional status was calculated. 44 children (I) presented with long-standing malnutrition due to celiac disease or food allergy and 105 children (II) were healthy.. Leptin concentrations in both age groups of undernourished boys (median 2.7 and 2.7 microg/L) and in younger undernourished girls (median 4.2 microg/L) did not differ from concentrations in healthy children (median 2.9, 2.9, and 3.4 microg/L, respectively). Leptin concentrations in older undernourished girls were significantly lower than in healthy girls (median 4.2 vs. 8.8 microg/L, respectively; p < 0.05) of comparable age. In healthy children, leptin levels correlated with gender, body mass, BMI, Cole ratio (r = 0.39-0.41, r = 0.33, r = 0.28, r = 0.22, respectively; p < 0.005), and height (r = 0.19; p < 0.05). Serum leptin concentrations in undernourished children correlated with gender, arm circumference, and BMI (r = 0.27-0.35, r = 0.27, r = 0.25, respectively; p < 0.05).. Our results show that serum leptin concentration is not a useful indicator of mild and moderate malnutrition in prepubertal children.

Topics: Child; Child, Preschool; Female; Humans; Leptin; Male; Malnutrition

Early postnatal nutrition is involved in metabolic programming. Small for gestational age and premature babies commonly receive insufficient dietary protein during the neonatal period due to nutrition intolerance, whereas high protein formulas are used to achieve catch up growth. Neither the short term, nor the long term effects of such manipulation of protein intake are known.. We hypothesized that high or low protein intake during infancy would induce metabolic alterations both during early-life and in adulthood.. Gastrostomized neonatal rat pups received either 50% (P50%), 100% (P100%), or 130% (P130%) of the normal protein content in rat milk from the 7th to the 15th day of life (D7 to D15), when they were either sacrificed or placed with mothers for the long term study. Glucose tolerance tests (GTT) were performed at D230. Long term rats were sacrificed at D250.. At D15, weight of P50% pups was lower than P100% and P130% pups. Neither liver and kidney mass, nor islet beta-cell areas were altered. Brain weight (adjusted to body weight) was higher in P50% vs. P130% (p<0.05). Insulin/glucose ratio was lower in P50% vs. P130%. Expression of GLUT4 on adipocyte cell membrane and GLUT2 in liver cytosol was significantly enhanced in P50% vs. P130%. Long term, neither GTT results nor body nor organ weights differed between groups.. In neonatal rats, higher protein intakes via the enteral route led to enhanced short term weight gain, insulin resistance, and modified expression of glucose transporters. However, these differences were not sustained.

Topics: Adiponectin; Animals; Animals, Newborn; Base Sequence; Blotting, Western; Body Weight; Dietary Proteins; DNA Primers; Enzyme-Linked Immunosorbent Assay; Female; Glucose Tolerance Test; Immunohistochemistry; Leptin; Malnutrition; Organ Size; Pregnancy; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction

This study was performed to investigate the serum zinc (Zn), plasma ghrelin, leptin levels and nutritional status, and to evaluate the potential association between malnutrition and these investigated parameters in malnourished hemodialysis (HD) patients. Fifteen malnourished HD patients, aged 42.9 +/- 2.11 years, who underwent the HD for 46.44 +/- 7.1 months and 15 healthy volunteers, aged 41.0 +/- 2.17 years, were included in this study. The nutritional status of the subjects was determined by the subjective global assessment (SGA). Anthropometric measurements were taken by bioelectrical impedance after HD. Blood samples were collected for the analysis of zinc (Zn), ghrelin, leptin, and selected blood parameters. The HD patients consumed less energy and nutrients than controls. In HD patients, body weight, body mass index (BMI) (p < 0.001), basal metabolic rate (BMR), body fat, lean body mass (LBM), serum Zn, copper (Cu) (p < 0.05), sodium (Na) (p < 0.01), glucose (p < 0.05), albumin (p < 0.01), total cholesterol (p < 0.001), and ghrelin (p < 0.05) were lower whereas body water ratio (p < 0.001), serum potassium (K) (p < 0.01), inorganic phosphorous (Pi), blood urea nitrogen, creatinine (p < 0.001), and plasma insulin (p < 0.05) levels were higher than the controls. No difference existed between HD patients and controls regarding plasma leptin levels. There were positive correlations for body weight-fasting glucose and body weight-leptin (p < 0.05), body weight-BMI and body weight-LBM (p < 0.01); body fat-leptin (p < 0.05); BMI-fasting glucose, BMI-leptin, and BMI-body fat (p < 0.05); albumin-hemoglobin and albumin-insulin (p < 0.05). Negative correlation was found for SGA score-ghrelin (p < 0.05). Malnutrition in HD patients may result from inadequate energy and nutrient intake and low Zn and ghrelin levels. Zinc supplementation to the diets of HD patients may be of value to prevent the malnutrition.

Topics: Adult; Blood Glucose; Body Composition; Body Mass Index; Ghrelin; Humans; Leptin; Malnutrition; Nutritional Status; Renal Dialysis; Zinc

Brain-derived neurotrophic factor (BDNF) mutant mice show hyperphagia and hyperleptinemia. Animal and cell-culture experiments suggest multiple interrelations between BDNF and the serotonin (5-HT) system. We studied serum BDNF in patients with anorexia nervosa and its associations with peripheral indicators of the 5-HT system. To control for secondary effects of acute malnutrition, we assessed acutely underweight patients with anorexia nervosa (acAN) in comparison to long-term weight-recovered patients with the disorder (recAN) and healthy controls.. We determined serum BDNF, platelet 5-HT content and platelet 5-HT uptake in 33 patients in the acAN group, 20 patients in the recAN group and 33 controls. Plasma leptin served as an indicator of malnutrition.. Patients in the acAN group were aged 14-29 years and had a mean body mass index (BMI) of 14.9 (standard deviation [SD] 1.4) kg/m(2). Those in the recAN group were aged 15-29 years and had a mean BMI of 20.5 (SD 1.3) kg/m(2) and the controls were aged 15-26 years and had a BMI of 21.4 (SD 2.1) kg/m(2). The mean serum BDNF levels were significantly increased in the recAN group compared with the acAN group (8820, SD 3074 v. 6161, SD 2885 pg/mL, U = 154.5, p = 0.001). There were no significant associations between BDNF and either platelet 5-HT content or platelet 5-HT uptake. Among patients with anorexia nervosa, we found significant positive linear relations between BDNF and BMI (r = 0.312, p = 0.023) and between BDNF and leptin (r = 0.365, p = 0.016).. We measured the signal proteins under study in peripheral blood.. Serum BDNF levels in patients with anorexia nervosa depend on the state of illness and the degree of hypoleptinemia. Upregulation of BDNF in weight-recovered patients with anorexia nervosa could be part of a regenerative process after biochemical and molecular neuronal injury due to prolonged malnutrition. Associations between the BDNF and the 5-HT system in humans remain to be established.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Brain-Derived Neurotrophic Factor; Case-Control Studies; Female; Humans; Leptin; Malnutrition; Serotonin

Malnutrition-inflammation-atherosclerosis syndrome (MIA) in haemodialysis (HD) patients is a common clinical condition characterized by increased mortality rate. The aim of this study was to analyze the frequency of MIA components in a selected population of HD patients with and without diabetic nephropathy.. The frequency of MIA components was analysed in 49 patients with an over 10-year history of diabetes before initiation of HD (DM group) and 49 non-diabetic HD patients (non-DM group).. The chance for occurrence of atherosclerosis (odds ratio = 3.26) was markedly higher in DM than non-DM subjects. The most frequent MIA component in DM and non-DM subjects was atherosclerosis (67.3% and 40.8%, respectively). Atherosclerosis frequently coexisted with inflammation in both groups (51.5% in DM and 20.0% in non-DM) and less frequently with malnutrition. The frequency of inflammation was only slightly higher in DM, while of malnutrition was similar. Patients with atherosclerosis in the DM group had significantly higher serum concentrations of interleukin-6 than the ones in the non-DM group: 11 (6-24) versus 5 (2-9) pg/mL, respectively (P = 0.002).. We can conclude that: (i) atherosclerosis is more common in HD patients with diabetic nephropathy; and (ii) this fact may explain the poor outcome of these patients and indicates the challenge in diagnostic and therapeutic management.

Topics: Aged; Atherosclerosis; Diabetic Nephropathies; Female; Humans; Inflammation; Leptin; Male; Malnutrition; Middle Aged; Renal Dialysis; Serum Albumin

Increasing evidence suggests a role for prenatal environment in the onset of cardiovascular and metabolic disease in later life. In the rat, undernutrition in utero and a postnatal high-fat diet gives rise to a phenotype similar to the metabolic syndrome. As endothelial dysfunction is a feature of both CVD and the metabolic syndrome we investigated the impact of maternal undernutrition and/or postnatal high-fat on endothelial function. Virgin Wistar rats were mated and randomly assigned to groups to receive food either ad libitum (control) or at 30% of ad libitum intake throughout gestation. At postnatal day 250, a cohort from each group was challenged with a high-fat diet (D12451, 45% energy from fat; Research Diets, Inc., New Brunswick, NJ, USA) for the remainder of the study. At 1 year of age, small mesenteric arteries were dissected and mounted on a wire myograph and responses to phenylephrine, endothelin, acetylcholine, leptin and sodium nitroprusside assessed. Vasoconstriction to endothelin was significantly enhanced in all groups compared with controls (-log effective concentration equal to 50% of the maximal response (pEC50); P < 0.001). Endothelium-dependent vasodilatation to acetylcholine was significantly blunted in all groups compared with controls (% maximum response; P < 0.01), while dilatation to leptin and sodium nitroprusside was similar in all groups. These data demonstrate that both maternal undernutrition and postnatal high fat lead to vascular alterations and suggest that maternal undernutrition alone is at least as detrimental to offspring endothelial function as a long-term exposure to a high-fat diet in the offspring.

Topics: Animals; Dietary Fats; Endothelium, Vascular; Female; Fetal Growth Retardation; Leptin; Male; Malnutrition; Mesenteric Arteries; Pregnancy; Prenatal Nutritional Physiological Phenomena; Random Allocation; Rats; Rats, Wistar; Vasoconstriction; Vasodilation

Nutrition during critical periods in early life may increase the subsequent risk of obesity, hypertension and metabolic diseases in adulthood. Few studies have focused on the long-term consequences of poor nutrition during the suckling period on the susceptibility to developing obesity when exposed to a palatable cafeteria-style high-fat diet (CD) after weaning.. This study examined the impact of early undernutrition, followed by CD exposure, on blood pressure, hormones and genes important for insulin sensitivity and metabolism and skeletal muscle mRNA expression of adiponectin receptor 1 (AdipoR1), carnitine palmitoyl-transferase I (CPT-1), cytochrome c oxidase 4 (COX4) and peroxisome proliferator-activated receptor alpha (PPARalpha). Following normal gestation, Sprague-Dawley rat litters were adjusted to 18 (undernourished) or 12 (control) pups. Rats were weaned (day 21) onto either palatable CD or standard chow.. Early undernourished rats were significantly lighter than control by 17 days, persisting into adulthood only when animals were fed chow after weaning. Regardless of litter size, rats fed CD had doubled fat mass at 15 weeks of age, and significant elevations in plasma leptin, insulin and adiponectin. Importantly, undernutrition confined to the suckling period, elevated circulating adiponectin regardless of post-weaning diet. Blood pressure was reduced in early undernourished rats fed chow, and increased by CD. Early undernutrition was associated with long-term elevations in the expression of AdipoR1, CPT-1, COX4 and PPARalpha in skeletal muscle.. This study demonstrates the important role of early nutrition on body weight and metabolism, suggesting early undernourishment enhances insulin sensitivity and fatty-acid oxidation. The long-term potential benefit of limiting nutrition in the early postnatal period warrants further investigation.

Topics: Adiponectin; Analysis of Variance; Animals; Blood Pressure; Body Fat Distribution; Carnitine O-Palmitoyltransferase; Diet; Energy Intake; Leptin; Malnutrition; Muscle, Skeletal; PPAR alpha; Rats; Rats, Sprague-Dawley; Receptors, Adiponectin; RNA, Messenger; Weaning

The most unique feature of ghrelin is the acyl-modification of a hydroxyl group of the Ser3 in the N-terminus. The Ser3 is commonly modified by n-octanoic acid in vertebrates being needed for its biological effects, at least in terms of feeding. Therefore, a critical question regarding the role of ghrelin was to characterize the mechanism involved in its acylation. The acyltransferase that catalyzes ghrelin octanoylation has been recently identified and named ghrelin O-acyltransferase (GOAT). The aim of this study was to clarify the physiological implications of GOAT in the regulation of energy balance, by assessing the effect of undernutrition, as well as fasting in adult male rats. We have determined GOAT mRNA expression levels by real time-PCR in the stomach mucosa. Our results show that chronic food restriction led to an increase in GOAT mRNA, particularly following long-term chronic malnutrition (21 days). Furthermore, following 48 h complete fasting, a situation with high-circulating ghrelin levels, we found similar mRNA expression of GOAT in fed and fasted rats; exogenous leptin administration markedly increase GOAT mRNA levels in the stomach mucosa of fasted rats. These findings suggest that increased GOAT mRNA levels may have a role in mediating the physiological responses to chronic undernutrition and could represent an adaptive response to prevent long-lasting alterations in energy balance and body weight homeostasis. Furthermore, our data also offer mechanistic insights into the reason why during fasting acylated ghrelin levels are not increased at a time when a marked increase in an orexigenic signal as important as acylated ghrelin will be expected.

Topics: Acyltransferases; Animals; Base Sequence; Chronic Disease; DNA Primers; Gastric Mucosa; Ghrelin; Leptin; Male; Malnutrition; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

To investigate the impact of abnormal nutrition during pregnancy on the insulin and leptin resistance of adult offsprings.. The model of abnormal nutrition during pregnancy was established, and these rats were fed whole-course low-protein or high-nutrition. After natural childbirth, the birth weight of each newborn rat was measured. According to the determining birth weights, the newborn rats were assigned into the small for gestational age (SGA) and large for gestational age (LGA) groups as well as the healthy control group, respectively. There was a total of 36 randomly selected rats in each group. The levels of insulin and leptin and the insulin sensitivity index (ISI) were determined by enzymelinked immunosorbent assay 4 and 12 weeks post birth, respectively.. In the low-protein group, the birth weight was significantly lower than in the control group (p<0.01) and 68.97% of the newborn rats were SGA; in the high-energy group, the birth weight of the newborn rats was significantly larger than in the control group (p<0.01), and 37.98% of the newborn were LGA. The body weights (BW) of the SGA 4 weeks post birth had no significant difference from that of the controls, while the perirenal fat weight (FW) and the FW/BW ratio were significantly larger than those of the controls (p<0.01 and p<0.05, respectively); however, the FW/BW of the LGA had no significant difference from that of the controls. Twelve weeks after birth, the BW of both SGA and LGA rats increased significantly compared to the controls (p<0.05 and p<0.01, respectively), and the FW/BW ratios of both were significantly larger than that of the controls (p<0.01). For the SGA rats 4 weeks post birth, the insulin and leptin level increased significantly (both p<0.05), while the ISI decreased significantly (p<0.05), with the occurrence of insulin resistance. For both SGA and LGA 12 weeks post birth, the insulin and leptin level significantly increased (both p<0.01).. Abnormal nutrition during pregnancy could lead to abnormal birth weight, and both low and high birth weight could cause abdominal obesity as well as insulin and leptin resistance in adulthood, although through different mechanisms.

Topics: Adipose Tissue; Animals; Animals, Newborn; Birth Weight; Drug Resistance; Female; Fetal Nutrition Disorders; Insulin Resistance; Leptin; Male; Malnutrition; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar

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

We examined the effects of prolonged undernutrition on plasma leptin and insulin levels and some serum protein metabolites in reindeer (Rangifer tarandus tarandus L.) during winter and spring. The reindeer (male <1 year) were fed their preferred winter feed, low-protein lichen ad libitum for 5 weeks, followed by 40% restriction of energy for 8 weeks and refeeding with high-protein pellets for 6 weeks. The control group received high-protein reindeer pellets ad libitum throughout the experiment. Plasma leptin decreased by 46% and insulin by 54% in the lichen group already during the ad libitum period between January and February, with parallel decreases in body weight, serum total proteins, albumin and urea. Leptin remained low during most of the energy restriction period in March and April, but increased at the end of April while body weight decreased. During the refeeding period in May and June, the body weight and insulin of the lichen group increased in parallel with total proteins and urea, but leptin remained unchanged. Similar significant reductions in plasma leptin (40%) as in the lichen group also took place in the control group fed high-protein pellets ad libitum in January and February, although their feed intake, serum total proteins and body weight remained unchanged. The results show that leptin decreases in reindeer during mid-winter, independent of food or protein intake, and suggest that the decrease may be cued by seasonal factors such as the short photoperiod.

Topics: Animals; Arctic Regions; Blood Glucose; Body Weight; Creatinine; Insulin; Leptin; Malnutrition; Photoperiod; Reindeer; Seasons; Serum Albumin; Time Factors; Urea

We investigated the effect of intrauterine undernourishment on some features of asthma using a model of allergic lung inflammation in rats. The effects of age at which the rats were challenged (5 and 9 wk) were also evaluated.. Intrauterine undernourished offspring were obtained from dams that were fed 50% of the nourished diet of counterparts and were immunized at 5 and 9 wk of age. They were tested for immunoglobulin E anti-ova titers (by passive cutaneous anaphylaxis), cell count in the bronchoalveolar fluid, leukotriene concentration, airway reactivity, mucus production, and blood corticosterone and leptin concentrations 21 d after immunologic challenge.. Intrauterine undernourishment significantly reduced the antigen-specific immunoglobulin E production, inflammatory cell infiltration into airways, mucus secretion, and production of leukotrienes B(4)/C(4) in the lungs in both age groups compared with respective nourished rats. The increased reactivity to methacholine that follows antigen challenge was not affected by intrauterine undernourishment. Corticosterone levels increased with age in the undernourished rats' offspring, but not in the nourished rats' offspring. Undernourished offspring already presented high levels of corticosterone before inflammatory stimulus and were not modified by antigen challenge. Leptin levels increased with challenge in the nourished rats but not in the undernourished rats and could not be related to corticosterone levels in the undernourished rats.. Intrauterine undernourishment has a striking and age-dependent effect on the offspring, reducing lung allergic inflammation.

Topics: Age Factors; Animals; Bronchoalveolar Lavage Fluid; Corticosterone; Disease Models, Animal; Female; Fetal Diseases; Immunoglobulin E; Immunohistochemistry; Leptin; Leukocytes; Leukotriene B4; Male; Malnutrition; Pregnancy; Prenatal Exposure Delayed Effects; Prenatal Nutritional Physiological Phenomena; Random Allocation; Rats; Rats, Wistar

Anorexia nervosa (AN) commonly arises during adolescence leading to interruptions of somatic and psychological development as well as to atrophic brain changes. It remains unclear whether these brain changes are related to the loss of neurons, glia, neuropil or merely due to fluid shifts. We determined leptin levels and two brain-derived damage markers: glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) of 43 acute AN patients and 50 healthy control woman (HCW). Peripheral GFAP and NSE concentrations of AN patients were not elevated and not different from HCW. Subjects with particularly low leptin concentration, indicating severe malnutrition, did not show abnormal values either. During weight recovery the marker proteins remained unchanged. Our preliminary results are in line with neuroimaging studies supporting the reversibility of brain changes in AN and do not substantiate hypotheses relying on the extensive damage of brain cells as an explanation for cerebral atrophy in AN.

Topics: Adaptation, Physiological; Adolescent; Adult; Anorexia Nervosa; Biomarkers; Body Mass Index; Brain; Down-Regulation; Female; Glial Fibrillary Acidic Protein; Humans; Interview, Psychological; Leptin; Malnutrition; Neurodegenerative Diseases; Neuroglia; Neurons; Personality Inventory; Phosphopyruvate Hydratase; Predictive Value of Tests; Reproducibility of Results

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

Evidence has emerged that undernutrition in utero is a risk factor for cardiovascular disorders in adulthood, along with genetic and environmental factors. Recently, the local expression of angiotensinogen and related bioactive substances has been demonstrated to play a pivotal role in cardiac remodeling, i.e. fibrosis and hypertrophy. The aim of the present study was to clarify the possible involvement of the local cardiac angiotensin system in fetal undernutrition-induced cardiovascular disorders. We developed a mouse model of undernutrition in utero by maternal food restriction, in which offspring (UN offspring) showed an increase in systolic blood pressure (8 wk of age, P < 0.05; and 16 wk, P < 0.01), perivascular fibrosis of the coronary artery (16 wk, P < 0.05) and cardiac cardiomegaly (16 wk, P < 0.01), and cardiomyocyte enlargement, concomitant with a significant augmentation of angiotensinogen (P < 0.05) and endothelin-1 (P < 0.01) mRNA expression and a tendency to increase in immunostaining for both angiotensin II and endothelin-1 in the left ventricles (16 wk). These findings suggest that fetal undernutrition activated the local cardiac angiotensin system-associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure.

Topics: Angiotensin II; Animals; Blood Pressure; Cardiovascular Diseases; Female; Fetal Nutrition Disorders; Heart Ventricles; Leptin; Malnutrition; Mice; Mice, Inbred C57BL; Nitric Oxide; Pregnancy; Prenatal Exposure Delayed Effects; Renin-Angiotensin System; Sodium Glutamate; Ventricular Remodeling

There is no single universally accepted biochemical marker of nutritional status in the elderly. Many markers are affected by non-nutritional factors.. The purpose of this study was to determine the biological parameters best related to anthropometric markers of malnutrition in an elderly polypathological population, and determine cutoff values for these potential parameters to diagnose malnutrition.. This prospective study enrolled 116 elderly hospitalized patients and 76 elderly outpatients. Nutritional status (albumin, transthyretin, body mass index (BMI), skinfold thickness) and biological parameters (leptin, insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), IGFBP-3, C-reactive protein (CRP), orosomucoid) were assessed. We defined malnutrition according to the lowest quartile of BMI and skinfold thickness measured in a large healthy elderly French sample population.. In this sample of elderly patients (age: 85+/-7 years old), leptin concentration was the only biological parameter significantly related to nutrition status. Independent correlations were found between leptin concentration and BMI, skinfold thickness and sex. The relationship between nutritional status and leptin concentration is significantly different in each sex: the more the patients are undernourished, the lower the leptin concentration in both sexes. The optimal leptin cutoff value for the diagnosis of malnutrition in this population was 4 microg/l in men (sensitivity 0.89, specificity 0.82) and 6.48 microg/l in women (sensitivity 0.90, specificity 0.83).. Leptin concentration is highly correlated with anthropometric data whereas albumin or transthyretin are known to be also influenced by morbidity and inflammatory conditions. Serum leptin concentration could be used for nutritional assessment in elderly patients with acute diseases.

Topics: Acute Disease; Aged, 80 and over; Biomarkers; Body Mass Index; Case-Control Studies; Diagnosis, Differential; Female; Geriatric Assessment; Health Status; Humans; Leptin; Male; Malnutrition; Nutrition Assessment; Nutritional Status; Prospective Studies; Reference Standards; Reference Values; Sensitivity and Specificity; Serum Albumin; Sex Factors; Skinfold Thickness

Leptin, a peptide hormone, is secreted by adipose tissue and is crucial to the regulation of feeding behaviour. The present study has shown that both male and female rats which have been undernourished since day six of gestation, show significantly decreased serum leptin levels on postnatal day 12; but when undernourishment continues into adulthood, only males continue to show decreased leptin levels. If nutritional rehabilitation is implemented early enough in males, serum leptin levels recover and nearly reach levels found in control adult males. Undernutrition also has a long term effect on body weight in both sexes, but nutritional rehabilitation leads to some degree of body weight recovery varying with sex and the age at which rehabilitation was implemented. Undernutrition seems to affect different developmental processes in males than in females, with males being more vulnerable than females in so far as long-term effects on serum leptin levels.

Topics: Adipose Tissue; Animals; Body Weight; Estrone; Female; Leptin; Male; Malnutrition; Nutritional Status; Rats; Rats, Wistar; Sex Characteristics; Testosterone

Loss of appetite is an important causal factor for malnutrition in the elderly, and age-associated changes of hormone levels seem to be of great relevance in this regard. At present there has been no study exploring the role of the appetite stimulating hormone ghrelin in geriatric hospital patients.. 121 (f 82, m 39) patients from two geriatric wards of our hospital. Mean age was 80.2+/-7.7 years.. The basal ghrelin level (mean 158.43+/-144.02 pg/ml) showed no gender difference. No association with the age of the patients could be demonstrated. There was an inverse correlation of basal ghrelin with BMI, upper arm circumference, triceps skin fold, basal leptin and insulin. No correlation between established screening/assessment tools for malnutrition - Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA), Nutritional Risk Screening (NRS) - could be shown. Even after grouping the ghrelin levels into six different disease categories, no significant difference could be shown between them.. For our patients aged 67 to 94, no correlation with age could be shown. Nevertheless the basal level of ghrelin is substantially lower when compared to a younger population with similar BMI, while the anorectic hormone leptin shows no substantial difference. This causes a more anorectic hormonal constellation which may contribute to the loss of appetite in geriatric patients.

Topics: Age Distribution; Aged; Aged, 80 and over; Aging; Anthropometry; Biomarkers; Body Constitution; Female; Geriatric Assessment; Germany; Ghrelin; Health Services for the Aged; Hospitalization; Humans; Leptin; Male; Malnutrition; Nutrition Assessment; Nutritional Status; Peptide Hormones

To discuss the effects of abnormal nutritional supply during pregnancy on the adult insulin and leptin resistance in rats.. We established the pregnant rat models given either low protein or high nutrition diet, and normal diet group served as control. There were 12 pregnant rats in each group. After vaginal delivery, the pups birth weight were measured. The randomly selected small for gestational age (SGA) from low protein diet group, large for gestational age (LGA) pups from high nutrition diet group and normal birth weight pups from control group were studied at both 4 weeks and 12 weeks after being born. Each group contained 36 rats. The insulin and leptin level were measured by the method of ELISA, and insulin sensitive index were calculated respectively.. The pups of mothers served with low protein showed obviously lower birth weight than those mothers with normal diet (P < 0.01), 69% pups were SGA. While pups of mothers with high nutrition diet showed obviously higher birth weight than those mothers with normal diet (P < 0.01), 38% were LGA. The body weight of rats in SGA group was similar with those in control group at 4-week-age (P > 0.05), while the weight of fat around kidney, the ratio of fat and body weight (FW/BW) were (0.36 +/- 0.14) g, 6.5 +/- 0.3, which were higher than those of control (0.19 +/- 0.13) g, 3.4 +/- 0.3 (P < 0.01, P < 0.05). FW/BW in LGA group showed no obvious difference from that of control. At 12-week-age, the body weight of SGA was (222 +/- 19) g, that of LGA was (257 +/- 24) g, both of them significantly higher than that of control (215 +/- 25) g (P < 0.05, P < 0.01). FW/BW in SGA was 10.5 +/- 5.1, in LGA it was 11.8 +/- 3.6, which were significantly higher than that of control, 7.2 +/- 3.6 (P < 0.01). The higher insulin (5.5 +/- 0.9) microg/L, leptin (6.1 +/- 0.7) microg/L level and lower ISI (3.4 +/- 0.3) were obvious at 4-week-age (all P < 0.05) in SGA group but not in LGA group. At 12-week-age, all of them in the two groups were significantly different compared with those in control (all P < 0.01).. Abnormal nutritional supply during pregnancy can lead to abnormal birth weight. Both low birth weight and high birth weight pups showed obesity with different characteristics and insulin, leptin resistance during adult period.

Topics: Animals; Animals, Newborn; Birth Weight; Dietary Proteins; Female; Insulin; Insulin Resistance; Leptin; Malnutrition; Overnutrition; Pregnancy; Prenatal Nutritional Physiological Phenomena; Rats; Rats, Wistar; Risk Factors

Malnutrition compromises immune function, resulting in reduced resistance to infection. Recent animal and human studies have suggested that leptin is capable of modulating the immune response and that its levels, which are regulated by nutritional status, fall rapidly during starvation. Leptin deficiency is associated with impaired cell-mediated immunity, an increased incidence of infectious disease and an associated increase in mortality. The purpose of this study was to examine the effect of leptin on activation and cytokine production in peripheral blood T cells from malnourished children. The data obtained in the present study demonstrate that leptin produced an increase in the percentage of CD4(+) and CD8(+) cells producing interleukin (IL)-2 and interferon (IFN)-gamma in 24-h cultures. Moreover, leptin decreased the percentage of CD4(+) and CD8(+) cells producing IL-4 and IL-10, and enhanced activation of circulating T cells when co-stimulated by phorbol 12-myristate 13 acetate (PMA)-ionomycin. Leptin enhanced the expression of activation markers CD69 and CD25 in both CD4(+) and CD8(+) cells after 5 h of stimulation. In conclusion, the results obtained show that leptin modulates CD4(+) and CD8(+) cell activation towards a T helper 1 (Th1) phenotype by stimulating the synthesis of IL-2 and IFN-gamma. In contrast, leptin decreases IL-4 and IL-10 production. Moreover, leptin enhanced the expression of CD69 and CD25 on CD4(+) and CD8(+) cells after stimulation with PMA-ionomycin.

Topics: CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cells, Cultured; Child, Preschool; Cytokines; Female; Humans; Infant; Interferon-gamma; Interleukins; Leptin; Lymphocyte Activation; Male; Malnutrition; Opportunistic Infections

The escalating rates of obesity and type 2 diabetes have reached pandemic proportions. It has been proposed that the risk of developing metabolic disorders in adult life is influenced by environmental factors, which operate during the early periods of development. We have previously shown that an interaction between the prenatal and the postnatal dietary environment amplifies the propensity towards diet-induced obesity, although the mechanisms are unclear. In the present study, we investigated the interaction between prenatal undernutrition and postnatal high-fat nutrition on key genes of the hypothalamic appetite regulatory network. Pregnant Wistar rats were fed a standard chow diet either ad libitum (AD) or at 30% of AD intake throughout gestation (UN). From weaning, female AD and UN offspring were fed either a standard chow (ADC n = 8, UNC n = 8) or a high-fat diet (45% kcal as fat; ADHF n = 8, UNHF n = 8) ad libitum for the remainder of the study. At 24 weeks of age, body composition was assessed by dual energy X-ray absorptiometry analysis and total RNA was extracted from whole rat hypothalami. Real-time PCR was performed to characterise pro-opiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related protein (AgRP) and OBRb gene expression at the mRNA level. Our results demonstrate that the amplification of postnatal obesity develops as a consequence of an interaction between prenatal under-nutrition and postnatal high-fat nutrition. This phenotype also shows significant alterations in POMC, NPY, AgRP and OBRb gene expression together with elevations in circulating levels of both plasma leptin and insulin. These findings are consistent with the predictive adaptive response hypothesis that neuroendocrine development during fetal life may be based on predictions about postnatal environmental conditions. Increased susceptibility to diet-induced obesity develops if a mismatch between the anticipated and the actual conditions are encountered.

Topics: Agouti Signaling Protein; Agouti-Related Protein; Animals; Appetite Regulation; Body Composition; Dietary Fats; Disease Susceptibility; Female; Gene Expression; Hyperphagia; Hypothalamus; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Malnutrition; Maternal Nutritional Physiological Phenomena; Neuropeptide Y; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Pro-Opiomelanocortin; Rats; Rats, Wistar; RNA, Messenger

Obesity has been suggested to have a detrimental impact on kidney structure and function, leading to focal glomerulosclerosis and hypertension. It is also associated with hyperleptinemia and elevated renal sympathetic nerve activity. Prenatal undernutrition promotes postnatal obesity, hypertension, and an altered renal structure and function. In this study, we examined the effects of prenatal nutrient restriction and juvenile obesity in sheep. We found that juvenile obesity led to chronic hyperleptinemia and reduced renal function as assessed by nuclear scintigraphy. Additional factors include hypertension, glomerulosclerosis, and increased kidney apoptosis. Prenatal undernutrition, synchronous with early kidney development, coupled postnatally with juvenile obesity had no effect on systemic pathophysiological sequalae associated with obesity per se. Hypertension, hyperleptinemia, and poor renal function were all observed in this group. All indices of renal pathology such as increased expression of proinflammatory cytokines, angiotensin II, glucocorticoid receptors, and increased apoptosis and glomerulosclerosis were entirely absent in obese prenatally undernourished offspring. Our data indicate that juvenile obesity per se leads to systemic hypertension and renal structural and functional pathology. Prenatal undernutrition effectively abolishes any renal histopathology associated with juvenile obesity.

Topics: Animals; Animals, Newborn; Apoptosis; Blood Pressure; Diet; Female; Glomerular Filtration Rate; Heart Rate; Hypertension; Kidney; Kidney Diseases; Leptin; Malnutrition; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Sheep

Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) are key factors in bone remodeling in patients with anorexia nervosa (AN) and osteopenia. The purpose of this study was to investigate basal serum levels of OPG, RANKL and leptin, as well as bone mineral density (BMD) measured by DEXA at lumbar vertebrae L1-L4, and their evolution during one year in two groups of patients with AN.. Group I included 10 adolescent girls suffering from malnutrition and secondary amenorrhea with an evolution of more than one year at the beginning of the study who received oral estrogen treatment throughout the follow-up period. Group II comprised 10 girls with malnutrition and secondary amenorrhea with an evolution of less than one year who received nutritional treatment only. All parameters were compared with those of a control group of 19 healthy, age-matched girls with normal BMI and regular menstrual cycles.. The OPG/RANKL ratio was significantly decreased (p<0.05) after 1 year in group I, a fact that was due to an increase (p<0.05) in serum RANKL values. A correlation between OPG/RANKL and BMD was found in group I at the beginning of the study (r = 0.95; p<0.001). Patients in this group showed lower BMD values (p<0.01), both at diagnosis and at the end of the study, than those of group II patients, who showed normal BMD values.. The decrease in the OPG/RANKL ratio in girls with AN could partly explain the increase in bone loss that occurs in these patients.

Topics: Absorptiometry, Photon; Adolescent; Amenorrhea; Anorexia Nervosa; Biomarkers; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Bone Resorption; Enzyme-Linked Immunosorbent Assay; Estradiol; Female; Follow-Up Studies; Humans; Leptin; Lumbar Vertebrae; Malnutrition; Osteoprotegerin; Radioimmunoassay; RANK Ligand; Receptors, Leptin; Reference Values; Treatment Outcome

Topics: Amenorrhea; Estradiol; Female; Humans; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Leptin; Malnutrition; Physical Exertion; Pituitary-Adrenal System; Weight Loss

Leptin might be more important as a starvation hormone than as a satiety signal. The role of the soluble leptin receptor (sOB-R) and its regulation in children with protein energy malnutrition (PEM) is poorly understood.. We elucidated the effect of intensive nutritional support on the leptin axis in 26 severely malnourished toddlers who received infant milk-based formula for 2 wk via continuous enteral tube feeding followed by 2 wk ad libitum feeding. Serum levels of leptin, sOB-R, IGF-I, and IGF-binding protein-3 as well as anthropometric measurements were determined at the beginning of the study and at 2-wk intervals. The control group consisted of 13 well-nourished children.. The following were changes in the PEM toddlers after the nutritional support. Leptin increased significantly (P < 0.001), reaching 166% of levels observed in control group. sOB-R decreased significantly (P < 0.001), and a 142-fold molar excess of sOB-R over leptin was found. There were significant correlations between leptin and IGF-I after 2 wk and IGF-binding protein-3 during the whole study. sOB-R was not correlated with any anthropometric data, whereas IGF-I was a predictor of sOB-R variance in the PEM toddlers (19.9%, P = 0.022).. It can be concluded that sOB-R has a modulatory effect on leptin in PEM children during nutritional recovery and participates in their adaptive survival mechanisms. Leptin and the molar excess of sOB-R over leptin are better biomarkers of nutritional status than IGF-I in PEM children during nutritional recovery.

Topics: Animals; Child, Preschool; Humans; Infant; Infant Food; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Malnutrition; Milk; Nutritional Physiological Phenomena; Receptors, Cell Surface; Receptors, Leptin; Reference Values

Topics: Animals; Critical Illness; Humans; Immunity; Leptin; Lung; Malnutrition; Mice; Pneumonia, Pneumococcal; Streptococcus pneumoniae

To investigate the correlation between serum leptin levels, body mass index, and triceps skin fold thickness, which are anthropometric measurements, as well as serum albumin levels in patients with chronic renal failure on hemodialysis.. We studied 75 patients (48 males, 27 females; ages between 18-82) at the Hemodialysis Unit, Cumhuriyet University Medical School; Private Sivas Dialysis Center; Hemodialysis Unit, Sultan Izzettin Keykavus Hospital; and the Hemodialysis Unit, SSK Sivas Hospital between January 2003 and February 2004. Patients were excluded if they had been on dialysis for less than one year, if they were anuric, or if they had been on dialysis with jugular or subclavian catheter and long-term permanent port catheter. Similarly, patients with diabetes mellitus, chronic pulmonary disorders, and hepatic cirrhosis or hepatitis B, hepatitis C carriers as well as those on active tuberculosis therapy were excluded. C-reactive protein was measured in all patients and those with above normal values were excluded.. While the mean age for the males was 44.52 +/- 16.53 years (18-77), it was 48.29 +/- 14.32 years (22-82) for the females. The mean triceps skin fold thickness for males was 6 +/- 1.81 mm (3-11.3 mm), and for females, it was 14.07 +/- 8.79 mm (4.3-33.3 mm). The mean body mass index for males was 20.77 +/- 2.61 kg/m2 (14.8-26.6 kg/m2), and for females, it was 25.36 +/- 6.47 kg/m2 (17.3-42.2 kg/m2). The mean serum leptin level for males was 4.61 +/- 4.20 ngr/dl (0.1-18.7 ngr/dl), and for females, it was 52.06 +/- 61.67 ngr/dl (0.6-172.5 ngr/dl). A positive correlation was observed between triceps skin fold thickness and leptin, both in the male group (r=0.478; p<0.05), and in the female group (r=0.876; p<0.05). Body mass index and leptin were also correlated positively both in the male group (r=0.502; p<0.05) and in the female group (r=0.905; p<0.05). No correlation was established between serum albumin levels and leptin. Leptin did not correlate with other measured parameters. Our study demonstrates that serum leptin levels positively correlated with body mass index and triceps skin fold thickness, which are malnutrition parameters. Therefore, the leptin hormone may be utilized in obtaining preliminary information regarding malnutrition.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Mass Index; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Malnutrition; Middle Aged; Renal Dialysis; Skinfold Thickness

Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-alpha.. Seventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups: group COPD IA (patients without malnutrition during acute exacerbation, n = 25), group COPD IB (patients without malnutrition during stable disease, n = 29), group COPD II (patients with malnutrition during stable disease, n = 18). To eliminate the effect of sex differences, all patients and controls were male. Body mass index (BMI), percent ideal body weight (IBW%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference (MAMC), serum leptin and TNF-alpha levels, serum prealbumin (PA), serum transferrin (TF), serum albumin (Alb), total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure (MIP) and maximal expiration pressure (MEP) were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed.. Serum leptin levels were significantly lower in group COPD II [(4.07 +/- 3.42) ng/ml] than in group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml] (P < 0.05). There was no statistically significant difference in serum leptin levels between group COPD IA [(10.82 +/- 6.40) ng/ml], group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml]. There was no statistically significant difference in serum TNF-alpha levels between group COPD II [(8.03 +/- 3.37) pg/ml], group COPD IA [(8.90 +/- 1.60) pg/ml], and group COPD IB [(7.25 +/- 2.08) pg/ml]. There was no significant correlation between leptin and TNF-alpha in any group.. Leptin was not involved in anorexia and weight loss of COPD patients. There was no statistically significant difference in serum leptin levels between COPD patients during stable stage and acute exacerbation, and there was no significant correlation between TNF-alpha and leptin during the regulation of the energy balance in COPD patients.

Topics: Adult; Aged; Anorexia; Humans; Leptin; Male; Malnutrition; Middle Aged; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha; Weight Loss

In the present study, it was investigated whether undernutrition affected the binding capacity, immunoreactivity and mRNA expression for uterine oestrogen and progesterone receptors (ER and PR, respectively) in sheep, as well as whether the responses were associated with changes in plasma concentrations of progesterone (P4), oestradiol (E2), glucose, fatty acids, insulin, leptin and insulin-like growth factor (IGF)-I during the oestrous cycle. Twenty ewes were fed either 1.5 (C) or 0.5 (L) times their maintenance requirements and were killed on Day 5 or 14 of the cycle (Day 0 = oestrus). Compared with Group C, Group L had higher concentrations of non-esterified fatty acids and lower concentrations of insulin, leptin and IGF-I. Group L also had higher plasma concentrations of P4 during the final days of the luteal phase. At oestrus in both treatment groups, there were peaks in the concentrations of glucose, insulin and IGF-I. For ER and PR, transcript expression, binding capacity and immunoreactivity were higher on Day 5 than on Day 14 of the cycle. The binding capacities for ER and PR were lower in Group L than in Group C on Day 5. Group C showed more immunoreactive staining for ER than did Group L in two of five cell types, whereas no effect of treatment was observed for PR immunoreactivity. There was more PR mRNA in the uterine horn contralateral to the corpus luteum in Group C than in Group L ewes. We conclude that undernutrition impairs steroid receptor expression and binding capacity. This may alter the uterine environment and help explain the reductions in embryo survival.

Topics: Animals; Blood Glucose; Estradiol; Estrous Cycle; Fatty Acids; Fatty Acids, Nonesterified; Female; Hormones; Insulin; Insulin-Like Growth Factor I; Leptin; Malnutrition; Progesterone; Receptors, Estrogen; Receptors, Progesterone; RNA, Messenger; Sheep; Sheep Diseases; Uterus

The metabolic syndrome (MS) describes a cluster of metabolic disturbances including type 2 diabetes and/or insulin resistance, hypertension, dyslipidemia and obesity, which predict a high risk of cardiovascular disorders. The associated hyperinsulinemia and hyperleptinemia may contribute to the cardiovascular risk. However, the operational value of the MS in elderly patients is questionable. We therefore investigated the prevalence and significance of the MS in geriatric care. In a survey of 98 consecutive admissions of diabetic patients, <40% had a MS; this is a low value compared to younger diabetic adults, due to a low prevalence of obesity and dyslipidemia. We found a high prevalence of low BMI (<20 kg/m2), hypoalbuminemia and low total cholesterol levels, suggesting that the MS may be modified by undernutrition. The interplay between the MS and undernutrition was further studied in 30 non-diabetic patients. Both leptinemia and insulin resistance indexes (HOMA-IR and QUICKI) were strongly associated with BMI and body fat (measured by Bioelectrical impedance Analysis). BMI, leptinemia and insulin resistance indexes were associated with the Mini Nutritional Assessment (MNA) score. Thus, undernutrition is associated with low leptin and insulin levels and may obscure the association of these parameters with cardiovascular risk. In conclusion, the MS has a low prevalence in our population of elderly diabetic patients, and is of questionable prognostic value. It can be oveshadowed by undernutrition, which is associated with low body weight, leptinemia and insulin resistance indexes. Prevention of undernutrition and/or adjustment to its consequences should receive higher priority in the care of elderly diabetic patients.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Hospitals, Special; Humans; Inflammation; Insulin; Insulin Resistance; Leptin; Malnutrition; Metabolic Syndrome; Nutrition Assessment; Risk Factors

Resistin is a specific fat-derived hormone that affects fuel homeostasis and insulin action in rodents. However, its role in human physiology and pathophysiologic conditions, such as malnutrition, remains uncertain.. To enhance understanding of the role of resistin in the pathophysiology of anorexia nervosa (AN), we measured plasma resistin levels in 13 women with a restrictive type of AN and in 16 healthy age-matched women (control). Further, we measured resistin levels in the subcutaneous adipose tissue of eight women from the AN group and eight women from the control group with an in vivo microdialysis technique (CMA/107 pump, CMA/60 catheters, CMA Microdialysis AB, Solna, Sweden).. Body mass index, percentage of body fat, fasting plasma leptin and insulin, and homeostasis model assessment index for insulin resistance were severely decreased in patients with AN compared with the control group. Plasma resistin levels were significantly decreased in patients with AN (P < 0.05), whereas subcutaneous adipose tissue resistin levels were significantly increased in patients with AN compared with the control group (P < 0.05). In both groups, plasma resistin levels showed no significant relation to resistin in dialysate, percentage of body fat, body mass index, homeostasis model assessment index for insulin resistance, and fasting plasma leptin levels.. We demonstrated that AN is associated with decreased plasma resistin levels and increased resistin levels in extracellular space of the abdominal adipose tissue. Plasma resistin levels in patients with AN or in healthy normal-weight women were not directly related to body mass index, percentage of body fat, plasma leptin levels, and insulin sensitivity.

Topics: Adipose Tissue; Adult; Anorexia Nervosa; Body Composition; Body Mass Index; Case-Control Studies; Female; Humans; Insulin; Leptin; Malnutrition; Microdialysis; Resistin

To ascertain the possible role of leptin in the resumption of postpartum menstruation in lactating women with differing nutritional statuses.. Analysis of data and blood samples collected during a previous prospective study.. Healthy volunteers in an academic research environment.. Undernourished (body mass index [BMI]< or =19 kg/m(2)) and well-nourished (BMI> or =26 kg/m(2)) lactating women who resumed regular menstruation before 24 weeks and at or after 24 weeks postpartum.. Venous blood samples at four-weekly intervals and other clinical data collected until resumption of regular menstruation.. Serum leptin concentrations.. Leptin concentrations were significantly higher in the well-nourished than in the undernourished women, irrespective of the time of resumption of menstruation. Time of resumption of menstruation did not significantly affect leptin levels within well-nourished and undernourished groups. Leptin significantly correlated with BMI (r = 0.78). The BMI (r = -0.53), but not leptin, was significantly and negatively correlated with the duration of lactational amenorrhea.. Leptin is unlikely to be a major determinant of early resumption of regular menstruation in well-nourished women.

Topics: Adult; Amenorrhea; Body Mass Index; Female; Humans; Lactation; Leptin; Malnutrition; Maternal Nutritional Physiological Phenomena; Menstruation; Nutrition Assessment

Topics: Animals; Blood-Brain Barrier; Dietary Fats; Humans; Hypothalamus; Infant Nutritional Physiological Phenomena; Infant, Newborn; Leptin; Malnutrition; Mice; Obesity; Risk Factors

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

Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We report a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin-treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. The present study suggests that the premature leptin surge alters energy regulation by the hypothalamus and contributes to "developmental origins of health and disease."

Topics: Animals; Animals, Newborn; Energy Metabolism; Female; Leptin; Malnutrition; Mice; Obesity; Pregnancy; Pregnancy Proteins; Uterus

To explore the function of serum leptin in COPD patients with malnutrition, and to investigate the relationship between leptin and TNF-alpha.. A total of 81 subjects (47 COPD patients and 34 control subjects) participated in this study. The 47 COPD patients were divided into 2 groups: group COPD I (patients without malnutrition during stable disease, n=29), group COPDII (patients with malnutrition during stable disease, n=18). To eliminate the effect of sex differences, all the patients and controls were male. Body mass index (BMI), percent ideal body weight (IBWå), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference(MAMC),serum leptin and tumor necrosis factor-alpha(TNF-alpha) levels, serum prealbumin (PA), serum transferrin (TF), serum albumin(Alb),total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure(MIP)and maximal expiration pressure(MEP)were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analysed.. (1) Serum leptin levels were significantly lower in group COPDII (4.07+/-3.42 microg/L) than in group COPD I (9.72+/-6.67 microg/L) and controls (8.21+/- 5.41 microg/L, P<0.05). (2) There were no statistical differences in serum TNF-alpha levels between group COPDII (8.03+/-3.37 ng/L)and group COPD I (7.25+/- 2.08 ng/L). (3) There was no significant correlation between leptin and TNF-alpha in any group.. Leptin was not involved in anorexia and weight loss of COPD patients. There was no significant correlation between TNF-alpha and leptin during the regulation of the energy balance in COPD patients.

Topics: Aged; Energy Metabolism; Enzyme-Linked Immunosorbent Assay; Humans; Leptin; Male; Malnutrition; Middle Aged; Nutritional Status; Pulmonary Disease, Chronic Obstructive; Radioimmunoassay; Respiratory Function Tests; Transferrin; Tumor Necrosis Factor-alpha

Leptin is a protein hormone secreted by adipocytes, regulating body fat and food intake. It has been reported that serum leptin levels are high in patients with chronic renal failure, and this fact has been associated with malnutrition and body composition changes in patients on hemodialysis. This present study investigated the relationship between plasma leptin concentrations and body composition and markers of malnutrition in nondiabetic patients diagnosed with end-stage chronic renal failure, treated with continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD).. A total of 152 HD and 32 CAPD patients were enrolled into the study. The body compositions of the patients were established by utilizing a Body Composition Analyzer. Triceps skinfold thickness (TSFT) was measured by using a Harpenden Skinfold Caliper. Serum leptin level was detected by radioimmunoassay in ng/mL through employing a DPC Gambyt-CR gamma counter. Standard laboratory methods were used for measuring the remaining parameters (total protein, albumin, blood urea nitrogen, creatinine, hemoglobin, hematocrit, high-sensitivity C-reactive protein [hsCRP]).. No significant difference was observed between the HD and CAPD groups regarding leptin levels. Leptin levels of female patients in both groups were markedly higher when compared with those of men (p = 0.001). Plasma leptin levels in total, as well as for both male and female HD and CAPD patients, significantly correlated positively with age, percent fat, fat mass, body mass index and TSFT (p = 0.001). Serum leptin levels were not found to be correlated with length of time on dialysis, lean body mass, total body water, hsCRP, total protein and albumin levels (p > 0.05).. The data obtained in this study indicated that serum leptin levels could be instrumental markers in establishing body fat ratio, as well as in determining metabolic and nutritional factors in patients with chronic renal failure.

Topics: Adult; Aged; Biomarkers; Body Composition; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Malnutrition; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

To determine the concentrations of leptin and ghrelin, which have opposite effects on appetite, energy expenditure, and weight control, in the plasma of patients with Crohn's disease (CD), which is often associated with weight loss and malnutrition.. Plasma leptin and ghrelin 'concentrations were determined in 28 outpatients with CD by radioimmunoassay. Age- and sex-matched controls with and without Helicobacter pylori (H pylori) infection (28 for each) were enrolled in the study. Circulating levels of these hormones were assessed with respect to CD activity, disease localization and medical treatment.. There were no significant differences in ghrelin levels between CD patients and H pylori-negative controls. However, circulating ghrelin levels were significantly lower in H pylori-infected subjects than in CD patients and uninfected controls. Plasma leptin levels were comparable among the groups. Localization and medication profile had no significant impact on circulating ghrelin and leptin levels.. Apart from H pylori infection, CD itself has no significant influence on circulating ghrelin and leptin levels in the outpatients who were mostly in inactive state.

Topics: Adolescent; Adult; Case-Control Studies; Crohn Disease; Female; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Malnutrition; Middle Aged; Peptide Hormones; Weight Loss

Caloric imbalance, particularly in critical periods of growth and development, is often the underlying cause of growth abnormalities. Serum levels of leptin are elevated in obesity and are low in malnutrition and malabsorption. The aim of the present study was to determine whether leptin integrates energy levels and growth in vivo, as shown previously in our ex vivo experiments, even in the presence of caloric restriction. In the first part of the study, mice were divided into three groups. Two groups were fed ad libitum and received leptin or vehicle only, and the third group was pair-fed with the group injected with leptin to dissociate leptin's effect on growth from its effect on food consumption. Mice given leptin had a significantly greater tibial length than untreated pair-fed animals and a similar tibial length as control mice fed ad libitum despite their lower weight. In addition, leptin significantly increased the overall size of the epiphyseal growth plate by 11%. On immunohistochemistry and in situ hybridization studies, leptin stimulated both the proliferation and differentiation of tibial growth plate chondrocytes without affecting the overall organization of the plate. There was also a marked increase in the expression and level of IGF-IR. In the second part of the study, two groups of mice were fed only 60% of their normal chow; one was injected with leptin, and the other was injected with vehicle alone. Caloric deprivation by itself reduced serum levels of IGF-I by 70% and the length of the tibia by 5%. Leptin treatment corrected the fasting-induced growth deficiency, but further reduced the level of serum IGF-I. These results indicate that leptin stimulates growth even in the presence of caloric restriction independently of peripheral IGF-I.

Topics: Animals; Caloric Restriction; Eating; Growth Plate; Insulin-Like Growth Factor I; Leptin; Male; Malnutrition; Mice; Mice, Inbred ICR; Tibia

We aimed to determine the importance of leptin in the regulation of luteinizing hormone (LH) and growth hormone (GH) secretion in ovariectomized (OVX) ewes. Lean and fat sheep were produced by dietary manipulation over 8 months and were then fasted for 32 h. Plasma concentrations of glucose, insulin and leptin were higher in the fat group. Fasting decreased plasma concentrations of glucose and insulin and increased concentrations of nonesterified fatty acids (NEFA) in fat and lean ewes, but leptin concentrations were reduced in the fat group only. Plasma GH concentrations were higher in the lean group and LH concentrations were lower; there was no effect of fasting. These data suggested that long-term changes in plasma leptin concentrations might affect LH and GH secretion, but acute changes with fasting had no effect. OVX ewes of normal body weight were fasted for 72 h with or without intracerebroventricular (i.c.v.) infusion of leptin (4 microg/h), achieving similar metabolic effects to the 32 h fast. The 72-h fast increased LH pulse amplitude, mean GH and cortisol concentrations, but these changes were corrected towards normal by leptin treatment. Thus, leptin could attenuate fasting-induced alterations in the secretion of LH, GH and cortisol. Finally, we food-restricted OVX ewes for 4 months (lean), leading to a 20-kg reduction in body weight. Plasma concentrations of leptin and insulin were decreased, and plasma GH concentrations increased, but there was no effect on plasma concentrations of LH, glucose or NEFA. Icv infusion of leptin did not affect any endocrine or metabolic parameter in these ewes. In summary, maintenance of a lean or fat condition for a prolonged period (8 months) or an extended fasting (72 h) can affect LH and GH secretion, but short-term food restriction (4 months) affected only GH secretion and short-term fasting (32 h) had no effect on either LH or GH secretion. This is in spite of altered plasma leptin concentrations in all circumstances studied. Although leptin treatment can restore plasma concentrations of LH, GH and cortisol towards normal in sheep fasted for 72 h, some other factor(s) must signal to the brain to cause shifts in neuroendocrine function in other conditions where nutritional/metabolic status is altered.

Topics: Animals; Blood Glucose; Body Composition; Fasting; Fatty Acids, Nonesterified; Female; Growth Hormone; Hydrocortisone; Injections, Intraventricular; Insulin; Leptin; Luteinizing Hormone; Malnutrition; Ovariectomy; Sheep; Time Factors

Topics: Anorexia; Body Mass Index; Energy Intake; Feeding Behavior; Humans; Kidney Failure, Chronic; Leptin; Malnutrition; Peritoneal Dialysis; Renal Dialysis

Hyperleptinemia is a common feature in hemodialysis (HD) patients. However, the role of increased serum leptin levels in the pathogenesis of HD-related anorexia is still controversial. The purpose of the present prospective study was to ascertain whether hyperleptinemia is causally implicated in the pathogenesis of HD-related anorexia.. We measured the serum leptin levels and the serum leptin/body mass index (BMI) ratio in 24 healthy subjects and in 49 end-stage renal disease patients on maintenance HD. HD patients were subdivided into anorexic (14/49, 28.5%) and non-anorexic (35/49, 71.5%) according to a questionnaire discriminating for the presence of anorexia-related symptoms.. Calorie (kcal/kg/day) and protein (g/ kg/day) intakes were significantly lower in anorexic than in non-anorexic patients (20.1 +/- 1.1 vs. 27.9 +/- 1.3, p = 0.004, and 0.82 +/- 0.05 vs. 1.19 +/- 0.05, p = 0.001, respectively). Accordingly, serum albumin, total lymphocyte count, mid-arm muscle circumference, and the protein equivalence of nitrogen appearance (PNA) were significantly lower in anorexic patients. The serum leptin concentration (ng/ml) was significantly higher in HD patients than in controls, in males (15.33 +/- 3.4 vs. 3.7 +/- 0.3, p = 0.003) and in females (42.3 +/- 7.2 vs. 10.5 +/- 1.3, p = 0.03). Similarly, serum leptin/BMI ratio was significantly higher in HD patients than in controls, in males (0.56 +/- 0.1 vs. 0.16 +/- 0.02, p = 0.0028) and in females (1.8 +/- 0.2 vs. 0.4 +/- 0.04, p < 0.0001). However, serum leptin levels were similar in anorexic and in non-anorexic patients, in males (15.3 +/- 5.6 vs. 16.9 +/- 4.2, p = 0.85) and in females (46.6 +/- 12.9 vs. 47.4 +/- 9.4, p = 0.96). No differences were observed between the 2 groups in the serum leptin/BMI ratio, in males (0.59 +/- 0.2 vs. 0.58 +/- 0.14, p = 0.92) and in females (1.5 +/- 0.4 vs. 1.8 +/- 0.3, p = 0.94). Similarly, no statistically significant differences in terms of serum leptin levels and leptin/BMI ratio were observed between patients with dietary energy intake of <30 or > or =30 kcal/kg/day and between those with a dietary protein intake of <1.2 or > or =1.2 g/kg/day. No significant correlations were found between serum leptin levels and PNA, albumin, cholesterol, total lymphocytes number, weight change, C-reactive protein, fibrinogen, ferritin, and complement.. The present results indicate that mechanisms other than increases in serum leptin levels might be involved in the pathogenesis of HD-related anorexia.

Topics: Aged; Anorexia; Blood Proteins; Body Mass Index; Case-Control Studies; Cholesterol; Comorbidity; Dietary Proteins; Energy Intake; Female; Humans; Kidney Failure, Chronic; Leptin; Leukocyte Count; Male; Malnutrition; Middle Aged; Renal Dialysis; Surveys and Questionnaires

To explore the factors influencing insulin resistance in children with different nutritional status during pubertal development.. Three hundred children with simple obese aged 7 to 17 years, and 300 normal healthy children and 300 children with malnutrition, matched for age (+/- 3 months) and height (+/- 2 cm), were selected. Fasting serum levels of leptin, insulin, glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) were measured for them.. Levels of fasting serum insulin in obese children, except for boys at Tanner stage I and girls at Tanner stage II, were higher than those in normal and malnutrition children (P < 0.01). Average serum level of leptin in obese boys and girls at varied Tanner stages was higher than that in normal children, and higher in normal children than that in children with malnutrition (P<0.01). Serum level of TG in obese children [(1.53 +/- 0.13) mmol/L] was higher than that in normal ones [(1.12 +/- 0.10) mmol/L] and in children with malnutrition [(1.03 +/- 0.09) mmol/L]. There was no significant difference in levels of fasting blood glucose and other blood lipids between the three groups of children. Insulin sensitivity decreased with pubertal development and its index reversely correlated with Tanner stage and serum level of leptin (r=-0.27 and -0.36, respectively, P<0.01).. Obesity (BMI), serum level of leptin and pubertal development were independent risk factors for insulin resistance in children aged 7 to 17 years.

Topics: Adolescent; Body Mass Index; Child; Estradiol; Growth Hormone; Humans; Insulin; Insulin Resistance; Leptin; Male; Malnutrition; Obesity; Puberty; Testosterone

Anorexia nervosa (AN) is characterized by low weight and self-imposed caloric restriction and leads to severe bone loss. Although amenorrhea due to acquired GnRH deficiency is nearly universal in AN, a subset of patients maintains menses despite low weight. The mechanisms underlying continued GnRH secretion despite low weight in these patients and the impact of gonadal hormone secretion on bone mineral density (BMD) in such eumenorrheic, low-weight patients remain unknown. We hypothesized that 1) eumenorrheic women with AN would have higher body fat and levels of nutritionally dependent hormones, including leptin and IGF-I, than amenorrheic women with AN and comparable body mass index; and 2) BMD would be higher in these women. We also investigated whether the severity of eating disorder symptomatology differed between the groups. We studied 116 women: 1) 42 low-weight women who fulfilled all Diagnostic and Statistical Manual of Mental Disorders (fourth edition) diagnostic criteria for AN, except for amenorrhea; and 2) 74 women with AN and amenorrhea for at least 3 months. The two groups were similar in body mass index (17.1 +/- 0.2 vs. 16.8 +/- 0.2 kg/m(2)), percent ideal body weight (78.2 +/- 0.8% vs. 76.7 +/- 0.8%), duration of eating disorder (70 +/- 13 vs. 59 +/- 9 months), age of menarche (13.2 +/- 0.3 vs. 13.5 +/- 0.2 yr), and exercise (4.5 +/- 1.0 vs. 4.2 +/- 0.5 h/wk). As expected, eumenorrheic patients had a higher mean estradiol level (186.6 +/- 19.0 vs. 59.4 +/- 2.5 nmol/liter; P < 0.0001) than amenorrheic subjects. Mean percent body fat, total body fat mass, and truncal fat were higher in eumenorrheic than amenorrheic patients [20.9 +/- 0.9% vs. 16.7 +/- 0.6% (P = 0.0001); 9.8 +/- 0.5 vs. 7.8 +/- 0.3 kg (P = 0.0009); 3.4 +/- 0.2 vs. 2.7 +/- 0.1 kg (P = 0.006)]. The mean leptin level was higher in the eumenorrheic compared with the amenorrheic group (3.7 +/- 0.3 vs. 2.8 +/- 0.2 ng/ml; P = 0.04). Serum IGF-I levels were also higher in the eumenorrheic than in the amenorrheic group (41.8 +/- 3.7 vs. 30.8 +/- 2.3 nmol/liter; P = 0.02). There were only minor differences in severity of eating disorder symptomatology, as measured by the Eating Disorders Inventory, and where differences were observed, eumenorrheic subjects manifested more severe symptomatology than amenorrheic subjects. Mean BMD at the posterior-anterior and lateral spine were low in both groups, but were higher in patients with eumenorrhea than in those with amenorrhea [posterior-an

Topics: Adult; Amenorrhea; Anorexia Nervosa; Body Composition; Body Mass Index; Bone Density; Estradiol; Female; Humans; Hypothalamo-Hypophyseal System; Insulin-Like Growth Factor I; Leptin; Malnutrition; Menstruation

Diets with restricted energy or protein during lactation programs body weight in the adult offspring. We have investigated the hypothesis that protein or energy-restricted diets during lactation alter the feeding response to peripheral leptin treatment of the adult offspring. Five Wistar rats were randomly assigned to one of the following groups on the day that the offspring were born: C, control diet with 23% protein; PR, protein restricted diet with 8% protein; and ER, energy-restricted, receiving the control diet in restricted quantities, which were calculated according to the mean ingestion of the PR group. After weaning (day 21), two animals from each litter (10 pups in each group) were randomly selected and placed together in the cage with free access to water and standard diet until 150 days of age, when they were tested for its response to either leptin (0.5 mg/kg body wt ip) for groups Clep, PRlep and ERlep or saline vehicle for groups Csal, PRsal and ERsal on food intake. In the control groups, food intake was reduced two hours (36%), four hours (41%) and six hours (25%) after leptin treatment. In contrast, no response was observed to leptin treatment in the PRlep and ERlep groups, suggesting leptin resistance. We demonstrated the development of resistance to the anorectic leptin effect and its program in a critical life period associated to nutritional and hormonal factors.

Topics: Aging; Animals; Animals, Newborn; Body Weight; Drug Resistance; Eating; Female; Injections, Intraperitoneal; Lactation; Leptin; Malnutrition; Mothers; Rats; Rats, Wistar

Increased leptin levels in patients with liver cirrhosis are postulated to result in malnutrition and increased energy expenditure. Since cirrhotic patients show improved nutritional status after a transjugular intrahepatic portosystemic stent shunt (TIPS), it was the aim of this study to evaluate plasma leptin levels and their influence on nutritional status prior to and after the TIPS procedure. We evaluated plasma leptin levels, body mass index (BMI), Child-Pugh score and pertinent biochemical parameters in 31 patients (19 men and 12 women) with severe complications of liver cirrhosis (74% ethyltoxic men, 50% ethyltoxic in women), prior to and after TIPS. Nineteen cirrhotic patients without TIPS served as controls. In women ascitic-free BMI significantly increased (from 22.8 +/- 4.6 kg/m2 to 23.9 +/- 4.9; p = 0.004 three months after TIPS), whereas in men only a tendency toward higher values (26.1 +/- 4.7 vs. 26.7 +/- 4.4; p = 0.28) was found. Analysis of peripheral venous leptin concentrations before and three months after TIPS revealed a significant increase in women (11.9 +/- 8.8 ng/ml vs. 18.6 +/- 14.9; p = 0.009) and in men (7.7 +/- 6.2 ng/ml vs. 12.2 +/- 9.0; p = 0.005). In addition, the leptin-BMI ratio increase significantly in women and men three months after TIPS implantation (women 0.49 +/- 0.29 vs. 0.73 +/- 0.52; p = 0.017; men 0.28 +/- 0.22 vs. 0.43 +/- 0.28; p = 0.002). On the other hand, patients without TIPS implantation showed no significant alterations of BMI and peripheral venous leptin concentrations. After TIPS implantation in liver cirrhotic patients, leptin levels were increased and the nutritional status improved. Therefore, our analysis suggests that in patients with predominantly ethyltoxic liver cirrhosis, elevated leptin levels are not a major reason for poorer body composition.

Topics: Adipose Tissue; Adult; Aged; Body Mass Index; Female; Humans; Insulin; Leptin; Liver Cirrhosis; Liver Function Tests; Male; Malnutrition; Middle Aged; Nutritional Status; Portasystemic Shunt, Transjugular Intrahepatic; Statistics, Nonparametric

Ghrelin is a peptide hormone that is involved in regulating growth hormone secretion as well as food intake and energy homeostasis. The aim of this study was to compare changes in plasma ghrelin levels in patients with malnutrition due to anorexia nervosa (AN) or short bowel syndrome (SBS). Blood samples for laboratory analyses were taken from 16 AN patients (plus 13 comparable healthy controls) and 27 SBS patients (plus 13 comparable healthy controls) after an overnight fast. In comparison with their respective control groups, plasma ghrelin levels were increased in the AN patients (p < 0.05) and significantly decreased in the patients with SBS (p < 0.01). These results suggest that quantitative ghrelin secretion in the gut wall is important in determining ghrelin concentrations in the systemic circulation.

Topics: Adipose Tissue; Adult; Anorexia Nervosa; Body Composition; Body Mass Index; Case-Control Studies; Fasting; Female; Ghrelin; Growth Hormone; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Malnutrition; Middle Aged; Nutrition Assessment; Peptide Hormones; Receptors, Cell Surface; Receptors, Leptin; Sex Characteristics; Short Bowel Syndrome; Skinfold Thickness