leptin and Feeding-and-Eating-Disorders

The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein

Topics: Autoantibodies; Feeding and Eating Disorders; Gastrointestinal Microbiome; Ghrelin; Humans; Insulin; Leptin; Melanocyte-Stimulating Hormones; Neuropeptide Y

The present review focuses on adipocytes-released peptides known to be involved in the control of gastrointestinal motility, acting both centrally and peripherally. Thus, four peptides have been taken into account: leptin, adiponectin, nesfatin-1, and apelin. The discussion of the related physiological or pathophysiological roles, based on the most recent findings, is intended to underlie the close interactions among adipose tissue, central nervous system, and gastrointestinal tract. The better understanding of this complex network, as gastrointestinal motor responses represent peripheral signals involved in the regulation of food intake through the gut-brain axis, may also furnish a cue for the development of either novel therapeutic approaches in the treatment of obesity and eating disorders or potential diagnostic tools.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Apelin; Brain; Calcium-Binding Proteins; DNA-Binding Proteins; Eating; Feeding and Eating Disorders; Gastrointestinal Motility; Gastrointestinal Tract; Humans; Leptin; Muscle, Smooth; Nerve Tissue Proteins; Nucleobindins; Obesity

Although food intake is necessary to provide energy for all bodily activities, considering food intake as a motivated behavior is complex. Rather than being a simple unconditioned reflex to energy need, eating is mediated by diverse factors. These include homeostatic signals such as those related to body fat stores, to food available and being eaten, and to circulating energy-rich compounds like glucose and fatty acids. Eating is also greatly influenced by non-homeostatic signals that convey information related to learning and experience, hedonics, stress, the social situation, opportunity, and many other factors. Recent developments identifying the intricate nature of the relationships between homeostatic and non-homeostatic influences significantly add to the complexity underlying the neural basis of the motivation to eat. The future of research in the field of food intake would seem to lie in the identification of the neural circuitry and interactions between homeostatic and non-homeostatic influences.

Topics: Amygdala; Brain; Cholecystokinin; Feeding and Eating Disorders; Feeding Behavior; Homeostasis; Humans; Hypothalamus; Insulin; Leptin; Motivation; Satiation; Stress, Psychological

Over the past century, overwhelming evidence has emerged pointing to the hypothalamus of the central nervous system (CNS) as a crucial regulator of systemic control of metabolism, including appetite and feeding behavior. Appetite (or hunger) is a fundamental driver of survival, involving complex behaviors governed by various parts of the brain, including the cerebral cortex. Here, we provide an overview of basic metabolic principles affecting the CNS and discuss their relevance to physiological and pathological conditions of higher brain functions. These novel perspectives may well provide new insights into future research strategies to facilitate the development of novel therapies for treating mental illness.

Topics: Antidepressive Agents; Cerebral Cortex; Depression; Feeding and Eating Disorders; Feeding Behavior; Gene Expression Regulation; Ghrelin; Humans; Hypothalamus; Insulin; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Leptin; Obesity; Serotonin; Signal Transduction; Synaptic Transmission

A large body of literature documents the occurrence of alterations in the physiology of both central and peripheral modulators of appetite in acute patients with anorexia nervosa (AN) and bulimia nervosa (BN). Until more recently the role of most of the appetite modulators in the control of eating behavior was conceptualized solely in terms of their influence on homeostatic control of energy balance. However, it is becoming more and more evident that appetite modulators also affect the non-homeostatic cognitive, emotional and rewarding component of food intake as well as non food-related reward, and, recently, AN and BN have been pathophysiologically linked to dysfunctions of reward mechanisms. Therefore, the possibility exists that observed changes in appetite modulators in acute AN and BN may represent not only homeostatic adaptations to malnutrition, but also contribute to the development and/or the maintenance of aberrant non-homeostatic behaviors, such as self-starvation and binge eating. In the present review, the evidences supporting a role of leptin, ghrelin, brain-derived neurotrophic factor and endocannabinoids in the homeostatic and non-homeostatic dysregulations of patients with AN and BN will be presented. The reviewed literature is highly suggestive that changes in the physiology of these modulators may play a pivotal role in the pathophysiology of eating disorders by providing a possible link between motivated behaviors, reward processes, cognitive functions and energy balance.

Topics: Animals; Brain-Derived Neurotrophic Factor; Eating; Endocannabinoids; Feeding and Eating Disorders; Ghrelin; Homeostasis; Humans; Leptin

Chronic inflammation is associated with cachexia and increased mortality risk in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Inflammation suppresses appetite and causes the loss of protein stores. In CKD patients, increased serum levels of pro-inflammatory cytokines may be caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions. Cachexia is brought about by the synergistic combination of a dramatic decrease in appetite and an increase in the catabolism of fat and lean body mass. Pro-inflammatory cytokines act on the central nervous system to alter appetite and energy metabolism and to provide a signal-through the nuclear factor-kappaB and ATP-ubiquitin-dependent proteolytic pathways-that causes muscle wasting. Further research into the molecular pathways leading to inflammation and cachexia may lead to novel therapeutic therapies for this devastating and potentially fatal complication of chronic disease.

Topics: Cachexia; Cardiovascular Diseases; Chronic Disease; Cytokines; Feeding and Eating Disorders; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Muscular Atrophy; Neuropeptides

The biological research predominant in the last decades have not brought a solution in the discovery of risk factors contributing to the development of eating disorders, and elaborating a more effective therapy. The large amount of molecular genetic studies, however, by showing the various genetic vulnerability, contributed significantly to recognizing a more specific effect of the environmental factors. The authors evaluate the genetic studies of eating disorders and present environmental factors having a role in the development of eating disorders. They report about recently published data of gene-environment interaction and conclude from the data clinically applicable consequences.

Topics: Anorexia Nervosa; Brain-Derived Neurotrophic Factor; Bulimia Nervosa; Family; Feeding and Eating Disorders; Genetic Predisposition to Disease; Ghrelin; Humans; Leptin; Melanocortins; Neuropeptide Y; Receptor, Melanocortin, Type 4; Receptors, Dopamine D4; Receptors, Estrogen; Receptors, Serotonin; Serotonin Plasma Membrane Transport Proteins; Social Environment; Twin Studies as Topic

Patients with chronic kidney disease frequently experience loss of appetite (anorexia), which increases in severity during the progression of the disease and may lead to protein-energy wasting, morbidity, and mortality. Anorexia represents a multiple, complex, and multifactorial disorder that may have its origin in renal failure (contemplating not only retention of uremic toxins but also peptides and cytokines) but that later on also involves metabolic abnormalities not yet corrected by dialysis therapy. This paper reviews current knowledge about the clinical signs of uremic anorexia as well as mechanisms involved. Based on megestrol acetate interventions and the recent observation that sex may modulate uremic appetite behavior, the potential role of sex hormones in treating chronic kidney disease anorexia needs to be further explored.

Topics: Anorexia; Appetite; Cytokines; Feeding and Eating Disorders; Homeostasis; Humans; Intestinal Absorption; Leptin; Nitric Oxide; Uremia

The first studies about fertility and nutrition date back to the 70ies and already showed a strict relation among female fertility, weight and body composition. However, the mechanisms of this connection started to be explained only after leptin's discovery. According to some authors' opinion, leptin could interact with reproductive axis at multiple sites with stimulatory effects at the hypothalamus and pituitary and stimulatory or inhibitory actions at the gonads. Leptin could play a role in other physiologic processes such as menstruation and pregnancy, and could initiate the complex process of puberty. It has been showed that conditions in which nutritional status is suboptimal, such as eating disorders, exercise induced amenhorrea, functional hypothalamic amenhorrea and polycystic ovarian syndrome, are associated with abnormal leptin levels. These conditions, are characterized by severe changes in body composition and dietary habits. Since leptin is regulated by body composition and dietary factors, (such as energy intake and macronutrient composition), a strict connection between nutritional intake and fertility regulated by leptin is confirmed. This review focuses on the current knowledge about nutritional factors that influence leptin levels. Since clinical and subclinical nutritional imbalance can determine the development and the maintenance of neuroendocrine and metabolic aberrations, studies on fertility need a deeper attention about dietary habits and nutritional status.

Topics: Adolescent; Adult; Body Composition; Energy Intake; Feeding and Eating Disorders; Feeding Behavior; Female; Fertility; Humans; Leptin; Menstruation; Nutritional Physiological Phenomena; Nutritional Status; Pregnancy; Puberty

It is suggested that the symptoms of anorexia nervosa are physiological responses to starvation. There is no evidence of a neural or non-neural dysfunction that predisposes women for anorexia nervosa and the endocrine and psychological consequences of starvation are reversed once patients have re-learnt how to eat and regained a normal body weight. Because variability in the supply of food may be a common evolutionary condition, it is more likely that body weight is variable than constant in normal circumstances. The role of the neuroendocrine system in times of feast and famine is to allow the individual to adopt behavioral strategies as needed rather than maintaining body weight homeostasis. Treatment of anorexic patients should aim at reducing their high level of physical activity in order to facilitate eating.

Topics: Anorexia Nervosa; Feeding and Eating Disorders; Female; Humans; Leptin; Mental Disorders; Neurosecretory Systems; Oligopeptides; Pyrrolidonecarboxylic Acid; Starvation

Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics frequently produces obesity and diabetes mellitus. However, the neural mechanisms underlying the pathophysiology of these behavioral and metabolic conditions are largely unknown. In this review, we first concentrate on the established brain machinery of food intake and body weight, especially on the melanocortin and neuropeptide Y (NPY) systems as illustration. These systems play a critical role in receiving and processing critical peripheral metabolic cues such as leptin and ghrelin. It is also notable that both systems modulate emotion and motivated behavior as well. Secondly, we discuss the significance and potential promise of multidisciplinary molecular and neuroanatomic techniques that will likely increase the understanding of brain circuitries coordinating energy homeostasis and emotion. Finally, we introduce several lines of evidence suggesting a link between the melanocortin/NPY systems and several neurotransmitter systems on which many of the psychotropic agents exert their influence.

Topics: alpha-MSH; Animals; Antipsychotic Agents; Appetite Regulation; Body Weight; Diabetes Mellitus; Emotions; Energy Metabolism; Feeding and Eating Disorders; Homeostasis; Humans; Leptin; Neuropeptide Y; Obesity; RNA, Messenger

Topics: Biomarkers; Cushing Syndrome; Diabetes Mellitus, Lipoatrophic; Diagnostic Techniques, Endocrine; Enzyme-Linked Immunosorbent Assay; Feeding and Eating Disorders; Gonadal Disorders; Humans; Leptin; Metabolic Syndrome; Obesity; Radioimmunoassay; Reagent Kits, Diagnostic; Receptors, Cell Surface; Receptors, Leptin; Reference Values; Specimen Handling

Health problems resulting from obesity could offset many of the recent health gains achieved by modern medicine, and obesity may replace tobacco as the number one health risk for developed societies. An estimated 300,000 deaths per year and significant morbidity are directly attributable to obesity, mainly due to heart disease, diabetes, cancer, asthma, sleep apnea, arthritis, reproductive complications and psychological disturbances. In parallel with the increasing prevalence of obesity, there has been a dramatic increase in the number of scientific and clinical studies on the control of energy homeostasis and the pathogenesis of obesity to further our understanding of energy balance. It is now recognized that there are many central and peripheral factors involved in energy homeostasis, and it is expected that the understanding of these mechanisms should lead to effective treatments for the control of obesity. This brief review discusses the potential role of several recently discovered molecular pathways involved in the control of energy homeostasis, obesity and eating disorders.

Topics: Adiponectin; Animals; Appetite; Child; Energy Metabolism; Feeding and Eating Disorders; Ghrelin; Homeostasis; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Obesity; Peptide Fragments; Peptide Hormones; Peptide YY; Proteins

Eating disorders are a group of disease states including anorexia nervosa, bulimia nervosa and binge eating on one end as well as episodic or chronic overeating resulting in obesity at the other end of the spectrum. These disorders are characterized by decreased and/or increased energy intake and are frequently associated with hormonal and metabolic disorders. The discovery of leptin, an adipocyte-secreted hormone acting in the brain to regulate energy homeostasis, and its subsequent study in human physiology have significantly advanced our understanding of normal human physiology and have provided new opportunities for understanding and possibly treating disease states, such as anorexia and bulimia nervosa. It has been recently discovered that leptin levels above a certain threshold are required to activate the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes in men, whereas the hypothalamic-pituitary-adrenal, renin-aldosterone, and growth hormone-IGF-1 axes may be largely independent of circulating leptin levels in humans. In this review, we summarize the latest findings related to the role of leptin in the regulation of several neuroendocrine axes, such as the hypothalamic-pituitary-gonadal and the hypothalamic-pituitary-thyroid axes in humans and discuss its potential pathophysiologic role in eating disorders.

Topics: Feeding and Eating Disorders; Humans; Leptin; Neurosecretory Systems

The etiology of eating disorders has not been defined yet. It is generally thought of as multi-dimensional, consisting of socio-cultural, psychological and biological factors. The biological factors include predisposing, precipitating and perpetuating factors. In recent years, genetics have been reported as predisposing factors, various neuropeptides which play an important role in regulation of feeding behavior have been discovered to be precipitating factors, and brain imaging studies investigating morphological changes have revealed perpetuating factors. This review gives an outline of recent information about biological factors in eating disorders.

Topics: Brain; Cholecystokinin; Corticotropin-Releasing Hormone; Diagnostic Imaging; Dopamine; Estrogens; Feeding and Eating Disorders; Feeding Behavior; Gastrin-Releasing Peptide; Genetic Predisposition to Disease; Humans; Leptin; Neuropeptide Y; Polymorphism, Genetic; Serotonin

Anorexia is one of the common symptoms caused by various psychiatric disorders. Increasing evidence indicates that neuroleptics can induce weight gain, obesity, and diabetes mellitus. However, the mechanisms underlying these conditions have not been fully elucidated. In this review, we describe molecular neuroanatomic aspects of current biology of energy homeostasis that would help to address the psychiatric issues noted above, focusing on the central leptin/melanocortin system. An adipocyte-derived hormone, leptin acts on the arcuate hypothalamic nucleus (Arc) to inhibit feeding behavior and simultaneously to promote energy expenditure. Leptin activates Arc neurons producing alpha-melanocyte-stimulating hormone (alpha-MSH) and inhibits those producing agouti-related protein (AgRP). alpha-MSH is an endogenous agonist for the melanocortin-4 receptor (MC4-R) that is expressed exclusively in the central nervous system (CNS), whereas AgRP acts as a MC4-R antagonist. It is also established that MC4-R blockade produces an over-eating/obesity syndrome in rodents and humans. Thus, MC4-R-expressing neurons are downstream targets of leptin. Of interest, MC4-R-positive neurons densely populate in CNS sites critical for energy homeostasis and associated with psychiatric disorders, including the paraventricular hypothalamic nucleus and central amygdaloid nucleus. In addition, Arc alpha-MSH neurons receive serotonergic inputs from raphe neurons. Finally, an AgRP gene polymorphism has been associated with anorexia nervosa. These findings suggest that the central melanocortin system is a target for psychiatry.

Topics: Agouti-Related Protein; alpha-MSH; Amygdala; Animals; Antipsychotic Agents; Energy Intake; Energy Metabolism; Feeding and Eating Disorders; Humans; Intercellular Signaling Peptides and Proteins; Lateral Thalamic Nuclei; Leptin; Mental Disorders; Neurons; Polymorphism, Single Nucleotide; Proteins; Receptor, Melanocortin, Type 4; Receptors, Cell Surface; Receptors, Leptin; Serotonin

Leptin is the major regulator of body fat. It is a 16 kD protein released by fat cells into the blood and crosses the blood-brain barrier (BBB) to interact with its receptors at the arcuate nucleus to affect feeding, thermogenesis, and other functions. Within normal and obese body weight ranges, serum and cerebrospinal fluid (CSF) levels of leptin directly correlate with body mass index and adiposity. In animals, leptin at high levels exerts effects on appetite and at low levels informs the brain when fat reserves are adequate to switch behavioral, endocrine, and immune functions from starvation mode. Leptin offers a unique therapeutic opportunity for conditions related to body weight control, such as reversal of obesity and anorexia, and as an indirect treatment for diseases related to being over- or under-weight, such as insulin resistant diabetes and the endocrine changes accompanying starvation. In humans and in many rodent models, obesity may be a consequence of leptin resistance. More specifically, resistance likely results from an impaired transport of leptin across the BBB. Peripheral administration of native leptin results in weight reduction in moderately obese individuals and weight loss and reversal of insulin resistance and dyslipidemia in individuals with low leptin levels. The peripheral pharmacokinetic and BBB transport characteristics of native leptin suggests strategies for improving the therapeutic profile of leptin. These strategies include the development of longer lasting and more permeable analogs, development of antagonists, enhancing the activity of the leptin transporter, and delivering leptin by intrathecal administration.

Topics: Animals; Blood-Brain Barrier; Central Nervous System; Dose-Response Relationship, Drug; Drug Delivery Systems; Feeding and Eating Disorders; Humans; Leptin; Receptors, Cell Surface; Receptors, Leptin

Eating disorders are an important health concern among adolescents. Young women frequently present with signs and symptoms of anorexia nervosa and bulimia nervosa. These disorders represent clinically significant illnesses with serious and sometimes permanent medical complications, including a number of endocrine conditions, that, in general, result from the body s adaptive response to malnutrition. Examples include disorders of metabolism, cortisol and leptin regulation, fluid and electrolyte homeostasis, thyroid function, glucose regulation, growth and development, and reproductive function with the development of amenorrhea as well as the risk of osteoporosis.

Topics: Adolescent; Adult; Amenorrhea; Anorexia Nervosa; Bulimia; Diabetes Mellitus, Type 1; Diagnosis, Differential; Endocrine System Diseases; Feeding and Eating Disorders; Female; Humans; Hydrocortisone; Leptin; Osteoporosis; Thyroid Hormones; Water-Electrolyte Balance

The objective of this review article is to present the genetic abnormalities in obese animal models up to present times and to suggest the mechanism of ingestive disorder. Leptin is an anorectic ob gene product and activates the anorexigenic POMC and CART neurons in the ARC and suppresses orexigenic NPY and AGRP neurons. TUB gene product also activates the anorexigenic POMC neurons. These anorexigenic neurons project to the second-order hypothalamic neuron, CRH, TRH and so on in the PVN and suppression of orexigenic neurons project to the orexin in the LHA.

Topics: Animals; Disease Models, Animal; Feeding and Eating Disorders; Leptin; Mice; Mice, Obese; Obesity; Rats; Rats, Zucker

Leptin is a 16-kDa adipocyte-secreted protein the serum levels of which reflect mainly the amount of energy stores but are also influenced by short-term energy imbalance as well as several cytokines and hormones. Leptin, by binding to specific receptors, alters the expression of several hypothalamic neuropeptides that regulate neuroendocrine function as well as energy intake and expenditure. More specifically, accumulating evidence suggests that this hormone may serve to signal to the brain information on the critical amount of fat stores that are necessary for LHRH secretion and activation of the hypothalamic-pituitary-gonadal axis. Rising leptin levels have been associated with initiation of puberty in animals and humans and normal leptin levels are needed for maintenance of menstrual cycles and normal reproductive function. Moreover, circadian and ultradian variations of leptin levels are associated with minute to minute variations of LH and estradiol in normal women. Falling leptin levels in response to starvation result in decreased estradiol levels and amenorrhea in subjects with anorexia nervosa or strenuously exercising athletes. In addition, leptin has a potentially important role during pregnancy and in the physiology of the neonate. Finally, recent evidence suggests that leptin may influence ovarian steroidogenesis directly, but the exact role of intraovarian leptin action in the physiology and pathophysiology of the human reproductive system needs to be further elucidated.

Topics: Feeding and Eating Disorders; Female; Humans; Infant, Newborn; Leptin; Obesity; Pregnancy; Pregnancy Complications; Puberty; Reproduction

Leptin, the ob gene product, is involved in the regulation of body weight in rodents, primates and humans. It provides a molecular basis for the lipostatic theory of the regulation of energy balance. White adipose tissue and placenta are the main sites of leptin synthesis. There is also evidence of ob gene expression in brown fat. Leptin seems to play a key role in the control of body fat stores by coordinated regulation of feeding behaviour, metabolic rate, autonomic nervous system regulation and body energy balance. Apart from the function of leptin in the central nervous system on the regulation of energy balance, it may well be one of the hormonal factors that signal to the brain the body's readiness for sexual maturation and reproduction. During late pregnancy and at birth when maternal fat stores have been developed, leptin levels are high. During these developmental stages leptin could be a messenger molecule signalling the adequacy of the fat stores for reproduction and maintenance of pregnancy. At later stages of gestation leptin could signal the expansion of fat stores in order to prepare the expectant mother for the energy requirements of full-term gestation, labour and lactation. Leptin serum concentrations change during pubertal development in rodents, primates and humans. In girls, leptin serum concentrations increase dramatically as pubertal development proceeds. The pubertal rise in leptin levels parallels the increase in body fat mass. In contrast, leptin levels increase shortly before and during the early stages of puberty in boys and decline thereafter. Testosterone has been found to suppress leptin synthesis by adipocytes both in vivo and in vitro. The decline of leptin levels in late puberty in boys accompanies increased androgen production during that time and most likely reflects suppression of leptin by testosterone and a decrease in fat mass and relative increase in muscle mass during late puberty in males. This overview focuses on those topics of leptin research which are of particular interest in reproductive and adolescent medicine.

Topics: Animals; Feeding and Eating Disorders; Female; Humans; Leptin; Male; Menstrual Cycle; Pregnancy; Puberty; Reproduction; Sexual Maturation

The discovery of leptin, the product of the obese (ob)-gene, has broadened the horizons of research on energy balance. This hormone, produced and secreted by adipose tissue and some placental cells, finds its way to the hypothalamus, where it binds to the leptin receptors and signals satiety through the neuroendocrine axis. The fact that adipose tissue is not merely a storage depot, but also an important endocrine tissue, has revived the interest in the "lipostatic" theory of body fat regulation and has initiated many research efforts in the field of obesity, anorexia nervosa, bulimia, reproduction and haematology.

Topics: Adipose Tissue; Animals; Carrier Proteins; Feeding and Eating Disorders; Humans; Hypothalamus; Leptin; Neurosecretory Systems; Obesity; Proteins; Receptors, Cell Surface; Receptors, Leptin

Topics: Adipose Tissue; Adolescent; Adult; Androgens; Child; Feeding and Eating Disorders; Female; Humans; Infertility; Leptin; Male; Obesity; Proteins; Reference Values

Serotonin (5-HT) has been implicated in the control of eating behavior and body weight. Stimulants of this monoamine reduce food intake and weight gain and increase energy expenditure, both in animals and in humans. This article reviews evidence that supports a role for hypothalamic serotonergic receptor mechanisms in the mediation of these effects. A variety of studies in rodents indicate that, at low doses, 5-HT or drugs that enhance the release of this neurotransmitter preferentially inhibit the ingestion of carbohydrate, more than fat or protein. This phenomenon is mediated, in part, by 5-HT receptors located in various medial hypothalamic nuclei. A negative feedback loop exists between the consumption of this macronutrient and the turnover of 5-HT in the hypothalamus. That is, carbohydrate ingestion enhances the synthesis and release of hypothalamic 5-HT, which in turn serves to control the size of carbohydrate-rich meals. A model is described that proposes the involvement of circulating hormones and glucose in this feedback process. These hormones, including insulin, corticosterone, and the adipose tissue-derived hormone, leptin, have impact on serotonergic function as well as satiety. This model further suggests that 5-HT exerts its strongest effect on appetite at the start of the natural feeding cycle, when carbohydrate is normally preferred. Clinical studies provide evidence that is consistent with the proposed model and that implicates 5-HT in disturbances of eating and body weight disorders.

Topics: Animals; Appetite Regulation; Body Weight; Choice Behavior; Circadian Rhythm; Dietary Carbohydrates; Dietary Fats; Disease Models, Animal; Eating; Energy Metabolism; Feedback; Feeding and Eating Disorders; Feeding Behavior; Humans; Hypothalamus; Leptin; Models, Neurological; Obesity; Proteins; Receptors, Serotonin; Satiation; Serotonin; Serotonin Agents; Sex Factors

Metreleptin treatment in lipodystrophy patients improves eating behavior with increased satiety and reduced hunger. However, no data are available whether effects are maintained beyond 52 weeks of treatment.. A prospective study with measurements at baseline and at >150 weeks of metreleptin treatment was performed. Five female lipodystrophy patients with indication for metreleptin were included. Behavioral aspects of hunger- and satiety regulation were assessed by validated eating behavior questionnaires and visual analog scales assessing hunger and satiety feelings before and after a standardized meal.. Hunger rated on visual analog scales at 120 min after the meal significantly decreased from 46 ± 10 mm at baseline to 17 ± 6 mm at long-term assessment. Furthermore, satiety at 5 and 120 min after the meal significantly increased from baseline to long-term assessment (5 min: 70 ± 7 mm to 87 ± 3 mm; 120 min: 43 ± 10 mm to 79 ± 8 mm). On the Three Factor Eating Questionnaire, the mean value of factor 3 (hunger) significantly decreased from 9.2 ± 0.2 at baseline to 2.6 ± 1.5 at long-term assessment. In the Inventory of Eating Behavior and Weight Problems Questionnaire, mean values for scale 2 (strength and triggering of desire to eat) and scale 7 (cognitive restraint of eating) significantly decreased from baseline (31.6 ± 4.8 and 11.4 ± 2.2, respectively) to long-term assessment (14.0 ± 2.1 and 10.0 ± 1.9).. First evidence is presented that long-term metreleptin treatment of >150 weeks has sustained effects on eating behavior with increased satiety, as well as reduced hunger and hunger-related measures.

Topics: Adult; Feeding and Eating Disorders; Feeding Behavior; Female; Humans; Hunger; Leptin; Lipodystrophy; Middle Aged; Surveys and Questionnaires

Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove definitively a causal role of leptin in the pathogenesis of HA, we performed a randomized, double-blinded, placebo-controlled trial of human recombinant leptin (metreleptin) in replacement doses over 36 wk in women with HA. We assessed its effects on reproductive outcomes, neuroendocrine function, and bone metabolism. Leptin replacement resulted in recovery of menstruation and corrected the abnormalities in the gonadal, thyroid, growth hormone, and adrenal axes. We also demonstrated changes in markers of bone metabolism suggestive of bone formation, but no changes in bone mineral density were detected over the short duration of this study. If these data are confirmed, metreleptin administration in replacement doses to normalize circulating leptin levels may prove to be a safe and effective therapy for women with HA.

Topics: Adolescent; Adult; Amenorrhea; Eating; Feeding and Eating Disorders; Female; Humans; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Leptin; Pituitary-Adrenal System; Time Factors

The aim of the present study was to determine the factors controlling leptin secretion and to clarify the role of leptin in eating disorders. The subjects were 152 eating-disordered women with different fat mass, eating behavior, and endocrine abnormalities and 24 age-matched control subjects. The body fat mass, eating behavior score, and plasma leptin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), triiodothyronine (T3), free thyroxine (T4), insulin, and cortisol levels were evaluated for each subject. In patients with eating disorder, logarithmic values for leptin were significantly correlated with the body fat mass (r = .828, P < .001), eating behavior score (r = .777, P < .001), and LH (r = .465, P < .001), FSH (r = .440, P < .001), T3 (r = .572, P < .001), insulin (r = .410, P < .001), and cortisol (r = -.389, P < .001) levels. After adjusting for fat mass, the partial correlations of log leptin with LH, FSH, insulin, and cortisol were not statistically significant, but log leptin remained correlated with T3 (r = .390, P < .01). Stepwise regression analysis showed that the body fat mass and eating behavior score were significant determinants of leptin levels. These results suggest that eating behavior, as well as the body fat mass, is the control factor for leptin secretion in eating disorders.

Topics: Adipose Tissue; Adult; Anorexia Nervosa; Body Composition; Bulimia; Feeding and Eating Disorders; Female; Hormones; Humans; Leptin; Proteins

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

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

With this case report we support our medical hypothesis that metreleptin treatment ameliorates starvation related emotional, cognitive and behavioral symptomatology of anorexia nervosa (AN) and show for the first time strong effects in a male patient with AN. A 15.9 year old adolescent with severe AN of eight-month duration was treated off-label with metreleptin. Hyperactivity was assessed with accelerometry. Visual analogue scales (VAS), validated self- and clinician rating scales and lab results tracked changes from baseline to end of the 24-day dosing period and a five-month follow-up. Substantial improvements of mood and eating disorder related cognitions and hyperactivity set in after two days of treatment. During dosing, sub-physiological testosterone and TT3 levels normalized; clinically libido reemerged. Weight did not increase substantially during the dosing period. During follow-up target weight was attained; mood did not deteriorate; hyperactivity ceased. The results substantiate the strong effects seen in female cases and underscore the need for a double-blind placebo-controlled trial to confirm the observed strong, multiple and rapid onset beneficial effects of metreleptin in AN.

Topics: Adolescent; Anorexia Nervosa; Feeding and Eating Disorders; Female; Humans; Hypogonadism; Leptin; Male; Testosterone

Eating disorders (EDs) are increasingly frequent. Their pathophysiology involves disturbance of peptide signaling and the microbiota-gut-brain axis. This study analyzed peptides and corresponding immunoglobulin (Ig) concentrations in groups of ED. In 120 patients with restrictive (R), bulimic (B), and compulsive (C) ED, the plasma concentrations of leptin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and insulin were analyzed by Milliplex and those of acyl ghrelin (AG), des-acyl ghrelin (DAG), and α-melanocyte-stimulating hormone (α-MSH) by ELISA kits. Immunoglobulin G (in response to an antigen) concentrations were analyzed by ELISA, and their affinity for the respective peptide was measured by surface plasmon resonance. The concentrations of leptin, insulin, GLP-1, and PYY were higher in C patients than in R patients. On the contrary, α-MSH, DAG, and AG concentrations were higher in R than in C patients. After adjustment for body mass index (BMI), differences among peptide concentrations were no longer different. No difference in the concentrations of the IgG was found, but the IgG concentrations were correlated with each other. Although differences of peptide concentrations exist among ED subtypes, they may be due to differences in BMI. Changes in the concentration and/or affinity of several anti-peptide IgG may contribute to the physiopathology of ED or may be related to fat mass.

Topics: Body Mass Index; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Feeding and Eating Disorders; Female; France; Glucagon-Like Peptide 1; Humans; Immunoglobulin G; Insulin; Leptin; Longitudinal Studies; Male; Peptide YY; Peptides

In this study, we evaluated the changes in leptin and ghrelin concentrations, eating behavior, depression, and impulsivity and their correlations within the luteal phase among women with premenstrual dysphoric disorder (PMDD).. In 63 women with PMDD and 53 healthy controls, we prospectively evaluated serum levels of leptin and ghrelin, Body Mass Index(BMI), and self-reported sweet cravings, cognitive restraint, uncontrolled eating, emotional eating, depression, and impulsivity during the early luteal (EL) and late luteal (LL) phases.. Compared with the controls, the women with PMDD had higher BMI, higher leptin concentrations in the EL and LL phase, and leptin concentrations increased from the EL to the LL phase. However, there is no significant difference in ghrelin. Women with PMDD increased sweet cravings and uncontrolled eating from EL to LL phase. No significant correlation was observed between the EL-LL changes in leptin or ghrelin concentrations and those in eating behaviors. Both depression and impulsivity correlated with sweet craving and uncontrolled eating. Depression mediated the association between PMDD and uncontrolled eating. The BMI of women with PMDD positively correlated with their EL-LL change in leptin, and LL depression levels and emotional eating.. Young women with PMDD had higher leptin concentrations and BMI in the luteal phase. The LL leptin level was not the primary factor responsible for the increased uncontrolled eating of PMDD. Whether the increased eating and depression in the LL phase contribute to the risk of obesity or hyperleptinemia among women with PMDD need to be evaluated in the future.

Topics: Adult; Body Mass Index; Case-Control Studies; Emotions; Feeding and Eating Disorders; Feeding Behavior; Female; Ghrelin; Humans; Leptin; Luteal Phase; Premenstrual Dysphoric Disorder; Young Adult

It has been hypothesized that leptin level alterations in Eating Disorders (EDs) represent a maintaining factor for pathological reward-related ED behaviors, given leptin role in the dopaminergic reward systems. The aim of the present study was to evaluate the role of leptin in EDs as a mediator for the relationship between Body Mass Index (BMI) and several pathological behaviors, such as dietary restraint, compensatory exercise, vomiting, binge eating and emotional eating. Sixty-two patients with EDs and 41 healthy controls (HC) had their blood drawn and completed psychometric tests for the evaluation of general psychopathology, ED psychopathology and emotional eating. Moderated linear regression models showed that, in the presence of high levels of ED psychopathology, leptin levels were negatively associated with dietary restraint and compensatory exercise, and positively with emotional eating and binge eating. Finally, leptin showed an indirect effect on the association between BMI and all these reward-related behaviors. These results suggest that a variation of BMI maintains these pathological ED behaviors through a variation in leptin levels. Considering the role of leptin in reward circuits, the results seem to confirm an aberrant food-related reward mechanism in ED patients.

Topics: Adult; Anorexia Nervosa; Binge-Eating Disorder; Body Mass Index; Body Weight; Bulimia; Case-Control Studies; Emotions; Exercise; Feeding and Eating Disorders; Female; Food; Humans; Leptin; Male; Psychopathology; Reward

Eating disorders (ED) are characterized by disruption of eating behaviour and alteration of food intake. Leptin, is one of the main hormones that modulate food intake and are altered in individuals diagnosed with ED. Genetic risk variants for obesity, like those reported inFTO and ABCA1, have also been associated to ED disorders. The present study aimed to analysed leptin circulating levels and the interaction between obesity-risk variants in FTO and ABCA1, in adolescents diagnosed with ED. A total of 99 individuals diagnosed with ED were genotype using Taqman probes for FTO (rs9939609) and ABCA1 (p.Arg230Cys, rs9282541). Commercial enzyme-linked immunosorbent assays were utilized to determined circulating leptin. Differences in leptin concentration were analysed by t-Student or ANOVA test. Gene-gene interaction were analysed using general estimation equations. Circulating leptin levels differed between the three diagnostic groups, lead by individuals diagnosed with binge eating-disorder. In individuals with more than 3 of episodes of binge-eating per week having the highest leptin levels. Also, we found that carriers of both risk alleles had the highest leptin levels. Our observations found an interaction between FTO rs9969609 and the native American-origin ABCA1 p.Arg230Cys to modulate circulating leptin levels in Mexican adolescents diagnosed with eating-disorders.

Topics: Adolescent; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; American Indian or Alaska Native; ATP Binding Cassette Transporter 1; Biomarkers; Epistasis, Genetic; Feeding and Eating Disorders; Female; Humans; Leptin; Male; Mexico; Obesity; Polymorphism, Single Nucleotide

Loss of control (LOC) eating in youth is associated with elevated fasting serum leptin, even after accounting for adiposity. Anxiety is closely linked to, and may exacerbate, LOC eating. Yet, it remains unclear how anxiety relates to leptin, or if the relationship is moderated by the presence of LOC eating. We examined whether self-reported trait anxiety interacted with LOC eating in relation to leptin in a convenience sample of youths (

Topics: Adiposity; Adolescent; Anxiety; Body Mass Index; Child; Fasting; Feeding and Eating Disorders; Feeding Behavior; Female; Humans; Leptin; Linear Models; Male

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

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

This study is an investigation of neuropsychological performance in patients with anorexia nervosa, bulimia nervosa, and binge eating disorder and hormonal secretion patterns for ghrelin, leptin, insulin, and glucose. An oral glucose tolerance test (OGTT) was performed in a cohort of n = 30 female patients suffering from eating disorders as well as n = 20 control females. All participants underwent the Wisconsin Card Sorting Test (WCST), the Trail Making Test (TMT), and a go/no-go task using food vs. neutral stimuli. Patients with anorexia nervosa differed from controls in their leptin response to the OGTT. While the four groups under investigation did not differ in neuropsychological performance, we found leptin responses to the OGTT to be associated with performance in the food-specific go/no-go task. These preliminary results may indicate a putative association between leptin concentrations and neuropsychological performance, particularly in measures of inhibitory control. Further studies investigating the role of leptin in impulsive behaviors in eating disorders would be useful.

Topics: Adult; Anorexia Nervosa; Binge-Eating Disorder; Blood Glucose; Bulimia Nervosa; Cognition; Feeding and Eating Disorders; Female; Food; Ghrelin; Glucose Tolerance Test; Humans; Insulin; Leptin; Task Performance and Analysis; Young Adult

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

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

Leptin secretory dynamics across the weight spectrum and their relationship with disordered eating psychopathology have not been studied. Our objective was to compare leptin secretory dynamics in 13 anorexia nervosa (AN), 12 overweight/obese (OB) and 12 normal-weight women using deconvolution analysis.. In this cross-sectional study conducted at a tertiary referral center, serum leptin levels were obtained every 20  min from 2000 to 0800  h. Dual energy X-ray absorptiometry was used to measure percent body fat. Disordered eating psychopathology was assessed by the Eating Disorders Examination-Questionnaire (EDE-Q) and the Eating Disorders Inventory-2 (EDI-2).. The groups differed for basal leptin secretion (BASAL) (P=0.02). Mean leptin pulse amplitude, pulse mass, total pulsatile secretion (TPS) and area under the curve (AUC) were significantly different between groups before and after adjustment for BASAL (P<0.0001 for all). Leptin AUC correlated strongly with TPS (r=0.97, P<0.0001) and less with BASAL (r=0.35, P=0.03). On multivariate analysis, only TPS was a significant predictor of leptin AUC (P<0.0001). TPS was inversely associated with most EDE-Q and EDI-2 parameters and the associations remained significant for EDE-Q eating concern (P=0.01), and EDI-2 asceticism, ineffectiveness and social insecurity (P<0.05) after adjusting for BASAL. These relationships were not significant when controlled for percent body fat.. Secretory dynamics of leptin differ across weight spectrum, with mean pulse amplitude, mean pulse mass and TPS being low in AN and high in OB. Pulsatile, rather than basal secretion, is the major contributor to leptin AUC. Decreased pulsatile leptin is associated with disordered eating psychopathology, possibly reflecting low percent body fat in AN.

Topics: Adiposity; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Case-Control Studies; Cross-Sectional Studies; Feeding and Eating Disorders; Female; Humans; Leptin; Obesity; Overweight; Thinness; Young Adult

This study examined the relationship between hypothalamic-associated hormones and behavioural and eating disorders in children with low birthweight.. We included 100 children (mean age 9.7 years): 39 were born preterm at <32 gestational weeks, 28 were full-term, but small for gestational age, and 33 were full-term controls. Behavioural histories were analysed, together with fasting blood samples of leptin, insulin, insulin-like growth factor-1 (IGF-I), prolactin, glucagon and cortisol.. Preterm children had lower prolactin (p = 0.01) and higher IGF-I than controls (p < 0.05, adjusted for confounders), despite being significantly shorter than the predicted target height (p < 0.001). More preterm children displayed behavioural disorders (38% versus 10%, p < 0.001) and eating disorders (26% versus 8%, p < 0.05) than full-term children. These disorders were associated with lower leptin (p < 0.01), insulin (p < 0.05) and IGF-I (p < 0.05), but correlations between these hormones and leptin were similar among the groups. Combined behavioural and eating disorders were only observed in preterm children, who were also the shortest in height.. Behavioural and eating disorders among preterm children were associated with low leptin, insulin and IGF-1. Low prolactin in all preterm children indicated an increased dopaminergic tonus, which might inhibit body weight incrementation. This raises speculation about IGF-I receptor insensitivity.

Topics: Child; Child Behavior Disorders; Feeding and Eating Disorders; Female; Gestational Age; Humans; Infant, Premature; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Prolactin

We undertook analysis of clinical and instrumental features of gallbladder pathology in patients with a weight deficit for the elucidation of peculiarities of eating behavior, blood leptin level, and cytokine content of gastric biopsies. Underweight patients with inflammatory and dysfunctional diseases of gallbladder more frequently than others presented with abdominal pain syndrome. All patients enrolled in the study showed every type of eating disorders with the predominance of the limiting behavior. Weight deficit in patients with chronic cholecystitis was associated with hyperleptinemia and increased production of proinflammatory cytokines.

Topics: Adult; Cytokines; Feeding and Eating Disorders; Female; Gallbladder Diseases; Humans; Leptin; Male; Thinness; Ultrasonography

Disordered eating occurs in women at both weight extremes of anorexia nervosa (AN) and obesity. Cortisol, peptide YY (PYY), leptin, and ghrelin are hormones involved in appetite and feeding behavior that vary with weight and body fat. Abnormal levels of these hormones have been reported in women with AN, functional hypothalamic amenorrhea (HA), and obesity. The relationship between appetite-regulating hormones and disordered eating psychopathology is unknown. We therefore studied the relationship between orexigenic and anorexigenic hormones and disordered eating psychopathology in women across a range of weights.. A cross-sectional study of 65 women, 18-45 years: 16 with AN, 12 normal-weight with HA, 17 overweight or obese, and 20 normal-weight in good health.. Two validated measures of disordered eating psychopathology, the Eating Disorders Examination-Questionnaire (EDE-Q) and Eating Disorders Inventory-2 (EDI-2), were administered. Fasting PYY, leptin, and ghrelin levels were measured; cortisol levels were pooled from serum samples obtained every 20 min from 2000 to 0800 h.. Cortisol and PYY levels were positively associated with disordered eating psychopathology including restraint, eating concerns, and body image disturbance, independent of body mass index (BMI). Although leptin levels were negatively associated with disordered eating psychopathology, these relationships were not significant after controlling for BMI. Ghrelin levels were generally not associated with EDE-Q or EDI-2 scores.. Higher levels of cortisol and PYY are associated with disordered eating psychopathology independent of BMI in women across the weight spectrum, suggesting that abnormalities in appetite regulation may be associated with specific eating disorder pathologies.

Topics: Adolescent; Adult; Analysis of Variance; Body Image; Body Mass Index; Cross-Sectional Studies; Feeding and Eating Disorders; Female; Ghrelin; Humans; Hydrocortisone; Leptin; Middle Aged; Peptide YY; Radioimmunoassay; Surveys and Questionnaires

Inflammation and loss of appetite is the most common problem in patients with chronic kidney disease (CKD). This comparative cross-sectional study aimed to characterize the changes in circulating levels of ghrelin, obestatin, leptin, all of which have an effect on food intake, and proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) in patients with CKD who were undergoing different treatments.. Study participants included 36 patients who had undergone hemodialysis (body mass index [BMI]: 22.3 ± 4.17 kg/m(2)); 41 who had undergone peritoneal dialysis (BMI: 23.5 ± 3.10 kg/m(2)), 30 with early stage CKD (BMI: 24.4 ± 3.32 kg/m(2)), and 31 healthy subjects (24.3 ± 2.14 kg/m(2)). The patients with CKD were kept under a standard diet with restricted salt, potassium, and protein intake.. Levels of leptin, acylated ghrelin, obestatin, TNF-α, and IL-6 were measured by commercially available enzyme-linked immunosorbent assay kits. Total nitrite/nitrate was analyzed using colorimetric assay kit.. Significantly high leptin levels, accompanied by low acylated ghrelin levels, were observed in patients with CKD. Maintenance dialysis did not affect these levels. TNF-α and IL-6 levels were significantly higher in CKD patients than in healthy subjects, the highest being in dialysis patients. Obestatin levels were relatively low in patients who had undergone hemodialysis.. Low acyl-ghrelin levels, accompanied with high levels of TNF-α and IL-6 may be involved in the loss of appetite and poor nutritional status in CKD patients.

Topics: Adolescent; Adult; Aged; Appetite; Body Mass Index; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Feeding and Eating Disorders; Female; Ghrelin; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nitrates; Nitrites; Nutritional Status; Renal Dialysis; Tumor Necrosis Factor-alpha; Young Adult

Alcoholism is associated with alterations of the hypothalamus-pituitary-gonadal hormone axis. We recently reported a leptin-mediated relation between the CAGn polymorphism of the androgen receptor and craving during alcohol withdrawal. This study investigated whether the TTTAn polymorphism of the aromatase (CYP19A1) is equally linked to craving. An association between TTTAn and compulsive craving (p=0.029) was revealed in our sample of 118 male alcohol addicts at day of hospital admission. Genotype-dependent subgroups showed differences in that the patients with short alleles suffered from lower compulsive craving during withdrawal than those with the longer alleles (p=0.027). The additional inclusion of leptin revealed no further significant association in the present study. Our finding is a further step on the way to elucidate the genesis of craving for alcohol with its extensive underlying interactions of different genetic and non-genetic factors. Future investigations should enrol women and consider sex hormone levels for further clarification of the observed TTTAn-craving relationship.

Topics: Alcoholism; Aromatase; Case-Control Studies; Compulsive Behavior; Feeding and Eating Disorders; Feeding Behavior; Gene Frequency; Genotype; Humans; Leptin; Male; Middle Aged; Patient Admission; Polymorphism, Genetic; Repetitive Sequences, Nucleic Acid; Sex Factors; Substance Withdrawal Syndrome

The purpose of the study was to identify diagnostic criteria that can distinguish between subjects with functional hypothalamic amenorrhea largely related to minimal energy deficiency and those in whom failure of adaptive response to stress prevails. We studied 59 young women with secondary amenorrhea related to modest eating disorders and 58 who complained of stressful events in their history. We assessed anthropometric measurements, body composition using dual energy X-ray absorptiometry (DEXA) and bioelectrical impedance analysis (BIA), and basal endocrine profile. Subjects with disordered eating had lower body mass index (BMI), fat mass (FM) measured with both techniques, lumbar mineral density and direct and indirect measures of lean mass. Leptin and free tri-iodothyronine(FT(3)) concentrations also proved lower in the group of subjects with eating disorders, although there was no significant difference in cortisol between the two groups. Leptin levels were positively associated not only with fat mass, but also with body cell mass indexed to height and phase angle, parameters studied with BIA as expression of active lean compartment. A multivariate model confirmed the utility of integrating endocrine data with the study of body composition. The use of bioelectrical impedance analysis proved to be, in clinical use, a valid diagnostic alternative to DEXA, especially considering body cell mass and phase angle.

Topics: Absorptiometry, Photon; Adaptation, Psychological; Adiposity; Adolescent; Adult; Amenorrhea; Body Composition; Body Mass Index; Bone Density; Electric Impedance; Feeding and Eating Disorders; Female; Humans; Hypothalamo-Hypophyseal System; Leptin; Lumbar Vertebrae; Multivariate Analysis; Stress, Psychological; Triiodothyronine; Young Adult

Apart from energy homeostasis leptin has been shown to be involved in a number of neuronal networks. The aim of this study was to investigate how the residual variance of leptin levels, after controlling for BMI, is linked to eating-disorder-specific psychopathology and sexual desire in patients with anorexia nervosa (AN) compared to healthy controls. The sample included 57 subjects with acute AN and 77 healthy controls. Psychopathology was determined by EDI-2 and SCL-90-R and sexual problems were rated according to the Structured Interview of Anorexia Nervosa and Bulimic Syndromes (SIAB-EX). Plasma leptin was assessed by ELISA. Patients with a high drive for thinness had lower leptin levels at a given BMI and low leptin levels were associated with sexual problems, i.e. the absence of sexual desire and intimate relationships. Our results are in accordance with recent animal experiments linking low leptin levels with decreased sexual interest irrespective of body weight.

Topics: Adolescent; Adult; Body Mass Index; Child; Enzyme-Linked Immunosorbent Assay; Feeding and Eating Disorders; Female; Humans; Leptin; Middle Aged; Models, Psychological; Psychopathology; Sexual Dysfunction, Physiological; Statistics, Nonparametric; Young Adult

Topics: Adult; Feeding and Eating Disorders; Humans; Hypogonadism; Leptin; Male; Osteoporosis

Patients with eating disorders often exhibit abnormal eating conditions like food restriction, adipocyte and body weight reduction, and pathologic anxiety-like behavior. The role of leptin, which is recognized as an adipocyte-derived hormone, on anxiety-like behavior in eating disorders is still unclear.. We investigated the role of leptin on anxiety-like behavior with or without semi-starvation using the elevated plus-maze test in adolescent female rats. In our first experiment, anxiety-like behavior was evaluated with the elevated plus-maze test 30 min after intracerebroventricular administration of 3 microg of leptin or vehicle. In our second experiment, the rats were allowed access to food for only 2 hr each day for 7 days. Then, leptin or vehicle was administered to the rats after the last 2 hr feeding period, and anxiety-like behaviors were evaluated in the same way as in the first experiment.. In the first experiment, there was no difference between the anxiety-like behaviors observed after leptin administration and those seen after vehicle administration. Under the conditions of semi-starvation, however, the percentage of time spent in the open arms in the rats given leptin was lower than that in rats given vehicle.. These results suggest that leptin administration causes anxiety-like behavior only after semistarvation. Leptin might play an important role in pathologic anxiety-like behavior in eating disorders.

Topics: Animals; Anorexia Nervosa; Anxiety; Corticotropin-Releasing Hormone; Estrus; Feeding and Eating Disorders; Female; Injections, Intraventricular; Leptin; Maze Learning; Rats; Rats, Wistar; Starvation

Leptin is a protein hormone controlling food intake and energy expenditure. In all infections including parasitic infections there is loss of appetite and anorexia. The aim of the present study was to clarify the relationship between intestinal parasites and serum leptin concentrations in children and adults. Forty patients with intestinal parasites and 34 healthy subjects took part in this study. Body weight, height and body mass index (BMI) were measured for all patients and controls. Patients were grouped according to age and parasitic infections (Giardia intestinalis, Blastocystis hominis, Enterobius vermicularis, Entamoeba histolytica/Entamoeba dispar, Entamoeba coli). Serum leptin concentrations were detected by immunoenzymometric assay using the Biosource Leptin EASIA kit. Statistical analysis was made by Mann-Whitney-U test using SPSS version 10.0. In children, the serum leptin levels were not statistically significant (patient: 1.49+/-1.97 ng/ml, control: 3.48+/-4.97; p=0.854) But for adults, although the BMI of patients were similar to that of the control group; the leptin levels of patients were low. These levels were not significant (patients: 9.06+/-10.34; controls: 4.7+/-9.02 ng/ml; p=0.271). There was no statistical difference for leptin levels in patient groups, children and adults due to intestinal parasitic infections. Further investigations are needed.

Topics: Adolescent; Adult; Age Factors; Blastocystis Infections; Body Mass Index; Body Weight; Child; Child, Preschool; Dysentery, Amebic; Enterobiasis; Feeding and Eating Disorders; Female; Giardiasis; Humans; Intestinal Diseases, Parasitic; Leptin; Male; Middle Aged; Young Adult

The eating disorders (ED) anorexia nervosa (AN) and bulimia nervosa (BN) are important psychiatric and somatic conditions occurring mainly in young women. The aetiology is unknown, but there are social, biological and psychological factors that play a relevant role in the pathogenesis, along with multiple endocrine abnormalities. Hypothalamic monoamines (especially serotonin), neuropeptides (especially neuropeptide Y and cholecystokinin) and leptin are involved in the regulation of the human appetite. ED share with migraine the same metabolic profile and aspect of psychiatric and psychological conditions. In support of this hypothesis in one study, it has been shown that the incidence of migraine is high in these patients; and it has been shown that the incidence in a female group that suffers from migraine was greater than in the normal population. In order to understand the possible relationship between migraine and ED, we have investigated the incidence of primary headache in a group of AN and BN patients. The result of this study shows that the prevalence of migraine in women affected by AN and BN is very high (75%) in comparison to the general population (12.5% headache incidence in normal population). In most patients the onset of migraine attacks began before or at the same time as the symptoms of AN and BN. We suggest that migraine is a predisposing condition for the occurence of AD in young women.

Topics: Adolescent; Adult; Biogenic Monoamines; Feeding and Eating Disorders; Female; Headache; Humans; Hypothalamus; Incidence; Leptin; Middle Aged; Neuropeptides

Ghrelin and leptin play important roles in the physiopathology of eating disorders, starting generally in infancy and adolescence. The aim of this study was to evaluate the effects of multidisciplinary short-term therapy on ghrelin and leptin concentrations, bulimia nervosa symptoms, binge eating disorder symptoms, body composition, and visceral and subcutaneous fat in obese adolescents.. Twenty obese adolescents with simple obesity (BMI >95th percentile, 36.93 +/- 4.14, CDC) were submitted to multidisciplinary (nutrition, psychology, exercise and clinical) therapy. Plasma ghrelin and leptin concentrations were measured by radioimmunoassay. Bulimic and binge eating behaviors were measured by the Bulimic Investigation Test Edinburgh and the Binge Eating Scale, respectively. Visceral and subcutaneous fat were measured by ultrasonography and body composition by plethysmography.. Significant reductions were observed in body weight (101.04 +/- 11.18 to 94.79 +/- 10.94 kg), BMI (36.93 +/- 4.14 to 34.27 +/- 4.78), fat% (41.96 +/- 6.28 to 39.14 +/- 7.62%), visceral fat (4.34 +/- 1.53 to 3.41 +/- 1.12 cm), leptin concentration (20.12 +/- 6.47 to 16.68 +/- 8.08 ng/ml), prevalence of bulimia nervosa (100 to 67%) and binge eating disorder symptoms (40 to 17%).. Short-term multidisciplinary therapy was effective in improving body composition, visceral fat, leptinemia and eating disorders in obese adolescents.

Topics: Adolescent; Adult; Body Composition; Brazil; Bulimia; Bulimia Nervosa; Combined Modality Therapy; Feeding and Eating Disorders; Female; Ghrelin; Humans; Leptin; Male; Obesity; Physical Therapy Modalities; Psychotherapy

The aim of the present study was to investigate the anthropometric and endocrine characteristics of subjects with amenorrhea related to eating disorders after weight recovery, in order to identify factors connected with the resumption of menses.. Clinical data, body composition parameters and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, cortisol, leptin and insulin were assessed in two groups of young women classified according to menstrual status after weight rehabilitation: 43 subjects who displayed persistent amenorrhea and 34 who resumed menses. Univariate and multivariate logistic regression analyses were used to examine the relationships between the different parameters and menstrual recovery.. The patients who resumed menses had low initial weight and BMI, and a greater difference between current and initial BMI (DeltaBMI), than those with amenorrhea. No differences were observed in lean mass, body fat or bone density between the two groups. Moreover, the reduction in FSH and the increase in LH, insulin and leptin emerged as significant predictors of menstrual recovery. Increased DeltaBMI and insulin continued to be positive predictors in the multivariate analysis.. Following weight rehabilitation, the individual's metabolic set point before weight loss and the current insulin levels appear significant in predicting the reactivation of reproductive function.

Topics: Adolescent; Adult; Amenorrhea; Body Composition; Body Mass Index; Feeding and Eating Disorders; Female; Follicle Stimulating Hormone; Humans; Hydrocortisone; Insulin; Leptin; Luteinizing Hormone; Menstruation; Ovary; Prognosis; Recovery of Function; Thyroid Hormones; Weight Gain; Young Adult

Topics: Brain; Cannabinoid Receptor Modulators; Eating; Energy Metabolism; Feeding and Eating Disorders; Ghrelin; Humans; Hypothalamus; Leptin; Neurobiology; Neurophysiology; Neurotransmitter Agents; Serotonin

The purpose of this study was to determine the association between drive for thinness (DT) and adaptations to energy deficiency in exercising women. This observational study evaluated psychometric and metabolic factors in sedentary (n=9, 27.9+/-2.0 yr) and exercising women (n=43, 24.0+/-1.1 yr). Volunteers were retrospectively grouped according to exercise status (sedentary or exercising) and a DT score of normal (sedentary or exercising) or high (exercising only). Resting energy expenditure (REE) and metabolic hormones (triiodothyronine, (TT3), ghrelin, leptin, insulin) were measured repeatedly over a 2-3 month period. The DT subscale successfully discriminated the groups based on energy status. Although the groups did not differ in body weight, the high DT group exhibited adaptations to chronic energy deficiency, including a REE below 90% of their predicted REE (86+/-3.0%), significantly lower TT3 levels and significantly higher ghrelin levels than the normal DT groups. Since energy deficiency plays a causal role in the Female Athlete Triad, DT may serve as a proxy indicator of underlying energy deficiency and may be useful for identifying individuals at risk for Triad disorders prior to the development of serious clinical sequelae.

Topics: Adaptation, Physiological; Adult; Amenorrhea; Basal Metabolism; Biomarkers; Energy Intake; Energy Metabolism; Exercise; Feeding and Eating Disorders; Female; Ghrelin; Humans; Insulin; Leptin; Peptide Hormones; Retrospective Studies; Sports; Thinness; Triiodothyronine

To determine trigger factors and neuropsychologic correlates of functional hypothalamic amenorrhea (FHA) in adolescence and to evaluate the correlations with the endocrine-metabolic profile.. Cross-sectional comparison of adolescents with FHA and eumenorrheic controls. Academic medical institution. Twenty adolescent girls with FHA (aged <18 years) and 20 normal cycling girls. All subjects underwent endocrine-gynecologic (hormone) and neuropsychiatric (tests and interview) investigations. A separate semistructured interview was also used to investigate parents.. Gonadotropins, leptin, prolactin, androgens, estrogens, cortisol, carrier proteins (SHBG, insulin-like growth factor-binding protein 1), and metabolic parameters (insulin, insulin-like growth factor 1, thyroid hormones) were assayed in FHA and control subjects. All girls were evaluated using a test for depression, a test for disordered eating, and a psychodynamic semistructured interview.. Adolescents with FHA showed a particular susceptibility to common life events, restrictive disordered eating, depressive traits, and psychosomatic disorders. The endocrine-metabolic profile was strictly correlated to the severity of the psychopathology.. Functional hypothalamic amenorrhea in adolescence is due to a particular neuropsychologic vulnerability to stress, probably related to familial relationship styles, expressed by a proportional endocrine impairment.

Topics: Adolescent; Amenorrhea; Anxiety; Body Mass Index; Cross-Sectional Studies; Depression; Feeding and Eating Disorders; Female; Gonadal Steroid Hormones; Gonadotropins; Hormones; Humans; Hydrocortisone; Hypothalamic Diseases; Insulin-Like Growth Factor Binding Protein 1; Leptin; Psychophysiologic Disorders; Sex Hormone-Binding Globulin; Stress, Psychological

Topics: Brain-Derived Neurotrophic Factor; Feeding and Eating Disorders; Ghrelin; Humans; Leptin; Molecular Biology; Neurotransmitter Agents; Peptide Hormones

Topics: Feeding and Eating Disorders; Female; Ghrelin; Humans; Leptin; Peptide Hormones

Leptin, which was discovered only a decade ago, is a peptide that informs hypothalamic areas about the energy balance of the body. New research findings, has suggested a possible role of leptin in eating disorders as well. Few data are available about the relationship between leptin, insulin and glucose metabolism in the pathomechanism of eating disorders. The authors were searching for answers to these relationships in their investigations.. The study groups included 56 patients with eating disorders and 22 healthy subjects served as controls. The diagnosis was based on DSM-IV criteria. For measuring leptin, insulin and C-peptide serum concentrations a radioimmunoassay method was applied, and serum glucose concentrations were detected by spectrofluorimetry. Detailed statistical analysis of the results was carried out.. A correlation between BMI and serum leptin concentration could be proved only in anorectic patients. In contrast to former findings, there was no correlation between BMI and leptin concentration in the bulimia group, and the leptin concentrations were significantly higher in bulimic patients than in the control group. During the glucose tolerance test, leptin levels showed a significant decrease in the anorexia group.. The results raise the possibility of a direct effect of central regulatory mechanisms of food intake in the pathomechanism of anorexia nervosa.

Topics: Adult; Anorexia Nervosa; Blood Glucose; Body Mass Index; Bulimia Nervosa; C-Peptide; Case-Control Studies; Feeding and Eating Disorders; Female; Glucose Tolerance Test; Humans; Insulin; Leptin; Male; Middle Aged; Radioimmunoassay; Spectrometry, Fluorescence

To evaluate the influence of Body Mass Index, body composition and hormonal factors on bone mass in young women with amenorrhea related to restrictive eating disorders.. Descriptive study of 55 patients with secondary amenorrhea due to restrictive eating disorders and 14 healthy girls used for comparison. Assessment of Bone Mineral Density, Fat Mass and Lean Mass by DEXA and of the serum hormonal profile.. Patients had lower BMI, lower Fat Mass and lower Bone Mass compared to controls; their serum levels of LH, FT(3), DHEAS, Insulin and Leptin were significantly reduced. Low Bone Density, especially in the lumbar region, correlated with concentrations of FT(3), Cortisol, Insulin and Leptin, hormones expressive of metabolic adjustment to malnutrition. Lean Mass was a strong predictor of osteopenia and osteoporosis.. Hormonal nutritional markers, together with soft tissue composition measurements, are viable options for ongoing monitoring of subjects with eating disorders.

Topics: Adolescent; Adult; Amenorrhea; Body Composition; Body Mass Index; Bone Density; Dehydroepiandrosterone Sulfate; Estradiol; Feeding and Eating Disorders; Female; Follicle Stimulating Hormone; Humans; Hydrocortisone; Insulin; Leptin; Luteinizing Hormone; Osteoporosis; Testosterone; Triiodothyronine

Night eating syndrome (NES) is characterized by evening hyperphagia and frequent awakenings with ingestion of food. It is associated with obesity and depressed mood. Greater understanding of hormonal influences on NES is desirable.. Our objective was to evaluate 25-h profiles of hormones involved in energy balance, sleep, and stress in NES.. Blood assays for glucose, insulin, ghrelin, leptin, melatonin, cortisol, TSH, and prolactin were sampled repeatedly among NES and control subjects. Food intake and depressive symptoms were assessed.. Fifteen NES and 14 matched control participants stayed three nights in a General Clinical Research Center.. We assessed differences between NES and control participants in the 25-h profiles of eight hormones.. Nocturnal food intake was higher among NES participants, although their daily calorie intake was similar to that of controls. Reflecting their increased nocturnal intake, insulin (P < 0.001) and glucose levels (P = 0.07) among NES participants were higher than those of controls. Ghrelin levels were significantly lower in NES participants than in controls from 0100-0900 h (P = 0.003). Levels of plasma cortisol, melatonin, leptin, and prolactin did not differ between groups, but there was a trend for TSH levels (P = 0.07) to be higher during the 25 h in NES. NES participants had greater depressive symptoms than controls (P < 0.001). The differences in the levels of glucose, insulin, and ghrelin between NES and controls are closely associated with nocturnal food intake.

Topics: Adult; Animals; Blood Glucose; Energy Intake; Feeding and Eating Disorders; Female; Ghrelin; Humans; Insulin; Leptin; Middle Aged; Peptide Hormones; Sleep; Stress, Psychological; Thyrotropin

The genetic property of subclinical eating behaviour (SEB) and the link between SEB and polycystic ovary syndrome (PCOS) has been studied before but the role of leptin within this connection has never been investigated. The objective of this study was 1). to study the genetic property of SEB. 2). To find a link between leptin, SEB and PCOS. One hundred and fifty four (77 pairs) female-female Iranian twins including 96 MZ individuals (48 pairs) and 58 DZ individuals (29 pairs) participated in the study. Clinical, biochemical and ultrasound tools were used to diagnose polycystic ovary syndrome. BITE questionnaire was filled out for subjects. Eight percent of subjects were diagnosed for subclinical eating disorder. No significant difference was found between intraclass correlation of MZ and DZ (z = 0.57, P = 0.569). Serum leptin level correlated significantly with bulimia score (P < 0.007). The mean (+/-SD) value for bulimia score was found to be higher among PCOS(positive) subjects (3.27 +/- 5.51) in comparison with PCOS(negative) subjects (2.06 +/- 4.48) (P < 0.001). The genetic property of subclinical eating disorder was not confirmed as shared environment might have played a major role in likeliness of DZ twins as well as MZ. Leptin is linked with both subclinical eating disorder and PCOS.

Topics: Adult; Bulimia Nervosa; Feeding and Eating Disorders; Female; Humans; Iran; Leptin; Polycystic Ovary Syndrome; Reference Values; Risk Assessment; Risk Factors; Surveys and Questionnaires; Twins, Dizygotic; Twins, Monozygotic

To compare the characteristics of obese persons with the night eating syndrome (NES) with those of nonobese persons with the NES.. Eighty subjects (40 with a body mass index [BMI] greater than 30 and 40 with a BMI less than 25) identified themselves on a website for the Night Eating Questionnaire (NEQ) as suffering from the NES. The responses of the 40 obese website subjects were compared with 21 obese persons with the NES who had undergone face-to-face interviews. The responses on the NEQ of the 40 obese and the 40 non-obese website subjects were then compared.. There was no difference in the NEQ results of the 40 website obese subjects and 21 obese night eaters who had undergone face-to-face interviews. The responses of these same 40 obese subjects showed very little difference compared with those of the 40 nonobese subjects. The major difference between the two groups was the considerable younger age of the normal-weight NES subjects.. The striking similarity in the characteristics between obese and nonobese subjects with the NES indicates that this disorder, considered until now to occur primarily among obese persons, also occurs among nonobese persons. The younger age of the nonobese subjects suggests that the NES may contribute to the development of obesity.

Topics: Adult; Body Mass Index; Circadian Rhythm; Feeding and Eating Disorders; Female; Humans; Leptin; Obesity; Sleep Wake Disorders; Surveys and Questionnaires

To study the functional contributions of the 5-HT4 receptor subtype of serotonin (5-HT), we have generated knockout mice lacking the 5-HT4 receptor gene. The male mutant mice exhibit a hyposensitivity to anorexic stress. Our recent data indicate that the pharmacological inactivation, using a systemic injection of the 5-HT4 receptor antagonist RS39604 (0.5 mg/kg), suppressed restraint stress-induced anorexia in wild-type female mice. In parallel, the same treatment reduced the 3,4-N-methylenedioxymethamphetamine (" ecstasy", 10 mg/kg)-induced anorexia in male wild-type mice. Our neurochemical analyses suggest that the mechanisms underlying feeding disorders in 5-HT4 receptor knockout mice are related to a lesser efficacy of 5-HT (hypothalamus, nucleus accumbens), leptin and the cocaine-amphetamine related transcript to reduce food intake following stress.

Topics: Animals; Anorexia; Appetite; Chromatography, High Pressure Liquid; Corticosterone; Feeding and Eating Disorders; Gene Expression Regulation; Leptin; Limbic System; Male; Mice; Mice, Knockout; N-Methyl-3,4-methylenedioxyamphetamine; Nerve Tissue Proteins; Piperidines; Propane; Receptors, Serotonin, 5-HT4; Restraint, Physical; Reverse Transcriptase Polymerase Chain Reaction; Serotonin; Serotonin 5-HT4 Receptor Antagonists; Serotonin Antagonists; Stress, Psychological

Body weight is crucial to eating disorders. Beyond gender, age, and height it is determined by anthropometric features of physique, i. e. somatotypes. We investigated their impact on the anthropometric and metabolic assessment of nutritional status, psychometrics, and other clinical aspects of eating disorders. In 133 eating disordered girls (ICD-10 & DSM-IV criteria) of well-recorded catamneses, various somatometric measures (n = 133), serum leptin (n = 30), plasma tryptophan (n = 108), and psychometric scales (n = 119; EDI-64 & EAT-40) were examined, preferably on repeated occasions of their treatment and in comparison to 41 healthy controls. Somatotyping was performed by gender- and age-specific quintiles of Strömgren's Metrik Index (MI) derived from 6995 volunteers constituting the anthropometric reference.Somatotypes represent a significant factor for assessing nutritional status. Exhibiting higher EDI-64 bulimia ratings at admission, more prevalent self-induced vomiting and purgative substance abuse as well as prolonged refractory illnesses with more previous inpatient treatment trials but later admissions, heavier somatotypes were significantly underrepresented in our total clinical sample but more prevalent among bulimic eating disorders (p < 0.05). Neglecting the anthropometry of physique biases against the detection and treatment of eating disorders in heavier somatotypes at weights below general average. Henceforth, this shall be avoided by somatotyping according to frame indices.

Topics: Anthropometry; Feeding and Eating Disorders; Female; Germany; Hospitals, Teaching; Humans; Leptin; Nutritional Status; Somatotypes; Tryptophan

Evidence has accumulated that in both acutely ill and recovered patients with either anorexia or bulimia nervosa circulating leptin levels (LL) are lower than in controls matched for body mass index (BMI; kg/m(2)). It is unknown if these lower leptin levels represent a state or trait marker.. We aimed to confirm the lowered leptin levels in eating disordered females and to identify underlying mechanisms.. We screened 181 female students of the nutritional sciences for eating disorders with the respective module of the M-Composite International Diagnostic Interview and the Cognitive Restraint scale of the Three Factor Eating Questionnaire. The physical assessment included determinations of BMI, body composition and LL. Each case fulfilling lifetime DSM-IV criteria for an eating disorder was BMI matched to two controls. We used a multivariate mixed regression model to evaluate if the observed difference in lg(10)-leptin level between cases and controls is actually due to the influence of restrained eating and/or previous weight loss after adjustment for BMI and percent body fat.. In accordance with our hypothesis the 32 (17.7 %) cases had a lower serum lg(10)-leptin level than the 64 BMI matched controls (one-sided p < 0.001). We were not able to detect an influence of restrained eating or previous weight loss.. We confirm that females with a lifetime history of an eating disorder have lower LL. We were not able to identify an underlying mechanism. Similar to most previous studies we found a high rate of eating disorders among female students of nutritional sciences.

Topics: Adult; Anorexia Nervosa; Body Composition; Body Mass Index; Bulimia; Case-Control Studies; Feeding and Eating Disorders; Female; Humans; Leptin; Psychometrics; Regression Analysis; Weight Loss

Osteopenia, which is correlated with amenorrhea and poor nutritional habits, has been well documented in elite ballet dancers. Estrogen replacement therapy and recovery from amenorrhea have not been associated with normalization of bone density. Thus, the osteopenia may be related to changes brought about by chronic dieting or other factors, such as a hypometabolic state induced by poor nutrition. The purpose of this study was to investigate the relationship of chronic dieting and resting metabolic rate (RMR) to amenorrhea and bone density. RMR, bone density, eating disorder assessments, leptin levels, and complete menstrual and medical histories were determined in 21 elite ballet dancers and in 27 nondancers (age, 20-30 yr). No significant correlations were found between high EAT26 scores, a measure of disordered eating, and RMR, bone densities, body weight, body fat, or fat-free mass. However, when RMR was adjusted for fat-free mass (FFM), a significant positive correlation was found between RMR/FFM and bone density in both the arms (P < 0.001) and spine (P < 0.05) in ballet dancers, but not in the normal controls. The dancers also demonstrated significantly higher EAT scores (22.9 +/- 10.3 vs. 4.1 +/- 2.4; P < 0.001) and lower RMR/FFM ratios (30.0 +/- 2.2 vs. 32.05 +/- 2.8; P < 0.01). The only variable to predict lower RMR/FFM in the entire sample was ever having had amenorrhea; this group had significantly higher EAT scores (18.0 +/- 13.5 vs. 10.3 +/- 10.2; P < 0.05), lower leptin levels (4.03 +/- 0.625 vs. 7.10 +/- 4.052; P < 0.05), and lower bone mineral density in the spine (0.984 +/- 0.11 vs. 1.10 +/- 0.13; P < 0.05) and arm (0.773 +/- 0.99 vs. 0.818 +/- 0.01; P < 0.05). We hypothesize that the correlation between low RMR and lower leptin levels and bone density may be more strongly related to nutritional habits in ballet dancers, causing significant depression of RMR, particularly for those with a history of amenorrhea.

Topics: Adult; Amenorrhea; Arm; Body Composition; Bone Density; Dancing; Diet; Feeding and Eating Disorders; Female; Humans; Leptin; Reference Values; Spine

Members of the muscarinic acetylcholine receptor family (M1-M5) have central roles in the regulation of many fundamental physiological functions. Identifying the specific receptor subtype(s) that mediate the diverse muscarinic actions of acetylcholine is of considerable therapeutic interest, but has proved difficult primarily because of a lack of subtype-selective ligands. Here we show that mice deficient in the M3 muscarinic receptor (M3R-/- mice) display a significant decrease in food intake, reduced body weight and peripheral fat deposits, and very low levels of serum leptin and insulin. Paradoxically, hypothalamic messenger RNA levels of melanin-concentrating hormone (MCH), which are normally upregulated in fasted animals leading to an increase in food intake, are significantly reduced in M3R-/- mice. Intra-cerebroventricular injection studies show that an agouti-related peptide analogue lacked orexigenic (appetite-stimulating) activity in M3R-/- mice. However, M3R-/- mice remained responsive to the orexigenic effects of MCH. Our data indicate that there may be a cholinergic pathway that involves M3-receptor-mediated facilitation of food intake at a site downstream of the hypothalamic leptin/melanocortin system and upstream of the MCH system.

Topics: Animals; Appetite Regulation; Body Weight; Eating; Feeding and Eating Disorders; Feeding Behavior; Female; Gene Targeting; Glucose Tolerance Test; Hormones; Insulin; Leptin; Locomotion; Male; Mice; Mice, Inbred C57BL; Neuropeptides; Oxygen Consumption; Receptor, Muscarinic M3; Receptors, Muscarinic; Thinness; Triglycerides

The present study investigates the mechanisms underlying the transient hypophagia occurring when rats adapted to high-fat, carbohydrate-free diets are switched to high-carbohydrate, low-fat diets. The hypophagia after the high-fat, carbohydrate-free to high-carbohydrate, low-fat diet shift seems to depend on the amount of carbohydrate in the diet, since an attenuation of hypophagia was observed when high-fat, carbohydrate-free-adapted rats were switched to a medium-carbohydrate, medium-fat diet. A role of glucose intolerance in the hypophagia is supported by the attenuation of carbohydrate anorexia in rats adapted to a high-fat diet containing n -3 polyunsaturated fatty acids from fish oil (60% of fat as fish oil), which has been shown to improve glucose tolerance in rats. Furthermore, the increased plasma glucose concentration in the high-fat, carbohydrate-free diet to high-carbohydrate, low-fat shifted rats despite the suppression in food intake also suggests an involvement of glucose intolerance in the hypophagia. The failure of the inhibitor of hepatic-fatty-acid oxidation mercaptoacetate (400 micromol/kg, i.p.) to counteract carbohydrate anorexia in the HF-adapted rats argues against an involvement of fatty-acids oxidation in the inhibition of eating after high-fat, carbohydrate-free to high-carbohydrate, low-fat diet shift. This is also supported by the failure to demonstrate a relationship between plasma beta-hydroxybutyrate and the severity of the hypophagia. A role of leptin in the hypophagia seems unlikely, since plasma leptin after diet shift was unchanged. Ingestion of the high-carbohydrate, low-fat diet also produced an aversion towards this diet in high-fat, carbohydrate-free-adapted rats. It is concluded that the transient hypophagia induced by switching rats from a high-fat to a high-carbohydrate diet is not related to fatty acid oxidation but to transiently impaired carbohydrate utilization.

Topics: Analysis of Variance; Animals; Blood Glucose; Body Weight; Diet; Dietary Carbohydrates; Dietary Fats; Fatty Acids, Unsaturated; Feeding and Eating Disorders; Leptin; Male; Rats; Rats, Sprague-Dawley; Taste

Topics: Circadian Rhythm; Feeding and Eating Disorders; Humans; Hydrocortisone; Leptin; Melatonin; Placebo Effect; Satiety Response

Well defined eating disorders such as anorexia nervosa and bulimia are associated with significant known health risks. Although binge eating behavior is increased in unsuccessfully dieting obese women, other health implications of this common eating pattern are unknown. We hypothesized that ingestion of an entire day's calories at one time in the evening, a common eating practice among Americans, would lead to disruptions in glucose, insulin, and leptin metabolism and in menstrual cyclicity, even in healthy young women. Seven lean women without a history of eating disorders were studied on two occasions separated by one or two menstrual cycles. During one admission, they ate three regular meals plus a snack on each of 3 days. On the other admission, they ate the same number of calories, macronutrient matched to the normal diet, in a single evening meal. Glucose, insulin, and leptin were measured frequently for 12-14 h beginning at 0800 h on the third day of each diet, and an insulin tolerance test was performed while the subjects were fasting on the fourth day. Daily blood samples were obtained until ovulation was documented to assess any impact on menstrual function. Ingestion of an entire day's calories at dinner resulted in a significant increase in fasting glucose levels and a dramatic increase in insulin responses to the evening meal. The diurnal pattern of leptin secretion was altered, such that the gradual rise in leptin from 0800 h observed during the normal diet was abolished, and leptin did not begin to rise during the binge diet until at least 2 h after the evening meal. No changes were demonstrated in insulin sensitivity, follicular growth, or ovulation between the two diets. We conclude that 1) ingestion of a large number of calories at one time (binge eating) impacts metabolic parameters even when total calories and macronutrients are appropriate for weight; 2) the timing of energy intake is an independent determinant of the diurnal rhythm of leptin secretion, indicating a relatively acute affect of energy balance on leptin dynamics; 3) the mechanism of exaggerated insulin secretion after a binge meal remains to be determined, but may be related to the altered diurnal pattern of leptin secretion; and 4) as most binge eating episodes in the population are associated with the ingestion of excess calories, it is hypothesized that binge eating behavior is associated with even greater metabolic dysfunction than that described herein.

Topics: Adult; Blood Glucose; Circadian Rhythm; Eating; Energy Intake; Feeding and Eating Disorders; Female; Food; Humans; Hydrocortisone; Insulin; Leptin; Menstrual Cycle; Proteins

Because the exact etiology of functional, or idiopathic, hypothalamic amenorrhea (FHA) is still unknown, FHA remains a diagnosis of exclusion. The disorder may be stress induced. However, mounting evidence points to a metabolic/nutritional insult that may be the primary causal factor. We explored the thyroid, hormonal, dietary, behavior, and leptin changes that occur in FHA, as they provide a clue to the etiology of this disorder. Fourteen cycling control and amenorrheic nonathletic subjects were matched for age, weight, and height. The amenorrheic subjects denied eating disorders; only after further, detailed questioning did we uncover a higher incidence of anorexia and bulimia in this group. The amenorrheic subjects demonstrated scores of abnormal eating twice those found in normal subjects (P < 0.05), particularly bulimic type behavior (P < 0.01). They also expended more calories in aerobic activity per day and had higher fiber intakes (P < 0.05); lower body fat percentage (P < 0.05); and reduced levels of free T4 (P < 0.05), free T3 (P < 0.05), and total T4 (P < 0.05), without a significant change in rT3 or TSH. Cortisol averaged higher in the amenorrheics, but not significantly, whereas leptin values were significantly lower (P < 0.05). Bone mineral density was significantly lower in the wrist (P < 0.05), with a trend to lower BMD in the spine (P < 0.08). Scores of emotional distress and depression did not differ between groups. The alterations in eating patterns, leptin levels, and thyroid function present in subjects with FHA suggest altered nutritional status and the suppression of the hypothalamic-pituitary-thyroid axis or the alteration of feedback set-points in women with FHA. Both lower leptin and thyroid levels parallel changes seen with caloric restriction. Nutritional issues, particularly dysfunctional eating patterns and changes in thyroid metabolism, and/or leptin effects may also have a role in the metabolic signals suppressing GnRH secretion and the pathogenesis of osteopenia despite normal body weight. These findings suggest that the mechanism of amenorrhea and low leptin in these women results mainly from a metabolic/nutritional insult.

Topics: Adult; Amenorrhea; Bone Density; Feeding and Eating Disorders; Female; Humans; Hypothalamic Diseases; Leptin; Proteins; Reference Values; Thyroid Hormones

Investigators first described the night-eating syndrome (NES), which consists of morning anorexia, evening hyperphagia, and insomnia, in 1955, but, to our knowledge, this syndrome has never been subjected to careful clinical study.. To characterize NES on the basis of behavioral characteristics and neuroendocrine data.. A behavioral observational study was conducted between January 1996 and June 1997 in a weight and eating disorders program at the University of Pennsylvania. A neuroendocrine study was conducted from May through August 1997 at the Clinical Research Center of the University Hospital, Tromso, Norway.. The behavioral study included 10 obese subjects who met criteria for NES and 10 matched control subjects. The neuroendocrine study included 12 night eaters and 21 control subjects. Behavioral study subjects were observed for 1 week on an outpatient basis, and neuroendocrine study subjects were observed during a 24-hour period in the hospital.. The behavioral study measured timing of energy intake, mood level, and sleep disturbances. The neuroendocrine study measured circadian levels of plasma melatonin, leptin, and cortisol.. In the behavioral study, compared with control subjects, night eaters had more eating episodes in the 24 hours (mean [SD], 9.3 [0.6] vs 4.2 [0.2]; P<.001) and consumed significantly more of their daily energy intake at night than did control subjects (56% vs 15%; P<.001). They averaged 3.6 (0.9) awakenings per night compared with 0.3 (0.3) by controls (P<.001). In night eaters, 52% of these awakenings were associated with food intake, with a mean intake per ingestion of 1134 (1197) kJ. None of the controls ate during their awakenings. In the neuroendocrine study, compared with control subjects, night eaters had attenuation of the nocturnal rise in plasma melatonin and leptin levels (P<.001 for both) and higher circadian levels of plasma cortisol (P = .001).. A coherent pattern of behavioral and neuroendocrine characteristics was found in subjects with NES.

Topics: Adult; Anorexia; Circadian Rhythm; Feeding and Eating Disorders; Feeding Behavior; Female; Humans; Hydrocortisone; Hyperphagia; Leptin; Male; Melatonin; Neurosecretory Systems; Obesity; Poisson Distribution; Proteins; Regression Analysis; Sleep Initiation and Maintenance Disorders; Statistics, Nonparametric; Syndrome

Topics: Animals; Appetite Regulation; Body Composition; Body Constitution; Body Weight; Disease Models, Animal; Feeding and Eating Disorders; Humans; Leptin; Proteins

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but little else is known about the physiological actions of leptin in humans. The aim of this study was to determine the role of leptin in severe eating disorders, and whether its levels are correlated with the specific disease or exclusively with body weight.. Serum concentrations of human leptin were analysed by specific radioimmunoassay and compared with the individual body mass indexes (BMI). The correlations between serum leptin concentrations and BMI, age and height were analysed.. A total of 65 women were studied: 25 patients with anorexia nervosa, 20 women with bulimia nervosa, 6 women with a diagnosis of nonspecific eating disorder, and 14 normal-weight women who acted as controls. At the time of the study, the patients were non-cured, under treatment, and at different stages of therapeutic evolution.. Plasma leptin levels were measured by specific radioimmunoassay.. The mean serum leptin in the normal-weight women was 10.5 +/- 1.1 micrograms/l, compared with 7.6 +/- 1.1 micrograms/l in the anorexia nervosa patients (P < 0.05). This reduction in leptin levels was paralleled by the differences in BMI (21.4 +/- 0.4 vs 18.8 +/- 0.2) P < 0.05. These differences between the controls and anorexia nervosa patients were not observed in patients with bulimia nervosa who had a mean serum leptin level of 9.9 +/- 1.4 micrograms/l and BMI of 21.3 +/- 0.6, neither significantly different from controls. On the contrary, patients with non-specific eating disorders showed a large reduction in BMI (17.9 +/- 1.2, P < 0.05 vs control), and a parallel reduction in serum leptin levels, 4.5 +/- 1.0 (P < 0.05 vs controls). When individual values of leptin were plotted against BMI a wide range was observed in all groups; in the control subjects from 5.6 to 17.7 micrograms/l, in anorexia nervosa patients from 2.1 to 28.1 micrograms/l, in patients with bulimia nervosa between 2.6 and 25.9 micrograms/l, and in women with non-specific eating disorder from 2.0 to 8.9. No correlation was observed with the specific disease but in each group a significant correlation was observed only with BMI.. Serum leptin levels in three groups of patients affected by severe eating disorders are not related to the specific pathology but are correlated with the individual BMI. The analysis of leptin values may be a useful index of assessing the adipose tissue stores in the clinical setting, but will be of no help for diagnosis nor prognosis of severe eating disorders.

Topics: Adult; Age Factors; Anorexia Nervosa; Body Height; Body Mass Index; Bulimia; Feeding and Eating Disorders; Female; Humans; Leptin; Proteins

1. Leptin is generally thought to play a key role in the regulation of eating. However, its real role in human eating behaviour is still poorly known. Therefore, the role of leptin in the regulation of eating was examined in obese binge- and non-binge-eating women during exposure to food and food-related stimuli. 2. Eleven binge- and ten non-binge-eating obese women took part in the study. In addition to serum leptin, serum insulin, non-esterified fatty acids, plasma glucose, salivation, the feeling of hunger and the desire to eat were repeatedly measured during the experiment. 3. Serum leptin levels did not differ between the binge- and non-binge-eating women. Neither were leptin levels associated with the feeling of hunger or the desire to eat food, nor with the amount or composition of food eaten. During food exposure leptin levels did not change, whereas at the same time serum insulin levels increased and serum non-esterified fatty acid levels decreased. The change in salivation during food exposure was inversely associated with the fasting leptin level. 4. This study indicates that serum leptin does not play a role in the regulation of eating in obese women, at least not in the short term. Furthermore, leptin levels are not different in obese binge-eating women as compared with obese non-binge-eating women. Interestingly, high fasting leptin levels may be associated with a decreased salivation response in the presence of food and food-related stimuli.

Topics: Adult; Aged; Appetite Regulation; Blood Glucose; Fatty Acids, Nonesterified; Feeding and Eating Disorders; Female; Humans; Hunger; Insulin; Leptin; Middle Aged; Obesity; Proteins; Salivation

Topics: Anorexia; Bulimia; Feeding and Eating Disorders; Humans; Leptin; Obesity; Proteins

Psychometrically defined restrained eaters consume fewer calories, take fewer meals, show higher preference for low calorie foods, have lower energy expenditure and a higher rate of ovarial dysfunction than unrestrained eaters. We hypothesized that restrained eaters as assessed with the factor cognitive restraint of the Three-Factor Eating Questionnaire have low leptin levels; therefore, we measured serum leptin levels in 136 underweight students and 49 overweight students, who had filled out the Three-Factor Eating Questionnaire. Body mass indexes, fat mass and percent body fat were determined. Spearman correlations revealed that log10 leptin levels of only the 67 underweight females were negatively correlated with cognitive restraint scores (r = -0.5; nominal P-value < 0.001). The restraint score explained 22% of the total variance of leptin levels in underweight females; in combination with percent body fat, 52% of the variance was accounted for. To our knowledge this is the first study to identify a relationship between a score on a psychometric scale and leptin levels. Restrained eating has a biological correlate in underweight females.

Topics: Adult; Anorexia; Body Mass Index; Feeding and Eating Disorders; Female; Humans; Leptin; Male; Proteins; Psychometrics