leptin and Anorexia-Nervosa

This narrative review addressed to both clinicians and researchers aims to assess the role of hypoleptinemia in disordered sleep with a particular focus on patients with anorexia nervosa (AN). After introducing circadian rhythms and the regulation of circulating leptin, we summarize the literature on disordered sleep in patients with AN and in fasting subjects in general. We highlight novel single-case reports of substantially improved sleep within days after initiation of off-label metreleptin treatment. These beneficial effects are set in relationship to current knowledge of disordered sleep in animal models of an impaired leptin signaling. Specifically, both absolute and relative hypoleptinemia play a major role in animal models for insomnia, obstructive sleep apnea and obesity hypoventilation syndrome. We pinpoint future research required to complement our understanding of the role of leptin in sleep in patients with acute AN. Moreover, within the section clinical applications we speculate that human recombinant leptin may be useful for the treatment of treatment-resistant sleep-wake disorders, which are associated with (relative) hypoleptinemia. Overall, we stress the role of the hormone leptin in sleep.

Topics: Animals; Anorexia Nervosa; Humans; Leptin; Rodentia; Sleep; Sleep Apnea, Obstructive

This narrative review aims to pinpoint mental and behavioral effects of starvation, which may be triggered by hypoleptinemia and as such may be amenable to treatment with leptin receptor agonists. The reduced leptin secretion results from the continuous loss of fat mass, thus initiating a graded triggering of diverse starvation related adaptive functions. In light of leptin receptors located in several peripheral tissues and many brain regions adaptations may extend beyond those of the hypothalamus-pituitary-end organ-axes. We focus on gastrointestinal tract and reward system as relevant examples of peripheral and central effects of leptin. Despite its association with extreme obesity, congenital leptin deficiency with its many parallels to a state of starvation allows the elucidation of mental symptoms amenable to treatment with exogenous leptin in both ob/ob mice and humans with this autosomal recessive disorder. For starvation induced behavioral changes with an intact leptin signaling we particularly focus on rodent models for which proof of concept has been provided for the causative role of hypoleptinemia. For humans, we highlight the major cognitive, emotional and behavioral findings of the Minnesota Starvation Experiment to contrast them with results obtained upon a lesser degree of caloric restriction. Evidence for hypoleptinemia induced mental changes also stems from findings obtained in lipodystrophies. In light of the recently reported beneficial cognitive, emotional and behavioral effects of metreleptin-administration in anorexia nervosa we discuss potential implications for the treatment of this eating disorder. We postulate that leptin has profound psychopharmacological effects in the state of starvation.

Topics: Animals; Anorexia Nervosa; Humans; Leptin; Mice; Obesity; Receptors, Leptin; Starvation

The association between adipokine dysregulation and weight loss of patients with anorexia nervosa (AN) has been long investigated, in search of a causal relationship. We sought to: a) synthesize the available evidence on potential differences between AN patients and controls with regards to adipokine measurements (namely, leptin, adiponectin, resistin, soluble leptin receptor, visfatin, vaspin and omentin), b) estimate the potential differences between constitutionally thin (CT) subjects and AN patients, and c) present the available evidence with regards to biomarker efficacy of adipokines in AN.. A structured literature search, last updated in 2/2019, was conducted in the following databases: MEDLINE, clinicaltrials.gov, PsycINFO, PSYNDEX and WHO Registry Network. The primary outcome was the standardized mean difference of each adipokine between AN patients and controls of normal BMI. Secondary outcomes included the correlation of leptin with BMI and bone mineral density among AN patients. The study protocol is published in PROSPERO (CRD42018116767).. In a total of 622 screened studies, after exclusion of non-relevant articles and duplicates, 84 reports on leptin, 31 reports on adiponectin, 12 on resistin, 10 on soluble leptin receptor, 5 on visfatin, 3 on vaspin and omentin were finally included in the meta-analysis. Publication bias assessment underlined the possibility of non-significant studies being underrepresented; still, significant heterogeneity renders this statement inconclusive. Leptin [ELISA: SMD (95% CI): -3.03 (-4, -2.06)], radioimmunoassay [RIA: -3.84 (-4.71, -2.98)] and resistin [-1.67 (-2.85, -0.48)] were significantly lower in patients with AN compared with controls, whereas visfatin decrease did not reach significance (-2.03 (-4.38, 0.3). Mean adiponectin, vaspin and soluble leptin receptor levels were significantly higher. In subgroup analysis, a significantly attenuated SMD was reported in ELISA studies compared with RIA studies. Leptin was significantly lower in AN patients compared to CT subjects and BMI marginally did not appear to confound the result. In all analyses, except for the correlation of leptin with BMI in AN patients, high heterogeneity was present. Meta-regression analysis indicated a potential confounding action of controls' BMI and age on leptin SMD and between-assay differences. Publication bias assessment underlined the possibility of nonsignificant studies being underrepresented; still, further investigation did not corroborate this and significant heterogeneity renders this statement inconclusive.. A distinct profile of adipokine dysregulation is apparent in AN patients, following the anticipated pattern of low BMI. A precise estimation of the magnitude is hindered by heterogeneity, partly caused by varying assays and methodologies. Interestingly, while mean leptin levels are lower in AN subjects compared with constitutionally thin women, there is an overlap in individual levels between the two groups and therefore, they cannot be used to differentiate between these states.

Topics: Adiponectin; Anorexia Nervosa; Female; Humans; Leptin; Receptors, Leptin; Resistin; Serpins; Thinness

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

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

The pathophysiology of anorexia nervosa (AN) and bulimia nervosa (BN) are still poorly understood, but psychobiological models have proposed a key role for disturbances in the neuroendocrines that signal hunger and satiety and maintain energy homeostasis. Mounting evidence suggests that many neuroendocrines involved in the regulation of homeostasis and body weight also play integral roles in food reward valuation and learning via their interactions with the mesolimbic dopamine system. Neuroimaging data have associated altered brain reward responses in this system with the dietary restriction and binge eating and purging characteristic of AN and BN. Thus, neuroendocrine dysfunction may contribute to or perpetuate eating disorder symptoms via effects on reward circuitry. This narrative review focuses on reward-related neuroendocrines that are altered in eating disorder populations, including peptide YY, insulin, stress and gonadal hormones, and orexins. We provide an overview of the animal and human literature implicating these neuroendocrines in dopaminergic reward processes and discuss their potential relevance to eating disorder symptomatology and treatment.

Topics: Animals; Anorexia Nervosa; Bulimia Nervosa; Ghrelin; Humans; Leptin; Neuroendocrinology; Reward

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

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

Antipsychotics (APs) are associated with metabolic syndrome, with increases in leptin proposed as an underlying mechanism of AP-induced weight gain. Currently available meta-analyses on this topic have limited their populations of interest to those diagnosed with schizophrenia. The purpose of this meta-analysis is to explore the relationship between leptin levels and AP use across multiple psychiatric diagnoses, and also in healthy controls.. Systematic electronic searches were conducted using PubMed and OVID: Medline. Longitudinal studies were included if showing leptin levels before and after AP use. We included participants with any psychiatric disorders and mentally healthy participants, if exposed to AP use. The differences in leptin levels were evaluated using Hedges' g with a random effects model.. Forty-two studies were found (36 schizophrenia, 2 bipolar disorder, 1 anorexia nervosa, and 3 healthy controls), encompassing 66 study arms and 1,156 participants. The meta-analysis showed that regardless of diagnoses, leptin levels increase with AP use (Hedges' g = 0.811, p ≤ .001).. Leptin increases induced by APs are present across all diagnoses. More comprehensive research is needed to understand the relationship between AP use and leptin levels across multiple diagnoses.

Topics: Anorexia Nervosa; Antipsychotic Agents; Bipolar Disorder; Humans; Leptin; Metabolic Syndrome; Schizophrenia

Anorexia nervosa is a psychiatric disorder characterized by altered body image, persistent food restriction and low body weight, and is associated with global endocrine dysregulation in both adolescent girls and women. Dysfunction of the hypothalamic-pituitary axis includes hypogonadotropic hypogonadism with relative oestrogen and androgen deficiency, growth hormone resistance, hypercortisolaemia, non-thyroidal illness syndrome, hyponatraemia and hypooxytocinaemia. Serum levels of leptin, an anorexigenic adipokine, are suppressed and levels of ghrelin, an orexigenic gut peptide, are elevated in women with anorexia nervosa; however, levels of peptide YY, an anorexigenic gut peptide, are paradoxically elevated. Although most, but not all, of these endocrine disturbances are adaptive to the low energy state of chronic starvation and reverse with treatment of the eating disorder, many contribute to impaired skeletal integrity, as well as neuropsychiatric comorbidities, in individuals with anorexia nervosa. Although 5-15% of patients with anorexia nervosa are men, only limited data exist regarding the endocrine impact of the disease in adolescent boys and men. Further research is needed to understand the endocrine determinants of bone loss and neuropsychiatric comorbidities in anorexia nervosa in both women and men, as well as to formulate optimal treatment strategies.

Topics: Adipokines; Anorexia Nervosa; Disease Management; Endocrine System Diseases; Female; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Leptin; Male; Pituitary-Adrenal System

Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization in many aspects is seen at recovery from undernutrition. Recent genome-wide association studies support that genetic factors play a role in the pathophysiology of AN, of which some are independent of BMI-related mechanisms. In this review, an update on blood-based biomarkers of AN is presented.

Topics: Anorexia Nervosa; Biomarkers; Brain-Derived Neurotrophic Factor; Ghrelin; Humans; Inflammation; Leptin; Oxytocin

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

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

Topics: Animals; Anorexia Nervosa; Endocrine System Diseases; Estrogens; Female; Humans; Leptin; Receptors, Estrogen

Feeding behaviour is crucial for the survival of an organism and is regulated by different brain circuits. Among these circuits the mesolimbic dopamine (DA) system is implicated in the anticipation and motivation for food rewards. This system consists of the dopaminergic neurons in the ventral tegmental area (VTA), and their projections to different cortico-limbic structures such as the nucleus accumbens and medial prefrontal cortex. While the importance of this system in motivational drive for different rewards, including drugs of abuse, has been clearly established, its role in energy balance remains largely unexplored. Evidence suggests that peripheral hormones such as leptin and ghrelin are involved in the anticipation and motivation for food and this might be partially mediated through their effects on the VTA. Yet, it remains to be determined whether these effects are direct effects of ghrelin and leptin onto VTA DA neurons, and to what extent indirect effects through other brain areas contribute. Elucidation of the role of leptin and ghrelin signalling on VTA DA neurons in relation to disruptions of energy balance might provide important insights into the role of this neural circuit in obesity and anorexia nervosa.

Topics: Anorexia Nervosa; Appetite; Dopamine; Energy Metabolism; Feeding Behavior; Ghrelin; Humans; Leptin; Motivation; Obesity; Reward; Signal Transduction; Ventral Tegmental Area

The estimated prevalence of anorexia nervosa is highest in teenagers and probably increasing in prepubertal girls, while morbidity rates in female adults remain constant. Childhood and adolescent AN often take a chronic and disabling course with severe consequences for somatic and mental health in adulthood and an eventually high mortality. Besides a reduced growth, diminished reproduction rate and an increased risk of osteoporosis a prolonged course of the disorder may impact on the development of the adolescent brain, probably by hormonal dysfunctions such as those of the corticoid and gonadal system and by severe changes in neuropeptides such as leptin. Thus, besides a genetic disposition, longer lasting effects of starvation on brain development might explain the high prevalence of mental disorders in adulthood of former AN patients. Neuropsychological findings resembling those in obsessive-compulsive disorder and autism spectrum disorders are of growing importance because they might contribute to more effective and specific interventions in both adolescent and adult eating disorders.

Topics: Adolescent; Adult; Anorexia Nervosa; Brain; Child; Chronic Disease; Cross-Sectional Studies; Female; Hormones; Humans; Incidence; Leptin; Male; Neuropsychological Tests; Prognosis; Risk Factors; Young Adult

Zinc is required by humans and animals for many physiological functions, such as growth, immune function, and reproduction. Zinc deficiency induces a number of physiological problems, including anorexia, growth retardation, dermatitis, taste disorder, and hypogonadism. Although it is clear that zinc deficiency produces specific and profound anorexia in experimental animals, the connection between zinc deficiency and anorexia is less certain. We were the first to show that orally, but not intraperitoneally, administered zinc rapidly stimulates food intake through orexigenic peptides coupled to the afferent vagus nerve using rats during early-stage zinc deficiency without decreased zinc concentrations in plasma and tissues. We confirmed that a zinc-sufficient diet containing zinc chloride acutely stimulated food intake after short-term zinc deprivation. We also found that orally administered zinc sulfate increased the expression of NPY and orexin mRNA after administration. Using vagotomized rats, we tested whether the increase in food intake after oral administration of zinc was mediated by the vagus nerve. In sham-operated rats, the oral administration of zinc stimulated food intake, whereas zinc and saline administrations did not exhibit differing effects in vagotomized rats. We conclude that zinc stimulates food intake in short-term zinc-deficient rats through the afferent vagus nerve with subsequent effects on hypothalamic peptides associated with food intake regulation. In this review, we describe recent research investigating the roles of zinc as an appetite stimulator in food intake regulation, along with research about hypothalamus, ghrelin, leptin and zinc receptor, and clinical application about anorexia nervosa, cachexia and sarcopenia. The article also presents some promising patents on zinc.

Topics: Animals; Anorexia Nervosa; Appetite; Cachexia; Deficiency Diseases; Energy Intake; Ghrelin; Humans; Hypothalamus; Leptin; Patents as Topic; Sarcopenia; Trace Elements; Zinc

The roles of corticotrophin-releasing factor (CRF), opioid peptides, leptin and ghrelin in anorexia nervosa (AN) were discussed in this paper. CRF is the key mediator of the hypothalamo-pituitary-adrenal (HPA) axis and also acts at various other parts of the brain, such as the limbic system and the peripheral nervous system. CRF action is mediated through the CRF1 and CRF2 receptors, with both HPA axis-dependent and HPA axis-independent actions, where the latter shows nil involvement of the autonomic nervous system. CRF1 receptors mediate both the HPA axis-dependent and independent pathways through CRF, while the CRF2 receptors exclusively mediate the HPA axis-independent pathways through urocortin. Opioid peptides are involved in the adaptation and regulation of energy intake and utilization through reward-related behavior. Opioids play a role in the addictive component of AN, as described by the "auto-addiction opioids theory". Their interactions have demonstrated the psychological aspect of AN and have shown to prevent the functioning of the physiological homeostasis. Important opioids involved are β-lipotropin, β-endorphin and dynorphin, which interact with both µ and κ opioids receptors to regulate reward-mediated behavior and describe the higher incidence of AN seen in females. Moreover, ghrelin is known as the "hunger" hormone and helps stimulate growth hormone (GH) and hepatic insulin-like-growth-factor-1(IGF-1), maintaining anabolism and preserving a lean body mass. In AN, high levels of GH due to GH resistance along with low levels of IGF-1 are observed. Leptin plays a role in suppressing appetite through the inhibition of neuropeptide Y gene. Moreover, the CRF, opioid, leptin and ghrelin mechanisms operate collectively at the HPA axis and express the physiological and psychological components of AN. Fear conditioning is an intricate learning process occurring at the level of the hippocampus, amygdala, lateral septum and the dorsal raphe by involving three distinct pathways, the HPA axis-independent pathway, hypercortisolemia and ghrelin. Opioids mediate CRF through noradrenergic stimulation in association with the locus coeruleus. Furthermore, CRF's inhibitory effect on gonadotropin releasing hormone can be further explained by the direct relationship seen between CRF and opioids. Low levels of gonadotropin have been demonstrated in AN where only estrogen has shown to mediate energy intake. In addition, estrogen is involved in regulating µ rece

Topics: Adolescent; Adult; Anorexia Nervosa; Child; Female; Ghrelin; Humans; Leptin; Opioid Peptides; Starvation; Young Adult

A moderate elevation of thyrotropin (TSH) concentrations, which is associated with triiodothyronine (T3) values in or slightly above the upper normal range, is frequently found in obese humans. These alterations seem rather a consequence than a cause of obesity since weight loss leads to a normalization of elevated thyroid hormone levels. Elevated thyroid hormone concentrations increase the resting energy expenditure (REE). The underlying pathways are not fully understood. As a consequence of the increased REE, the availability of accumulated energy for conversion into fat is diminished. In conclusion, the alterations of thyroid hormones in obesity suggest an adaptation process. Since rapid weight loss is associated with a decrease of TSH and T3, the resulting decrease in REE may contribute towards the difficulties maintaining weight loss. Leptin seems to be a promising link between obesity and alterations of thyroid hormones since leptin concentrations influence TSH release.

Topics: Adipokines; Animals; Anorexia Nervosa; Body Weight; Energy Metabolism; Humans; Leptin; Obesity; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Triiodothyronine

The prevalence of anorexia nervosa has increased in recent years and a large proportion of patients with this disorder have low bone density at diagnosis and, therefore, an increased risk of early and late fractures. The mechanism of bone loss in anorexia nervosa is not well understood, yet it likely includes hypogonadism, alterations of the GH-IGF-1 axis and hypercortisolism. DEXA is the most effective tool for assessing and monitoring bone density in these patients, and it is important to improve or at least stabilize bone metabolism in those with low bone mass. No agent has yet been proven to be effective in improving bone density. However, sustained weight recovery and menses besides an adequate intake of calcium and vitamin D are recommended to optimize the conditions in which bone mass accrual may occur.

Topics: Adipose Tissue; Adolescent; Adult; Anorexia Nervosa; Bone and Bones; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Calcium; Cushing Syndrome; Fractures, Bone; Gonadal Steroid Hormones; Humans; Hypogonadism; Intercellular Signaling Peptides and Proteins; Leptin; Male; Minerals; Osteoporosis; Vitamin D; Young Adult

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

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

Menstrual cycle irregularities are often observed among physically active women and athletes who participate in physical activity ranging from recreational to competitive exercise training. Further, such irregularities have been casually linked to an energy deficiency where caloric intake is inadequate for exercise energy expenditure resulting in a suppressive effect on growth and reproduction. Adaptations consistent with chronic energy deficiency, including reductions in resting energy expenditure and total triiodothyronine, have been observed in exercising women with functional hypothalamic amenorrhea (FHA). Gut peptides and adipocytokines also appear to be altered in exercising women with FHA and have been hypothesized to be involved in the etiology of FHA. Ghrelin concentrations are elevated in exercising women with FHA. Interestingly, while fasting ghrelin, an orexigenic peptide, is elevated in women with FHA, PYY, an orexigenic peptide, is paradoxically also elevated in women with anorexia nervosa and exercising women with FHA. Leptin, an adipocytokine, is also suppressed in FHA associated with exercise and anorexia. A critical leptin concentration threshold is suggested to be necessary for regular menses to occur. Ghrelin, PYY, and leptin all have the ability to cross the blood brain barrier and, in the hypothalamus, can modulate appetite and food intake, and are hypothesized to affect the hypothalamic-pituitary-ovarian axis. Future studies are needed to determine if ghrelin, PYY, or leptin play a direct role in the regulation of the hypothalamic-pituitary-ovarian axis, and if these signals can be altered by improving energy status secondary to increasing caloric intake and initiate the reversal of amenorrhea.

Topics: Adipokines; Anorexia Nervosa; Blood-Brain Barrier; Energy Intake; Energy Metabolism; Feeding Behavior; Female; Ghrelin; Humans; Leptin; Menstruation Disturbances; Motor Activity; Peptide YY

Anorexia nervosa (AN), a disorder characterized by the refusal to sustain a healthy weight, has the highest mortality of any psychiatric disorder. This review presents a model of AN that ties together advances in our understanding of how leptin, serotonin, and hypogonadism are brought about in AN and how they influence bone mass. Serotonin (5-hydroxytryptamine) is a key regulator of satiety and mood. The primary disturbance in AN results from alterations in serotonin signaling. AN patients suffer from serotonergic hyperactivity of Htr1a-dependent pathways that causes dysphoric mood and promotes restrictive behavior. By limiting carbohydrate ingestion, anorexics decrease their serotonin levels. Reduced serotonergic signaling in turn suppresses appetite through Htr1a/2b, decreases dysphoric mood through Htr1a/2a, and activates the sympathetic nervous system (SNS) through Htr2c receptors in the ventromedial hypothalamus. Activation of the SNS decreases bone mass through β2-adrenergic signaling in osteoblasts. Additional topics reviewed here include osteoblastic feedback of metabolism in anorexia, mechanisms whereby dietary changes exacerbate bone loss, the role of caloric restriction and Sirt1 in bone metabolism, hypothalamic hypogonadism's effects on bone mass, and potential treatments.

Topics: Animals; Anorexia Nervosa; Bone Density; Bone Diseases, Metabolic; Bone Resorption; Humans; Leptin; Serotonin; Signal Transduction; Sympathetic Nervous System

Anorexia nervosa (AN) has the highest mortality rate between psychiatric disorders, and evidence for managing it is still very limited. So far, pharmacological treatment has focused on a narrow range of drugs and only a few controlled studies have been performed. Furthermore, the studies have been of short duration and included a limited number of subjects, often heterogenic with regard to stage and acute nutritive status. Thus, novel approaches are urgently needed. Body weight homeostasis is tightly regulated throughout life. With the discovery of orexigenic and anorectic signals, an array of new molecular targets to control eating behavior has emerged. This review focuses on recent advances in three important signal systems: leptin, ghrelin, and endocannabinoids toward the identification of potential therapeutical breakthroughs in AN. Our review of the current literature shows that leptin may have therapeutic potentials in promoting restoration of menstrual cycles in weight restored patients, reducing motor restlessness in severely hyperactive patients, and preventing osteoporosis in chronic patients. Ghrelin and endocannabinoids exert orexigenic effects which may facilitate nutritional restoration. Leptin and endocannabinoids may exert antidepressive and anxiolytic effects. Finally, monitoring serum concentration of leptin may be useful in order to prevent refeeding syndrome.

Topics: Animals; Anorexia Nervosa; Anxiety; Body Weight; Cannabinoid Receptor Modulators; Depression; Endocannabinoids; Ghrelin; Humans; Leptin; Menstrual Cycle

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

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

The discovery of leptin has significantly advanced our understanding of the metabolic importance of adipose tissue and has revealed that both leptin deficiency and leptin excess are associated with severe metabolic, endocrine, and immunological consequences. We and others have shown that a prominent role of leptin in humans is to mediate the neuroendocrine adaptation to energy deprivation. Humans with genetic mutations in the leptin and leptin receptor genes have deregulated food intake and energy expenditure leading to a morbidly obese phenotype and a disrupted regulation in neuroendocrine and immune function and in glucose and fat metabolism. Observational and interventional studies in humans with (complete) congenital leptin deficiency caused by mutations in the leptin gene or with relative leptin deficiency as seen in states of negative energy balance such as lipoatrophy, anorexia nervosa, or exercise-induced hypothalamic and neuroendocrine dysfunction have contributed to the elucidation of the pathophysiological role of leptin in these conditions and of the clinical significance of leptin administration in these subjects. More specifically, interventional studies have demonstrated that several neuroendocrine, metabolic, or immune disturbances in these states could be restored by leptin administration. Leptin replacement therapy is currently available through a compassionate use program for congenital complete leptin deficiency and under an expanded access program to subjects with leptin deficiency associated with congenital or acquired lipoatrophy. In addition, leptin remains a potentially forthcoming treatment for several other states of energy deprivation including anorexia nervosa or milder forms of hypothalamic amenorrhea pending appropriate clinical trials.

Topics: Adrenal Glands; Amenorrhea; Anorexia Nervosa; Cognition; Female; Humans; Hypothalamo-Hypophyseal System; Leptin; Lipodystrophy; Male; Models, Biological; Neurosecretory Systems; Reproduction; Thyroid Gland

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

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

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

Anorexia nervosa (AN) belongs to a group of eating disorders and is characterized by extreme body weight loss. AN patients show combination of physical, psychological and behavioral disturbances. Neuropeptides partly control energy homeostasis and modulate hormone release. Leptin, a peptide secreted by adipocytes, may influence the interactions between central and peripheral signals. Hypoleptinaemia found in AN is connected with disturbed control of appetite and hormonal dysfunction as well as has implications for the hypothalamo-pituitary-gonadal axis, bone mineral density and physical hyperactivity. Low leptin levels are increased with refeeding. However, the prolonged hypoleptinaemia in weight recovered AN patients may result in persistent hypothalamic amenorrhoea. The hyperactivity has been observed in 31-80 % of AN cases. The mechanisms underlying the hyperactivity found in patients with anorexia nervosa seem to be more complicated as many factors including neuropeptides may be involved. Orexins may affect not only appetite but also behavior and psychophysical activity as they may regulate reproductive and stress hormone secretion, stimulate a variety of stereotypic behaviors including eating and stress reaction, and affect the hypothalamo-pituitary-adrenal (HPA) axis, alter glucocorticoid and catecholamine secretion and activate the sympathetic nervous system. Orexins influence the mechanism regulating arousal and sleep, cardiovascular function, temperature, metabolic rate and locomotive activity. It is worth considering how abnormal activity of hypothalamic neuropeptides or their receptors may play a role in the mechanisms of hyperactivity, disturbed control of appetite and hormonal dysfunction in patients with anorexia nervosa.

Topics: Anorexia Nervosa; Humans; Hypothalamo-Hypophyseal System; Intracellular Signaling Peptides and Proteins; Leptin; Neuropeptides; Orexins; Pituitary-Adrenal System; Psychomotor Agitation

Up to 80% of patients with Anorexia Nervosa (AN) demonstrate hyperactivity. Hyperactivity counteracts weight gain during treatment and is associated with poor outcome of the disease. We hypothesized that hyperactivity in AN patients has a neurobiological basis and used an animal model-based translational approach to gain insight in mechanisms underlying this hyperactivity. Previously we and others showed that leptin treatment attenuates hyperactivity in the rat activity-based anorexia (ABA) model. The mechanisms involved in this process are, however, unknown. Here we describe potential downstream effector mechanisms involved in the attenuation of hyperactivity by leptin treatment in ABA rats.

Topics: Animals; Anorexia Nervosa; Disease Models, Animal; Humans; Hyperkinesis; Leptin; Motor Activity

Leptin is a hormone with pleiotropic functions affecting several tissues. Because leptin has a crucial role in the adaptation of an organism to semi-starvation, anorexia nervosa (AN) serves as a model disorder to elucidate the functional implications of hypoleptinaemia; vice versa, several symptoms in patients with this eating disorder are related to the low leptin levels, which are characteristic of acute AN. Weight gain in AN patients can induce relative hyperleptinaemia in comparison to controls matched for body mass index; circulating leptin concentrations in AN patients thus transverse from subnormal to supranormal levels within a few weeks. We review findings on leptin secretion in AN and focus on implications, particularly for the hypothalamus-pituitary-gonadal axis, bone mineral density and physical hyperactivity. Undoubtedly, the elucidation of leptin's function as a trigger of diverse neuroendocrine adaptations to a restricted energy intake has substantially advanced our knowledge of the pathogenesis of distinct symptoms of AN, including amenorrhoea that represents one of the four diagnostic criteria. The fact that hypoleptinaemia can induce hyperactivity in a rat model for AN has led to a series of studies in AN patients, which support the notion that application of leptin to severely hyperactive patients might prove beneficial.

Topics: Animals; Anorexia Nervosa; Humans; Leptin; Starvation

Leptin, a key hormone in energy homeostasis and neuroendocrine function, has a permissive role in initiating puberty and is crucial in the pathogenesis of reproductive dysfunction in several disease states of energy imbalance. KiSS1 neurons have recently been suggested to mediate leptin's effect on the reproductive system. New insights from recent animal studies and clinical trials are discussed.. Alterations in the expression profile of the KiSS1 gene and the kisspeptin receptor have been linked to reproductive dysfunction in leptin-deficient states. Neuroendocrine, including reproductive, dysfunction can be restored in humans and animals by leptin-replacement therapy. These insights have significantly advanced our understanding of hormonal systems needed to maintain normal reproduction. These data, if confirmed, also suggest a role for leptin as a novel therapeutic approach in several disease states.. Recent proof-of-concept studies involving leptin administration to humans underline the critical role of leptin not only in regulating energy homeostasis, but also in maintaining normal reproductive function. Leptin-replacement therapy is currently under intensive investigation as a potential novel therapeutic option for several conditions associated with reproductive dysfunction due to hypoleptinemia.

Topics: Amenorrhea; Animals; Anorexia Nervosa; Energy Metabolism; Female; Gonads; Humans; Hypothalamo-Hypophyseal System; Infertility; Kisspeptins; Leptin; Male; Menarche; Obesity; Polycystic Ovary Syndrome; Puberty; Reproduction; Sex Characteristics; Tumor Suppressor Proteins

This paper discusses the hypothesis that a 'drive for activity" in the presence of physiological and endocrine changes consistent with starvation is a characteristic symptom of acute anorexia nervosa (AN). This 'drive for movement', along with alertness and lack of fatigue, so unlike the motor slowing and loss of energy observed in simple starvation has been recognized in AN throughout history, but has received little attention in the past fifty years. Clinical reports and experimental evidence suggest that 'restlessness' and a 'drive for activity' vary in intensity, they appears to be starvation-dependent and to wane with food intake. Central nervous system (CNS) systems known to be involved in mediating activity and arousal levels that are altered by the negative energy expenditure in AN are reviewed. Among these, the corticotropin-releasing hormone (CRH) system, the melanocyte stimulating hormone/agouti-related protein (MSH/AGRP) system and the norepinephrine/epinephrine (NE/EPI) and dopamine (DA) system may contribute to the 'drive for activity' and alertness in AN. AN appears to represent a disorder of gene/environment interaction. Future research will reveal whether in individuals predisposed to AN, the 'drive for activity' reflects the reactivation of mechanisms important in food scarcity, controlled by one or more evolutionary conserved genes including those regulating foraging behavior. Recognition of the 'drive for activity' as a diagnostic symptom of AN and its assessment prior to re-nutrition would permit clarification of its role in the etiology of AN.

Topics: Anorexia Nervosa; Corticotropin-Releasing Hormone; Dopamine; Humans; Hypothalamo-Hypophyseal System; Leptin; Melanocyte-Stimulating Hormones; Norepinephrine; Pituitary-Adrenal System; Psychomotor Agitation; Serotonin; Thyrotropin

This review focuses on recent publications concerning medical complications in patients with eating disorders, including anorexia nervosa and bulimia nervosa.. Recent literature continues to reflect that multiple organ systems are frequently affected by eating disorders. The literature underscores the frequently cited risk of premature death in those with anorexia nervosa. A plethora of dermatologic changes have been described, some signaling serious underlying pathophysiology, such as purpura, which indicates a bleeding diathesis. Much of the literature continues to delineate the fact that diabetic patients with eating disorders are at high risk of developing diabetic complications. Gastrointestinal complications can be serious, including gastric dilatation and severe liver dysfunction. Acrocyanosis is common, and patients with anorexia nervosa are at risk of various arrhythmias. Low-weight patients are at high risk for osteopenia/osteoporosis. Nutritional abnormalities are also common, including sodium depletion and hypovolemia, hypophosphatemia and hypomagnesemia. Resting energy expenditure, although very low in low-weight patients, increases dramatically early in refeeding.. Medical complications are common and often serious in patients with eating disorders, particularly those with anorexia nervosa.

Topics: Anorexia Nervosa; Bone Diseases; Bulimia Nervosa; Cardiovascular Diseases; Endocrine System Diseases; Gastrointestinal Diseases; Humans; Leptin; Lung Diseases; Nutrition Disorders; Skin Diseases

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

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

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

Amenorrhea is a hallmark sign of anorexia nervosa. Its cause is multifactorial and its resolution necessitates treatment of the underlying eating disorder. The neuroendocrine changes associated with menstrual abnormalities in underweight and weight recovered anorexia nervosa, recent research on osteopenia, and treatment recommendations are addressed.

Topics: Adolescent; Adult; Anorexia Nervosa; Bone Density; Bone Diseases, Metabolic; Exercise; Female; Humans; Hypothalamic Diseases; Leptin; Menstruation Disturbances; Risk Factors

Leptin is an adipocyte-derived hormone, which is involved predominantly in the long-term regulation of body weight and energy balance by acting as a hunger suppressant signal to the brain. Leptin is also involved in the modulation of reproduction, immune function, physical activity, and some endogenous endocrine axes. Since anorexia nervosa (AN) and bulimia nervosa (BN) are characterized by abnormal eating behaviors, dysregulation of endogenous endocrine axes, alterations of reproductive and immune functions, and increased physical activity, extensive research has been carried out in the last decade in order to ascertain a role of this hormone in the pathophysiology of these syndromes. In this article, we review the available data on leptin physiology in patients with eating disorders. These data support the idea that leptin is not directly involved in the etiology of AN or BN. However, malnutrition-induced alterations in its physiology may contribute to the genesis and/or the maintenance of some clinical manifestations of AN and BN and may have an impact on the prognosis of AN.

Topics: Adipose Tissue; Animals; Anorexia Nervosa; Body Weight; Brain; Bulimia; Energy Metabolism; Humans; Hunger; Leptin

Topics: Adult Children; Animals; Anorexia Nervosa; Anxiety; Behavior, Addictive; Bulimia; Family; Humans; Hypothalamus; Leptin; Memory; Psychotherapy; Self Concept

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

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

Adipose tissue secretes a large number of physiologically active peptides that often share structural properties with cytokines, and are therefore collectively referred to as "adipocytokines". Some of these are almost exclusively secreted by adipose tissue. Leptin, adiponectin and resistin are specific fat-derived hormones that affect fuel homeostasis and insulin action, and may also be involved in hematopoiesis and immune functions. Anorexia nervosa is characterized by chronic self-starvation and severe weight loss, mainly at the expense of adipose tissue. Starvation-induced depletion of fat stores is accompanied by alterations of circulating adipocytokines. Plasma leptin and likely resistin levels are decreased in anorectic patients, while plasma adiponectin levels are increased. These alterations may have potential repercussions in the pathophysiology of anorexia nervosa. Thus, low leptin and high adiponectin may separately or in concert contribute to altered hematopoiesis and immunity, enhanced insulin sensitivity, neuroendocrine disturbances or osteopenia in anorexia nervosa.

Topics: Adipocytes; Adiponectin; Animals; Anorexia Nervosa; Hormones, Ectopic; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Proteins; Resistin

Growth hormone (GH) plays a key role not only in the promotion of linear growth but also in the regulation of intermediary metabolism, body composition, and energy expenditure. On the whole, the hormone appears to direct fuel metabolism towards the preferential oxidation of lipids instead of glucose and proteins, and to convey the energy derived from metabolic processes towards the synthesis of proteins. On the other hand, body energy stores and circulating energetic substrates take an important part in the regulation of somatotropin release. Finally, central and peripheral peptides participating in the control of food intake and energy expenditure (neuropeptide Y, leptin, and ghrelin) are also involved in the regulation of GH secretion. Altogether, nutritional status has to be regarded as a major determinant in the regulation of the somatotropin-somatomedin axis in animals and humans. In these latter, overweight is associated with marked impairment of spontaneous and stimulated GH release, while acute dietary restriction and chronic undernutrition induce an amplification of spontaneous secretion together with a clear-cut decrease in insulin-like growth factor I (IGF-I) plasma levels. Thus, over- and undernutrition represent two conditions connoted by GH hypersensitivity and GH resistance, respectively. Anorexia nervosa (AN) is a psychiatric disorder characterized by peculiar changes of the GH-IGF-I axis. In these patients, low circulating IGF-I levels are associated with enhanced GH production rate, highly disordered mode of somatotropin release, and variability of GH responsiveness to different pharmacological challenges. These abnormalities are likely due not only to the lack of negative IGF-I feedback, but also to a primary hypothalamic alteration with increased frequency of growth hormone releasing hormone discharges and decreased somatostatinergic tone. Given the reversal of the above alterations following weight recovery, these abnormalities can be seen as secondary, and possibly adaptive, to nutritional deprivation. The model of AN may provide important insights into the pathophysiology of GH secretion, in particular as regards the mechanisms whereby nutritional status effects its regulation.

Topics: Animals; Anorexia Nervosa; Body Composition; Body Weight; Cytokines; Eating; Energy Metabolism; Ghrelin; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Nutritional Status; Peptide Hormones; Pituitary Gland

Genetic analysis of eating disorders is complex phenotypically and genotypically. As seen in the leptin/melanocortin system, however, the results can lead to a deeper understanding and to new therapies. Benefits are expected for eating disorders that stem from genetic and psychologic causes. Finally, an awareness of possible genetic causes of eating disorders will help determine the causes--and thus the treatments--in children and adolescents with eating disorders, as exemplified by obese patients with mutations in the POMC, PC1, leptin, and MC4R loci.

Topics: Adolescent; alpha-MSH; Anorexia Nervosa; Aspartic Acid Endopeptidases; Bulimia; Child; Child, Preschool; Energy Metabolism; Genotype; Humans; Infant; Leptin; Obesity; Phenotype; Proprotein Convertases; Receptor, Melanocortin, Type 4; Receptors, Corticotropin; Receptors, Leptin; Twin Studies as Topic

Despite the seriously undernourished state of patients with anorexia nervosa (AN) and bulimia nervosa (BN), controversial findings have been published regarding some aspects of the immune system that are otherwise impaired in more typical types of malnutrition, such as protein-energy malnutrition. In general, adaptation processes seem to occur enabling immune function to be preserved during long periods of the illness. However, cell-mediated immunity is usually altered in AN and BN as reflected by lymphocyte subset counts and the response to delayed hypersensitivity tests. Regarding the helper/cytotoxic T cell ratio (CD4:CD8), an immunological marker of the nutritional status, the results of our studies on AN and BN patients showed that the duration of the eating disorder and the time when appropriate treatment is achieved are likely contributors to the alteration of this ratio. Despite these findings, it has been repeatedly pointed out that anorexic patients seem to be free of common viral infections at least until the most advanced stages of debilitation. Some hypotheses that could explain the lack of infection symptoms are reviewed. Cytokines and the altered acute phase response to infection, as well as cortisol and leptin, are considered to be potential factors involved in the adaptation processes occurring in these syndromes. Further progress in the knowledge of the psychoneuroendocrine-immune interactions established in AN and BN will be relevant to the understanding of the aetiology and maintenance mechanisms of these pathologies.

Topics: Adaptation, Physiological; Anorexia Nervosa; Bulimia; Cytokines; Disease Susceptibility; Humans; Hydrocortisone; Immune System; Immunity, Cellular; Leptin; Nutrition Disorders; Nutritional Status

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

Anorexia nervosa is a chronic illness that involves a reduction in caloric intake, loss of weight and amenorrhoea, either primary or secondary. In addition to prolonged amenorrhoea, osteopenia and osteoporosis are the most frequent complications. Patients exhibit an alteration in the hypothalamic-pituitary-gonadal axis, which is responsible for the menstrual disorders. The increase in gonadotrophin secretion that can be observed after ponderal recuperation suggests that malnutrition could be the most important mechanism involved in the decrease in gonadotrophin secretion. The loss of fat tissue, as a consequence of the restriction of nutrients, has been associated with hypoleptinaemia, abnormal secretion of peptides implicated in food control (neuropeptide Y, melanocortins and corticotrophin-releasing hormone, among others) and diminution of the amount of total body fat. Despite oestrogen therapy, the severe loss of bone mass may progress. Other factors such as weight loss, duration of amenorrhoea and low insulin-like growth factor-I (IGF-I) levels could contribute to the loss of bone mass in women with anorexia nervosa. The recuperation of weight and, in particular, the amount of total body fat could lead to the spontaneous recuperation of menstruation.

Topics: Adipocytes; Anorexia Nervosa; Biomarkers; Bone Density; Bone Remodeling; Energy Metabolism; Female; Hormones; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Leptin; Models, Theoretical; Nutrition Disorders; Ovary

This review focuses on current knowledge of leptin biology and the role of leptin in various physiological and pathophysiological states. Leptin is involved in the regulation of body weight. Serum leptin can probably be considered as one of the best biological markers reflecting total body fat in both animals and humans. Obesity in man is accompanied by increased circulating leptin concentrations. Gender differences clearly exist. Leptin is not only correlated to a series of endocrine parameters such as insulin, glucocorticoids, thyroid hormones, testosterone, but it also seems to be involved in mediating some endocrine mechanisms (onset of puberty, insulin secretion) and diseases (obesity, polycystic ovary syndrome). It has also been suggested that leptin can act as a growth factor in the fetus and the neonate.

Topics: Adipose Tissue; Animals; Anorexia Nervosa; Body Weight; Carrier Proteins; Female; Humans; Infant, Newborn; Leptin; Male; Obesity; Polycystic Ovary Syndrome; Puberty; Receptors, Cell Surface; Receptors, Leptin; Sex Characteristics; Thyroid Gland

Underweight is a key symptom in anorexia nervosa. In this review we summarize recent findings pertaining to weight regulation in this eating disorder. The observation that a body mass index below 13 kg/m2 upon admission for inpatient treatment is associated with a high mortality rate and chronic persistence of underweight is of obvious clinical relevance. A lowered leptin secretion, which results from the weight loss, is presumably of major importance for the development of amenorrhea. We discuss findings pertaining to a reduced body weight in other psychiatric disorders during adolescence in the light of Kretschmer's findings related to body frame and psychopathology.

Topics: Animals; Anorexia Nervosa; Body Mass Index; Humans; Leptin; Proteins

Leptin is a hormone synthesized in adipocytes and secreted into the bloodstream. It plays an important role in the regulation of body weight, the adaptation to semi-starvation and in reproductive function. Hence, clinical studies pertaining to anorexia nervosa can serve to further elucidate the functions of this hormone in light of the unique features of this disorder.. Circulating concentrations of leptin are exceedingly low during the acute stage of anorexia nervosa. Which symptoms result from these diminished concentrations must be clarified. Furthermore, research is required to evaluate whether or not a too rapid weight gain might induce a physiological counter-regulation which would predispose to renewed loss of weight.. This review summarizes findings to date pertaining to leptin secretion in patients with anorexia nervosa. In addition, possible diagnostic, pathophysiological and therapeutic implications are discussed.

Topics: Adipose Tissue; Adolescent; Animals; Anorexia Nervosa; Body Weight; Child; Female; Homeostasis; Humans; Leptin; Mice; Mice, Obese; Proteins

Topics: Amenorrhea; Anorexia Nervosa; Female; Humans; Leptin; Obesity; Proteins

What is the signal between the metabolic state and reproductive function--it is one of the scientific puzzles in gynecological endocrinology. Previously it was suggested that such substances as insulin, amino acids, IGFBP-I may play a role as a metabolic signal. Leptin a newly discovered hormonal product of obesity (ob) gene is expressed by adipocytes and thought to play a role in the regulation of food intake, metabolism and reproduction. In this article some informations about leptin secretion, its regulation and localization of leptin receptors have been presented. Particular attention to leptin influence on GnRH secretion have been paid. Probably on the base of this mechanism leptin acts as a link between metabolic state and reproductive system. Some data about leptin secretion in obesity, weight loss related amenorrhoea and anorexia nervosa have been discussed. The putative role of leptin in the pathophysiology of polycystic ovary syndrome and initiation of puberty also have been analyzed.

Topics: Adipocytes; Amenorrhea; Anorexia Nervosa; Carrier Proteins; Eating; Female; Gonadotropin-Releasing Hormone; Humans; Leptin; Obesity; Polycystic Ovary Syndrome; Proteins; Receptors, Cell Surface; Receptors, Leptin; Reproduction

There is a need for novel treatment approaches in anorexia nervosa (AN). While there is broad knowledge with regard to altered appetite regulation and neuropsychological deficits in AN patients on the one hand, and the effects of estrogen replacement upon neuropsychological performance in healthy subjects on the other, up to now, no study has implemented estrogen replacement in AN patients, in order to examine its effects upon AN-associated and general psychopathology, neuropsychological performance and concentrations of peptide components of the hypothalamus-pituitary-adrenal (HPA) axis and within appetite-regulating circuits.. This is a randomized placebo-controlled clinical trial on the effects of a 10-week oral estrogen replacement (combination of ethinyl estradiol 0.03 mg and dienogest 2 mg) in adult female AN patients. The primary target is the assessment of the impact of sex hormone replacement upon neuropsychological performance by means of a neuropsychological test battery consisting of a test for verbal intelligence, the Trail making test A and B, a Go/No-go paradigm with food cues and the Wisconsin Card Sorting Test. Secondary targets include a) the examination of safety and tolerability (as mirrored by the number of adverse events), b) assessments of the impact upon eating disorder-specific psychopathology by means of the Eating Disorder Examination Questionnaire (EDE-Q) and the Eating Disorder Inventory-2 (EDI-2), c) the influence upon anxiety using the State-Trait-Anxiety Inventory (STAI), d) assessments of plasma cortisol levels during a dexamethasone-suppression test and appetite-regulating plasma peptides (ghrelin, leptin, insulin, glucose) during an oral glucose tolerance test and, e) a possible impact upon the prescription of antidepressants.. This is the first study of its kind. There are no evidence-based psychopharmacological options for the treatment of AN. Thus, the results of this clinical trial may have a relevant impact on future treatment regimens. Novel approaches are necessary to improve rates of AN symptom remission and increase the rapidity of treatment response. Identifying the underlying biological (e.g. neuroendocrinological) factors that maintain AN or may predict patient treatment response represent critical future research directions. Continued efforts to incorporate novel pharmacological aspects into treatments will increase access to evidence-based care and help reduce the burden of AN.. European Clinical Trials Database, EudraCT number 2015-004184-36, registered November 2015; ClinicalTrials.gov Identifier: NCT03172533 , retrospectively registered May 2017.

Topics: Adolescent; Adult; Anorexia Nervosa; Antidepressive Agents; Anxiety; Combined Modality Therapy; Double-Blind Method; Estrogen Replacement Therapy; Female; Ghrelin; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Inpatients; Leptin; Middle Aged; Pituitary-Adrenal System; Psychotherapy; Young Adult

The level of physical activity is inappropriately high in up to 80% of the patients suffering of anorexia nervosa (AN), as a result of conscious efforts to lose weight, affect regulation and biological adaptive changes to starvation induced by hypothermia and neuroendocrine mechanisms. The purposes of this paper were to (1) assess the effect of dronabinol-a synthetic cannabinoid agonist-on physical activity in patients with chronic and stable AN, and to (2) unravel the role of leptin and cortisol in this process.. This prospective, randomised, double-blind, crossover study was conducted at a specialised care centre for eating disorders. Twenty-four adult women with AN of at least 5-year duration received either the dronabinol-placebo or placebo-dronabinol sequence. Physical activity was monitored during the fourth week of each intervention. Body weight, leptin and urinary free cortisol excretion were measured repeatedly during the trial. Changes in behavioural dimensions related to AN were assessed by Eating Disorder Inventory-2.. The total duration of physical activity did not change, while its average intensity increased by 20% (P = 0.01) during dronabinol therapy, resulting in an increased energy expenditure with 68.2 kcal/day (P = 0.01) above placebo.. This randomised, double-blind study revealed that cannabinoid agonist treatment was associated with a modest increase in physical activity in adult women with severe and longstanding AN. Additionally, we detected a strong relationship between the circulating levels of leptin and physical activity in these chronically undernourished patients.

Topics: Actigraphy; Adult; Anorexia Nervosa; Body Weight; Cross-Over Studies; Double-Blind Method; Dronabinol; Energy Intake; Female; Humans; Leptin; Middle Aged; Motor Activity; Treatment Outcome; Young Adult

Anorexia nervosa (AN) is characterised by complex neuroendocrine disturbances due to severe underweight, physical hyperactivity and purging behaviour. Cannabinoid agonists are used to palliate cachexia of various causes, but their interactions with the hormonal systems that are involved in energy metabolism have not been previously described in humans. Therefore we found it of interest to assess interactions between the synthetic cannabinoid agonist dronabinol and insulin-like growth factor I (IGF-I), urinary free cortisol (UFC) and adipokines in patients with chronic AN.. This was a prospective, double-blind randomised crossover study, conducted at a specialised care centre for eating disorders. The results are based on twenty-four adult women with chronic AN, who completed the study. The participants received dronabinol (oral capsules, 5mg daily) and matching placebo over four weeks, separated by a four-week washout period. Bioactive IGF was determined by a cell-based bioassay, whereas total IGF-I, IGFBP-2 and -3 and the two adipokines leptin and adiponectines were measured by immunoassays. The UFC excretion was determined by mass spectrometry.. As previously reported, dronabinol treatment caused a small, yet significant increase in BMI as compared to placebo (+0.23 kg/m(2); P = 0.04). This modest weight gain predicted a corresponding increase in bioactive IGF-I, while the amount of daily energy expenditure due to physical activity had a comparable but opposite effect. Nevertheless, neither IGF-I, bioactive IGF nor the IGFBPs levels changed significantly during dronabinol intervention as compared to placebo. Adiponectin also remained unaffected by the weight gain, whereas plasma leptin showed a transient increase at three weeks (P < 0.05). UFC levels were decreased during dronabinol intervention.. Our results showed that low-dosage therapy with the synthetic cannabinoid agonist dronabinol affected neither the concentration nor the activity of the circulating IGF-system in women with severe and chronic AN. However, our results suggest that such treatment may alleviate the increased hypothalamic-pituitary-adrenal axis activity seen in these patients.

Topics: Adipokines; Adiponectin; Adult; Anorexia Nervosa; Body Weight; Cannabinoid Receptor Agonists; Cross-Over Studies; Double-Blind Method; Dronabinol; Energy Metabolism; Female; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Leptin; Prospective Studies; Young Adult

The aim of this study was to determine whether girls with anorexia nervosa (AN) exhibited any relationships between serum levels of LP, ADIPO, RES, VISF, APE-36, APE-12, and bone markers, OPG and sRANKL.. Serum levels of selected adipose tissue hormones, OC, CTx, OPG and sRANKL were assessed using ELISA in 86 study participants suffering from AN and 21 healthy controls, all aged 13 to 18 years.. Girls with AN showed a significant reduction in body mass, BMI, serum concentrations of LP, RES, VISF, APE-36, APE-12, OC, CTx and increased ADIPO concentration. These changes were associated with significant increases in OPG and sRANKL and a decrease in the OPG/sRANKL ratio. Significant positive correlations were revealed between BMI and LP, APE-36, CTx, OPG/sRANKL ratio; OC and VISF; OPG and ADIPO; OPG/sRANKL ratio and LP, APE-36, APE-12. Significant negative correlations were revealed between CTx, sRANKL and RES, APE-36; OPG and APE-36, APE-12; OPG/sRANKL ratio and ADIPO. VISF was shown to be an independent predictor of OC. APE-36 and RES turned out to be independent predictors of CTx, and sRANKL, APE-36 and ADIPO were independent predictors of OPG while APE-36, LP and ADIPO were independent predictors of the OPG/sRANKL ratio.. Changes in bone markers, OPG, sRANKL and/or the OPG/sRANKL ratio exhibited by girls with AN have been found to be associated with changes in the levels of the selected adipose tissue hormones. Abnormal relationships between bone metabolism and LP, ADIPO, RES, VISF and APE might adversely affect the balance of the OPG/sRANKL system and thus potentially compromise the mechanism which compensates for bone remodelling disturbances.

Topics: Adiponectin; Adipose Tissue; Adolescent; Anorexia Nervosa; Apelin; Biomarkers; Bone and Bones; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Osteoprotegerin; RANK Ligand; Resistin

The aim of the current study was to analyze the relationships between plasma hormones, body weight parameters and stressful life events in anorexia nervosa (AN).. 72 females in the active phase of AN were evaluated. 52 healthy women constituted the control group. RIA kits were used to measure plasma hormone levels.. The concentrations of leptin, insulin, IGF-1, triiodothyronine, LH, FSH, estradiol, and testosterone were significantly lower and those of cortisol and growth hormone significantly higher in the AN than the control group. No hormonal differences between restrictive and binge-purging AN subtypes were found. Leptin, IGF-1, gonadotropins, and sex steroids correlated significantly negatively and growth hormone positively with total reduction of body weight or the degree of undernutrition. Associations were also found between lower insulin concentration and family violence, lower cortisol and psychiatric diseases in the family, higher testosterone and patient's alcohol or drug abuse.. The changed activity of the somatotropin-somatomedin, gonadal, and corticotrophin axes corresponds to the clinical stage of AN. Plasma IGF-1 seems to be the most sensitive and useful independent hormonal marker of cachexia.

Topics: Adult; Alcoholism; Anorexia Nervosa; Biomarkers; Cachexia; Divorce; Domestic Violence; Estradiol; Female; Hormones; Humans; Hydrocortisone; Insulin; Insulin-Like Growth Factor I; Leptin; Life Change Events; Nutritional Status; Parent-Child Relations; Sibling Relations; Substance-Related Disorders; Testosterone; Young Adult

Follow-up visits of patients recovering from anorexia nervosa (AN) have shown that some patients do not resume menstrual cycles despite returning to the normal weight for their age and height.. To verify whether leptin, insulin-like growth factor 1 (IGF-1) or another hormonal marker could be a good predictor of the return of menses.. This prospective study included female adolescents diagnosed with AN or eating disorders not otherwise specified (EDNOS) and who were being treated in an ambulatory care unit during nutritional recovery. Body mass index and leptin, luteinizing hormone, estradiol and IGF-1 levels of these patients were evaluated. Blood samples were collected in the 1st (T1), 5th (T2), 10th (T3), 15th (T4) and 20th (T5) weeks of treatment. The hormone levels during nutritional recovery and at the time of the resumption of menses were analyzed.. The hormonal profiles improved after nutritional recovery, with IGF-1 correlating the most with the resumption of menses and nutritional recovery (p = 0.0001). At the resumption of menstruation, the patients showed IGF-1 levels >342.8 ng/ml.. IGF-1 was the best predictor of the return of menses in female adolescents with AN or EDNOS.

Topics: Adolescent; Anorexia Nervosa; Body Mass Index; Child; Female; Follow-Up Studies; Humans; Insulin-Like Growth Factor I; Leptin; Luteinizing Hormone; Menstrual Cycle; Prospective Studies

Anorexia nervosa (AN), a state of chronic nutritional deprivation, is characterized by GH resistance with elevated GH levels and decreased levels of IGF-I. The effects of supraphysiological recombinant human GH (rhGH) on GH resistance in AN are not currently known.. The aim was to investigate whether supraphysiological rhGH increases IGF-I levels in AN.. We conducted a randomized, placebo-controlled study in a Clinical Research Center.. We studied 21 women with AN, 10 (mean age, 28 ± 2.1 yr) treated with rhGH and 11 (mean age, 29.2 ± 2.6 yr) treated with placebo.. rhGH (mean maximum daily dose, 1.4 ± 0.12 mg/d) or placebo was administered to patients for 12 wk.. IGF-I, N-terminal propeptide of type 1 procollagen, type I collagen C-telopeptide, glucose, and insulin levels were measured at wk 0, 1, 2, 3, 4, 8, and 12; C-terminal propeptide of type 1 procollagen, leptin, and free fatty acid levels were measured at wk 0 and 12. Body composition, including total fat and lean mass, was measured by dual-energy x-ray absorptiometry at wk 0 and 12.. IGF-I levels did not differ between the groups at baseline or after treatment (median after 12 wk-rhGH, 124 ng/ml, interquartile range, 94.5, 170.3; vs. placebo, 85.5 ng/ml, interquartile range, 62, 139; P = 0.3). Similarly, changes in glucose, insulin, free fatty acids, and bone markers did not differ between the groups. Total fat mass and percentage fat mass (rhGH, -2.5 ± 0.6%, vs. placebo, 2.2 ± 1.1%; P = 0.004) decreased significantly in the rhGH group compared to placebo despite comparable weight.. Supraphysiological rhGH administration decreases fat mass in AN without increasing IGF-I levels, supporting the role of GH as a mediator of lipolysis independent of IGF-I.

Topics: Absorptiometry, Photon; Adult; Analysis of Variance; Anorexia Nervosa; Blood Glucose; Body Composition; Collagen Type I; Female; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Radioimmunoassay; Recombinant Proteins; Treatment Outcome

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

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

Fibroblast growth factor 19 (FGF19) and FGF21 are novel metabolic regulators that improve insulin sensitivity and decrease adiposity in mice. However, little is known about the nutritional regulation of these factors in humans.. The objective of this study was to measure plasma FGF19 and FGF21 levels in patients with anorexia nervosa (AN) and to explore its relationship with anthropometric and endocrine parameters.. This was a single-center cross-sectional study.. The study was performed in a university hospital.. Seventeen untreated women with a restrictive type of AN and 17 healthy women (control group) were included.. Fasting plasma FGF19 and FGF21, serum insulin, leptin, soluble leptin receptor, adiponectin, resistin, and C-reactive protein were the main outcome measures.. Plasma FGF19 levels did not significantly differ between the groups studied, whereas plasma FGF21 levels were significantly reduced in AN relative to the control group. Plasma FGF21 positively correlated with body mass index and serum leptin and insulin and was inversely related to serum adiponectin in both groups. In contrast, plasma FGF19 was not related to any of parameters studied. Partial realimentation significantly reduced plasma FGF21 levels in AN.. Circulating levels of FGF21 but not FGF19 are strongly related to body weight and serum levels of leptin, adiponectin, and insulin in both anorectic and normal-weight women. We suggest that reduced plasma FGF21 levels could be involved in the pathophysiology of AN or in a complex adaptive response to this disease.

Topics: Adaptation, Biological; Adiponectin; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Case-Control Studies; Cross-Sectional Studies; Eating; Female; Fibroblast Growth Factors; Humans; Insulin; Leptin; Triiodothyronine

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

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

The goal of this study was to investigate the relationship of body composition and neuroendocrine levels with clinical outcome in women with anorexia nervosa in a relapse-prevention trial.. Body composition and fasting cortisol and leptin levels were assessed before random assignment in 32 weight-recovered subjects with anorexia nervosa from the New York site of the Fluoxetine to Prevent Relapse in Women With Anorexia Nervosa trial. Clinical outcome at the end of study participation was defined using modified Morgan-Russell criteria (full, good, fair, poor), then dichotomized into treatment "success" or "failure.". In a binary logistic regression model examining the effect of percent body fat, body mass index, anorexia nervosa subtype, waist-to-hip ratio, and serum cortisol and leptin levels on treatment outcome, only percent body fat was significantly associated with outcome.. In recently weight-restored women with anorexia nervosa, lower percent body fat was associated with poor long-term outcome.

Topics: Adipose Tissue; Adiposity; Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Female; Fluoxetine; Humans; Hydrocortisone; Leptin; Logistic Models; Longitudinal Studies; Middle Aged; Prognosis; Secondary Prevention; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Waist-Hip Ratio

This study describes: 1. The therapeutic effects on anorexia nervosa (AN) and bulimia nervosa (BN) patients of a psycho-nutritional intensive day-hospital program; 2. The possible correlation between the changes observed in the psychometric tests and the variations of a number of biological parameters. Forty-six female patients (24 AN and 22 BN) were assessed through a semi-structured clinical interview based on DSM-IV criteria for Eating Disorders (ED) and a number of psychometric tests (SCL-90R, BDI, EDI-2, EAT-40, BITE, BAT) at the beginning and at the end of treatment, and after a 6-month follow-up. At these three times, we also assessed the plasma level of leptin, cortisol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and 17beta-estradiol together with body mass index (BMI) and menstrual cycle. From beginning to discharge, the scores on all psychometric tests improved in the whole sample, except for the Perfectionism subscale of EDI-2 in both groups (AN and BN), the Anger-Hostility, Phobic Anxiety and Paranoid Ideation subscales of SCL-90 and the Interpersonal Distrust subscale of EDI-2 in the BN group. At follow-up, there was a worsening of the BITE scores and of a number of EDI-2 subscales, especially in the AN subgroup - with these changes correlating with the trend of BMI. In AN patients, plasma leptin levels changed from the beginning to the end of treatment and at follow-up according to BMI changes. The mean plasma leptin level in the BN subgroup was higher than in the AN one. We found a statistically significant correlation with the scores of BDI, SCL-90R Depression and Ineffectiveness subscales, EAT-40, BITE-Symptom subscale and the trend of menses dividing these patients into two subgroups (according to the plasma leptin concentration, higher or lower than the top leptin level in the anorexics). These data seem to confirm that leptin secretion doesn't correlate univocally to BMI.

Topics: Adolescent; Adult; Anorexia Nervosa; Biomarkers; Body Mass Index; Bulimia; Female; Humans; Inpatients; Leptin; Menstrual Cycle; Psychiatric Status Rating Scales; Psychometrics; Treatment Outcome

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

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

The obese gene product--leptin (LEP)--is a hormone released from adipose tissue implicated in the regulation of nutritional state and energy balance. The aim of this study was to assess the relationship between plasma LEP levels and nutritional state, secretion of hormones of the hypothalamic-pituitary axis, and personality traits in patients with anorexia nervosa (AN). The study was performed in 22 women with AN aged 19.45 +/- 0.92 yrs, mean BMI of 15.48 +/- 0.29 kg/m2, 14 healthy women with normal body weight (NW), aged 29.71 +/- 2.4 yrs, mean BMI of 21.22 +/- 0.43 kg/m2, and 19 obese women without metabolic disorders (OTY), aged 34.5 +/- 2.65 yrs, mean BMI of 37.47 +/- 2.06 kg/m2. Hormone levels were measured with RIA test kits. Psychological examination was carried out by means of Gough-Helibrun's and Catell's personality tests. Body mass index (BMI) and body composition, i.e. body fat mass (BF) and body fat percentage (%BF) were determined with a DEXA instrument (Lunar Co., WI, USA). Absolute plasma LEP levels and the LEP/%BF index were lowest in patients with AN whereas LEP/BF index did not differ among AN, NW, and OTY groups (Table 1). In all groups, LEP levels were positively correlated with BMI, BF, and %BF (Table 2). Plasma neuropeptide Y (NPY), beta-endorphin (B-EP), and galanin (GAL) levels in AN were significantly higher than in NW and OTY groups (Table 3). Plasma GAL levels were positively correlated with LEP/BF and LEP/%BF in AN patients only. Moreover in the AN group, serum/plasma levels of insulin (I), insulin-like growth hormone-1 (IGF-1), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), and free triiodothyronine (fT3) were significantly lower, and levels of cortisol (F) significantly higher than in NW and OTY groups (Table 4). Plasma LEP levels in AN patients were positively correlated with IRI, IGF-1, free thyroxine (fT4), and FSH levels, and negatively correlated with thyrotrophin (TSH) levels. Personality traits in patients with AN were significantly correlated with hormone levels (Tables 5 and 6), BMI and body fat content (Table 6).. 1) Leptin secretion from adipose tissue is not related to the nutritional state. 2) High levels of NPY, beta-EP, and GAL in AN confirm that starvation is deliberate in these patients. Low LEP levels in AN may lead to secondary amenorrhea and thyroid function disorders, as well as enhanced cortisol and growth hormone secretion of hypothalamic origin. A positive correlation between levels of LEP and IGF-1 and IRI may reflect mechanisms preserving adipose tissue and protecting from hypoglycemia and insulin resistance. A positive correlation between LEP and fT4 levels suggests a tendency to energy-sparing under conditions of low energy intake. Lack of correlation between LEP and F levels apparently reflects peripheral cortisol resistance in AN. 3) Both undernutrition and abnormal hormone secretion (LEP, F, fT3, IGF-1, LH, E2) are related to social self-withdrawal, defensive attitudes, low self-esteem and high level of self-supervision in AN.

Topics: Adipose Tissue; Adult; Amenorrhea; Anorexia Nervosa; Female; Human Growth Hormone; Humans; Hydrocortisone; Hypothalamus; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Metabolic Diseases; Nutritional Status; Starvation; Thyroid Diseases

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

(1) To investigate normal circulating levels of leptin in children at various stages of pubertal maturation (Tanner stages) according to sex; and (2) to analyze serum leptin levels in pediatric patients with eating disorders (obesity, anorexia nervosa, and bulimia nervosa).. Fasting leptin levels were studied in normal healthy boys and girls throughout development. Obese pediatric subjects and patients with anorexia nervosa were studied at the time of diagnosis and after 6 months and 1 year of treatment for weight reduction or weight recuperation, respectively. Patients with bulimia nervosa were studied at the moment of diagnosis.. Leptin levels in both boys and girls vary significantly depending on the maturational stage, being low in both sexes at Tanner stage I and rising significantly by Tanner stage III. In girls, there was a further increase by Tanner stage V and a significant decrease in boys, resulting in a sexual dimorphism in Tanner V subjects. In obese prepubertal patients, leptin levels were significantly elevated at the time of diagnosis and declined significantly with weight loss (ANOVA: p < 0.0001). In anorexia nervosa patients' leptin levels are significantly reduced compared with age- and sex-matched controls (p < 0.0001). These levels remain significantly lower even after recovery of at least 10% of the original body weight and 1 year later. In patients with bulimia leptin levels were reduced at the time of diagnosis but were significantly higher than in patients with anorexia.. In normal pediatric subjects leptin levels are highly correlated with the body mass index, but this is not the case in eating disorders, where the body mass index is either significantly elevated or reduced. Both age and sex should be taken into consideration when analyzing serum leptin levels.

Topics: Adolescent; Analysis of Variance; Anorexia Nervosa; Body Mass Index; Bulimia; Child; Fasting; Female; Humans; Leptin; Male; Obesity; Proteins; Reference Values

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

The amygdala is a subcortical limbic structure consisting of histologically and functionally distinct subregions. New automated structural magnetic resonance imaging (MRI) segmentation tools facilitate the. T1-weighted MRI scans were subsegmented and multi-stage quality controlled using FreeSurfer. Left/right hemispheric amygdala nuclei volumes were cross-sectionally compared between females with AN (. Globally, most amygdala nuclei volumes in both hemispheres were reduced in AN. In AN, amygdala nuclei are altered to different degrees. Severe volume loss in rostral-medially clustered nuclei, collectively involved in olfactory/food-related reward processing, may represent a structural correlate of AN-related symptoms. Hypoleptinemia might be linked to rostral-medial amygdala alterations.

Topics: Amygdala; Anorexia Nervosa; Female; Gray Matter; Humans; Leptin; Magnetic Resonance Imaging

Topics: Anorexia Nervosa; Body Mass Index; Humans; Leptin

The amygdaloid complex plays a pivotal role in emotion processing and has been associated with rumination transdiagnostically. In anorexia nervosa (AN), we previously observed differential reductions of amygdala nuclei volumes (rostral-medial cluster substantially affected) and, in another study, elevated food-/weight-related rumination. Both amygdala volumes and rumination frequency correlated with characteristically suppressed leptin levels in AN. Thus, we hypothesized that amygdala nuclei alterations might be associated with AN-related rumination and potentially mediate the leptin-rumination relationship in AN.. Rumination (food-/weight-related) was assessed using ecological momentary assessment for a 14-day period. We employed frequentist and Bayesian linear mixed effects models in females with AN (n = 51, 12-29 years, majority admitted to inpatient treatment) and age-matched healthy females (n = 51) to investigate associations between rostral-medial amygdala nuclei volume alterations (accessory basal, cortical, medial nuclei, corticoamygdaloid transitions) and rumination. We analyzed mediation effects using multi-level structural equation models.. Reduced right accessory basal and cortical nuclei volumes predicted more frequent weight-related rumination in AN; both nuclei fully mediated the effect of leptin on weight-related rumination. In contrast, we found robust evidence for the absence of amygdala nuclei volume effects on rumination in healthy females.. This study provides first evidence for the relevance of specific amygdala substructure reductions regarding cognitive symptom severity in AN and points toward novel mechanistic insight into the relationship between hypoleptinemia and rumination, which might involve the amygdaloid complex. Our findings in AN may have important clinical value with respect to understanding the beneficial neuropsychiatric effects of leptin (treatment) in AN and potentially other psychiatric conditions such as depression.

Topics: Amygdala; Anorexia Nervosa; Bayes Theorem; Ecological Momentary Assessment; Female; Humans; Leptin

Anorexia nervosa (AN) is a metabo-psychiatric disorder where alterations of cytokines, neuropeptides, neurotransmitters, and the interactions between these factors can play an important role. Thus, the primary goal of the presented study was a cross-sectional analysis of immune-related proteins in patients with AN. Moreover, the correlations between these molecules and selected neuropeptides were studied. Twenty-five adolescent inpatients girls in the acute stage of a restrictive type of AN were enrolled in the study within the first year of the disease. Additionally, thirty similar in age and height controls (CG) were also assessed. The levels of 24 immune-related proteins, including cytokines, chemokines, and proteases, were measured. Moreover, selected adipocytokines, gastrointestinal hormones, and centrally produced neuropeptides levels were determined. Finally, the correlations between these molecules were analyzed. The fasting levels of CXCL1, CXCL9, FGF2, GrB, IL1, IL6, IL8, MMP8, MMP9, CTSS were statistically lower in AN than in the CG. The concentrations of many immune-related proteins remain unchanged despite their metabolic and mental condition. Moreover, significant correlations were found between leptin and CXCL1, CXCL9, GrB, IL1, IL6, and MMP8. Leptin receptors were correlated with GrB, while resistin was associated with MMP9. Our findings suggest that the initial stage of restrictive AN among adolescents within the first year of the disease is not connected with a pro-inflammatory state. Some immune-related protein changes may be associated with altered neuropeptides, primarily leptin, its receptors, and resistin. Future research should clarify which changes are primary and secondary to weight loss and whether these changes normalize with increasing weight. This would aid in understanding the complex etiopathogenesis of AN and in the search for new methods of treatment.

Topics: Adiponectin; Adolescent; Anorexia Nervosa; Cytokines; Fasting; Female; Humans; Leptin; Resistin

Anorexia nervosa (AN) is a serious and complex mental disorder affecting mainly young adult women. AN patients are characterized by low body weight in combination with self-induced starvation, intense fear of gaining weight, and distortion of body image. AN is a multifactorial disease, linked by recent evidence to a dysregulation of the immune system.. In this pilot study, 22 blood serums from AN patients were tested for the presence of autoantibodies against primate hypothalamic periventricular neurons by immunofluorescence and by a home-made ELISA assay. Cellular fluorescence suggests the presence of autoantibodies which are able to recognize these neurons (both to body cell and fiber levels). By means of ELISA, these autoantibodies are quantitatively evaluated. In addition, orexigenic and anorexigenic molecules were measured by ELISA. As control, 18 blood serums from healthy age matched woman were analysed.. All AN patients showed a reactivity against hypothalamic neurons both by immunofluorescence and ELISA. In addition, ghrelin, pro-opiomelanocortin (POMC), and agouti-related peptide (AGRP) were significantly higher than in control serums (p < 0.0001). In contrast, leptin was significantly lower in AN patients than controls (p < 0.0001).. Immunoreaction and ELISA assays on AN blood serum suggest the presence of autoantibodies AN related. However, it is not easy to determine the action of these antibodies in vivo: they could interact with specific ligands expressed by hypothalamic cells preventing their physiological role, however, it is also possible that they could induce an aspecific stimulation in the target cells leading to an increased secretion of anorexigenic molecules. Further studies are needed to fully understand the involvement of the immune system in AN pathogenesis.. V, descriptive study.

Topics: Agouti-Related Protein; Animals; Anorexia Nervosa; Autoantibodies; Female; Ghrelin; Humans; Leptin; Phobic Disorders; Pilot Projects; Pro-Opiomelanocortin

Anorexia nervosa (AN) is a severe mental disorder that is characterized by restriction of energy intake, low weight, and endocrine abnormalities. One of the known endocrine changes in relation to underweight is in the GH/IGF-I axis. The aim of the study was (a) to investigate longitudinal characteristics of the IGF-I-change during therapy and weight gain in adult AN, (b) to determine relationships between IGF-I and leptin, (c) to characterize patients with weak and pronounced hormonal reactions to underweight.. Data was assessed from 19 AN patients. Over the first two months, serum IGF-I concentrations were assessed on a weekly basis; thereafter on a monthly basis. The trend of IGF-I values over time was analyzed using individual growth models.. In total, n = 177 IGF-I measurements were analyzed. IGF-I increased significantly dependent on BMI (slope = 20.81, p < 0.001), not modulated by duration of disease. The increase in IGF-I was significantly related to the increase in leptin concentrations over time (slope = 15.57, p < 0.001). Patients with a weaker hormonal reaction to underweight were significantly older compared to patients with a pronounced hormonal reaction (t(17) = 3.07, p = 0.007).. During treatment, IGF-I change is clearly related to BMI as well as to leptin. Age appears to be associated with the IGF-I response to underweight.

Topics: Adult; Anorexia Nervosa; Body Mass Index; Humans; Inpatients; Insulin-Like Growth Factor I; Leptin; Thinness

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

To assess pancreatic exocrine function in patients with anorexia nervosa using a breath test with. Anthropometric measurements, biochemical and hormonal parameters (serum leptin, soluble leptin receptor (sLR), acylated and desacylated ghrelin, free leptin index (FLI)), and MTG-BT were performed in a group of 31 girls with the restrictive type of AN, as well as 38 healthy girls (C).. The average cumulative dose of. In girls with AN, the pancreatic efficiency of lipase secretion was found to be normal, while the kinetics of this enzyme secretion were disturbed. These changes may result from disorders in the functioning of the adipose-insular and islet-acinar axes.

Topics: Adolescent; Anorexia Nervosa; Breath Tests; Carbon Dioxide; Case-Control Studies; Child; Female; Ghrelin; Humans; Leptin; Pancreas, Exocrine; Receptors, Leptin; Triglycerides

Topics: Affect; Anorexia Nervosa; Behavior; Cognition; Humans; Leptin; Time Factors

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

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

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

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

The hypothesis linking hyperactivity with weight loss associated hypoleptinemia in anorexia nervosa gained momentum after a study showing that leptin suppressed semi-starvation induced hyperactivity in rats. Alternatively, ambient temperature is a key modulating factor of activity in semi-starved rats. The aim of the study is to compare the efficacy of leptin with increased ambient temperature in the prevention of hyperactivity in semi-starved rats. 74 Sprague-Dawley male rats were employed in two experiments with the difference residing in the length of baseline. After an extended (28 days), or shorter (14 days) baseline with free access to food and the running wheel, housed at 21 °C, animals were either ad-lib feed or food restricted (60% of food ingested during previous week) and infused with same amount of leptin at 21 °C, 25 °C, or vehicle at 21 °C, 25 °C and 32 °C for a week. Animals housed at 32 °C significantly reduced wheel running and weight loss during food restriction while animals given leptin did not yield no differences in activity or weight loss. Moreover, unlike animals housed at 32 °C, body temperature of leptin infused animals housed at 21 °C was significantly reduced during food restriction. Furthermore, leptin treated rats without a preceding stable pattern of activity displayed a severe dysregulation of circadian rhythm in activity and a collapse of body temperature. Housing temperature plays a more critical role than leptin in the regulation of semi-starvation induced hyperactivity in rats, which may be of relevance for the management of hyperactivity in anorexia nervosa.

Topics: Animals; Anorexia Nervosa; Hyperkinesis; Leptin; Male; Motor Activity; Physical Conditioning, Animal; Psychomotor Agitation; Rats; Rats, Sprague-Dawley; Starvation; Temperature

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

To examine the hypothesis that normalization of low circulating leptin levels in patients with anorexia nervosa ameliorates hyperactivity, three seriously ill females with hyperactivity were treated off-label with metreleptin (recombinant human leptin) for up to 14 days. Drive for activity, repetitive thoughts of food, inner restlessness, and weight phobia decreased in two patients. Surprisingly, depression improved rapidly in all patients. No serious adverse events occurred. Due to obvious limitations of uncontrolled case series, placebo-controlled clinical trials are mandatory to confirm the observed rapid onset of beneficial effects. Our findings suggest an important role of hypoleptinemia in the mental and behavioral phenotype of anorexia nervosa.

Topics: Anorexia Nervosa; Body Weight; Cognition; Female; Humans; Leptin

Topics: Absorptiometry, Photon; Adiponectin; Adolescent; Adult; Anorexia Nervosa; Biomarkers; Cross-Sectional Studies; Echocardiography, Doppler; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intra-Abdominal Fat; Leptin; Linear Models; Male; Middle Aged; Obesity; Pericardium; Sirtuin 1; Young Adult

Endocrine Consequences of Anorexia Nervosa

Topics: Anorexia Nervosa; Endocrine System Diseases; Female; Humans; Leptin; Pituitary Gland; Thyroid Gland

Psychological and neuroendocrine alterations are typical characteristics in anorexia nervosa patients. The role of adipokines and cytokines as mediators of body systems' adaptations to the patients' abnormal eating behavior is not well understood. The duration of disease seems to be a determinant of nutritional status and associated hormone changes. We aimed to assess whether alterations in adipokines, cytokines and cortisol do already exist in patients with a recent disease onset by means of a case-control study.. Forty-one adolescent female patients on their first-episode and diagnosed with anorexia nervosa, were matched by age and socioeconomic status (SES) (1:1) with healthy girls. Leptin, soluble leptin receptor (sOB-R), adiponectin, cortisol, and the cytokines IL-1β, IL-2, IL-6 and TNF-α were examined.. The results showed reduced leptin and increased sOB-R and cortisol levels in AN patients. Adiponectin was also increased but opposite to the previous biomarkers did not correlate with BMI Z-score. Serum TNF-α and IL-2 showed significantly lower and higher values, respectively, in the AN patients than in the controls. Cortisol showed the strongest correlation with sOB-R (r=0.436; P=0.005).. Our study confirms previous findings on adipokine and cortisol alterations in AN patients, while overall cytokine results did not show a clear disruption in AN patients with short disease duration. The results highlight the need to disentangle the role of the sOB-R in the interactions between leptin and cortisol secretion.

Topics: Adipokines; Adiponectin; Adolescent; Anorexia Nervosa; Biomarkers; Case-Control Studies; Cytokines; Early Diagnosis; Female; Humans; Hydrocortisone; Interleukin-1beta; Interleukin-2; Interleukin-6; Leptin; Tumor Necrosis Factor-alpha

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

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

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

Anorexia nervosa (AN) is an eating disorder characterised with extremely low weight. Adipokines are adipose tissue-derived substances that show a wide spectrum of biological activities. We aimed to assess selected adipokine levels in women with AN before and after nutritional intervention. We also sought to examine whether BMI is the only confounding factor influencing adipokine assessment in AN.. Sixty-five women participated in the study: 20 individuals with AN before any treatment, 18 AN patients after nutritional intervention lasting for at least six months, and 27 women as controls. In all participants blood collection and anthropometric measurements were performed. ELISA was used for evaluation of leptin receptor, adiponectin and its isoforms, and resistin. Leptin was assessed with RIA, and visfatin was measured with EIA assay.. Leptin and free leptin index (FLI) were lowest in treatment-naïve AN women. HMW-adiponectin and visfatin were enhanced in AN. Other adipokine levels showed no significant differences. When two subsets of anorexia nervosa were compared, only leptin, leptin receptor, and FLI were markedly different. When data were adjusted to BMI, leptin and FLI remained significantly different in the pre-treated AN subgroup when compared with the control group.. Our results suggest that leptin is the most important adipokine in AN. It is also important that in our AN population leptin and FLI are the only factors that are influenced not only by the fat content.

Topics: Adipokines; Adiponectin; Adolescent; Adult; Anorexia Nervosa; Cytokines; Female; Humans; Leptin; Nicotinamide Phosphoribosyltransferase; Receptors, Leptin; Resistin; Young Adult

Constitutional thinness (CT) is an underweight state characterized by normal menstruations and no change in feeding behaviour. Thinness is the only resemblance between Anorexia Nervosa (AN) and CT. Removal of amenorrhea from the new DSM 5 definition of AN might result in misdiagnosis between these two populations. The objective of this study was to compare CT, AN and Control subjects in terms of biological, anthropometric, and psychological markers in order to better distinguish AN from CT subjects.. Body composition, nutritional markers, pituitary hormones, bone markers and psychological scores were evaluated in three groups of young women: fifty-six CT, forty restrictive-type AN and fifty-four Control subjects. For every marker, a receiver Operator Characteristics (ROC) curve was calculated to evaluate the accuracy of differentiation between AN and CT groups.. For most studied parameters, CT subjects were similar to Controls but dramatically different from AN subjects. DEBQ Restrained Eating subscale score was identified by ROC data analysis as the only psychological parameter tested to successfully differentiate AN from CT. Free-T3 and Leptin were shown to be powerful markers to differentiate AN and CT populations as they were highly specific and sensitive ones.. The exclusive use of psychological testing criteria is not always sufficient to differentiate AN and CT patients. Minimally, additional testing of Free T3 levels, which is cheap and widely accessible for general practitioners, should be completed to avoid misdiagnosis which could result in the implementation of ineffective treatment plans and social stigmatization for CT women.

Topics: Adult; Anorexia Nervosa; Anthropometry; Biomarkers; Body Composition; Body Mass Index; Body Weight; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Leptin; Thinness; Thyroid Hormones

High physical activity (PA) in patients with anorexia nervosa (AN) is hypothesized to be, at least in part, a consequence of hypoleptinemia. However, most studies on the association of leptin and PA in AN were performed in adolescents or young adults, and PA was generally measured with subjective tools. We aimed to explore the association of leptin and PA in adults with AN using an objective technique to quantify PA. Using a cross-sectional, observational design, we analyzed body fat (bioelectrical impedance), PA (accelerometry, SenseWear™ armband) and plasma leptin (ELISA) in 61 women with AN (median age: 25 years, range: 18-52 years; median BMI: 14.8 ± 2.0 kg/m²) at the start of hospitalization. Results indicated a mean step count per day of 12,841 ± 6408 (range: 3956-37,750). Leptin was closely associated with BMI and body fat (ρ = 0.508 and ρ = 0.669,

Topics: Actigraphy; Adiposity; Adolescent; Adult; Anorexia Nervosa; Biomarkers; Body Mass Index; Cross-Sectional Studies; Electric Impedance; Exercise; Female; Fitness Trackers; Humans; Leptin; Linear Models; Machine Learning; Middle Aged; Multivariate Analysis; Young Adult

Topics: Adolescent; Adult; Anorexia Nervosa; Behavior Therapy; Body Mass Index; Feeding Behavior; Female; Humans; Leptin; Young Adult

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

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

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

Patients with anorexia nervosa (AN) suffer from neuropsychological deficits including memory impairments. Memory partially depends on 17β-oestradiol (E2), which is reduced in patients with AN. We assessed whether memory functions correlate with E2 plasma levels in the activity-based anorexia (ABA) rat model.. Nine 4-week-old female Wistar rats were sacrificed directly after weight loss of 20-25% (acute starvation), whereas 17 animals had additional 2-week weight-holding (chronic starvation). E2 serum levels and novel object recognition tasks were tested before and after starvation and compared with 21 normally fed controls.. Starvation disrupted menstrual cycle and impaired memory function, which became statistically significant in the chronic state (oestrous cycle (P < 0.001), E2 levels (P = 0.011) and object recognition memory (P = 0.042) compared to controls). E2 reduction also correlated with the loss of memory in the chronic condition (r = 0.633, P = 0.020).. Our results demonstrate that starvation reduces the E2 levels which are associated with memory deficits in ABA rats. These effects might explain reduced memory capacity in patients with AN as a consequence of E2 deficiency and the potentially limited effectiveness of psychotherapeutic interventions in the starved state. Future studies should examine whether E2 substitution could prevent cognitive deficits and aid in earlier readiness for therapy.

Topics: Animals; Anorexia Nervosa; Body Weight; Disease Models, Animal; Estradiol; Estrous Cycle; Female; Humans; Leptin; Memory Disorders; Rats; Rats, Wistar

Leptin, a hormone secreted by adipose tissue, appears to play a major role in the homeostasis of body weight and psychobiological processes associated with anorexia nervosa (AN). However, there is scarce data on its exact influence on this disorder, in particular data over time.. The present study addresses whether leptin changes during inpatient treatment play a role for treatment outcome and psychological factors in underweight AN patients.. In order to understand whether leptin's role differs in relation to AN severity, data were assessed from 11 patients with a very low BMI and a higher chronicity (high severity group; HSS; mean BMI at the beginning of the study = 13.6; mean duration of illness = 5.1 years) vs. nine with less severe symptoms (LSS; mean BMI = 16.2; mean duration of illness = 3.7 years). During the course of treatment, serum leptin concentrations were assessed weekly while weight (BMI) was assessed twice per week. Concomitantly, psychological variables were obtained by means of electronic diaries. Unconditional linear growth models were calculated to evaluate the temporal course of leptin in relation to BMI. For HSS patients, two phases of treatment (BMI < 16 and BMI ≥ 16 kg/m2) were investigated.. Leptin increased significantly with BMI in both groups of patients. For HSS patients, the increase of leptin in the first treatment phase did not predict later increases in BMI. Furthermore, the relationship of leptin and psychological factors was modulated by symptom severity. In HSS patients, higher leptin levels were associated with greater feelings of depression, anxiety, and stress whereas in LSS patients a higher leptin level showed the trend to be associated with lower psychological symptom burden.. Our results suggest that leptin changes are differently associated with weight gain and psychological symptoms depending on the severity of starvation.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Case-Control Studies; Depression; Female; Humans; Inpatients; Leptin; Longitudinal Studies; Male; Middle Aged; Patient Discharge; Young Adult

Anorexia nervosa is a psychiatric illness characterized by low weight, disordered eating, and hallmark neuroendocrine dysfunction. Behavioral phenotypes are defined by predominant restriction or bingeing/purging; binge-eating/purging type anorexia nervosa is associated with poorer outcome. The pathophysiology underlying anorexia nervosa types is unknown, but altered hormones, known to be involved in eating behaviors, may play a role.. To examine the role of anorexigenic hormones in anorexia nervosa subtypes, we examined serum levels of peptide YY (PYY; total and active [3-36] forms), brain-derived neurotrophic factor (BDNF), and leptin as primary outcomes in women with DSM-5 restricting type anorexia nervosa (n = 50), binge-eating/purging type anorexia nervosa (n = 25), and healthy controls (n = 22). In addition, women completed validated secondary outcome measures of eating disorder psychopathology (Eating Disorder Examination-Questionnaire) and depression and anxiety symptoms (Hamilton Rating Scales for Depression [HDRS] and Anxiety [HARS]). The study samples were collected from May 22, 2004, to February 7, 2012.. Mean PYY 3-36 and leptin levels were lower and BDNF levels higher in binge-eating/purging type anorexia nervosa than in restricting type anorexia nervosa (all P values < .05). After controlling for body mass index, differences in PYY and PYY 3-36 between anorexia nervosa types were significant (P < .05) and differences in BDNF were at the trend level (P < .10). PYY 3-36 was positively (r = 0.27, P = .02) and leptin was negatively (r = -0.51, P < .0001) associated with dietary restraint; BDNF was positively associated with frequency of purging (r = 0.21, P = .04); and leptin was negatively associated with frequency of bingeing (r = -0.29, P = .007) and purging (r = -0.31, P = .004).. Among women with anorexia nervosa, the anorexigenic hormones PYY, BDNF, and leptin are differentially regulated between the restricting and binge/purge types. Whether these hormone pathways play etiologic roles with regard to anorexia nervosa behavioral types or are compensatory merits further study.

Topics: Adult; Anorexia Nervosa; Appetite; Binge-Eating Disorder; Brain-Derived Neurotrophic Factor; Comorbidity; Female; Humans; Leptin; Peptide YY; Young Adult

Reduced plasma leptin and elevated homocysteine (Hcy) are known to lead to increased β-amyloid (Aβ) production, besides being hallmarks of anorexia nervosa (AN) of the restrictive type. AN subjects display several neuropsychiatric manifestations, which may entail Aβ-mediated altered synaptic functions. The aim of this study consisted in assessing Aβ plasma levels in AN patients.. A total of 24 adolescent female AN outpatients were recruited together with 12 age-comparable healthy controls. For each subject we assessed Aβ40 and leptin plasma levels, as well as APOE genotype. Hcy plasma levels were also determined in AN patients who underwent clinical characterization, including the Eating Disorder Inventory-3 (EDI-3), the Children's Depression Inventory (CDI) and the estimation of the speed of BMI loss (DPI, disease progression index).. Plasma Aβ40 levels were similar between patients and controls, while a marked reduction was observed for leptin (∼80%) in AN patients. Aβ40 plasma levels failed to correlate with leptin, while a linear correlation was present with Hcy (r = 0.50, p < 0.03). Examined clinical features were not related with Aβ40 plasma levels, with the only exception of the DPI (r = 0.47, p < 0.03).. This exploratory study does not support a significant role for altered Aβ production in AN-associated dysfunctions. Further studies are required to clarify whether exceptions to this conclusion can be drawn for those patients expressing significantly elevated Hcy plasma levels or for those progressing more rapidly.

Topics: Adolescent; Amyloid beta-Peptides; Anorexia Nervosa; Apolipoproteins E; Chi-Square Distribution; Child; Female; Homocysteine; Humans; Leptin; Linear Models; Outpatients; Peptide Fragments; Psychiatric Status Rating Scales; Young Adult

Betatrophin is produced primarily by liver and adipose tissue and has been recently reported as a novel hormone promoting β-cell proliferation and β-cell mass and improving glucose tolerance.. Because it is markedly regulated by nutritional status, we hypothesized that circulating betatrophin levels might be affected by pathophysiological conditions altering body weight.. We analyzed circulating betatrophin levels in 149 female patients, including 99 with extreme body mass index (30 anorexia nervosa, 24 obese, 45 morbid obese, and 50 healthy eating/weight controls).. Serum betatrophin levels and its correlations with different anthropometric and biochemical parameters were measured.. Plasma betatrophin levels were significantly elevated in anorexic patients, whereas its levels were reduced in morbidly obese women when compared with normal-weight women. Plasma betatrophin correlated negatively with weight, body mass index, fat percentage, glucose, insulin, and homeostatic model assessment index and positively correlated with high-density lipoprotein.. These results suggest that metabolic status is an important regulator of circulating betatrophin levels.

Topics: Adolescent; Adult; Angiopoietin-Like Protein 8; Angiopoietin-like Proteins; Anorexia Nervosa; Blood Glucose; Female; Humans; Insulin; Insulin Resistance; Leptin; Middle Aged; Obesity, Morbid; Peptide Hormones; Young Adult

The one-carbon metabolism, also known as methionine-homocysteine cycle, governs the dynamics of DNA methylation, epigenetically regulating gene expression, and has been reported altered in anorexia nervosa (AN) adult patients. The aim of this study consisted in assessing whole-blood DNA methylation in adolescent AN patients, assessing its significance in relationship to clinical and hormonal variables.. Whole-blood global DNA methylation was measured as incorporation of [(3)H]dCTP following HpaII cut in 32 adolescent females affected by restrictive type AN and compared to 13 healthy controls. Homocysteine, vitamin B12 and folate plasma levels were assessed as well as fasting plasma levels of leptin and steroid hormones. Clinical variables, including severity and associate states and traits, were assessed by means of the EDI-3, CDI and STAI-Y scales.. We confirm that whole-blood global DNA methylation is modestly albeit significantly reduced in AN adolescents with respect to controls, correlating with plasma leptin and steroid hormone levels. Conversely, clinical traits did not correlate with the outcome variable.. A better definition of the epigenetic dysregulation underlying AN pathology or vulnerability might lead to develop useful markers for diagnosis, prognostic classification and tailored therapeutic interventions in these vulnerable patients since the earliest phases of their disease.

Topics: Adolescent; Anorexia Nervosa; Biomarkers; DNA Methylation; Female; Gonadal Steroid Hormones; Humans; Hydrocortisone; Leptin

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

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

Although low weight is a key factor contributing to the high mortality in anorexia nervosa (AN), it is unclear how AN patients sustain low weight compared with bulimia nervosa (BN) patients with similar psychopathology. Studies of genes involved in appetite and weight regulation in eating disorders have yielded variable findings, in part due to small sample size and clinical heterogeneity. This study: (1) assessed the role of leptin, melanocortin, and neurotrophin genetic variants in conferring risk for AN and BN; and (2) explored the involvement of these genes in body mass index (BMI) variations within AN and BN.. Our sample consisted of 745 individuals with AN without a history of BN, 245 individuals with BN without a history of AN, and 321 controls. We genotyped 20 markers with known or putative function among genes selected from leptin, melanocortin, and neurotrophin systems.. There were no significant differences in allele frequencies among individuals with AN, BN, and controls. AGRP rs13338499 polymorphism was associated with lowest illness-related BMI in those with AN (p = 0.0013), and NTRK2 rs1042571 was associated with highest BMI in those with BN (p = 0.0018).. To our knowledge, this is the first study to address the issue of clinical heterogeneity in eating disorder genetic research and to explore the role of known or putatively functional markers in genes regulating appetite and weight in individuals with AN and BN. If replicated, our results may serve as an important first step toward gaining a better understanding of weight regulation in eating disorders.

Topics: Adult; Agouti-Related Protein; Anorexia Nervosa; Body Mass Index; Body Weight; Bulimia Nervosa; Case-Control Studies; Female; Genotyping Techniques; Humans; Leptin; Melanocortins; Membrane Glycoproteins; Middle Aged; Nerve Growth Factors; Polymorphism, Single Nucleotide; Protein Kinases; Protein-Tyrosine Kinases; Receptor, trkB

Anorexia nervosa is a primary psychiatric disorder, with non-negligible rates of mortality and morbidity. Some of the related alterations could participate in a vicious cycle limiting the recovery. Animal models mimicking various physiological alterations related to anorexia nervosa are necessary to provide better strategies of treatment.. To explore physiological alterations and recovery in a long-term mouse model mimicking numerous consequences of severe anorexia nervosa.. C57Bl/6 female mice were submitted to a separation-based anorexia protocol combining separation and time-restricted feeding for 10 weeks. Thereafter, mice were housed in standard conditions for 10 weeks. Body weight, food intake, body composition, plasma levels of leptin, adiponectin, IGF-1, blood levels of GH, reproductive function and glucose tolerance were followed. Gene expression of several markers of lipid and energy metabolism was assayed in adipose tissues.. Mimicking what is observed in anorexia nervosa patients, and despite a food intake close to that of control mice, separation-based anorexia mice displayed marked alterations in body weight, fat mass, lean mass, bone mass acquisition, reproductive function, GH/IGF-1 axis, and leptinemia. mRNA levels of markers of lipogenesis, lipolysis, and the brown-like adipocyte lineage in subcutaneous adipose tissue were also changed. All these alterations were corrected during the recovery phase, except for the hypoleptinemia that persisted despite the full recovery of fat mass.. This study strongly supports the separation-based anorexia protocol as a valuable model of long-term negative energy balance state that closely mimics various symptoms observed in anorexia nervosa, including metabolic adaptations. Interestingly, during a recovery phase, mice showed a high capacity to normalize these parameters with the exception of plasma leptin levels. It will be interesting therefore to explore further the central and peripheral effects of the uncorrected hypoleptinemia during recovery from separation-based anorexia.

Topics: Adipocytes, Brown; Adiponectin; Adipose Tissue; Animals; Anorexia Nervosa; Anxiety, Separation; Body Composition; Disease Models, Animal; Eating; Estrous Cycle; Feeding Behavior; Female; Gene Expression Regulation; Glucose Tolerance Test; Growth Hormone; Insulin-Like Growth Factor I; Leptin; Lipid Metabolism; Mice, Inbred C57BL; Oxidation-Reduction; Phenotype; Reproduction; Time Factors; Weight Loss

The aim of the present study was to verify the influence of hyperactivity on internistic and psychiatric parameters in early onset anorexia nervosa restricting type (ANR).. Seventy-three adolescent females (mean age 13.5 years, SD: 2.27) with a diagnosis of ANR (DSM-IV-TR) were consecutively enrolled in the Child and Adolescent Eating Disorders Unit of the IRCCS-Stella Maris and assessed by an extensive clinical protocol. All patients completed: psychiatric evaluation for description of the DCA and comorbidities; pediatric assessment including complete auxological data, blood pressure, heart rate and other electro/echo cardiographic and biohumoral parameters. The hyperactivity was estimated by the application of the "Structured Interview for Anorexic and Bulimic Disorder-Expert Form" (Item 40) in the context of clinical observation. Subjects were identified according to their level of hyperactive (ANR+H) and non-hyperactive (ANR-H) activity.. In the ANR+H group heart rate, leptin, sodium, potassium and gamma plasma proteins significantly differ compared to the group ANR-H. Patients with hyperactivity also have a complete form of ANR in 94% of cases compared with 66.7% of non-hyperactive; significant differences were found also in thought and attention CBCL and YSR subscales, combined with major internalizing problems.. This study provides preliminary data which can orient research towards the development of specific treatments for the hyperactivity, in order to improve the prognosis and thus avoid the chronicity of the disorder and the development of complications in adult life.

Topics: Adolescent; Adolescent Behavior; Anorexia Nervosa; Biomarkers; Body Mass Index; Comorbidity; Female; Heart Rate; Humans; Italy; Leptin; Potassium; Prognosis; Psychomotor Agitation; Serum Albumin; Sodium; Surveys and Questionnaires

Altered expression and/or function, both peripherally and centrally, of various neuropeptides is involved in the neurophysiology of anorexia nervosa (AN). Diazepam-binding inhibitor (DBI) is an interesting peptide for understanding this crosstalk. The aim of this work was to assess fasting plasma levels of DBI and leptin in patients with AN.. Twenty-four AN adolescents were recruited together with 10 age-comparable healthy controls. Neuropeptide determinations were performed on plasma samples by enzyme-linked immunosorbent assays. Patients with AN were further characterized for the presence of a depressive state or anxiety by using, respectively, the Children's Depression Inventory or the State-Trait Anxiety Inventory form Y.. Levels of both plasma DBI and leptin were reduced in patients with AN (∼40 and ∼70%, respectively). DBI levels displayed a tendency to increase in the presence of a depressive state, although not with anxiety, whereas leptin levels correlated exclusively with body mass index.. These data further extend our knowledge of neuropeptide dysfunction in AN, and plasma DBI may represent a marker for this disease, in particular considering its correlation with comorbid mood disorders.

Topics: Adolescent; Anorexia Nervosa; Anxiety; Biomarkers; Body Composition; Body Mass Index; Case-Control Studies; Depression; Diazepam Binding Inhibitor; Fasting; Female; Humans; Leptin

Anorexia nervosa (AN) is the third most common chronic disorder affecting adolescents and is associated with high mortality risk. The predominant symptom of anorexia nervosa is persistent and intentional striving to achieve weight loss initiated and/or sustained by the patient, leading to cachexia. Until now the cause of the condition remains unknown, but seems to be multifactoral. Patients with AN develop multi-organ complications and endocrine disorders affecting multiple disturbances of energy metabolism. Neuropeptide Y and leptin can be found between chemical substances regulating feelings of hunger and satiety. Neuropeptide Y plays the main role in the regulation of energetic homeostasis of the organism, feeding customs, sexual and reproductive functions. Concentration of neuropeptide Y increases during starvation and decreases after feeding. In anorexia nervosa the concentration of neuropeptide Y increases and, by doing that, decreases the excrection of gonadoliberines and gonadotropines. Leptin influences the feeling of hunger and its synthesis takes part, among others, in adiposal tissue. It also influences the menstruation disturbances. Rising leptin concentrations, with accompanying increasing adiposity is known to be the main factor influencing the puberty and the reverse of the malfunction of hypothalamic-pituitary-gonadal axis in malnourished persons. During hunger and low calorie intake, leptin concentration decreases, independently of adiposity.. The main aim of the study was to assess concentrations of neuropeptide Y, leptin and leptin receptor in teenagers treated for anorexia nervosa.. The study was conducted between 2007- 2011 in a group of 45 female teenagers with anorexia nervosa and a control group consisting of 59 healthy regularly menstruating female age peers. Concentrations of leptin, leptin receptor and neuropeptide Y (NPY) have been determined by using immunoenzymatic tests. Blood samples were obtained in fasting state. The Ethics Committee of the Medical University of Lodz approved of the study.. There were statistically significant differences between mean values of BMI (14.6 vs. 19.83), median value of leptin concentration (3.79 vs. 12.09), proportions of LEP/BMI (0.1986 vs. 0.5701) in the study group when compared to controls. Higher values were found in the study group if compared to the percentage of body mass insufficiency--(23.09 vs. 3.97), neuropeptide Y concentration--(0.33 vs. 0.19), proportions of NPY/BMI--(0.023 vs. 0.0095), concentration of leptin receptor--(30.25 vs. 19.45), proportions of LR/BMI--(2.1048 vs. 0.9744).. Low concentrations of leptine correlate to high concentrations of leptin receptor. A positive correlation between low body mass index and leptin receptor concentration and proportions of LR to BMI was found. A negative correlation was found between body mass loss and leptin concentration. The increasing concentration of neuropeptide Y, correlated to body mass deficency with existing high concentrations of leptin, could suggest disturbances of their regulatory axis.

Topics: Adolescent; Anorexia Nervosa; Biomarkers; Body Constitution; Body Mass Index; Body Weight; Case-Control Studies; Energy Metabolism; Female; Humans; Leptin; Neuropeptide Y; Poland; Receptors, Leptin; Reference Values; Risk Factors

Starvation-induced depletion of fat stores in anorexia nervosa (AN) is known to be accompanied by alterations in some circulating adipocytokines. We analyzed a panel of circulating adipocytokines in women with AN compared with normal-weight controls and their relation with the disease duration and weight restoration.. We analyzed circulating adipocytokine levels in 28 patients with AN and in 33 normal-weight controls who were eating healthily. We determined by enzyme-linked immunosorbent assay the circulating levels of total and high molecular weight (HMW) adiponectin, lipocalin-2 (LCN2), leptin, tumor necrosis factor receptor-II (TNFRII), interleukin-6 (IL6), adipocyte fatty acid binding protein-4 (FABP4), ghrelin, and resistin.. The two circulating forms of adiponectin are higher in AN women compared with controls. Both total and HMW adiponectin related negatively to the duration of the disease (r = -0.372, p = 0.033; r = -0.450, p = 0.038, respectively). Furthermore, the lipid binding-proteins LCN2 and FABP4 are lower in AN compared to the control group. Finally, leptin levels are lower in AN against controls and correlated positively with disease duration (r = 0.537, p = 0.007). Resistin, ghrelin, TNFRII, and IL6 have similar values in both groups, although TNFRII and ghrelin related negatively to body mass index variation at the end of treatment (r = -0.456, p = 0.039; r = -0.536, p = 0.015, respectively).. These results suggest there is a need to investigate if changes in adipocytokine levels could serve as weight restoration biomarkers. Further studies are warranted to elucidate the specific role of these molecules in the timing of weight restoration.

Topics: Adipokines; Adiponectin; Adult; Anorexia Nervosa; Biomarkers; Body Mass Index; Body Weight; Case-Control Studies; Fatty Acid-Binding Proteins; Female; Ghrelin; Humans; Interview, Psychological; Leptin; Resistin; Risk Assessment; Spain

Hyperactivity is a potential neurobiological marker and a core psychopathological trait in anorexia nervosa (AN). We investigated the processing of hyperactivity-related information in fifteen AN patients, 15 athletes and 15 non-athletes to examine if they represent disorder-related reward information using eye tracking. We assessed the extent of individually performed physical activity, mood, trait reward sensitivity and serum leptin levels. Results revealed a pronounced bias in overall attentional engagement toward stimuli associated with physical activity in patients and athletes as compared to non-athletes. In patients, relevant correlations were found: trait reward sensitivity and attentional orienting were strongly correlated and amount of physical activity correlated with attentional orienting and engagement. Compared to non-athletes, patients and athletes rated exercise stimuli as more pleasant. Findings suggest that exercise-related stimuli are perceived as rewarding by AN patients. Positive motivational valence of physical activity might contribute to disorder development and maintenance.

Topics: Adult; Anorexia Nervosa; Attention; Female; Humans; Hyperkinesis; Leptin; Motivation; Motor Activity; Orientation; Reward

Patients with anorexia nervosa (AN) are often observed to have high levels of physical activity, which do not necessarily diminish after a successful therapy. Previous studies have shown that body fat tissue recovery in these patients is associated with a disproportional restoration of the adipocyte hormone, leptin. Therefore, we wondered whether the individual variation in physical activity in AN patients prior to treatment may be related to body fat percentage and plasma leptin level outcome.. Body fat percentage, leptin serum, and physical activity levels (accelerometer) were measured in adolescents with an (n=37, age 13 to 17.5 years) at initial assessment, at the end of study participation (median 12 months), and at one-year follow-up.. Accelerometer data were used to split the patients in two groups: those with low (n=26) and those with high levels of physical activity (HLPA, n=11). These groups did not differ in terms of age, IQ, presence of menses, BMI and season of admission. The HLPA group was characterized by a longer total duration of illness. Physical activity levels during therapy decreased for the group with initially HLPA and increased for the group with low levels of physical activity (to comparable levels). Physical activity remained stable after one year. The increase in body fat percentage and leptin levels were dependent on the recovery status; however, recovered patients with initially HLPA had significantly higher fat mass during the follow-up.. HLPA, an important modulator of AN progression in adolescents, can be successfully diminished by therapeutic intervention. Among recovered patients, those with initially HLPA had higher fat mass levels than those with low levels of physical activity. This finding suggests that HLPA are an important modulator of the body composition recovery mechanism.

Topics: Adipose Tissue; Adolescent; Anorexia Nervosa; Body Composition; Body Mass Index; Female; Humans; Leptin; Motor Activity; Weight Gain

Adolescents with anorexia nervosa (AN) have low bone mineral density (BMD). Omentin- 1, the main circulating adipocytokine, plays an important role in bone metabolism in healthy individuals. However, their association with bone metabolism in AN is unknown.. Serum omentin-1, bone turnover biochemical markers, and BMD were determined in 26 girls with AN and 24 healthy girls (15-18 years old).. Omentin-1 levels increased in AN subjects, and the differences became greater after controlling for fat mass. Omentin-1 was negatively correlated with BMD. In the multiple linear stepwise regression analysis, omentin-1, body mass index and lean mass, but not fat mass, were independent predictors of BMD for the combined group. Significant negative correlations were found between omentin-1 and bone-specific alkaline phosphatase, bone cross-linked N-telopeptides of type I collagen. Omentin-1 was also independently associated with BMD and bone turnover markers in the AN and control groups considered separately.. Omentin-1 was an independent predictor of BMD in adolescents with AN, and negatively correlated with bone turnover markers. This suggested that omentin-1 may exert a negative effect on bone mass by inhibiting bone formation in girls with AN.

Topics: Adiponectin; Adolescent; Anorexia Nervosa; Biomarkers; Body Composition; Body Mass Index; Bone Density; Bone Remodeling; Case-Control Studies; Cytokines; Female; GPI-Linked Proteins; Humans; Lectins; Leptin; Regression Analysis

Previous studies have shown relationships between personality styles and markers of serotonergic functioning, but data on patients with anorexia nervosa (AN) are scarce.. The personality styles and disorder inventory was administered to 47 acute patients with anorexia nervosa (acAN), 27 weight-recovered patients (recAN) and 72 healthy controls (HC) aged between 14 and 21 years. Platelet monoamine oxidase (MAO-B) activity was assayed with [14C]-β-phenylethylamine as substrate.. AcAN had significant elevated scores on 9 of the 14 personality style subscales when compared to HC, whereas recAN were largely normal. Platelet MAO-B activity and "ambitious/narcissistic" scores correlated negatively in acAN. In recAN we found positive correlations between MAO-B and personality subscores.. The inverse relationship between a cluster B personality style and MAO-B activity in acAN is in accordance with studies in other patient populations. In contrast, positive associations between problematic personality styles and MAO-B activity in recAN combined with the overall decreased MAO-B activity in this group adds to the existing evidence suggesting a general dysfunction of the serotonergic system as a trait marker for AN.

Topics: Adolescent; Anorexia Nervosa; Biomarkers; Blood Platelets; Body Mass Index; Carbon Radioisotopes; Case-Control Studies; Female; Humans; Leptin; Monoamine Oxidase; Personality; Phenethylamines; Weight Gain; Young Adult

Topics: Adolescent; Adult; Anorexia Nervosa; Brain-Derived Neurotrophic Factor; DNA Methylation; Female; Humans; Leptin; Male; Middle Aged; Pilot Projects; Promoter Regions, Genetic; Receptors, Dopamine D2; Serotonin Plasma Membrane Transport Proteins; Young Adult

Nutritional infertility is very common in societies where women fail to eat enough to match their energy expenditure and such females often present as clinical cases of anorexia nervosa. The cellular and molecular mechanisms that link energy balance and central regulation of reproduction are still not well understood. Peripheral hormones such as estradiol, testosterone and leptin, as well as neuropeptides like kisspeptin and neuropeptides Y (NPY) play a potential role in regulation of reproduction and energy balance with their primary target converging on the hypothalamic median eminence-arcuate region. The present study was aimed to explore the effects of negative energy state resulting from intermittent fasting dietary restriction (IF-DR) regimen on complete hypothalamo-hypophysial-gonadal axis in Wistar strain young female and male rats. Significant changes in body weight, blood glucose, estrous cyclicity and serum estradiol, testosterone and LH level indicated the negative role of IF-DR regimen on reproduction in these young animals. Further, it was elucidated whether serum level of metabolic hormone, leptin plays a mechanistic role in suppressing hypothalamo-hypophysial-gonadal (HPG) axis via energy regulators, kisspeptin and NPY in rats on IF-DR regimen. We also studied the effect of IF-DR regimen on structural remodeling of GnRH axon terminals in median eminence region of hypothalamus along with the glial cell marker, GFAP and neuronal plasticity marker, PSA-NCAM using immunostaining, Western blotting and RT-PCR. Together these data suggest that IF-DR regimen negatively influences reproduction in young animals due to its adverse effects on complete hypothalamus-hypophysial-gonadal axis and may explain underlying mechanism(s) to understand the clinical basis of nutritional infertility.

Topics: Animals; Anorexia Nervosa; Estradiol; Estrous Cycle; Fasting; Female; Gonads; Humans; Hypothalamus; Infertility, Female; Leptin; Male; Neuronal Plasticity; Neurons; Neuropeptide Y; Pituitary Gland; Rats; Rats, Wistar; Reproduction; Testosterone

Leptin is anorexigenic, and levels are markedly decreased in women with low body weight and high in women with obesity. Ghrelin opposes leptin effects on appetite and is negatively associated with body mass index. These appetite-regulating hormones may have opposing effects on mood and stress pathways. Women with anorexia nervosa (AN), hypothalamic amenorrhoea (HA) and obesity are at increased risk of depression and anxiety. It is unknown whether dysregulation of leptin or ghrelin contributes to the development of depression and/or anxiety in these disorders. We investigated the relationship between leptin and ghrelin levels and symptoms of depression, anxiety and perceived stress in women across the weight spectrum.. Cross-sectional.. 64 women: 15 with AN, 12 normal-weight with HA, 17 overweight or obese (OB) and 20 normal-weight in good health (HC).. Fasting serum leptin and plasma ghrelin levels were measured. Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) and the Perceived Stress Scale were administered.. Leptin levels were inversely associated with HAM-D, HAM-A and Perceived Stress scores. The negative relationships between leptin and severity of symptoms of both depression and anxiety remained significant after controlling for body fat or weight. There was no relationship between ghrelin and symptoms of depression or anxiety. Although ghrelin levels were positively associated with the degree of perceived stress, this relationship was not significant after controlling for body fat or weight.. Leptin may mediate depressive symptoms across the weight spectrum. Further investigation of the role of leptin in modulating mood will be important.

Topics: Adipose Tissue; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Cross-Sectional Studies; Depression; Fasting; Female; Ghrelin; Humans; Leptin; Obesity

The impact of undernutrition on endocrine and exocrine gonadatrope function is poorly known in male anorexia nervosa (AN) patients.. The aim of this study was to compare the pituitary-gonadal function of male AN subjects with that of healthy controls, Kallmann syndrome (KS) patients, and female AN subjects.. Observational monocentric cross-sectional study performed in 31 male and 25 female subjects with restrictive-type AN, 22 male and 20 female controls, and nine male KS patients.. Hormonal parameters are as follows: follicule stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, estradiol, testosterone, inhibin B, thyroid hormones, growth hormone (GH), insulin-like growth factor 1 (IGF-1), cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate, and leptin.. Similar abnormalities of free T3, GH, IGF-I, cortisol, and leptin were found in men as in AN women with equivalent undernutrition status when compared with corresponding controls. Low levels of LH, FSH were found in both male and female AN patients. In male AN, total testosterone was found lower than in controls but higher than in KS, while a lack of estradiol was noticed in AN women. Sex hormones variations were directly related to weight gain only in AN men. No relationship was found between sex hormones and leptin variation for both sexes. In AN men, inhibin B levels were similar to that of controls and did not correlate with testosterone levels.. Significant differences of undernutrition impact on gonadal status were noticed between male and female AN subjects, including partial preservation of testosterone release and probable preservation of exocrine function, according to the normal inhibin B levels.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Anorexia Nervosa; Case-Control Studies; Cross-Sectional Studies; Dehydroepiandrosterone Sulfate; Estradiol; Female; Follicle Stimulating Hormone; Human Growth Hormone; Humans; Hydrocortisone; Inhibins; Insulin-Like Growth Factor I; Kallmann Syndrome; Leptin; Luteinizing Hormone; Male; Sex Factors; Sex Hormone-Binding Globulin; Testosterone; Thyroid Hormones; Young Adult

Topics: Anorexia Nervosa; Humans; Leptin

Preadipocyte factor-1 (Pref-1) is a member of epidermal growth-factor like family of proteins that regulates adipocyte and osteoblast differentiation. Experimental studies suggest that circulating Pref-1 levels may be also involved in the regulation of lipid and glucose metabolism and energy homeostasis. We hypothesized that alterations in Pref-1 levels may contribute to the ethiopathogenesis of anorexia nervosa or its underlying metabolic abnormalities. We measured Pref-1 concentrations and other hormonal, biochemical and anthropometric parameters in eighteen patients with anorexia nervosa and sixteen healthy women and studied the influence of partial realimentation of anorexia nervosa patients on these parameters. The mean duration of realimentation period was 46±2 days. At baseline, anorexia nervosa patients had significantly decreased body mass index, body weight, body fat content, fasting glucose, serum insulin, TSH, free T4, leptin and total protein. Partial realimentation improved these parameters. Baseline serum Pref-1 levels did not significantly differ between anorexia nervosa and control group (0.26±0.02 vs. 0.32±0.05 ng/ml, p=0.295) but partial realimentation significantly increased circulating Pref-1 levels (0.35±0.04 vs. 0.26±0.02 ng/ml, p<0.05). Post-realimentation Pref-1 levels significantly positively correlated with the change of body mass index after realimentation (r=0.49, p<0.05). We conclude that alterations in Pref-1 are not involved in the ethiopathogenesis of anorexia nervosa but its changes after partial realimentation could be involved in the regulation of adipose tissue expansion after realimentation.

Topics: Adipose Tissue; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Calcium-Binding Proteins; Eating; Female; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Male; Membrane Proteins; Young Adult

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

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

Women with anorexia nervosa (AN) have elevated marrow fat mass despite low visceral and subcutaneous fat depots, which is inversely associated with bone mineral density (BMD). Whether marrow fat mass remains persistently elevated or decreases with recovery from AN is currently unknown. In this study, we investigated changes in marrow fat in women who have recovered from AN (AN-R). We also studied the relationship between preadipocyte factor (Pref)-1-a member of the EGF-like family of proteins and regulator of adipocyte and osteoblast differentiation-and fat depots and BMD in AN-R compared with women with AN and healthy controls (HC). We studied 29 women: 14 with active or recovered AN (30.7 + 2.2 years [mean ± SEM]) and 15 normal-weight controls (27.8 ± 1.2 years). We measured marrow adipose tissue (MAT) of the L4 vertebra and femur by (1) H-magnetic resonance spectroscopy; BMD of the spine, hip, and total body by DXA; and serum Pref-1 and leptin levels. We found that MAT of the L4 vertebra was significantly lower in AN-R compared with AN (p = 0.03) and was comparable to levels in HC. Pref-1 levels were also significantly lower in AN-R compared with AN (p = 0.02) and comparable to levels in healthy controls. Although Pref-1 was positively associated with MAT of the L4 vertebra in AN (R = 0.94; p = 0.002), we found that it was inversely associated with MAT of the L4 vertebra in HC (R = -0.71; p = 0.004). Therefore, we have shown that MAT and Pref-1 levels decrease with recovery from AN. Our data suggest that Pref-1 may have differential effects in states of nutritional deprivation compared with nutritional sufficiency.

Topics: Adipose Tissue; Adiposity; Adult; Anorexia Nervosa; Body Composition; Bone Density; Bone Marrow; Calcium-Binding Proteins; Diaphyses; Female; Femur; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Lumbar Vertebrae; Magnetic Resonance Imaging; Membrane Proteins

Animal data suggest that oxytocin is a satiety hormone. We have demonstrated that anorexia nervosa (anorexia), a disorder characterized by food restriction, low weight, and hypoleptinemia, is associated with decreased nocturnal oxytocin secretion. We have also reported functional magnetic resonance imaging (fMRI) hypoactivation in anorexia in brain regions involved in food motivation. The relationships between oxytocin, food-motivation neurocircuitry, and disordered eating psychopathology have not been investigated in humans.. The objective of the study was to determine whether the oxytocin response to feeding in anorexia differs from healthy women and to establish the relationship between oxytocin secretion and disordered eating psychopathology and food-motivation neurocircuitry.. This was a cross-sectional study.. The study was conducted at a clinical research center.. Participants included 35 women: 13 anorexia (AN), nine weight-recovered anorexia (ANWR), and 13 healthy controls (HC).. Peripheral oxytocin and leptin levels were measured fasting and 30, 60, and 120 min after a standardized mixed meal. The Eating Disorder Examination-Questionnaire was used to assess disordered eating psychopathology. fMRI was performed during visual processing of food and nonfood stimuli to measure brain activation before and after the meal.. Mean oxytocin levels were higher in AN than HC at 60 and 120 min and lower in ANWR than HC at 0, 30, and 120 min and AN at all time points. Mean oxytocin area under the curve (AUC) was highest in AN, intermediate in HC, and lowest in ANWR. Mean leptin levels at all time points and AUC were lower in AN than HC and ANWR. Oxytocin AUC was associated with leptin AUC in ANWR and HC but not in AN. Oxytocin AUC was associated with the severity of disordered eating psychopathology in AN and ANWR, independent of leptin secretion, and was associated with between-group variance in fMRI activation in food motivation brain regions, including the hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula.. Oxytocin may be involved in the pathophysiology of anorexia.

Topics: Adolescent; Adult; Anorexia Nervosa; Cerebral Cortex; Cross-Sectional Studies; Eating; Fasting; Feeding Behavior; Female; Humans; Hydrocortisone; Leptin; Magnetic Resonance Imaging; Oxytocin; Postprandial Period; Severity of Illness Index; Young Adult

The aim of this study was to verify the relationship between eating disorders (binge eating and bulimia nervosa) and body image dissatisfaction with BMI, anorexigenic and orexigenic factors in adolescents. Thirty-two adolescents, (13 obese [BMI=36.65±5.68] and 19 non-obese [BMI=22.18±3.11]), aged between 14 and 19y, were recruited. Symptoms of eating disorders were measured by self-report questionnaires (BSQ, BITE and BES). Hormones, cytokines and neuropeptides were determined by Elisa kits (Phoenix peptide). A positive correlation was found between: leptin and BES (r=.724), BSQ (r=.705) and BITE (r=.696); BMI and BES (r=.663), BSQ (r=.525) and BITE (r=.732); the same pattern was observed to insulin and TNF-α. A negative correlation was found in α-MSH and AgRP with BES, BSQ and BITE. Blood levels of hormones and neuropeptides could be the link between obesity and eating disorders in adolescents. However, it is not clear which is the cause and which is the consequence.

Topics: Adolescent; Agouti-Related Protein; alpha-MSH; Anorexia Nervosa; Body Image; Body Mass Index; Bulimia; Bulimia Nervosa; Cross-Sectional Studies; Female; Humans; Insulin; Leptin; Obesity; Surveys and Questionnaires; Tumor Necrosis Factor-alpha; Young Adult

Hyperactivity in anorexia nervosa (AN) is associated with low plasma leptin levels and negatively impacts on disease outcome. Using an animal model that mimics features of AN including food-restriction induced hyperlocomotion, we demonstrate that central leptin injections in the lateral ventricle and local injections of leptin into the ventral tegmental area (VTA) suppress running wheel activity. The results support that falling levels of leptin, that accompany caloric restriction, result in increased activity levels because of decreased leptin signaling in the VTA, part of the mesolimbic reward system.

Topics: Animals; Anorexia Nervosa; Body Weight; Disease Models, Animal; Eating; Female; Hyperkinesis; Infusions, Intraventricular; Insulin; Leptin; Motor Activity; Rats; Rats, Wistar; Ventral Tegmental Area

Due to their sub-normally low fat mass, leptin levels in patients with acute anorexia nervosa (AN) are well below reference levels for age and sex-matched controls. This hypoleptinemia entails endocrinological and behavioral characteristics observed in AN patients during starvation. We aimed to study the appropriateness of hypoleptinemia as a diagnostic marker for AN by assessing sensitivity, specificity and likelihood ratios for different referral serum leptin levels for predicting anorexia nervosa and healthy leanness. For prediction, we additionally generated a score based on a multivariate logistic model including body mass index (BMI; kg/m²) and leptin level. For this purpose, we measured leptin levels in 74 female patients with acute AN upon admission for inpatient or outpatient treatment. Adolescent and adult patients were recruited according to DSM-IV criteria from two multi-center studies. Additionally, leptin levels were measured in 65 female healthy, lean students. Mean serum leptin level was significantly decreased in patients with AN compared to underweight controls (0.87 ± 0.90 vs. 6.43 ± 3.55 μg/L, p < 0.001). Leptin predicted AN independently of BMI; we confirmed a cutoff value in the range of 2 μg/L as having both high specificity and sensitivity. Hypoleptinemia represents a state marker of acute AN and is useful for a laboratory-based diagnostic screening.

Topics: Adolescent; Adult; Anorexia Nervosa; Biomarkers; Body Mass Index; Child; Cohort Studies; Female; Humans; Leptin; Mass Screening; Middle Aged; Predictive Value of Tests; Young Adult

The aim of the study was to analyze the pattern of leptin and orexin A plasma levels in patients with the restrictive type of anorexia nervosa (AN-R), during the course of treatment. Thirty females with AN-R, aged 18.0 ± 1.6 years (mean ± SD), range of 15.5-21.0 years, were investigated before and after 2, 3, and 6 months of treatment, which included a normocaloric diet and cognitive-behavioral psychotherapy. The control group consisted of 20 age-matched, healthy control females.. Before the therapy, both leptin and orexin A plasma levels were significantly lower than in the control group and were negatively correlated. During treatment, leptin levels increased and, after 6 months, showed a correlation with body mass index (BMI). Orexin A levels showed a further decrease during treatment, with no correlation with BMI.. The results corroborate those of other researchers showing a decrease of leptin levels in patients with AN-R and its increase with body mass increment. They may also suggest a possible relationship between leptin and orexin A plasma level patterns in such patients.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Female; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Neuropeptides; Orexins; Young Adult

An imbalance in appetite-regulating neuropeptides of the central nervous system has been associated with anorexia nervosa (AN), but the mechanisms of action are poorly understood. Agouti-related protein (AGRP), an orexigenic mediator of the hypothalamus, increases food intake and decreases energy expenditure in times of negative energy balance. The aim of the present study was to investigate AGRP in acute and fully weight-restored patients with AN, as well as during weight gain.. Plasma AGRP and leptin levels were assessed using an enzyme-linked immunosorbent assay kit in a total of 175 female participants, including 75 patients with acute AN, 37 weight-restored AN patients and 63 healthy controls. Of the patients with acute AN, 33 were reassessed after partial weight gain.. In weight-restored AN patients plasma AGRP levels were similar to those in healthy controls, whereas in patients with acute AN, AGRP was elevated. AGRP was inversely correlated with indicators of undernutrition such as body mass index and plasma leptin. In addition, AGRP levels normalized during weight gain of longitudinally assessed AN patients.. Our results underline the significance of undernutrition and hypoleptinemia for the interpretation of peripheral AGRP concentrations. This provides support for the hypothesis that abnormal AGRP plasma levels in AN patients reflect undernutrition, rather than disease-specific traits.

Topics: Adolescent; Adult; Agouti-Related Protein; Analysis of Variance; Anorexia Nervosa; Biomarkers; Body Mass Index; Case-Control Studies; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Malnutrition; Weight Gain; Young Adult

Orexin A (OXA) is a hypothalamic neuropeptide involved in regulation of food intake and nutritional status. There are multiple disturbances of neuropeptide signaling described in girls with anorexia nervosa (AN), but OXA levels have not been addressed in this population to date. Therefore, we analyzed OXA levels of AN girls in this study.. OXA (radioimmunoassay/RIA/method), leptin, insulinlike growth factor-1 (IGF-1), and insulinlike growth factor-1 binding protein-3 (IGFBP-3) levels were measured before and after 8 weeks of realimentation in 36 girls with AN and in 14 healthy controls (control group: CG).. Average weight increased significantly in AN during the study (p < .0001), while plasma levels of OXA decreased (before realimentation: 56.2 ± 2.4 pg/ml; after realimentation: 47.5 ± 1.4 pg/ml; p = .0025). OXA levels before realimentation differed from levels in the CG (47.15 ± 2.6 pg/ml, p = .034), but not afterward. We did not find any correlation between OXA and age, height, weight, BMI; or IGF-1, IGFBP-3, and leptin levels.. OXA levels in untreated AN patients differ significantly from healthy subjects and decrease during realimentation. These findings indicate that OXA may be involved in the nutritional regulation of malnourished children and adolescents.

Topics: Adolescent; Anorexia Nervosa; Body Weight; Eating; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Intracellular Signaling Peptides and Proteins; Leptin; Neuropeptides; Nutritional Status; Orexins

Despite having low visceral and sc fat depots, women with anorexia nervosa (AN) have elevated marrow fat mass, which is inversely associated with bone mineral density (BMD). Adipocytes and osteoblasts differentiate from a common progenitor cell, the human mesenchymal stem cell. Therefore, understanding factors that regulate this differentiation process may provide insight into bone loss in AN.. The objective of the study was to investigate the relationship between preadipocyte factor-1 (Pref-1), a member of the epidermal growth factor-like family of proteins and regulator of adipocyte and osteoblast differentiation, and fat depots and BMD in AN.. This was a cross-sectional study.. The study was conducted at a clinical research center.. Patients included 20 women with AN (26.8 +/- 1.5 yr) and 10 normal-weight controls (29.2 +/- 1.7 yr).. There were no interventions.. Pref-1, leptin, IGF-I, IGF binding protein (IGF-BP)-2 and estradiol levels were measured. BMD of the spine and hip was measured by dual-energy x-ray absorptiometry. Marrow fat content of the L4 vertebra and femur was measured by (1)H-magnetic resonance spectroscopy.. Pref-1 levels were significantly higher in AN compared with controls (P = 0.01). There was a positive correlation between Pref-1 and marrow fat of the proximal femoral metaphysis (R = 0.50, P = 0.01) and an inverse association between leptin and L4 marrow fat (R = -0.45, P < 0.05). There was an inverse association between Pref-1 and BMD of both the anteroposterior spine and lateral spine (R = -0.54, P = 0.003; R = -0.44, P = 0.02, respectively).. Pref-1 is elevated in AN. Pref-1, IGF-I, IGF-BP2 and leptin are associated with marrow adiposity and BMD.

Topics: Adiposity; Adult; Anorexia Nervosa; Bone Density; Bone Marrow; Calcium-Binding Proteins; Case-Control Studies; Estradiol; Female; Humans; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Leptin; Membrane Proteins; Young Adult

Anorexia nervosa (AN), a state of chronic nutritional deprivation, is characterized by GH resistance with elevated GH levels and decreased levels of IGF-I. Fibroblast growth factor (FGF)-21, a hormone produced in the liver and adipocytes, is induced in the liver by fasting and peroxisome proliferator-activated receptor-alpha agonists. In a transgenic mouse model, FGF-21 reduces IGF-I levels by inhibiting signal transducer and activator of transcription-5, a mediator of the intracellular effects of GH.. The objective of the study was to investigate the relationship between FGF-21, GH, and IGF-I in AN.. This was a cross-sectional study.. The study was conducted at a clinical research center.. Patients included 23 girls: 11 with AN (16.5 +/- 0.6 yr) and 12 normal-weight controls (15.7 +/- 0.5 yr).. There were no interventions.. We measured fasting FGF-21, glucose, insulin, IGF-I, and total area under the curve for GH (GH-AUC) and leptin during 12-h overnight frequent sampling.. FGF-21 levels were significantly higher in AN compared with controls, and there was a positive correlation between FGF-21 and GH-AUC (P = 0.03) after controlling for percent body fat and insulin resistance. In subjects with elevated FGF-21 levels, there was a strong inverse association between FGF-21 and IGF-I (R = -0.88, P = 0.004). FGF-21 strongly correlated with total area under the curve for leptin (R = 0.67, P = 0.02).. FGF-21 levels are higher in AN independent of the effects of percent body fat and insulin resistance. The positive association between FGF-21 and GH-AUC and the inverse association between elevated FGF-21 levels and IGF-I suggests that above the normal range, FGF-21 may mediate a state of GH resistance in AN.

Topics: Adolescent; Anorexia Nervosa; Area Under Curve; Blood Glucose; Body Composition; Case-Control Studies; Drug Resistance; Female; Fibroblast Growth Factors; Health; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Prognosis

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

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

Methods: Leptin levels were measured in 103 consecutive women with anorexia nervosa. Results: Spine BMD and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD.. The purpose of this study was to assess leptin levels and other biological variables in a population of anorexia nervosa patients.. Leptin levels were measured consecutively in 103 women with anorexia nervosa (AN) with a mean age of 24.9 +/- 7.4 years. Osteodensitometry was also performed by dual energy X-ray absorptiometry (DXA).. Spine bone mineral density (BMD) and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. The mean leptin level was 3.9 +/- 4.6 ng/mL (normal values, 3.5-11 ng/mL). The distribution of leptin values was not a Gaussian distribution, and a log-transformed was therefore performed. A significant correlation was found between leptin level and spinal BMD (r = 0.3; p = 0.002); significant correlations were observed for both femoral neck and total hip BMDs. When leptin level values were divided into tertiles, spine BMD and Z-score values were found to be significantly lower in the lower tertile (p = 0.04 and p = 0.02) compared with the highest tertile. For femoral neck BMDs, the T-score was slightly lower between low and high tertile, but the difference was not statistically significant (p = 0.07). When multivariate analyses were performed, two independent factors which could possibly account for the variance in spinal BMDs were found. Duration of amenorrhea and leptin level accounted for 27% of the variance (p < 0.0001).. The mechanisms underlying bone loss in AN patients remain unclear and complex, involving hypoestrogenia as well as nutritional factors such as insulin-like growth factor and leptin.

Topics: Absorptiometry, Photon; Adolescent; Adult; Amenorrhea; Anorexia Nervosa; Bone Density; Female; Femur Neck; Hip Joint; Humans; Leptin; Lumbar Vertebrae; Osteoporosis; Young Adult

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

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

Investigating the effect of leptin on energy expenditure in undernutrition might lead to a better understanding of the role of leptin in regulating body weight in humans.. 73 underweight female adolescents with anorexia nervosa (AN) were compared with 23 healthy normal weight (nwC), and 9 overweight girls (OW); 37 AN were followed during 7 months of weight recovery. Resting energy expenditure (REE, by indirect calorimetry), body composition (fat mass, FM; lean tissue mass, LTM; by Dual-Energy X-Ray Absorptiometry) and plasma hormones of leptin and 3,5,3'-Triiodothyronine (T(3)) were measured.. In underweight, leptin, T(3) and REE adjusted for lean tissue mass (REE(LTM)) were decreased; in OW, FM and leptin were increased at unchanged T(3) and REE(LTM). There was a significant positive relation between FM and leptin at low and normal (AN, r(2) = 0.26; nwC, r(2) = 0.51, p < 0.001), but not at high adiposity. Leptin and REE(LTM) were positively associated in underweight (r(2) = 0.14, p = 0.001) but not in normal or overweight subjects. T(3) was linearly related to REE(LTM) over the whole range of adiposity (r(2) = 0.42, p < 0.001). With weight gain in AN (5.0 ± 3.5 kg) the relationship between leptin and REE(LTM) changed toward the conditions seen in normal weight controls.. At low adiposity the interrelated fall of leptin and REE reflect an adaptive mechanism to preserve body weight. High leptin production associated with excessive adiposity was without effect on metabolic adaptation.

Topics: Absorptiometry, Photon; Adipose Tissue; Adiposity; Adolescent; Anorexia Nervosa; Body Composition; Body Mass Index; Calorimetry, Indirect; Case-Control Studies; Energy Metabolism; Female; Humans; Leptin; Linear Models; Overweight; Rest; Thinness; Triiodothyronine; Weight Gain

To investigate which factors predict the resumption of menstruation by patients with anorexia nervosa (AN).. Participants were AN patients who, even after weight recovery by inpatient treatment, had prolonged amenorrhea (N=11), AN patients who resumed menstruation after weight recovery (N=9), and age-matched healthy controls (N=12). Anthropometric data and the serum levels of leptin, insulin-like growth factor I (IGF-1), cortisol, luteinizing hormone (LH), estradiol (E2), and other hormones were measured at the beginning of the inpatient treatment and after weight recovery.. Of the baseline anthropometric and hormonal factors, logistic regression analysis extracted a high serum cortisol level as a predictor of the inhibition of the resumption of menstruation. After weight recovery, the E2 and leptin levels were significantly higher for eumenorrheic patients than for amenorrheic patients.. The baseline serum cortisol level was a predictor of the prolonged inhibition of menstrual recovery.

Topics: Adolescent; Adult; Amenorrhea; Analysis of Variance; Anorexia Nervosa; Body Mass Index; Estradiol; Female; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Leptin; Logistic Models; Luteinizing Hormone; Menstruation; Predictive Value of Tests

The aim of our study was to determine whether eating behaviors and/or physical activity level may explain contradicting results in adipocytokines levels in anorexia nervosa (AN).. Fasting levels of circulating adipocytokines (adiponectin, resistin and leptin), insulin, glucose, C-reactive protein, cytokines (tumor necrosis factor-alpha and interleukin (IL)-1beta), body composition and resting energy expenditure were measured in 24 women AN patients and 14 women controls. These parameters were compared according to AN subtypes: 15 patients with restrictive (R-AN) form versus 9 patients with binge/purge (BP-AN) form; 15 patients with hyperactive (H-AN) form versus 9 patients with nonhyperactive (NH-AN) form.. BP-AN patients had significantly higher serum adiponectin levels compared with R-AN patients (P<0.05), and H-AN patients had higher serum leptin and lower serum resistin levels compared with NH-AN patients (P<0.05 for both).. Our study shows specific adipocytokines profiles depending on the subtype of AN: restrictive versus binge/purge and hyperactive versus Nonhyperactive forms. We suggest that these biological signatures could interfere with the outcome of the disease.

Topics: Adiponectin; Adolescent; Adult; Anorexia Nervosa; Bulimia Nervosa; Female; Humans; Hyperkinesis; Leptin; Motor Activity; Resistin; Young Adult

The prohormone preproenkephalin (ppE) and its derived peptides are involved in leukocyte functioning as well as in the regulation of hunger and satiety. Various abnormalities of the immune and endocrine systems have been described in states of malnutrition such as anorexia nervosa (AN). We hypothesized that ppE expression in AN patients may vary depending on the state of the disorder and the extent of malnutrition.. Expression of ppE mRNA was analysed in peripheral blood mononuclear cells of 29 underweight and 29 weight-recovered patients with AN and compared to that in 29 healthy control women. The extent of malnutrition was characterized by BMI and plasma leptin. Psychological distress and eating disorder specific-psychopathology was determined with the Symptom Checklist-90-Revised and the Eating Disorders Inventory-2.. ppE gene expression was similar in all 3 groups and was not related to nutritional status or eating disorder symptoms. However, a significant negative correlation was found between ppE expression and obsessive-compulsive, depressive and anxious symptoms. In addition, ppE expression was higher in smokers compared to non-smokers.. Although malnutrition and hypoleptinaemia as seen in patients with AN were not related to peripheral ppE expression, we demonstrated reduced ppE expression in patients with elevated psychological distress. Similar associations have been shown in animal models of stress. It remains speculative if psychological symptoms and/or stress may augment immune abnormalities in AN patients via a pathway that is independent of nutritional status and involves ppE.

Topics: Adolescent; Adult; Anorexia Nervosa; Anxiety; Basal Metabolism; Depression; Enkephalins; Female; Gene Expression; Humans; Leptin; Leukocytes, Mononuclear; Obsessive-Compulsive Disorder; Protein Precursors; Psychiatric Status Rating Scales; Severity of Illness Index; Stress, Psychological; Thinness

Serum adipocyte fatty acid-binding protein (FABP) concentrations are linked to human obesity and other features of metabolic syndrome. Whether FABP associates with metabolic alterations in chronic malnutrition is unknown. In the present study, we measured fasting serum levels of FABP, leptin, soluble leptin receptor, adiponectin, resistin, C-reactive protein (CRP), insulin, glucose, cholesterol and triglycerides in 19 patients with a restrictive type of anorexia nervosa (AN) and in 16 healthy age-matched control women (C). Body mass index, serum leptin, and CRP concentrations were significantly lower, while serum adiponectin and soluble leptin receptor levels were significantly higher in AN relative to C group. Serum insulin, glucose, cholesterol and triglyceride levels did not differ between the groups studied. Serum FABP levels were unchanged in patients with AN and were not related to any of parameters studied. We conclude that, in contrast to patients with obesity where FAPB is a prominent marker of metabolic alterations, chronic malnutrition in AN does not significantly affect its serum levels.

Topics: Anorexia Nervosa; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Cholesterol; Fatty Acid-Binding Proteins; Female; Humans; Leptin; Lipid Metabolism; Metabolic Syndrome; Nutritional Status; Obesity; Receptors, Leptin; Young Adult

Most previous studies investigating amino acid levels in anorexia nervosa (AN) have focused on acutely underweight patients. The present study assessed the availability of aromatic amino acids in the plasma of weight-recovered outpatients with AN (recAN) in comparison to acutely underweight AN patients (acAN) and healthy control woman (HCW).. Plasma tryptophan (TRP), tyrosine (TYR), and phenylalanine (PHEN) as well as leptin concentration were determined in 32 recAN, 32 acAN, and 32 HCW.. Both recAN and acAN patients showed significantly lower levels of TRP and PHEN when compared to HCW. TYR was reduced in acAN patients only.. Normal weight and normal leptin levels but lower availability of TRP and PHEN in recAN patients might indicate that outside a tightly controlled setting these patients still engage in abnormal eating patterns. Reduced peripheral availability of these precursor amino acids could impact on 5-HT and catecholamine functioning in the brain.

Topics: Acute Disease; Adolescent; Adult; Aged; Anorexia Nervosa; Child; Convalescence; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Leptin; Middle Aged; Phenylalanine; Tryptophan; Weight Gain; Young Adult

Data regarding serum adipocytokine and ghrelin concentrations in different stages of anorexia nervosa (AN) is conflicting.. Our aim is to determine serum concentrations of adiponectin (ApN), leptin and ghrelin in different stages of AN and to evaluate their relationships with study parameters.. Study group was composed of four subgroups: Group 1: patients with a recent diagnosis of AN (n = 19); group 2: weight recovered (10% increase in body weight compared with baseline) subgroup of group 1 during follow-up (n = 10); group 3: recovered patients with a previous history of AN but normal menstrual cycles and body weight currently (n = 10); group 4: control group (n = 10). Venous blood was obtained for measurements of biochemical/hormonal parameters, ApN, leptin and ghrelin. Body composition was determined by bioimpedance analysis.. Changes in adipocytokine and ghrelin concentrations and relationships with anthropometric/biochemical parameters.. Leptin: fat mass (kg) ratio was significantly higher in group 1 patients compared with group 4 (4.3 +/- 4.6 vs. 1.1 +/- 0.5 microg/l kg, P < 0.01). No significant difference was observed among ghrelin concentrations. Leptin showed significant positive correlation with body fat mass in all groups. ApN showed significant positive association with body mass index in Group 1.. Leptin concentrations indexed to fat mass may indicate a nonphysiological higher set point of leptin per unit fat mass in treatment-naive AN patients. Correlation pattern between ApN and fat mass is modified also. Altered adipocytokine profile in AN may contribute to anorectic behaviour.

Topics: Adiponectin; Adipose Tissue; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Female; Ghrelin; Humans; Leptin; Male; Young Adult

Excessive physical activity is commonly described as symptom of Anorexia Nervosa (AN). Activity-based anorexia (ABA) is considered an animal model for AN. The ABA model mimics severe body weight loss and increased physical activity. Suppression of hyperactivity by olanzapine in anorectic patients as well as in ABA rats suggested a role of dopamine and/or serotonin in this trait. Here, we investigated the effect of a non-selective dopamine antagonist in the ABA model. A dose-response curve of chronic treatment with the non-selective dopaminergic antagonist cis-flupenthixol was determined in the ABA model. Treatment reduced activity levels in both ad libitum fed and food-restricted rats. Treated ABA rats reduced body weight loss and increased food intake. These data support a role for dopamine in anorexia associated hyperactivity. Interestingly, in contrast to leptin treatment, food-anticipatory activity still persists in treated ABA rats.

Topics: Adipose Tissue; Analysis of Variance; Animals; Anorexia Nervosa; Behavior, Animal; Body Composition; Body Temperature; Body Weight; Disease Models, Animal; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Delivery Systems; Eating; Female; Flupenthixol; Food Deprivation; Insulin; Leptin; Motor Activity; Radioimmunoassay; Rats; Rats, Wistar

Visfatin is an adipose tissue-derived hormone shown to correlate with visceral fat mass in patients with obesity. Its possible role in patients with different types of eating disorders is unknown. We measured fasting serum levels of visfatin and leptin and surrogate measures of insulin sensitivity in 10 untreated patients with anorexia nervosa (AN), 10 untreated patients with bulimia nervosa (BN) and 20 age-matched healthy women (C) to study the possible role of visfatin in these disorders. Patients with AN had severely decreased body mass index (BMI) and body fat content. BMI of BN group did not significantly differ from that of C group, whereas body fat content of BN group was significantly lower compared to C and higher compared to AN group, respectively. Serum glucose levels did not significantly differ among the groups studied, whereas serum insulin and leptin levels and HOMA index were significantly decreased in AN group relative to both C and BN group. In contrast, serum visfatin levels in both patients with AN and BN did not differ from those of C group. We conclude that circulating visfatin levels are not affected by the presence of chronic malnutrition in AN or binge/purge eating behavior in BN.

Topics: Adiposity; Adult; Anorexia Nervosa; Biomarkers; Blood Glucose; Body Mass Index; Bulimia Nervosa; Cytokines; Female; Humans; Insulin; Leptin; Nicotinamide Phosphoribosyltransferase; Nutritional Status; Young Adult

In food-restricted rats, leptin as well as corticotropin releasing factor attenuate semistarvation-induced hyperactivity (SIH). Results from studies in patients with anorexia nervosa (AN) showed an association between excessive physical activity (PA) and leptin. One recent report suggests a role for cortisol in PA. In this study, we assessed the relationships between PA and both, cortisol and leptin levels at the same time in patients with acute anorexia nervosa (acAN) in comparison to recovered patients (recAN).. Plasma leptin, plasma cortisol, body mass index (BMI), and expert-ratings of qualities of PA were assessed in 36 acAN patients, 27 recAN patients and 44 healthy control woman (HCW). Regression analyses were used to predict PA using BMI, leptin and cortisol levels as predictor variables.. Leptin levels but not cortisol significantly contributed to the prediction of PA in acAN. In recAN PA was not elevated and not related to endocrine parameters but correlated positively with core eating disorder symptoms.. Our work lends support to the proposed inverse association between peripheral leptin levels and excessive physical activity in AN. This relationship is specific to the state of semistarvation. The role of additional mediators remains to be clarified.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Weight; Electrochemistry; Female; Humans; Hydrocortisone; Hyperkinesis; Leptin; Regression Analysis; Young Adult

An association between anorexia nerviosa (AN) and low bone mass has been demonstrated. Bone loss associated with AN involves hormonal and nutritional impairments, though their exact contribution is not clearly established. We compared bone mass in AN patients with women of similar weight with no criteria for AN, and a third group of healthy, normal-weight, age-matched women. The study included forty-eight patients with AN, twenty-two healthy eumenorrhoeic women with low weight (LW group; BMI < 18.5 kg/m2) and twenty healthy women with BMI >18.5 kg/m2 (control group), all of similar age. We measured lean body mass, percentage fat mass, total bone mineral content (BMC) and bone mineral density in lumbar spine (BMD LS) and in total (tBMD). We measured anthropometric parameters, leptin and growth hormone. The control group had greater tBMD and BMD LS than the other groups, with no differences between the AN and LW groups. No differences were found in tBMD, BMD LS and total BMC between the restrictive (n 25) and binge-purge type (n 23) in AN patients. In AN, minimum weight (P = 0.002) and percentage fat mass (P = 0.02) explained BMD LS variation (r2 0.48) and minimum weight (r2 0.42; P = 0.002) for tBMD in stepwise regression analyses. In the LW group, BMI explained BMD LS (r2 0.72; P = 0.01) and tBMD (r2 0.57; P = 0.04). We concluded that patients with AN had similar BMD to healthy thin women. Anthropometric parameters could contribute more significantly than oestrogen deficiency in the achievement of peak bone mass in AN patients.

Topics: Adolescent; Adult; Age of Onset; Anorexia Nervosa; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Diagnostic and Statistical Manual of Mental Disorders; Estrogens; Female; Human Growth Hormone; Humans; Leptin; Organ Size; Reference Values; Thinness; Young Adult

Adipocyte fatty acid binding protein (A-FABP) has been suggested to play an important role in fat metabolism linking obesity and the metabolic syndrome. Increasing A-FABP plasma levels were observed during greatest weight loss after bariatric surgery suggesting that A-FABP may indicate changes in fat mass in dynamic situations.. As there are no data on weight gain, we investigated the effect of refeeding anorexic patients on body composition and A-FABP plasma levels.. Parameters of glucose and lipid metabolism as well as plasma levels of leptin and A-FABP were prospectively assessed in 16 female patients with anorexia nervosa during inpatient weight restoration. Body composition was determined by multifrequency body impedance analysis.. After 28 days, fat mass increased from 4.4 +/- 2.5 kg at baseline to 5.5 +/- 2.2 kg (P < 0.01), constituting 40% of total weight gain. Conversely, A-FABP concentrations decreased from 32.56 +/- 35.59 ng/ml at baseline to 21.27 +/- 13.68 ng/ml (P < 0.05), which corresponds to a significant decrease in the proportion of A-FABP per kilogram fat mass from 7.86 +/- 5.23 to 4.09 +/- 2.12 ng/ml/kg (P

Topics: Adipocytes; Adolescent; Adult; Anorexia Nervosa; Body Composition; Body Mass Index; Bulimia Nervosa; Electric Impedance; Enzyme-Linked Immunosorbent Assay; Fatty Acid-Binding Proteins; Female; Humans; Leptin; Matched-Pair Analysis; Middle Aged; Regression Analysis; Weight Gain; Young Adult

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

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

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

Anorexia nervosa (AN) is characterized by markedly changes in hormone secretion influencing food intake, energy homeostasis and long-term body weight regulation. The aim of this study was to determine neuropeptide Y (NPY), ghrelin and leptin plasma levels and their changes after six weeks of nutritional-rehabilitation program in severely malnourished anorexia nervosa patients.. Ten women with DSM-IV diagnosed anorexia nervosa, hospitalized (BMI 14.74 +/- 0.43; age 23.3 +/- 1.0) and ten age-matched healthy women (BMI 21.45 +/- 0.72; age 24.3 +/- 0.8) were enrolled to the study. Fasting plasma levels of NPY, ghrelin and leptin were measured before and after the treatment.. Fasting plasma ghrelin and NPY levels were significantly increased in AN patients comparing to healthy women, while plasma leptin was decreased. After six weeks of the treatment plasma ghrelin levels significantly decreased and plasma leptin levels increased. Plasma NPY levels didn't change during the treatment, average BMI significantly increased in AN patients.. We confirmed that ghrelin and leptin plasma levels express actual nutritional status of a body and did change during the six-weeks refeeding in AN patients. Plasma leptin levels together with constantly increased NPY levels indicate to persisting dysregulation of appetite and body weight control mechanisms in AN patients.

Topics: Adult; Anorexia Nervosa; Female; Ghrelin; Humans; Leptin; Neuropeptide Y; Young Adult

To compare general and eating disorder-specific psychopathology in patients with acute anorexia nervosa (acAN), weight-recovered patients (recAN) and healthy control women (HCW).. One hundred anorexia nervosa patients (66 acAN and 34 recAN) and 88 HCW were included in our study. Psychopathology was assessed by self-report questionnaires [Symptom Check List 90 Revised (SCL-90-R), Eating Disorder Inventory-2 (EDI- 2)] as well as by interview [Structured Interview of Anorexia Nervosa and Bulimic Syndromes (SIAB-EX)] and compared using multivariate analysis of variance. Plasma leptin levels were determined using enzyme linked immunosorbent assay.. Mean comparisons indicated highly significant differences between acAN and recAN subjects on all psychopatholgy variables, except for perfectionism. RecAN subjects did not differ from HCW. Partial weight recovery was associated with decreasing levels of psychopathology. Correlational analyses suggested strong negative associations between leptin levels and psychopathology.. Prolonged malnutrition, as indicated by suppressed plasma leptin levels, is strongly related to eating disorder-specific as well as general psychopathological symptoms. Weight recovery is associated with the absence of psychopathology. These data emphasize the interaction between somatic and psychological variables.

Topics: Adaptation, Psychological; Adolescent; Adult; Anorexia Nervosa; Biomarkers; Body Weight; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interview, Psychological; Leptin; Multivariate Analysis; Surveys and Questionnaires; Thinness; Young Adult

The pathogenesis of anorexia nervosa (AN) is still poorly understood. The Diagnostic and Statistical Manual of Mental Disorders (4th edition) classification differentiates 2 AN types: the restricting type (AN-R) and the binge eating/purging type (AN-BP). We investigated 4 young women suffering from AN (2 with AN-R and 2 with AN-BP). Four women, age matched, with other psychiatric disorders (paranoid schizophrenia, adjustment disorder, mental retardation) served as the reference group. The oligonucleotide microarray method (HG-U133A, Affymetrix) was used to determine the expression profile of 13 genes connected with the orexigenic and anorexigenic system: leptin, leptin receptor-coding gene, hypocretin (orexin) receptor-coding gene, hypocretin (orexin) neuropeptide precursor-coding gene and growth hormone secretagogue receptor. A hierarchical analysis of the results showed that AN-BP and AN-R patients were grouped into different clusters. Also, expression levels of leptin receptor-coding gene showed significant differences between AN-BP and AN-R patients and between AN-R and control subjects. This preliminary study suggests that the microarray technique may contribute to elucidating molecular genetics of the pathogenesis of both types of AN.

Topics: Adolescent; Adult; Anorexia Nervosa; Case-Control Studies; Cluster Analysis; Female; Gene Expression Profiling; Genetic Linkage; Ghrelin; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Matched-Pair Analysis; Mental Disorders; Neuropeptides; Oligonucleotide Array Sequence Analysis; Orexin Receptors; Orexins; Receptors, G-Protein-Coupled; Receptors, Leptin; Receptors, Neuropeptide; Statistics, Nonparametric

Topics: Anorexia Nervosa; Body Mass Index; Child; Female; Fluid Therapy; Ghrelin; Heart Rate; Hematocrit; Hospitalization; Humans; Hypotension; Insulin; Leptin; Nutritional Support; Social Support; Weight Gain

Anorexia nervosa (AN) is a condition of severe undernutrition associated with altered regional fat distribution in females. Although primarily a disease of females, AN is increasingly being recognized in males and is associated with hypogonadism. Testosterone is a major regulator of body composition in males, and testosterone administration in adults decreases visceral fat. However, the effect of low testosterone and other hormonal alterations on body composition in boys with AN is not known.. We hypothesized that testosterone deficiency in boys with AN is associated with higher trunk fat, as opposed to extremity fat, compared with control subjects.. We assessed body composition using dual-energy X-ray absorptiometry and measured fasting testosterone, estradiol, insulin- like growth factor-1, leptin, and active ghrelin concentrations in 15 boys with AN and in 15 control subjects of comparable maturity aged 12-19 y.. Fat and lean mass in AN boys was 69% and 86% of that in control subjects. Percentage extremity fat and extremity lean mass were lower in boys with AN (P = 0.003 and 0.0008); however, percentage trunk fat and the trunk to extremity fat ratio were higher after weight was adjusted for (P = 0.005 and 0.003). Testosterone concentrations were lower in boys with AN, and, on regression modeling, positively predicted percentage extremity lean mass and inversely predicted percentage trunk fat and trunk to extremity fat ratio. Other independent predictors of regional body composition were bone age and weight.. In adolescent boys with AN, higher percentage trunk fat, higher trunk to extremity fat ratio, lower percentage extremity fat, and lower extremity lean mass (adjusted for weight) are related to the hypogonadal state.

Topics: Absorptiometry, Photon; Adipose Tissue; Adolescent; Anorexia Nervosa; Body Composition; Case-Control Studies; Child; Estradiol; Extremities; Ghrelin; Humans; Insulin-Like Growth Factor I; Leptin; Male; Testosterone; Thorax; Young Adult

Central serotonergic pathways may play an important role in the etiology of anorexia nervosa (AN). Although platelet monoamine oxidase activity (MAO-B) has been proposed as an index of cerebral serotonin activity, studies in patients with AN are scarce.. Platelet MAO-B activity was determined in 59 acutely underweight AN patients (acAN, aged 14-29 years, BMI=15.2+/-1.4), 35 weight-recovered AN patients (recAN, aged 15-29, BMI=20.8+/-2.2) and 59 healthy control women (HCW, aged 14-26, BMI=21.6+/-2.1). Plasma leptin served as an indicator of malnutrition. Results were compared by ANCOVA controlling for confounding variables.. Platelet MAO-B activity in acAN patients (5.2+/-1.4 nmol/10 (9)pltx15 min) was similar to HCW (5.5+/-1.9) but significantly lower in recAN patients (4.4+/-1.5). BMI and leptin showed a significant negative correlation with MAO-B activity in AN patients, but not in HCW.. Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Whether low MAO-B activity in weight-recovered AN patients indicates a premorbid trait or a secondary change due to recovery remains to be elucidated.

Topics: Adipocytes; Adolescent; Adult; Anorexia Nervosa; Blood Platelets; Body Weight; Eating; Energy Metabolism; Female; Gonads; Humans; Hypothalamo-Hypophyseal System; Leptin; Monoamine Oxidase; Nutritional Physiological Phenomena; Psychiatric Status Rating Scales; Serotonin; Thinness; Young Adult

The aim of this study was to examine somatic and psychological factors related to the body mass index (BMI) of anorexia nervosa (AN) patients.. The analysis was of 24 hospitalized AN patients from the day after admission to the 4th day. The somatic factors analyzed were duration of AN, daily food intake, eating regulatory substances in blood (acylated ghrelin, desacyl ghrelin, leptin), serum cortisol, insulin and estimated creatinine clearance (CCr). The psychological factors analyzed were depression, anxiety, Eating Disorder Inventory (EDI), and hunger/fullness feeling. Measurement of BMI and collection of blood samples were done on the morning after hospitalization. Statistical analysis was by multiple linear regression analysis.. BMI showed a reverse correlation with desacyl ghrelin (beta=-0.486, p=0.015) and maturity fears (beta=-0.375, p=0.046), but was not associated with any other factor by multiple regression analysis.. The results suggest that desacyl ghrelin and maturity fears play important roles in the prolonged malnutrition state seen in AN patients.

Topics: Adult; Anorexia Nervosa; Anxiety; Biomarkers; Body Mass Index; Creatinine; Depression; Eating; Fear; Female; Ghrelin; Humans; Hunger; Hydrocortisone; Inpatients; Insulin; Leptin; Linear Models; Male; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Factors; Satiety Response; Time Factors; Young Adult

Obestatin is a recently identified ghrelin gene product that was reported to inhibit appetite and gastric motility in contrast to ghrelin. We investigated fasting obestatin and ghrelin levels in patients with obesity and anorexia nervosa.. Fasting plasma obestatin, acyl-ghrelin, desacyl-ghrelin, leptin, glucose serum adiponectin, and insulin were measured in 10 obese subjects, 11 restricting-type anorexics, and 11 control subjects.. Obese group had significantly lower levels of obestatin (p < .01), while anorexic group had significantly higher levels (p < .01). Obestatin was negatively correlated with body mass index (BMI) (r = -.74), glucose (r = -.56), insulin (r = -.55), leptin (r = -.66), and also with the homeostasis model assessment of insulin resistance (HOMA-R) (r = -.49) and was positively correlated with acyl-ghrelin (r = .65) and desacyl-ghrelin (r = .60). No correlation was seen between obestatin and adiponectin, but the latter was negatively correlated with both acyl-ghrelin and desacyl-ghrelin. Desacyl-ghrelin to acyl-ghrelin ratio was significantly different between anorexic and control groups (p < .05), while no difference was seen between obese and control groups.. Both obestatin and ghrelin are increased in anorexic and decreased in obesity. We suggest that obestatin is a nutritional marker reflecting body adiposity and insulin resistance.

Topics: Adolescent; Adult; Analysis of Variance; Anorexia Nervosa; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Ghrelin; Humans; Insulin Resistance; Leptin; Male; Obesity

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

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

S100B protein is mainly synthesized in glial cells and modulates the balance between cell proliferation and differentiation in neurons and glial cells. However, S100B is not CNS-specific since its production was detected in numerous non-cerebral tissues e.g. adipocytes. In this study we investigated the influence of chronic fasting and subsequent weight gain on serum levels of S100B in patients with anorexia nervosa. We found that nutritional status was an important factor influencing serum levels of S100B.

Topics: Adolescent; Age Factors; Anorexia Nervosa; Biomarkers; Body Composition; Body Mass Index; Chronic Disease; Dietary Proteins; Down-Regulation; Female; Humans; Leptin; Nerve Growth Factors; Nutritional Status; Predictive Value of Tests; Recovery of Function; Reference Values; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Starvation; Weight Gain

Anorexia nervosa (AN) commonly arises during adolescence, leading to interruptions of somatic and psychological development as well as to cortical atrophy and reductions of brain volume. While most brain changes shift towards normal with weight restoration, it is not certain whether they are related to the loss of brain cells, neuropil or merely due to fluid shifts. We measured S100B serum concentrations and psychometric characteristics in 34 patients with acute AN, 19 weight-recovered patients and 35 healthy control women (HCW). Plasma tryptophan and leptin levels were determined as markers for malnutrition and neuroendocrine adaptation to semi-starvation. Peripheral S100B concentrations of acute and former AN patients were not elevated and not statistically different from HCW. BMI, peripheral leptin levels and measures of psychopathology as well as executive cognitive functioning did not correlate with S100B. Plasma tryptophan was positively related to S100B. Our results are in line with our previous findings showing unaltered GFAP and NSE plasma levels in patients with acute AN. Together they do not support hypotheses comprising the degeneration of glial or neuronal cells to explain common signs of brain atrophy in patients with acute AN.

Topics: Adolescent; Adult; Anorexia Nervosa; Case-Control Studies; Female; Humans; Leptin; Nerve Growth Factors; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Thinness; Tryptophan; Weight Gain

The aim of this study was to analyze thyroid hormones in female adolescents with obesity and anorexia nervosa (AN) before and after normalization of weight.. Thyroid-stimulating hormone (TSH), fT3, and fT4 were determined in 100 obese girls, 32 normal-weight girls and 20 girls with AN aged 14-18 years at baseline and 1 year later. Additionally, leptin, insulin, and the insulin resistance index HOMA were analyzed in the obese and normal-weight girls.. TSH and fT3 levels of girls with AN were significantly lower compared to TSH concentrations of normal-weight girls, while TSH and fT3 levels of the obese girls were significantly higher. The 21 obese females with weight loss >5% demonstrated a significant decrease in fT3 and TSH, while the 9 adolescents with AN and weight gain >5% showed a significant increase in fT3 and TSH. Insulin and HOMA were not significantly correlated to TSH, fT3 and fT4, while leptin was correlated to TSH and fT3 in both cross-sectional and longitudinal analysis.. Thyroid function seems to be reversibly related to weight status with increased TSH and fT3 concentrations in obesity and decreased TSH and fT3 levels in AN. We hypothesize that leptin may be the link between weight status and TSH.

Topics: Adolescent; Anorexia Nervosa; Body Weight; Female; Follow-Up Studies; Humans; Insulin; Insulin Resistance; Leptin; Obesity; Thyrotropin; Thyroxine; Triiodothyronine

Constitutional thinness (CT) is characterized by a low and stable body mass index (BMI) without any hormonal abnormality. To understand the weight steadiness, energetic metabolism was evaluated. Seven CT, seven controls, and six anorexia nervosa (AN) young women were compared. CT and AN had a BMI <16.5 kg/m(2). Four criteria were evaluated: 1) energy balance including diet record, resting metabolic rate (RMR) (indirect calorimetry), total energy expenditure (TEE) (doubly labeled water), physical activity; 2) body composition (dual-energy X-ray absorptiometry); 3) biological markers (leptin, IGF-I, free T3); 4) psychological profile of eating behavior. The normality of free T3 (3.7 +/- 0.5 pmol/l), IGF-I (225 +/- 93 ng/ml), and leptin (8.3 +/- 3.4 ng/ml) confirmed the absence of undernutrition in CT. Their psychological profiles revealed a weight gain desire. TEE (kJ/day) in CT (8,382 +/- 988) was not found significantly different from that of controls (8,793 +/- 845) and AN (8,001 +/- 2,152). CT food intake (7,565 +/- 908 kJ/day) was found similar to that of controls (7,961 +/- 1,452 kJ/day) and higher than in AN (4,894 +/- 703 kJ/day), thus explaining the energy metabolism balance. Fat-free mass (FFM) (kg) was similar in CT and AN (32.5 +/- 2.9 vs. 34.1 +/- 1.9) and higher in controls (37.8 +/- 1.6). While RMR absolute values (kJ/day) were lower in CT (4,839 +/- 473) than in controls (5,576 +/- 209), RMR values adjusted for FFM were the highest in CT. TEE-to-FFM ratio was also higher in CT than in controls. Energetic metabolism balance maintains a stable low weight in CT. An increased energy expenditure-to-FFM ratio differentiates CT from controls and could account for the resistance to weight gain observed in CT.

Topics: Adipose Tissue; Adolescent; Adult; Anorexia Nervosa; Basal Metabolism; Body Composition; Body Constitution; Body Mass Index; Body Weight; Diagnosis, Differential; Energy Metabolism; Female; Humans; Leptin; Thinness

Anorexia nervosa (AN) is characterized by self-induced starvation leading to severe weight and fat loss. In the present study, we measured fasting plasma levels of adiponectin, leptin, resistin, insulin and glucose in 10 women with a restrictive type of AN and in 12 healthy women (C). Insulin sensitivity was determined according to homeostasis model assessment of insulin resistance (HOMA-R). Plasma resistin, leptin and insulin levels were significantly decreased, whereas plasma adiponectin levels were significantly increased in patients with AN compared to the C. HOMA-R was significantly decreased in patients with AN compared to the C group. Plasma adiponectin and leptin concentrations negatively and positively correlated with the body mass index and percentage body fat in both groups. Plasma adiponectin levels were negatively related to plasma insulin levels in the AN group only. In conclusion, we demonstrated that AN is associated with significantly decreased plasma leptin and resistin levels, markedly increased plasma adiponectin levels and increased insulin sensitivity. Plasma leptin and adiponectin levels were related to the body size and adiposity. Hyperadiponectinemia could play a role in increased insulin sensitivity of patients with AN. Neither body size and adiposity nor insulin sensitivity are the major determinants of plasma resistin levels in AN.

Topics: Adipokines; Adiponectin; Adiposity; Adult; Anorexia Nervosa; Blood Glucose; Body Mass Index; Case-Control Studies; Female; Humans; Insulin; Insulin Resistance; Leptin; Models, Biological; Resistin

Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is limited and contradicting.. Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in body mass index, leptin, insulin sensitivity, and additional endocrine parameters.. We conducted a longitudinal controlled study of 38 female adolescent malnourished AN inpatients, with 13 young, lean, healthy women serving as controls. Blood samples were obtained upon admission and thereafter at 1, 3, and 5 months (at target weight).. Changes in body mass index, leptin, adiponectin, insulin sensitivity, and adiponectin multimeric forms were measured.. At admission, leptin levels of AN patients were significantly lower, whereas insulin sensitivity (assessed by homeostasis model assessment-insulin resistance), adiponectin levels, and the ratio of high molecular weight (HMW) adiponectin to total adiponectin were significantly higher compared with controls. During weight recovery, leptin levels and homeostasis model assessment-insulin resistance increased significantly, whereas adiponectin and HMW adiponectin/total adiponectin ratio decreased significantly, to levels similar to controls. An initial increase in adiponectin levels was observed after 1 month of refeeding. There was no correlation between adiponectin and either T(4) or cortisol levels.. Our study demonstrates hyperadiponectinemia, increased adiponectin HMW isoform, and increased insulin sensitivity in adolescent AN female patients and reversal of these findings with weight rehabilitation. We hypothesize that increased adiponectin levels may have a protective role in maintaining energy homeostasis during extreme malnourishment.

Topics: Adiponectin; Adolescent; Adult; Anorexia Nervosa; Blood Glucose; Body Height; Body Mass Index; Body Weight; Female; Hormones; Humans; Insulin Resistance; Isomerism; Leptin; Weight Gain

Plasma leptin concentrations are markedly reduced in malnourished patients with anorexia nervosa (AN). Whether the long-term underweight and low-fat stores affect the leptin response to exercise remains unknown. We investigated the effect of 45-minute cycle ergometer exercise (2 W kg-1 of lean body mass [LBM]) on plasma leptin, norepinephrine (NE), glycerol, and insulin levels in 10 patients with AN and in 15 healthy age-matched women (C). Plasma leptin levels immediately and 90 minutes after the exercise bout were significantly reduced compared with basal leptin levels in both AN and C groups (P<.05). Compared with the control trial, leptin levels were significantly lower immediately and 90 minutes after exercise in the AN group (P<.05) but not in the C group. Basal and exercise-induced plasma glycerol and NE levels did not differ significantly between the groups. Basal and exercise-induced plasma insulin levels were significantly lower in the AN group compared with the C group (P<.05). In conclusion, we demonstrated that a single bout of low-intensity exercise significantly reduces plasma leptin levels in patients with AN. In healthy women, exercise had no effect on lowering leptin concentrations beyond the diurnal decrease that occurs in the absence of exercise. Neither NE nor insulin are responsible for the different response of leptin to exercise in AN.

Topics: Adult; Anorexia Nervosa; Body Weight; Exercise; Glycerol; Humans; Insulin; Leptin; Norepinephrine; Radioimmunoassay

Food intake is controlled by the arcuate nucleus through integration of peripheral hormonal signals such as leptin, ghrelin, peptide YY (PYY), and glucagon-like peptide 1 (GLP-1). The most common condition resulting in underweight young women in the developed world is restrictive anorexia nervosa (AN). However, constitutional thinness (CT) is also known to exist in the same low-weight range. Women with CT have normal menstrual periods and do not have the psychological or hormonal features of AN. Little is currently known about regulation of food intake in subjects with CT.. We tested the hypothesis that concentrations of leptin, ghrelin, PYY, and GLP-1 in persons with AN are significantly different from those in persons with CT.. Concentrations of PYY, GLP-1, ghrelin, and leptin were measured in 3 groups of young women: normal weight (n = 7), CT (n = 10), and AN (n = 12). Samples were collected every 4 h for 24 h.. PYY concentrations were significantly higher in CT subjects than in AN or control subjects. GLP-1 concentrations were significantly higher in AN than in CT subjects, whereas ghrelin was significantly higher in AN subjects than in control and CT subjects. CT subjects had the lowest ghrelin concentrations. Leptin concentrations were significantly lower in AN subjects. PYY and leptin circadian variations were not significantly different between CT and control subjects, whereas these profiles were blunted in AN subjects.. Orexigenic and anorexigenic hormones in CT contrast with an adaptative profile characterizing AN. The hormones appear to be valuable biomarkers for distinguishing these 2 categories of severely underweight subjects.

Topics: Absorptiometry, Photon; Adult; Analysis of Variance; Anorexia Nervosa; Appetite Regulation; Body Composition; Body Mass Index; Case-Control Studies; Circadian Rhythm; Energy Intake; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Peptide Hormones; Peptide YY; Thinness

In anorexia nervosa (AN), hyperactivity is observed in about 80% of patients and has been associated with low leptin levels in the acute stage of AN and in anorexia animal models. To further understand the importance of this correlation in AN, we investigated the relationship between hypoleptinaemia and hyperactivity in AN patients longitudinally and assessed their predictive value for recovery. Body weight, activity levels, and serum leptin levels were assessed in adolescents and adult AN patient groups at the start and during treatment, up to a year. In the adolescent group, initial leptin and activity levels were correlated. This negative correlation changes over time into a positive correlation with physiological recovery. Treatment outcome in both groups could be predicted by initial BMI and leptin levels but not by activity levels. No major relationship of activity with the course of recovery was detected, suggesting that in contrast to the acute stage of the disease, leptin and activity levels during the recovery process are dissociated.

Topics: Acute Disease; Adolescent; Anorexia Nervosa; Cohort Studies; Female; Follow-Up Studies; Humans; Hyperkinesis; Leptin; Prospective Studies; Recovery of Function; Young Adult

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

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

Changes in body composition, hormone secretions, and heart function with increased risk of sudden death occur in eating disorders. In this observational clinical study, we evaluated sympathovagal modulation of heart rate variability (HRV) and cardiovascular changes in response to lying-to-standing in patients with anorexia (AN) or bulimia nervosa (BN) to analyze: a) differences in autonomic activity between AN, BN, and healthy subjects; b) relationships between autonomic and cardiovascular parameters, clinical data and leptin levels in patients with eating disorders. HRV, assessed by power spectral analysis of R-R intervals, blood pressure (BP) and heart rate (HR) were studied by tilt-table test in 34 patients with AN, 16 with BN and 30 healthy controls. Autonomic and cardiovascular findings were correlated with clinical data, and serum leptin levels. Leptin levels were lowered in AN vs BN and healthy subjects (p<0.0001), but both AN and BN patients showed unbalanced sympathovagal control of HRV due to relative sympathetic failure, prevalent vagal activity, impaired sympathetic activation after tilting, independently from their actual body weight and leptin levels. No significant correlations were obtained between HRV data vs clinical data, BP and HR findings, and leptin levels in eating disorders. Body mass indices (BMI) (p<0.02), and leptin levels (p<0.04) correlated directly with BP values. Our data showed alterations of sympathovagal control of HRV in eating disorders. These changes were unrelated to body weight and BMI, diagnosis of AN or BN, and leptin levels despite the reported effects of leptin on the sympathetic activity.

Topics: Adult; Anorexia Nervosa; Autonomic Nervous System Diseases; Blood Pressure; Body Mass Index; Body Weight; Bulimia Nervosa; Female; Heart Rate; Humans; Leptin; Posture; Tilt-Table Test; Vagus Nerve

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

Osteoporosis is one of the major complications in anorexia nervosa (AN) patients. Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) have been identified as important regulators of bone turnover. The objective of this study was to clarify the role of RANK-RANKL-OPG system, and their relationship with other regulators for bone metabolism in AN patients. We investigated serum levels of RANKL, OPG, and bone turnover markers of 26 Japanese young female AN patients and 7 age-matched healthy women. We measured serum levels of estradiol (E2), insulin like growth factor-I (IGF-I) and triiodothyronin (T3) from the same samples and studied their relationship with RANKL or OPG. Mean serum levels of E2, IGF-I, T3 and leptin in AN patients were significantly lower than those of controls (p<0.05). Serum levels of OPG in AN patients were significantly higher than those in controls and negatively correlated with body mass index (BMI), E2, IGF-I or leptin. Serum levels of free RANKL could not be detected except for only one healthy control in both groups. These results suggest that serum OPG levels may be increased by a compensatory mechanism for malnutrition and estrogen deficiency which induces an increase in bone resorption.

Topics: Adolescent; Adult; Alkaline Phosphatase; Anorexia Nervosa; Bone and Bones; Bone Density; Calcium; Collagen Type I; Estradiol; Female; Humans; Insulin-Like Growth Factor I; Leptin; Osteoprotegerin; Parathyroid Hormone; Peptides; Phosphates; RANK Ligand; Statistics, Nonparametric; Triiodothyronine

In food-restricted rats, leptin suppresses semistarvation-induced hyperactivity (SIH) and decreases exploratory behavior. Leptin ameliorates anxiety-related movement in ob/ob mice. In this study, we assessed the relationship between leptin and qualities of physical activity and restlessness in acute anorexia nervosa (AN).. Serum leptin, body mass index (BMI), % body fat, and self- and expert-ratings of qualities of physical activity and restlessness were assessed in 26 inpatients with acute AN. Accelerometry was also performed. Regression analyses were used to predict activity and restlessness using BMI, % body fat, and leptin levels as predictor variables.. Leptin levels significantly contributed to the prediction of all measures of activity and restlessness.. This is the first study linking hypoleptinemia in AN patients to subjective and objective measures of higher physical activity and motor and inner restlessness. Leptin may directly or indirectly (or both) influence behaviors and cognitions contributing to hyperactivity and motor restlessness.

Topics: Adolescent; Adolescent Behavior; Anorexia Nervosa; Body Composition; Body Mass Index; Female; Humans; Kinetocardiography; Leptin; Motor Activity; Predictive Value of Tests; Psychomotor Agitation; Self Disclosure; Surveys and Questionnaires

Neuroendocrine abnormalities in anorexia nervosa (AN) include hypercortisolemia, hypogonadism, and hypoleptinemia, and neuroendocrine predictors of menstrual recovery are unclear. Preliminary data suggest that increases in fat mass may better predict menstrual recovery than leptin. High doses of cortisol decrease luteinizing hormone (LH) pulse frequency, and cortisol predicts regional fat distribution. We hypothesized that an increase in fat mass and decrease in cortisol would predict menstrual recovery in adolescents with AN. Thirty-three AN girls 12-18 y old and 33 controls were studied prospectively for 1 y. Body composition [dual energy x-ray absorptiometry (DXA)], leptin, and urinary cortisol (UFC) were measured at 0, 6, and 12 mo. Serum cortisol was measured overnight (every 30 min) in 18 AN subjects and 17 controls. AN subjects had higher UFC/cr x m2 and cortisol area under curve (AUC), and lower leptin levels than controls. Leptin increased significantly with recovery. When menses-recovered AN subjects were compared with AN subjects not recovering menses and controls, menses-recovered AN subjects had higher baseline cortisol levels and greater increases in leptin than controls and greater increases in fat mass than AN subjects not recovering menses and controls (adjusted for multiple comparisons). In a logistic regression model, increasing fat mass, but not leptin, predicted menstrual recovery. Baseline cortisol level strongly predicted increases in the percentage of body fat. We demonstrate that 1) high baseline cortisol level predicts increases in body fat and 2) increases in body fat predict menses recovery in AN.

Topics: Adipose Tissue; Adolescent; Anorexia Nervosa; Body Composition; Body Mass Index; Child; Female; Humans; Hydrocortisone; Leptin; Menstruation; Prospective Studies

Serotonin (5-HT) plays an important role in controlling food intake and regulating body weight. In addition, clinical studies suggest a possible role for 5-HT in the etiology of anorexia nervosa. Recently, we have examined the effects of pharmacological manipulation of the 5-HT system in female rats exposed to conditions that promote activity-based anorexia (ABA). In this animal model of anorexia nervosa, rats are food restricted (2 h access/day) while given the opportunity to exercise in running wheels. These conditions promote symptoms of anorexia nervosa including hypophagia, hyperactivity, progressive weight loss, and disruptions of the ovarian reproductive cycle. Previously, we demonstrated that increased 5-HT activity increased the weight loss associated with ABA in female rats. Here, we investigated whether decreased 5-HT activity would attenuate symptoms of ABA. Food-restricted female rats received injections of 8-OH-DPAT, a drug that reduces serotonergic neurotransmission, or saline vehicle 40 min prior to food access. During this restricted-feeding phase, food intake was similar between groups; however, 8-OH-DPAT prevented the hyperactivity observed in saline-treated rats. This resulted in less weight loss in 8-OH-DPAT-treated rats, suggesting that decreased activation of the 5-HT system attenuates the development of ABA.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Anorexia Nervosa; Body Temperature; Eating; Estrus; Female; Leptin; Motor Activity; Rats; Rats, Long-Evans; Serotonin; Serotonin Receptor Agonists; Weight Loss

Hypothalamic amenorrhea in anorexia nervosa often precedes weight loss and may persist after re-feeding and restoration of a stable normal weight.. To assess the rate of persistent amenorrhea in anorexia nervosa (AN) after re-feeding and the relations of this condition with body composition changes and other endocrine parameters.. A cohort of 250 female outpatients was studied to assess persistent amenorrhea prevalence after stable weight recovery. Among these, we selected 20 AN female patients (age 16.5-35), 10 with amenorrhea (group 1) and 10 with normal menses (group 2). We collected data such as age, age at menarche, age at onset of AN, actual body mass index (BMI) and at onset of AN, duration of disease. Physical activity has been evaluated as minute per day. The following data were obtained: prolactin, growth hormone, estradiol, luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone, free triiodothyronine, free thyroxine, free urinary cortisol, serum calcium and phosphates, urinary calcium, phosphaturia and alkaline phosphatase. Body composition was assessed with a dual energy x-ray absorptiometry (DEXA).. Thirty-five patients (14%) over a cohort of 250 where still amenorrhoic after stable weight recovery. No significance was found in the evaluation of blood biochemical tests of the 2 groups. Free urinary cortisol was significantly higher in amenorrhoic patients (58.14+/-0.4 vs 15.91+/-9.5), p=0.02. The analysis of body composition has shown a percentage of fat of 22.23+/-5.32% in group 1 and of 26.03%+/-9.1% in group 2, respectively, showing no significant differences. Amenorrhoic patients carried on doing a significantly heavier physical activity than eumenorrhoic patients.. An adequate body composition and a well represented fat mass are certainly a necessary but not sufficient condition for the return of the menstrual cycle. Such menstrual cycle recovery would probably need other conditions at present being studied and evaluated to occur, such as secretory patterns of leptin and its correlations with adrenal function.

Topics: Adolescent; Adult; Amenorrhea; Anorexia Nervosa; Body Composition; Body Mass Index; Cohort Studies; Exercise; Female; Follicle Stimulating Hormone; Humans; Hydrocortisone; Hypothalamic Diseases; Leptin; Luteinizing Hormone

Anorexia nervosa is a serious eating disorder with the highest mortality rate of any psychiatric disorder. The DSM-IV classification differentiates two AN types: the restricting type (AN-R) and the binge-eating/purging type (AN-BP). Leptin (LEP) levels can be thought of as a signal to the body of its energy reserves. The leptin receptor (including all its mRNA isoforms) is expressed in many tissues. Our aim was to discover the transcript expression profile of the LEP receptor-coding gene in the peripheral blood mononuclears in AN-R and AN-BP patients. Three young women suffering from Anorexia nervosa (one with AN-BP and two with AN-R) took part in the study, along with three non-anorexic subjects as our reference group. LEP receptor gene expression was examined using the oligonucleotide microarray method (HG-U133A, Affymetrix). The results were normalized using RMAExpress. Next, the accumulation analysis method was used (clustering). Hierarchical clustering resulted in three groups of separate clusters. The first group (cluster I) consisted of AN-R patients. The next group (cluster II) consisted of reference group patients suffering from different psychic disorders not related to eating disorders. Cluster III consisted of two patients--the first with AN-BP and the second with an adaptive disorder.

Topics: Adolescent; Adult; Anorexia Nervosa; Biomarkers; Body Mass Index; Female; Gene Expression Profiling; Humans; Leptin; Oligonucleotide Array Sequence Analysis; Receptors, Leptin; RNA, Messenger; Transcription, Genetic

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

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

Agouti-related protein (AGRP) is the competitive antagonist of alpha-melanocyte stimulating hormone (alpha-MSH) located at melanocortin receptors 3 and 4 (MC3R and MC4R), and also acts as an MC4R inverse agonist. Hypothalamic AGRP controls food intake and body weight in rodents. It has also been found in human plasma. To study the possibility of disturbances in melanocortin receptor-related peptides in eating disorders, plasma AGRP, alpha-MSH, and leptin levels were measured in 18 female patients with anorexia nervosa (AN) (age, 23.5+/-7.1 yr; body mass index (BMI) 14.5+/-1.8 kg/m(2)) and 17 age-matched female controls (age, 25.8+/-3.9 yr; BMI 20.2+/-1.6 kg/m(2)). Blood samples were collected after overnight fasting, and plasma peptides levels were measured using ELISA. Plasma AGRP levels increased significantly in AN patients when compared with controls (P<0.01) while plasma alpha-MSH levels were not significantly different. Plasma leptin levels decreased significantly in AN patients when compared with controls (P<0.001). In addition, plasma AGRP levels were negatively correlated with leptin (r=-0.41, P<0.01) and BMI (r=-0.40, P<0.05) in all subjects. In conclusion, plasma AGRP elevation may be related to energy homeostasis disturbance in AN, and in addition to leptin, peripheral AGRP levels could be used as a nutritional marker in AN patients.

Topics: Adolescent; Adult; Agouti-Related Protein; alpha-MSH; Anorexia Nervosa; Biomarkers; Energy Metabolism; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Matched-Pair Analysis; Receptors, Melanocortin; Reference Values

To find differences in heart rate before and after refeeding and to identify which parameters of autonomic activity and endocrine function are associated with these differences.. Before and after the start of refeeding, body weight, RR interval (RRI), heart rate variability, endocrine function, and energy expenditure were measured in nine female anorexia nervosa patients.. After short-term refeeding, mean daytime heart rate rose from 54.9 to 69.4 bpm (P<.05). The changes in sympathetic activity were correlated negatively with the changes in RRI (r=-.933, P<.001). Urine C-peptide, IGF-1, and fT3 increased significantly, and norepinephrine tended to increase.. We demonstrated that autonomic nervous activity was relevant to changes in heart rate during refeeding, and it is speculated that the increases in insulin secretion, thyroid function, and IGF-1 were responsible for the mechanisms.

Topics: Adolescent; Adult; Anorexia Nervosa; Asian People; Body Mass Index; Energy Intake; Energy Metabolism; Epinephrine; Feeding Behavior; Female; Heart Rate; Humans; Leptin; Norepinephrine; Parasympathetic Nervous System; Pilot Projects; Severity of Illness Index; Sympathetic Nervous System

Adolescence is a common time for the onset of anorexia nervosa (AN), a condition associated with long-term medical and hormonal consequences.. The objective was to compare the nutrient intakes of community-dwelling girls with AN with those of healthy adolescents and to describe the associations between specific nutrient intakes and nutritionally dependent hormones.. Nutrient intakes in 39 community-dwelling girls with AN and 39 healthy adolescents aged 12.1-18.7 y were determined by using 4-d food records. Fasting adiponectin, leptin, ghrelin, insulin, and insulin-like growth factor I (IGF-I) concentrations were measured. Indirect calorimetry was used to assess respiratory quotient and resting energy expenditure.. In contrast with the control group, the AN group consumed fewer calories from fats (P < 0.0001) and more from carbohydrates (P = 0.0009) and proteins (P < 0.0001). Intake of individual fat components was lower and of dietary fiber higher in the AN group. No significant between-group differences were observed in dietary intakes of calcium, zinc, and iron; however, total intake was greater in the AN group because of greater supplement use (P = 0.006, 0.02, and 0.01, respectively). The AN group had greater intakes of vitamins A, D, and K and of most of the B vitamins, and significantly more girls with AN met the Dietary Reference Intake for calcium (P = 0.01) and vitamin D (P = 0.02) from supplement use. Fat intake predicted ghrelin, insulin, and IGF-I concentrations; carbohydrate intake predicted adiponectin. Resting energy expenditure was lower (P < 0.0001) and leisure activity levels higher in the AN group.. Despite outpatient follow-up, community-dwelling girls with AN continue to have lower fat and higher fiber intakes than do healthy adolescents, which results in lower calorie intakes. Nutritionally related hormones are associated with specific nutrient intakes.

Topics: Adiponectin; Adolescent; Adult; Anorexia Nervosa; Basal Metabolism; Body Composition; Bone Density; Calorimetry, Indirect; Case-Control Studies; Child; Diet Records; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Energy Intake; Feeding Behavior; Female; Ghrelin; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Nutrition Surveys; Peptide Hormones; Residence Characteristics; Trace Elements; Vitamins

To study the role of adipose tissue-derived hormones in the pathophysiology of eating disorders, circulating levels of adiponectin, resistin, and other hormonal and metabolic parameters were measured in 16 females with the restrictive subtype of anorexia nervosa (R-AN), 10 females with the binge/purge subtype of anorexia nervosa (P-AN), 15 females with bulimia nervosa (BN), and 12 age-matched healthy females (C). Body mass index (BMI), body fat content, and serum leptin levels were severely decreased in R-AN and moderately decreased in P-AN patients, whereas the BN group did not differ from C in these parameters. Serum soluble leptin receptor levels were increased in R-AN and P-AN and unchanged in BN patients. Circulating adiponectin levels were inversely related to BMI and were unchanged in BN patients and increased by 53% in P-AN and by 96% in R-AN relative to C group, respectively. In contrast, resistin levels in malnourished R-AN and P-AN were not different from either C or BN groups and showed no significant relationship to BMI or body fat content. We suggest that increased adiponectin levels reflect decreased body fat content in AN patients. In contrast, circulating resistin levels do not appear to be closely related to the nutritional status.

Topics: Adiponectin; Adipose Tissue; Anorexia Nervosa; Blood Glucose; Body Mass Index; Bulimia; Female; Homeostasis; Hormones, Ectopic; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Receptors, Cell Surface; Receptors, Leptin; Resistin

The adipocyte-derived hormone leptin is involved in energy metabolism and body weight regulation. Plasma leptin concentrations are significantly reduced in patients with anorexia nervosa (AN) and with severe malnutrition. Whether reduced plasma leptin is reflected by its decreased production by the adipose tissue is unknown.. In the present study we measured leptin concentrations locally in the abdominal subcutaneous adipose tissue of 9 female AN patients and 11 healthy controls by in vivo microdialysis.. Adipose tissue free leptin levels were not different in patients with AN compared to controls (2.59+/-1.99 vs 2.36+/-0.25 ng/ml, P>0.05). Plasma leptin soluble receptor (sOb-R) levels were significantly higher in patients with AN than in healthy subjects (58.05+/-38.69 vs 12.79+/-5.08 U/ml, P<0.01). The area of adipocyte in AN was considerably smaller than in the controls (183+/-104.01 microm2 compared to 2145.8+/-1003.41).. We conclude that decreased plasma leptin levels in patients with AN are not directly related to dialysate leptin levels in the abdominal subcutaneous adipose tissue.

Topics: Adipose Tissue; Adult; Anorexia Nervosa; Case-Control Studies; Female; Humans; Leptin; Microdialysis; Receptors, Cell Surface; Receptors, Leptin

The effects of changes in body mass index (BMI) and other factors on plasma leptin levels in children and adolescents with anorexia nervosa (AN) were examined.. Plasma leptin levels and BMI was measured before and after initiation of refeeding therapy every 2 weeks for 8 weeks in 12 children and adolescents with AN. The plasma levels of insulin, cortisol, insulin-like growth factor-I (IGF-I), and tumor necrosis factor-alpha (TNF-alpha) were also measured in these subjects before and after 8 weeks of the refeeding therapy, and the results were compared with those from 12 age-matched healthy girls.. The plasma leptin and IGF-I levels, as well as the BMI, in the AN patients before refeeding therapy were significantly lower than both of these indices in the AN patients 8 weeks after initiation of the therapy and in the controls. The plasma leptin levels and BMI in the AN patients 8 weeks after initiation of the therapy were still significantly lower than those in the controls. Significant correlations between the plasma leptin levels and BMI were detected in the AN patients both before and 8 weeks after initiation of the refeeding therapy, as well as in the controls. The BMI showed a significant increase beginning at 2 weeks after initiation of the therapy compared with that before refeeding, but the plasma leptin levels did not significantly increase until 4 weeks after the initiation of therapy.. The results suggest that plasma leptin levels reflect changes in body fat content in children and adolescents with AN, although there is a delay in the recovery of plasma leptin levels compared with those of BMI in the early period of refeeding therapy, which is probably regulated by other factors.

Topics: Adolescent; Anorexia Nervosa; Body Mass Index; Child; Female; Humans; Hydrocortisone; Insulin; Insulin-Like Growth Factor I; Leptin; Tumor Necrosis Factor-alpha

To examine the determinants of adiponectin levels (i) in 23 women with anorexia nervosa (mean BMI 15.0 +/- 1.2) and 43 healthy normal weight females (mean BMI 22.3 +/- 2.3; cross-sectional design) as well as (ii) after six and twelve weeks of weight gain in subgroups of 18 and 11 anorectic patients (mean weight gain 5.8 kg; longitudinal design). Plasma adiponectin and leptin concentrations were measured and their relationships to body composition (fat mass by bioelectrical impedance analysis and anthropometrics), different hormones and metabolic parameters (insulin, ACTH, cortisol, glucose, FFA, lipid profile) were investigated.. In anorectic patients, adiponectin levels were higher (+29 %) and leptin levels were lower (-75 %) than in control subjects. There was a high variance in adiponectin levels in patients ranging from 2.6 to 18 nM. Combining patients and controls, an inverse linear correlation was observed between adiponectin levels and fat mass (r = -0.36, p < 0.05), while a positive exponential relation was found between leptin levels and fat mass (r = 0.82, p < 0.001). In anorectic patients, there were no significant correlations between adiponectin and hormonal or metabolic parameters. Weight gain resulted in increasing leptin (+0.17 +/- 0.12 nM; p < 0.001) and a nonsignificant decrease in adiponectin concentrations (-1.12 +/- 2.51 nM). Changes in leptin levels were mainly explained by a gain in fat mass (r = 0.85, p < 0.001). In contrast, changes in adiponectin levels were closely linked to initial adiponectin levels (r = -0.84, p < 0.001) but not to changes in fat mass or BMI.. Cross-sectionally serum adiponectin concentration followed a linear inverse function with fat mass when patients and controls were combined. Longitudinally gain in fat mass was not associated with changes in adiponectin levels suggesting other yet unidentified influences on adiponectin secretion in anorexia nervosa.

Topics: Adiponectin; Adipose Tissue; Anorexia Nervosa; Anthropometry; Body Composition; Case-Control Studies; Cross-Sectional Studies; Electric Impedance; Female; Hormones; Humans; Leptin; Longitudinal Studies; Weight Gain

Leptin, an adipocytokine that suppresses appetite and may regulate neuroendocrine pathways, is low in undernourished states like anorexia nervosa (AN). Although leptin exhibits pulsatility, secretory characteristics have not been well described in adolescents and in AN, and the contribution of hypoleptinemia to increased growth hormone (GH) and cortisol in AN has not been explored. We hypothesized that hypoleptinemia in AN reflects decreased basal and pulsatile secretion and may predict increased GH and cortisol levels. Sampling for leptin, GH, cortisol, and ghrelin was performed every 30 min (from 2000 to 0800) in 23 AN and 21 controls 12-18 yr old, and data were analyzed using Cluster and deconvolution methods. Estradiol, thyroid hormones, and body composition were measured. AN girls had lower pulsatile and total leptin secretion than controls (P < 0.0001) subsequent to decreased burst mass (P < 0.0001) and basal secretion (P = 0.02). Nutritional markers predicted leptin characteristics. In a regression model including BMI, body fat, and ghrelin, leptin independently predicted GH burst interval and frequency. Valley leptin contributed to 56% of the variability in GH burst interval, and basal leptin and fasting ghrelin contributed to 42% of variability in burst frequency. Pulsatile leptin independently predicted urine free cortisol/creatinine (15% of variability). Valley leptin predicted cortisol half-life (22% of variability). Leptin predicted estradiol and thyroid hormone levels. In conclusion, hypoleptinemia in AN is subsequent to decreased basal and pulsatile secretion and nutritionally regulated. Leptin predicts GH and cortisol parameters and with ghrelin predicts GH burst frequency. Low leptin and high ghrelin may be dual stimuli for high GH concentrations in undernutrition.

Topics: Adolescent; Anorexia Nervosa; Cluster Analysis; Estradiol; Female; Ghrelin; Human Growth Hormone; Humans; Hydrocortisone; Insulin Resistance; Leptin; Nutritional Status; Peptide Hormones; Pulsatile Flow; Reference Values

Leptin has been considered a starvation hormone, but its role in malnourished patients is unknown.. We aimed to characterize the role of leptin in metabolic adaptation in women with anorexia nervosa (AN).. In a cross-sectional study, 57 women with AN [mean (+/-SD) body mass index (kg/m(2)) on admission: 15.2 +/- 1.5] were compared with 49 healthy, normal-weight women (mean body mass index: 22.3 +/- 2.3). Nineteen patients were reinvestigated during weight gain 43 and 84 d after baseline. We measured serum concentrations of leptin, soluble leptin receptor, insulin, ghrelin, and thyroid hormones [thyrotropin, triiodothyronine (T(3)), and thyroxine]; fat mass (FM) and fat-free mass (FFM); resting energy expenditure (REE); energy intake; and eating behavior.. Compared with values in the control women, leptin, T(3), REE, FM, and FFM were lower in the women with AN, but the leptin secretion rate was not significantly different. Leptin correlated with FM (r = 0.83, P < 0.001), T(3) (r = 0.68, P < 0.001), respiratory quotient (r = -0.47, P < 0.001), and REE (r = 0.58, P < 0.001). The association with REE weakened after adjustment for FFM and disappeared after further adjustment for T(3). Hunger and appetite had positive, whereas satiety and restraint had negative, associations with leptin. During weight gain (9.0 +/- 3.3 kg in 84 d), serum leptin and the leptin secretion rate increased. Changes in leptin secretion were associated with energy intake and REE. The initial changes in the leptin secretion rate (ie, the difference between baseline and 43 d) were negatively associated with changes in body weight from 43 to 84 d.. Leptin contributes to metabolic adaptation in women with AN. The leptin response is associated with weight gain.

Topics: Adolescent; Adult; Anorexia Nervosa; Basal Metabolism; Body Mass Index; Body Weight; Case-Control Studies; Cross-Sectional Studies; Eating; Energy Intake; Energy Metabolism; Female; Humans; Leptin; Middle Aged; Nutritional Status

The aim of our study was to compare serum concentrations of adiponectin, leptin and other selected parameters in female patients with restrictive subtype of anorexia nervosa (n=15), (RMA), binge/purge subtype of anorexia nervosa (n=11) (PMA) with age-matched healthy females, (C, n=14).. RMA patients had the most severely decreased body mass index (BMI) and serum leptin levels of the three groups studied. These parameters were also significantly lower in PMA relative to C group. (BMI: RMA 14.61 +/- 0.49 kg/m2, PMA 17.30 +/- 0.25 kg/m2, C 23.21 +/- 0.96 kg/m2; leptin: RMA 1.39 +/- 0.31 ng/ml, PMA 3.72 +/- 0.77 ng/ml, C 9.17 +/- 1.53 ng/ml). In contrast, serum adiponectin levels were markedly increased in RMA patients (57.28 +/- 4.86 ug/ml) relative to other groups (PMA 40,25 +/- 2.18 microg/ml, K 26.84 +/- 2.40 microg/ml). Serum leptin levels positively correlated with BMI in all groups studied (r = 0.56, p = 0.002), while the inverse relationship was found for adiponectin levels and BMI (r = -0.72, p = 0.000003). The hormonal concentrations were measured by commercially available RIA and ELISA kits.. The most significant changes of serum adiponectin and leptin levels were found in the RMA group with most severely decreased BMI and body fat content relative to rest of the groups. Possible role of increased adiponectin levels in the etiopathogenesis and/or metabolic changes in patients with anorexia nervosa is under the scope of our current investigations.

Topics: Adiponectin; Anorexia Nervosa; Body Mass Index; Bulimia; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Receptors, Cell Surface; Receptors, Leptin

Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa (AN). In ABA, scheduled feeding together with voluntary access to a running wheel results in increased running wheel activity (RWA), hypophagia, and body weight loss. Previously it was shown that leptin treatment reduced semi-starvation-induced hyperactivity in rats. The present study was performed to confirm and extend this finding, to evaluate leptin's effect on energy balance in ABA.. The effects of chronic leptin treatment (intracerebroventricular, 4 microg/day) in ABA rats, ad libitum-fed running rats, and sedentary rats exposed to ad libitum feeding or scheduled feeding were investigated.. Leptin treatment decreased RWA in ABA rats. Additionally, leptin treatment reduced food intake and increased energy expenditure by thermogenesis in ABA rats. Ad libitum-fed running/sedentary rats or food-restricted sedentary rats did not reduce activity after leptin treatment, whereas all leptin-treated rats showed hypophagia. Body temperature was slightly increased in leptin-treated food-restricted sedentary rats.. Although leptin treatment reduced RWA in ABA rats, it also prevented hypothermia and decreased food intake. Altogether, this resulted in a stronger negative energy balance and body weight loss in leptin-treated ABA rats.

Topics: Animals; Anorexia Nervosa; Appetite Regulation; Disease Models, Animal; Energy Intake; Energy Metabolism; Female; Hormones; Injections, Intraventricular; Leptin; Motor Activity; Physical Conditioning, Animal; Rats; Rats, Wistar

The pathogenesis of anorexia nervosa (AN) remains still unclear. It has been reported that neuropeptides may play a role in the control of appetite and hormone release contributing to hormonal disturbances in AN. However the question if neuropeptide alterations are consequence or cause of malnutrition is still unresolved.. Serum leptin, neuropeptide Y (NPY) concentrations as well as hormones (FSH, LH, estradiol, cortisol and fT4) serum levels were prospectively estimated in 19 girls aged 11.7-17.7 years (mean 15.5 years) with anorexia nervosa (AN) at the admission to the hospital (baseline) and at follow-up after 7.21+ 2.32 months of treatment. The treatment consisted of hypercaloric diet, psychotherapy and vitamins supplementation.. Mean leptin concentration significantly increased from 7.99 + 2.6 to 9.98 + 2.48 microg/ml (p<0.01), whereas mean NPY concentration significantly decreased from 34.10 + 9.81 to 29.6 + 8.04 pmol/l (p<0.01). Leptin/BMI ratio was constant, while NPY/BMI ratio decreased. There were no significant differences between leptin and NPY serum concentrations at baseline and follow-up in eumenorrheic vs. amenorrheic patients. Simple linear correlation analysis showed negative correlation between leptin and NPY concentrations at baseline (r=-0.67; p<0.05) and at follow-up (r=-0.76; p<0.05) only in eumenorrheic subgroup. There were no significant correlations between leptin, NPY and BMI and body weight values.. 1) Serum concentration of leptin increases and serum concentration of NPY decreases significantly during the treatment of anorectic girls. 2) These changes do not correspond with increasing body weight and BMI suggesting disregulation of appetite and body weight control mechanisms in AN. 3) Altered neuroregulation of the neuropeptides (leptin and NPY) secretion may contribute persistent amenorrhea after weight gain in anorectic patients with low initial BMI.

Topics: Adolescent; Amenorrhea; Anorexia Nervosa; Appetite; Body Weight; Child; Energy Intake; Estradiol; Female; Follicle Stimulating Hormone; Humans; Hydrocortisone; Leptin; Luteinizing Hormone; Neuropeptide Y; Psychotherapy; Thyroxine; Vitamins

To study the influence of dietary intervention on plasma ghrelin levels in obese children and adolescents with anorexia nervosa (AN). Study design Prepubertal obese children (n=16) and 16 anorexic adolescents were studied at three different points: clinical diagnosis and after a reduction or recuperation of 25% and 50% of the initial BMI SD score. Controls included 21 Tanner growth stage 1 and 36 Tanner growth stage 5 subjects. We analyzed plasma ghrelin levels and their correlation with plasma levels of leptin, insulin, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 1 (IGFBP-1), insulin-like growth factor binding protein 2 (IGFBP-2), insulin-like growth factor binding protein 3 (IGFBP-3), and integrated concentration of growth hormone (ICGH) before and after dietary intervention.. At diagnosis, ghrelin levels were significantly decreased in obese children (52% of control levels) and significantly increased in adolescents with AN (164% of control levels). After dietary intervention, ghrelin increased in obese patients but without reaching control levels even after a 50% reduction in body mass index (BMI). In adolescents with AN, ghrelin levels normalized after a 25% increase in BMI. Ghrelin correlated negatively with the BMI and positively with IGFBP-1 levels in controls but not in obese patients or in patients with AN at diagnosis. The positive correlation between ghrelin and IGFBP-1 was recovered after dietary intervention.. Plasma ghrelin levels present opposite changes in obesity and AN after dietary intervention, suggesting that ghrelin is a good marker of nutritional status.

Topics: Adolescent; Anorexia Nervosa; Body Mass Index; Female; Ghrelin; Growth Hormone; Humans; Leptin; Linear Models; Male; Nutritional Status; Obesity; Peptide Hormones; Weight Loss

To study the role of adiponectin, a novel adipocyte-specific secreted protein, on the pathophysiology of eating disorders, circulating levels of fasting adiponectin, leptin, insulin, and glucose were measured in 31 female patients with anorexia nervosa (AN) and in 11 with bulimia nervosa. Hormone levels were compared with 16 age-matched, normal body weight controls, six healthy constitutionally thin subjects, and nine obese subjects. Moreover, changes in levels were reevaluated after nutritional treatment and weight gain in 13 patients with AN. Serum adiponectin concentrations in AN and bulimia nervosa were significantly lower than those in normal-weight controls. These results were unexpected because the levels were high in constitutionally thin subjects and low in obese subjects, which provide a negative correlation with body mass index (BMI) and body fat mass. In contrast, serum leptin levels correlated very well with BMI and fat mass among all the patients and controls. The insulin resistance was significantly low in AN and high in obese subjects. The concentrations of adiponectin after weight recovery increased to the normal level despite a relatively small increase in BMI. These findings suggest that abnormal feeding behavior in the patients with eating disorders may reduce circulating adiponectin level, and weight recovery can restore it.

Topics: Adiponectin; Adipose Tissue; Adult; Anorexia Nervosa; Body Composition; Body Mass Index; Bulimia; Case-Control Studies; Female; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Middle Aged; Nutrition Therapy; Obesity; Osmolar Concentration; Proteins; Thinness; Weight Gain

The changes in cytokines and hormones involved in hematopoiesis were studied in the serum of 7 girls with anorexia nervosa, 15-24 yr old, on admission and after 5% and 10% weight gain. Hematopoiesis was studied by in-vitro culturing of circulating granulocyte-macrophage colony forming cells and erythroid burst forming cells. Nutritional status was studied by anthropometric measurements and resting energy expenditure. On admission, granulocyte-macrophage colony forming cells and erythroid burst forming cells were significantly lower than in age-matched controls and increased significantly along weight gain. Blood leptin and erythropoietin levels increased significantly with weight gain. TNF-alpha levels tended to decrease while IL-1beta levels were lower than in the controls on admission (p <0.05) and did not change significantly during weight gain. IL-3, GM-CSF and IL-6 were undetected on admission or along weight gain. The changes in granulocyte-macrophage colony forming cells and erythroid burst forming cells positively correlated with changes in resting energy expenditure and fat free mass. These results may suggest that undernutrition affects hematopoiesis as indicated by the reduction of hematopoietic progenitor cells before treatment and the significant increase with weight gain. The changes in the levels of hormones and cytokines known to be involved in hematopoiesis along refeeding may suggest a role for these factors in anorexia nervosa.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Weight; Cells, Cultured; Cytokines; Erythropoietin; Female; Hematopoiesis; Hormones; Humans; Leptin; Nutritional Status

Anorexia nervosa (AN) is associated with very low levels of leptin, a cytokine secreted by adipose tissue and known to suppress appetite. Leptin may play a permissive role in onset of puberty and in resumption of gonadal function in conditions of undernutrition. The soluble leptin receptor (sOB-R) is the main leptin binding protein, and the ratio of serum leptin to sOB-R provides a measure of the free leptin index (FLI), which may be a more accurate determinant of leptin function. Determinants of sOB-R and FLI have not been examined in an adolescent population. We examined levels of sOB-R, leptin, and FLI, and body composition and hormonal determinants of these variables in 23 adolescent girls with AN and 21 healthy adolescent girls of comparable maturity prospectively over 1 yr. Measures of insulin resistance and adiponectin were also examined. We determined changes in levels of sOB-R, leptin, and FLI with weight recovery (defined as an increase in body mass index of >/=10%, n = 11), and with resumption of menstrual cycles (n = 13). Girls with AN had significantly higher levels of sOB-R (P = 0.0008) and significantly lower levels of leptin and FLI (P < 0.0001 for both) than healthy controls, and levels of FLI were reduced more than levels of leptin in girls with AN compared with controls. An inverse correlation was noted between levels of leptin and sOB-R for the group as a whole (r = -0.64, P < 0.0001) but not in girls with AN considered alone. The most important predictor of levels of sOB-R was cortisol in the group as a whole (r = 0.61, P < 0.0001) and in girls with AN considered alone (r = 0.66, P = 0.0008). Other independent predictors of sOB-R levels for the entire group were percent body fat (r = -0.44, P = 0.003) and levels of IGF-I (r = -0.37, P = 0.01). The most important predictors of leptin and FLI were body mass index and percent body fat. An inverse relationship was noted between measures of insulin resistance and sOB-R levels, whereas a positive association was noted between these measures and leptin and FLI. Adiponectin values did not differ in girls with AN compared with healthy controls and did not correlate with sOB-R, leptin, or FLI. Weight recovery resulted in significant decreases in levels of the sOB-R (24.7 +/- 1.7 to 17.6 +/- 1.2 U/ml, P = 0.004), and increases in levels of leptin (4.4 +/- 1.0 to 13.7 +/- 2.9 microg/liter, P = 0.02). Resumption of menstrual function, but not weight recovery alone, was associated with significant

Topics: Adipose Tissue; Adolescent; Anorexia Nervosa; Body Composition; Body Mass Index; Body Weight; Case-Control Studies; Female; Humans; Hydrocortisone; Insulin Resistance; Leptin; Menstrual Cycle; Receptors, Cell Surface; Receptors, Leptin; Recovery of Function; Solubility

Osteopenia and osteoporosis are among the most frequent and severe complications in adolescents with anorexia nervosa.. The aim of this study was to assess the influence of nutritional therapy on bone metabolism during adolescent anorexia nervosa.. We studied 19 anorectic patients aged 14.1 +/- 1.4 y (x +/- SD) with a body mass index (BMI; in kg/m(2)) of 14.2 +/- 1.4 and 19 age-matched control subjects aged 15.1 +/- 2.3 y with a BMI of 20.8 +/- 1.9 for 1 y. Blood samples were taken for the measurement of bone markers, insulin-like growth factor I (IGF-I), and leptin.. BMI rose significantly from 14.2 +/- 1.4 at baseline to 17.4 +/- 0.6 (P < 0.0001) at week 15. Compared with concentrations in the control subjects, concentrations of the bone formation markers procollagen type I propeptide (PICP) and bone alkaline phosphatase (bAP) in the anorectic patients were lower at baseline (PICP: P = 0.0071; bAP: P = 0.0012), increased with nutritional therapy (PICP: P = 0.0060, bAP: P = 0.0147), and were no longer significantly different (P > 0.05) during the follow-up period. Concentrations of IGF-I and leptin were significantly lower (P < 0.0001 for both) in the anorectic patients than in the control subjects at baseline. IGF-I increased with nutritional therapy but was still significantly lower (P = 0.0036) than that in the control group and decreased again during the follow-up period (P = 0.0126). In contrast, serum C-telopeptide decreased with nutritional therapy (P = 0.0446).. Nutritional therapy improves concentrations of bone formation markers in adolescent patients with anorexia nervosa.

Topics: Adolescent; Adolescent Nutritional Physiological Phenomena; Alkaline Phosphatase; Anorexia Nervosa; Biomarkers; Body Mass Index; Body Weight; Bone and Bones; Case-Control Studies; Collagen Type I; Female; Follow-Up Studies; Humans; Inpatients; Insulin-Like Growth Factor I; Leptin; Nutrition Therapy; Nutritional Status; Osteogenesis; Treatment Outcome

Topics: Adipose Tissue; Age of Onset; Amenorrhea; Anorexia Nervosa; Body Composition; Body Weight; Diagnosis, Differential; Exercise; Female; Humans; Hypothalamic Diseases; Leptin; Obesity; Thinness

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

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

Anorexia nervosa (AN) is a state of leptin and gonadotropin deficiency. Leptin levels are decreased in normal weight women with hypothalamic amenorrhea and leptin may be a sensitive marker of overall nutritional status. The aim of the study is to provide additional information on plasma leptin levels and on gonadotropin responses after clomiphene testing in patients with AN who recovered weight but were still amenorrheic. We evaluated 17 patients with AN, female age 20+/-1.2 yr who reached goal weight [body mass index (BMI) 14.9+/-0.5 to 19.3+/-0.4 kg/m2]. At diagnosis serum leptin levels were 2.2+/-0.1 microg/l while after behavioural therapy and hypercaloric diet for 6-12 months serum leptin levels rose to 6.4+/-1.4 microg/l significantly lower compared with those in the control (no.=10, age 28+/-6.2 yr, BMI 21.1+/-0.3 kg/m2, leptin 9.3+/-0.7 pg/l; p<0.05). None of the patients resumed spontaneous menstrual cycles after weight gain. They were tested with a 10-day administration of clomiphene citrate. All had a significant rise in LH secretion (from 1.7+/-0.3 IU/l to 8.3+/-0.9 IU/l, p<0.01) and serum estradiol levels (from 19.0+/-5.4 to 937.7+/-241.2 pg/ml, p<0.03). Nine out of 17 patients menstruated after clomiphene. Serum leptin levels were not different in those who menstruated from those who did not (6.4+/-1.4 to 6.8+/-1.4 microg/l, p>0.05). Body compositon was studied in 12 additional carefully matched patients with AN who recovered weight. Six of them resumed spontaneous menstrual cycles. Neither BMI, body fat, nor leptin appeared as significant determinants of menstrual status. In conclusion, relative hypoleptinemia persists, independent of fat mass, in weight recovered patients with AN. A normal response to clomiphene in weight-recovered yet still amenorrhoeic patients with AN, offers reassurance that the axis is intact and that the problem lies in the hypothalamus. It is reasonable to believe that nutritional disturbances, fat intake and persisting psychological factors still affect plasma leptin levels and reproductive functions in weight-recovered patients with amenorrhea.

Topics: Adolescent; Adult; Amenorrhea; Anorexia Nervosa; Body Mass Index; Body Weight; Case-Control Studies; Clomiphene; Estrogen Antagonists; Female; Gonadotropins; Humans; Hypothalamus; Leptin; Nutritional Status; Weight Gain

Adiponectin (ApN) is a fat-derived hormone that enhances insulin sensitivity, controls body weight, prevents atherosclerosis and negatively regulates haematopoiesis and immune functions. In contrast to many proteins secreted by adipose tissue, the circulating level of ApN falls in obesity and insulin resistance states. The influence of starvation-induced depletion of fat stores on ApN concentrations is yet unknown. We therefore investigated plasma ApN in anorexia nervosa (AN).. We measured plasma ApN in 26 female anorectic patients and examined its relationships to several anthropometric or metabolic parameters. Twenty-four age-matched healthy female controls (C) were also studied.. Body mass index (BMI) and fat mass were markedly decreased in AN. However, plasma ApN levels were 30% higher in anorectic than in control subjects (P < 0.01), while a reverse pattern was observed for leptin concentrations. When normalized for fatness, ApN values almost doubled in AN. ApN levels were negatively correlated with BMI and fat mass (P < 0.05 in the combined population, AN + C). Insulin sensitivity tended to be 40% higher in AN (n = 7) than in C (n = 12) subjects, and plasma ApN levels were positively correlated with insulin sensitivity (P < 0.05 in AN + C subgroups). Total and low density lipoprotein (LDL)-cholesterol were higher, or tended to be higher, in AN, but there were no correlations between plasma ApN and plasma lipids. By contrast, ApN was related to the lipid profile, in a manner consistent with its antiatherogenic role, in healthy controls [i.e. negatively correlated with triglycerides, total and LDL-cholesterol and total/high density lipoprotein (HDL) cholesterol; P < 0.05 or less for each parameter]. In a multiple regression analysis, BMI and insulin sensitivity in AN were independent determinants for ApN levels, explaining up to approximately 80% of the variance in this measure.. Plasma adiponectin levels are increased in anorexia nervosa. This may, at least in part, be due to the lack of negative feedback exerted by fat mass on adiponectin production and/or to enhanced insulin sensitivity. We speculate that hyperadiponectinaemia could, in turn, contribute to maintain a state of enhanced insulin sensitivity and possibly exacerbate haematological and infectious complications of anorexia nervosa.

Topics: Adiponectin; Adipose Tissue; Adult; Anorexia Nervosa; Anthropometry; Body Mass Index; Female; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Lipids; Proteins; Regression Analysis

Ghrelin, a 28-amino acid octanoylated peptide, has recently been identified in rat stomach as an endogenous ligand for the GH secretagogue receptor. In addition to GH-releasing properties, exogenous ghrelin injections exert orexigenic effects in both rodents and humans. As the endogenous peptide appears directly related to feeding behavior, we assessed its plasma levels in anorexia nervosa (AN) patients before and after renutrition and in constitutionally thin subjects with body mass indexes (BMIs) equivalent to those of AN women but with no abnormal feeding behavior. The relationships between plasma ghrelin levels and other neuroendocrine and nutritional parameters, such as GH, leptin, T3, and cortisol, were also investigated. In AN patients, morning fasting plasma ghrelin levels were doubled compared with levels in controls, constitutionally thin subjects, and AN patients after renutrition. Twenty-four-hour plasma ghrelin, GH, and cortisol levels determined every 4 h were significantly increased, whereas 24-h plasma leptin levels were decreased in AN patients compared with controls and constitutionally thin subjects. Both plasma ghrelin and leptin levels returned to control values in AN patients after renutrition. Constitutionally thin subjects displayed intermediate 24-h plasma ghrelin and leptin levels, significantly different from controls and AN patients, whereas GH and cortisol were not modified. Ghrelin was negatively correlated with BMI, leptin, and T(3) in controls, constitutionally thin subjects, and AN patients, whereas no correlation was found between GH and ghrelin or between cortisol and ghrelin. Ghrelin and BMI or T3 were still correlated after renutrition, suggesting that ghrelin is also a good nutritional indicator. Basal and GHRH-stimulated GH release were significantly increased in AN patients only. In conclusion, ghrelin is increased in AN and constitutionally thin subjects who display very low BMI but different eating behaviors, suggesting that not only is ghrelin dependent on body fat mass, but it is also influenced by nutritional status. Even though endogenous ghrelin is not strictly correlated with basal GH secretion, it may be involved in the magnitude of GHRH-induced GH release in AN patients.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Circadian Rhythm; Female; Ghrelin; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Hydrocortisone; Immunologic Techniques; Leptin; Peptide Hormones; Reference Values; Thinness; Triiodothyronine

Subjects with anorexia nervosa (AN) at low weight display metabolic, endocrine, and behavioral abnormalities. Whether these various differences are a consequence of the condition and persist after recovery is unclear. We tested the hypothesis that abnormalities in the insulin and leptin axes and in the desire to eat persisted in subjects who had recovered from AN in terms of body mass index (BMI) and menstrual function. Endocrine, metabolic, and psychological parameters were assessed by sampling under fasting conditions and serially in response to a standard meal. Subjects included 18 females recovered from AN and 18 female controls and measures included plasma insulin, leptin, glucose and beta-hydroxybutyrate (beta-HBA) concentrations together with desire to eat. Fasting glucose concentrations were normal in both groups, but fasting insulin concentrations were significantly lower and the fasting glucose/insulin ratio significantly higher in the recovered subjects. The glucose concentration was significantly higher at the end of the meal period in the recovered group. The peak increase of insulin during the meal was significantly less in the recovered group and in response to the meal, glucose/insulin ratios were significantly higher for the first 45 minutes indicating a delayed insulin response. Fasting beta-HBA concentrations were not significantly different between groups, but postmeal decreases were significant and larger in the recovered AN group. Fasting and meal-related leptin concentrations were not significantly different between the groups and in both groups were correlated with BMI. In controls, but not in recovered subjects, the reported desire to eat was correlated with plasma glucose and leptin concentrations. The insulin, glucose and beta-HBA data indicated the presence of insulin hypersensitivity in the recovered subjects. As the insulin response to the meal was blunted and apparently delayed, there may be a persistent alteration in pancreatic function as a long-term pathological consequence of the anorexia. Alternatively, these data indicate a possible trait marker for AN.

Topics: 3-Hydroxybutyric Acid; Adult; Anorexia Nervosa; Appetite; Blood Glucose; Body Mass Index; Fasting; Female; Food; Humans; Insulin; Kinetics; Leptin

The adipocyte hormone leptin plays an important part in the reproductive function and in energy homeostasis. Only single studies have addressed the relationship between leptin and the hypothalamus-pituitary-gonadal axis (HPG) in anorexia nervosa (AN). In the present study 18 female adolescents with AN were investigated during weight gain. Leptin, LH, FSH, fT3, BMI and body composition were measured in the 1(st), 3(rd), 7(th) and 11(th) week of inpatient treatment. 18 eumenorrheic age- and gender-matched controls were examined once during the early follicular phase of their menstrual cycle. Our results demonstrate a critical leptin level of 1.2 ng/ml for an increase of FSH and confirmed a leptin threshold level of 1.85 ng/ml for LH. It may be concluded that leptin represents a metabolic gate to gonadotropin secretion. Once this is exceeded other biological mechanisms seem to be important for the complete recovery of the reproductive function and the resumption of menses.

Topics: Adolescent; Analysis of Variance; Anorexia Nervosa; Body Mass Index; Female; Gonadotropins; Humans; Leptin; Reproduction; Statistics, Nonparametric; Weight Gain

The aim of the present study was to examine the effects of anorexia nervosa (AN) on adipocytokines (leptin and adiponectin) plasma concentrations and insulin-stimulated glucose disposal in adolescent and young adult women. Adiponectin and leptin plasma levels, along with insulin-stimulated glucose disposal (as measured by the euglycemic-hyperinsulinemic glucose clamp) and oxidative and nonoxidative glucose metabolism (as measured by indirect calorimetry during the last 60 min of the insulin clamp), were measured in 11 anorectic patients and 26 normal-weight healthy female controls. Leptin levels were significantly lower in AN patients, according to the reduced body mass index and their respective fat mass. On the contrary, adiponectin plasma levels were significantly higher in AN patients than in control women. Likewise, insulin-stimulated glucose disposal and nonoxidative glucose metabolism were significantly lower in AN patients. In conclusion, our study shows that young women affected by AN have higher adiponectin plasma levels than healthy female controls of similar age, despite the presence of an impairment of insulin-stimulated glucose disposal, with a prevalent failure of nonoxidative glucose metabolism. Taken together, these data suggest that the reduction of fat mass may play the major role in the control of adiponectin release, with respect to changes in insulin sensitivity.

Topics: Adiponectin; Adult; Anorexia Nervosa; Blood Glucose; Body Mass Index; Calorimetry, Indirect; Female; Glucose Clamp Technique; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Oxidation-Reduction; Proteins

The present study characterizes the relationships between severe malnutrition, sleep, growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis, and leptin levels in anorexia nervosa (AN) patients before and after weight gain. Eleven restricting-type anorectic females (mean age = 19.7 years) with severe starvation state [mean body mass index (BMI) = 13.3] were studied using polysomnography and spectral power analysis. The hormone levels were measured in the morning after sleep recording. Eleven normal-weight, age- and gender-matched healthy volunteers without a history of any eating disorder served as controls. After nutritional treatment for about 2 months (65.7 +/- 6.4 days), sleep examinations and blood tests were repeated. At this stage, the study group consisted of 5 patients (mean BMI = 15.6). Higher IGF-1 and leptin levels were associated with longer and deeper sleep among anorectics. The sleep parameters including the percentages of stage 1 sleep and SWS as well as IGF-1 tended to normalize after only limited weight gain. Sleep disturbances in anorectics may be mediated through changes in the levels of the GH-IGF-1 axis hormones, as well as the levels of leptin.

Topics: Adolescent; Adult; Analysis of Variance; Anorexia Nervosa; Body Mass Index; Electroencephalography; Female; Fluoroimmunoassay; Growth Hormone; Humans; Insulin-Like Growth Factor I; Leptin; Normal Distribution; Polysomnography; Radioimmunoassay; Sleep; Sleep Stages; Statistics, Nonparametric

Our aim was to examine the relationship between resting energy expenditure (REE) and circulating leptin levels during long-term refeeding in adolescent girls with anorexia nervosa (AN).. We measured REE, the plasma leptin level, the free T(3) level, body surface area (BSA), and dietary energy intake in AN adolescents before and 8 weeks after refeeding therapy.. All parameters in AN subjects before the refeeding therapy were significantly lower than those in AN subjects after the therapy and in the controls. There were no significant differences in REE and BSA between posttherapy AN subjects and controls, but plasma leptin levels in the posttherapy AN subjects were still significantly lower than those in the controls. Significant correlations between REE and BSA were detected in the AN subjects both before and after the refeeding therapy, but REE did not correlate significantly with plasma leptin level in either of the AN groups.. Our results suggest that the REE in AN subjects after long-term refeeding therapy is not associated with the changes in plasma leptin levels but with BSA.

Topics: Adolescent; Anorexia Nervosa; Child; Energy Metabolism; Female; Humans; Leptin; Rest

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

Demographic, psychopathological and hormonal parameters of 22 women with previous anorexia nervosa (AN) presently recovered, in a state of stabilized nutritional normalization for 3 months to 2 years but with persistent amenorrhoea, and of 20 psychophysically healthy age- and sex-matched normally menstruating controls were studied. Body mass index (BMI) values did not differ in patients and controls. Psychological examination, monitored by Eating Disorder Inventory 1, Bulimic Investigation Test Edinburgh, Yale-Brown-Cornell Eating Disorder Scale, and Tridimensional Personality Questionnaire rating scales, showed the persistence of some of the psychopathological symptoms of AN. Hormonal examinations included basal plasma concentrations of follicle stimulating hormone, luteotropic hormone, estrogens (E), progesterone, thyrotropic hormone, FT(3), FT(4) (immunoradiometric assays), leptin (LEP) (enzymatic-linked-immunosorbent assay) and 24 h urinary free cortisol (immunoradiometric assay). Hormone values were the same in patients and controls, except for E and LEP levels, which were significantly lower in patients than in controls. The concentrations of the two hormones were not correlated with the BMI of the patients, but LEP values were correlated negatively with the difference between the present BMI and the preanorexic one. The values of both hormones correlated negatively with some of the psychopathological aspects typical of AN, in particular with high 'body dissatisfaction', 'ineffectiveness', and 'interpersonal distrust' and with low 'interoceptive awareness'.

Topics: Adult; Amenorrhea; Anorexia Nervosa; Body Mass Index; Estrogens; Female; Humans; Hydrocortisone; Leptin; Personality Disorders; Personality Inventory; Progesterone; Recovery of Function; Recurrence; Thyrotropin-Releasing Hormone; Weight Gain

Leptin is an adipocyte-derived signal factor (167 amino acid protein) encoded by the ob gene in chromosome 7q31 that regulates eating behaviour via central neuroendocrine mechanisms. It has been shown that serum leptin levels correlate with weight and percentage body fat in normal and obese individuals, but the exact correlation between leptin and body weight in anorexic and bulimic patients has not yet been clarified. We investigated leptin levels in the serum of 58 female subjects aged 15-36 years: 10 with bulimia nervosa (BN); 12 with anorexia nervosa (AN); 12 overweight controls (not BN); 12 weight-reduced controls (not AN); and 12 normal weight controls. The aim of the study was to evaluate the possible correlations between leptin levels and the body mass index (BMI) in all five groups. Our results showed that the serum leptin levels of the bulimic patients were similar to those of the healthy controls, with a positive correlation between leptin and BMI. Although bulimic patients have very bad nutritional behaviour, their leptin levels do not appear altered. Serum leptin was significantly (p<0.001) reduced in the anorexic patients because of the dramatic decrease in adipose mass caused by the nutritional defect, as: is further supported by the significantly (p<0.001) low level of transferrinemia. Our data suggest that, although significantly reduced, serum leptin levels in fasting anorexic patients are non-linearly related to body weight (BMI).

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Bulimia; Female; Humans; Leptin

Anorexia nervosa is an eating disorder with typically chronic course. Two subtypes of anorexia nervosa have been described based on the pattern of eating behavior. Restrictive form of anorexia nervosa is characterized by chronically decreased food intake, while the purgative subtype typically consists of alternating episodes of fasting and overnutrition with factitious vomiting.. The aim of this study was to compare anthropometric parameters, serum levels of fat-derived hormone leptin, cholesterol, triacylglycerols and serum leptin/body mass index ratio in patients with restrictive and purgative subtypes of anorexia nervosa respectively. Significantly lower body weight (37.79 +/- 3.93 vs. 49.63 +/- 9.84 kg, p < 0.05), body mass index (13.51 +/- 1.43 vs. 17.75 +/- 2.64 kg/m2, p < 0.05),), body fat percentage (13.28 +/- 2.83 vs. 18.9 +/- 5.65%, p < 0.05), serum leptin (1.117 +/- 0.95 vs. 5.88 +/- 4.7 ng/ml, p < 0.05) and cholesterol levels (4.14 +/- 1.78 vs. 6.31 +/- 1.27 mmol/l, p < 0.05) were found in patient with restrictive relative to purgative subtype of anorexia nervosa. In contrast, no difference in triglyceride levels between both groups was found. Serum leptin levels positively correlated with body mass index and body fat percentage only in patients with purgative subtype of anorexia nervosa (body mass index r = 0.95, p < 0.001, body fat percentage r = 0.64, p < 0.05) but not in those with restrictive subtype.. In conclusion, we demonstrated that serum leptin levels were significantly lower in restrictive relative to purgative subtype of anorexia nervosa. We suggest that this difference is primarily due to distinctions in body fat content.

Topics: Adult; Anorexia Nervosa; Body Mass Index; Bulimia; Female; Humans; Leptin; Lipids

Low leptin levels are an endocrinological hallmark of acute anorexia nervosa (AN); a subthreshold leptin secretion in adipocytes as a consequence of a reduced energy intake is presumed to be the major trigger of the adaptation of an organism to semistarvation. The aim of the current study is to define symptoms of AN that are potentially linked to low leptin levels. For this purpose, quantitative somatic and psychopathological variables were obtained in 61 inpatients with acute AN (study group 1) upon referral for inpatient treatment, and they were concomitantly blood sampled to allow determination of serum leptin levels. Correlations between these variables and logarithmic transformed (lg10) leptin levels were descriptively assessed. Apart from the well-known correlations between leptin levels and anthropometric measurements, the strongest correlation was observed between lg10 serum leptin levels and expert ratings of motor restlessness (r = -0.476; nominal P = 0.003) upon use of visual analog scales. We thus generated the hypothesis that physical activity levels in AN patients are related to serum leptin levels. This hypothesis was tested in an independent study group of 27 adolescent inpatients (study group 2) who were also assessed upon referral. Physical activity levels, which, in this study group, were assessed with the activity module of the expert rating form of the Structured Inventory for Anorexic and Bulimic Syndromes, were significantly correlated with lg10 leptin levels (r = -0.51; one-sided P = 0.006). A regression model based on the independent variables body mass index and lg10 leptin levels explained 37% of the variance of physical activity (R(2) = 0.37; P = 0.003); only the lg10 leptin levels contributed significantly to the variance (P = 0.003). Our results suggest that, similar to semistarvation-induced hyperactivity in rats, hypoleptinemia in patients with AN may be one important factor underlying the excessive physical activity.

Topics: Acute Disease; Adaptation, Physiological; Adolescent; Adult; Anorexia Nervosa; Child; Female; Humans; Leptin; Motor Activity; Psychomotor Agitation

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

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

It has been reported that neuropeptides may play a role in the control of appetite and in the mechanism of hormone release. Neuropeptides such as beta-endorphin, neuropeptide Y (NPY), galanin and leptin may affect hormones release, on the other hand the hormonal status may modulate neuropeptide activity.. The material consisted of 90 obese women, 30 women with Anorexia Nervosa, and 30 healthy, lean women of control group. Plasma beta-endorphin, NPY, leptin, somatostatin and serum pituitary and gonadal hormones concentrations were measured with RIA methods.. We observed the highest plasma NPY levels in obese hypertensive and diabetic patients. After carbohydrate administration (OGTT) a marked increase of insulin, beta-endorphin and NPY was found. The blunted response of GH to GH-RH may be connected with increased somatostatin activity and hyperinsulinemia. The abnormal response of LH to opioid blockade may be a result of disturbed opioid and NPY activities in obese patients. However in patients with anorexia nervosa, plasma leptin and NPY concentrations were low. The disturbances in beta-endorphin release are also observed.. The neuroendocrine disturbances in obesity and in anorexia nervosa are opposite. The feedback mechanism between leptin and NPY is disturbed in both in obesity and in anorexia nervosa. An abnormal activity of neuropeptides may lead to disturbed control of appetite and hormonal dysregulation in eating disorders.

Topics: Adult; Anorexia Nervosa; Appetite; beta-Endorphin; Diabetes Mellitus; Feedback, Physiological; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Hypertension; Leptin; Luteinizing Hormone; Neuropeptide Y; Neuropeptides; Obesity; Somatostatin

To evaluate serum leptin levels in anorectic women, menstruating women with low body mass indexes (BMI) and normally menstruating women with normal BMI.. Prospective study.. University clinics.. Fourteen amenorrheic patients with anorexia nervosa (group A), 11 menstruating women with a BMI <18 kg/m(2) (group B), and 20 normal controls.. Determination of BMI, caloric intake, total fat mass, ovarian volume, and serum leptin, insulin-like growth factor I, FSH, LH, E(2), PRL, and TSH levels.. None.. Mean BMI and fat mass were similar in groups A and B and significantly higher in controls. Mean caloric intake was significantly lower in group A than in group B and controls. Median serum leptin levels were significantly lower in group A than in group B and controls, and significantly lower in group B than in controls. Median serum insulin-like growth factor I levels were significantly lower in group A than in group B and controls. Binary segmentation analysis of groups A and B showed that LH was the most relevant variable in differentiating the two groups, followed by leptin.. A threshold of leptin levels exist above which, even in the presence of low body mass indexes, the menstrual function is preserved.

Topics: Adult; Amenorrhea; Anorexia Nervosa; Body Composition; Body Mass Index; Female; Humans; Insulin-Like Growth Factor I; Leptin; Luteinizing Hormone; Menstruation

Leptin is thought to modulate feeding behaviour, body weight and energy metabolism by acting through specific cellular receptors. Derangements of leptin production have been repeatedly reported in patients with anorexia nervosa (AN) or bulimia nervosa (BN), but no information has been provided on the functional status of leptin receptors in these disorders. Therefore, we measured plasma levels of leptin and its soluble receptor (Ob-Re) in a total of 130 women, including 22 patients with AN, 45 patients with BN, 18 patients with the binge-eating disorder (BED), 12 non-binge eating obese women and 33 healthy women. Circulating leptin was drastically reduced in underweight anorexics and normal-weight bulimics, but increased in overweight BED patients and non-binge-eating obese women. Conversely, plasma levels of Ob-Re were significantly increased in patients with AN or BN, but decreased in BED and non-binge-eating obese women. Significant inverse correlations were detected between plasma levels of leptin and those of Ob-Re in all the subject groups, except in non-binge-eating obese subjects. These results show, for the first time, that opposite modifications occur in circulating levels of leptin and Ob-Re across the eating-disorder spectrum. The relevance of these findings to the pathophysiology and treatment of eating disorders remains to be elucidated.

Topics: Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Bulimia; Estradiol; Female; Humans; Hydrocortisone; Leptin; Prolactin; Receptors, Cell Surface; Receptors, Leptin; Reference Values

Leptin is bound in human blood by a high affinity binding protein, which appears to be identical with the soluble leptin receptor (sOB-R). Using a ligand-mediated immunofunctional assay for the determination of serum sOB-R, we investigated its course during childhood, puberty, and adolescence in a large cohort of 581 healthy children and adolescents and a small group of 13 patients with anorexia nervosa. In the first years of life, sOB-R is detectable in remarkably high concentrations. Thereafter, a continuous decline of sOB-R levels was found. Consequently, correlation analyses demonstrated significant inverse relationships (P < 0.001) of sOB-R with age, IGF-I levels, pubertal stage, auxological and body composition parameters, as well as with leptin concentrations. Multiple regression analysis revealed that height, IGF-I, and age (only in girls) were independent predictors of sOB-R levels; these variables account for approximately 65% and 48% of the variation of sOB-R levels in boys and girls, respectively. The courses of age-dependent median values for the free leptin index (FLI, ratio between leptin and sOB-R levels) and for leptin levels were parallel in both genders. Correlation analyses demonstrated that in particular parameters of growth and sexual maturation are more closely related to the FLI than to leptin alone; this closer relationship is more pronounced among boys. Weight gains of patients with anorexia nervosa resulted in a significant increase in leptin and IGF-I levels (P < 0.01), whereas the median of sOB-R values decreased (P < 0.01). sOB-R and IGF-I levels were again significantly correlated (r = -0.55, P < 0.01). These findings suggest that high levels of sOB-R in emaciation may reflect an up-regulation of the sOB-R to suppress leptin action during energy deficiency. Furthermore, determinations of sOB-R and FLI are additional valuable tools to investigate the leptin axis during growth and sexual maturation.

Topics: Adolescent; Adult; Aging; Anorexia Nervosa; Body Composition; Body Height; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Insulin-Like Growth Factor I; Leptin; Male; Puberty; Receptors, Cell Surface; Receptors, Leptin; Reference Values; Regression Analysis; Solubility; Weight Gain

To examine whether changes of serum soluble leptin receptor levels (S-LEPR) can modify leptin half-life and its tissue effects. The aim of our study was to measure S-LEPR levels in patients with anorexia nervosa (AN) before and 6 weeks after partial refeeding.. Anthropometric variables, serum leptin, S-LEPR, insulin, cortisol and TNF-alpha were measured in 15 AN patients before and after partial refeeding and 15 healthy control women.. S-LEPR levels in AN patients were significantly higher than in healthy subjects (26.8 +/- 8.1 vs. 16.36+/-2.6U/mL, p < 0.01) and were not affected by partial refeeding (26.8 +/- 8.1 vs. 24.2 +/- 6.1 U/mL). In contrast, body mass index (BMI), body fat content, and serum leptin levels in AN patients increased significantly after partial refeeding. Except for the inverse relationship of S-LEPR levels to BMI and body fat content no clear relationship of this parameter to serum leptin, cortisol, insulin or TNF-alpha was found.. S-LEPR levels are significantly increased in AN patients and this increase is unaffected by partial refeeding. The possibility of etiological role of increased S-LEPR levels in AN patients by affecting leptin central and/or peripherial effects should be further elucidated.

Topics: Adipose Tissue; Anorexia Nervosa; Body Composition; Body Mass Index; Female; Food; Humans; Insulin; Leptin; Receptors, Cell Surface; Receptors, Leptin; Reference Values; Solubility

Topics: Anorexia Nervosa; Female; Ghrelin; Growth Hormone; Humans; Insulin-Like Growth Factor I; Leptin; Peptide Hormones

Ghrelin is recently discovered peptide hormone involved in the regulation of growth hormone secretion as well as in the regulation of food intake and energetic homeostasis. The study was aimed to describe the changes in ghrelin serum levels in patients with anorexia nervosa and its relationship to some other studied parameters. Sixteen women patients with anorexia nervosa and thirteen healthy women of comparable age were examined clinically and blood samples were taken for estimation of serum levels of ghrelin, leptin, soluble leptin receptor, IGF-I, IGFBP-1 and IGFBP-3. Ghrelin serum levels were significantly increased in the group of patients with anorexia nervosa (p < 0,05). In contrary, serum leptin levels were decreased in the group of patients with anorexia nervosa (p < 0,01). Serum ghrelin levels did not correlate with any other of studied parameters with exception of BMI. We can conclude that serum ghrelin levels are increased in patients with anorexia nervosa and their increase fails to significantly stimulate food intake in this group of patients.

Topics: Adult; Anorexia Nervosa; Body Mass Index; Female; Ghrelin; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Peptide Hormones; Receptors, Cell Surface; Receptors, Leptin

The present study was conducted in order to analyze the relationship existing between leptin, insulin and neuropeptide Y (NPY) levels in massive weight loss and weight recovery. Twenty-three patients with severe obesity, 23 patients with anorexia nervosa and 28 healthy control subjects were studied. Patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet during 16 weeks, with evaluation taking place before (Body mass index, BMI, 52,1 8 Kg/m2) and after the drastic weight loss (BMI 39,2 6,2 Kg/m2). Patients with anorexia nervosa were treated with nutritional therapy exclusively during 16 weeks, and they were evaluated in the low weight situation (BMI 15,3 1,7 Kg/m2) and after weight recovery (BMI 18,9 2,8 Kg/m2). Normal subjects had a normal BMI from 20 to 27 (average 21,8 2 Kg/m2). BMI, percentage of body fat, and serum levels of leptin, insulin, and NPY, were determined in each patient and normal subjects. In severe obese patients serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 48,8 19,2 to 24,3 9,8 ng/ml; insulin: from 26,2 10,8 to 18 6 U/ml). In patients with anorexia nervosa serum leptin mean levels were significantly higher after weight recovery (3,7 1,9 vs 9,2 5,1 ng/ml). In subjects with morbid obesity NPY levels decreased after weight loss below those of control group (43,5 16,1 vs 57,3 12,8 pmol/l). On the other hand, patients with anorexia nervosa had NPY levels superior to those of control group. In subjects with anorexia, NPY levels decreased after weight recovery (69,1 16,7 a 59,1 20,3 pmol/l). In the whole population, Leptin and NPY plasma levels were correlated with body fat percentage. Leptin was positively correlated with BMI and body fat percentage in obese and anorectic subjects after weight loss or recovery, respectively. NPY was inversely correlated with body fat percentage in controls and obese subjects before treatment. These data reveal that the concentration of serum leptin and NPY correlates significantly with the total adiposity in subjects with a wide weight range and caloric intake. Leptin plasma levels are proportional to fat stores in patients with severe obesity and anorexia nervosa after drastic weight loss or recovery, respectively. NPY serum levels are negatively correlated with de total body fat in normal weight subjects and obese patients in their initial weight.

Topics: Adult; Anorexia Nervosa; Anthropometry; Body Composition; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Female; Gastroplasty; Humans; Insulin; Leptin; Male; Middle Aged; Neuropeptide Y; Obesity, Morbid; Radioimmunoassay; Recurrence; Weight Gain; Weight Loss

Topics: Anorexia Nervosa; Bulimia; Humans; Leptin; Nervous System

Studies of the role of leptin in patients with anorexia nervosa and bulimia nervosa have conflicted in their data and interpretation. Such differences may be a result of the assay methods used or the way results are compared with those from normal controls. To investigate these possibilities, we analyzed serum leptin levels in anorexic, bulimic, obese, and control individuals, thereby spanning the full range of human body weights, using three frequently employed commercial kits. Kits from Linco (St Louis, MO) and DSL (Webster, TX) employ a radioimmunoassay method, and the R&D Systems kit (Minneapolis, MN) uses an enzyme-linked immunosorbent assay. We found that the three kits provide results that are highly linearly correlated with each other and remarkably linearly related to percent ideal body weight (%IBW) over more than three orders of magnitude (Linco, r = 0.90; R&D, r = 0.87; DSL, r = 0.86). For very low leptin levels, the more sensitive kits from R&D and Linco appeared to give more reliable results. Measurement method does not appear to explain the literature conflicts. We found that patients with anorexia nervosa have serum leptin values that lie above the line extrapolated from the %IBW/leptin curve generated from analysis of all non-anorexic patients. Therefore, in anorexia nervosa, inappropriately high leptin levels for %IBW may contribute to a blunted physiologic response to underweight and consequent resistance to dietary treatment. By contrast, most bulimic patients have leptin levels significantly below those predicted from the same %IBW/leptin curve. The relative leptin deficiency in bulimic subjects may contribute to food-craving behavior. We propose that using the %IBW/ leptin curve can facilitate identification of true pathophysiologic abnormalities in eating-disordered individuals and provide a basis for the design of therapeutic interventions or monitoring of response to treatment.

Topics: Anorexia Nervosa; Body Weight; Bulimia; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Linear Models; Obesity; Radioimmunoassay; Reagent Kits, Diagnostic; Sensitivity and Specificity

In animals, somatostatin (SRIH) and growth hormone (GH)-releasing hormone (GHRH) increase feeding via a common neural mechanism. Furthermore, SRIH counteracts the suppressive action of corticotrophin-releasing hormone (CRH) on food intake. Hypothetically, SRIH could be involved in the central feeding mechanism in anorexia nervosa (AN). Peripheral administration of pyridostigmine (PD) minimizes the release of hypothalamic SRIH.. To study the influence of hypothalamic somatostatinergic inhibition on the exaggerated somatotroph responsiveness to GHRH in patients with severe AN, two GHRH stimulation tests were performed in random order following pretreatment with placebo or PD 2 mg/kg body weight in 13 patients and in 10 age-matched healthy controls. The test procedure was repeated in the patients after weight gain.. In controls, PD potentiated the GHRH-stimulated GH rise but this effect was absent in AN patients. The relative potentiating effect of PD was inversely correlated to cortisol excretion levels and positively correlated to leptin serum levels. After weight gain the relative PD effect increased twofold.. The pyridostigmine-GHRH responsive pattern points indirectly to greater SRIH withdrawal and greater GHRH release in anorexia nervosa. Moreover, hypothalamic SRIH activity seems to be inversely related to cortisol levels, indirectly supporting the hypothesis that SRIH and CRH neuronal activity are inversely related in anorexia nervosa. Leptin, which is believed to act on hypothalamic feeding mechanisms, seems to be positively related to SRIH activity. Finally, the present data demonstrate that the potentiating effect of pyridostigmine in anorexia nervosa is related to body mass index and increases upon weight gain, suggesting that the low somatostatinergic tone is not primary but is related to the weight loss.

Topics: Adult; Anorexia Nervosa; Body Mass Index; Cholinesterase Inhibitors; Drug Synergism; Female; Growth Hormone-Releasing Hormone; Hormones; Human Growth Hormone; Humans; Hypothalamus; Leptin; Pyridostigmine Bromide; Weight Gain

Amenorrhea in female patients with anorexia nervosa is associated with low leptin secretion, thus suggesting a causal link. In an attempt to address the hypothesis that leptin also influences the hypothalamo-pituitary-gonadal function in males, we studied three male patients with acute anorexia nervosa longitudinally. Serum levels of leptin, LH, FSH, testosterone, and SHBG were measured on a biweekly basis during weight gain. Leptin levels at low body mass index values were below the 5th percentile. During weight gain, leptin levels reached or surpassed the 95th percentile. The temporal dynamics of body mass index and fat mass were closely related to those of leptin concentrations in serum. Leptin increments were paralleled by increments of gonadotropins, testosterone, and the free androgen index (FAI). In each of the patients, serum concentrations of leptin were positively correlated with those of testosterone (P = 0.0001, P = 0.01, P = 0.07, respectively) and FAI (P = 0.0001, P = 0.0001, P = 0.09, respectively). In addition, in the combined data set of all patients changes of leptin over time were positively correlated with changes in LH (P = 0.01), FSH (P = 0.0001), testosterone (P = 0.002), and FAI (P = 0.002). In conclusion, these data suggest that leptin might also play an important role in the regulation of the hypothalamo-pituitary-gonadal axis and fertility in underweight males as has previously been shown in underweight females.

Topics: Adipose Tissue; Adolescent; Anorexia Nervosa; Body Composition; Body Mass Index; Child; Follicle Stimulating Hormone; Humans; Kinetics; Leptin; Longitudinal Studies; Luteinizing Hormone; Male; Sex Hormone-Binding Globulin; Testosterone; Weight Gain

It has been reported that leptin and neuropeptide Y (NPY) play a role in the control of appetite and in the regulation of hormonal secretion.. Plasma leptin, neuropeptide Y (NPY) and galanin concentrations were estimated in 13 women with bulimia nervosa (BN) 19 women with anorexia nervosa (AN) and in 19 healthy women of the control group (CG).. Plasma leptin concentration in BN was significantly higher than that in AN and it was lower as compared with the control group, despite the same BMI (body mass index) in both the groups. Plasma leptin level in AN was significantly lower as compared with the controls. Plasma galanin concentrations in AN and BN did not differ significantly from the control group. Plasma NPY concentration in AN was lower than that in the control group. However, plasma NPY level in BN was significantly higher as compared with AN and with the control group (CG). The observed increase of NPY in BN was independent of BMI because BMI in bulimia nervosa was normal.. The data may suggest that other factors than body weight changes may be involved in the modulation of leptin and NPY release in BN. The pathological behaviour of patients with bulimia nervosa may result from disturbed NPY release which is the strongest orexigenic factor.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Bulimia; Female; Galanin; Humans; Leptin; Neuropeptide Y; Reference Values

To study the longitudinal changes in plasma levels of leptin, insulin and cortisol during the transition from the state of starvation to the state of refeeding focussing on diurnal secretion characteristics and their temporal relationships.. Leptin, insulin and cortisol were measured every 2h for 24h during acute starvation (T1). Sampling was repeated after reaching half the target-body mass index (BMI) (T2) and again at target-BMI (17. 5kg/m(2); T3). The temporal relationships between the diurnal secretion patterns were assessed by cross-correlation analysis.. Although BMIs at T1 were uniformly low, leptin levels varied widely within a range clearly below normal levels (0.03-1. 7microg/l). With increasing body fat during the course of refeeding, mean leptin levels increased from 0.64microg/l (range: 0.27-1. 73microg/l) (T1) to 1.61microg/l (range: 0.36-4.2microg/l) (T2) and to 3.67microg/l (range: 0.7-9.8microg/l) (T3). Circadian leptin secretion patterns showed maximal values uniformly around 0200h and minimal values around 0800h at all stages of the study. At all three weight levels, plasma leptin levels were highest between midnight and the early morning hours and lowest around the late morning hours. Refeeding neither profoundly changed secretion patterns of leptin nor did it change the positive, time-delayed relationship between leptin and insulin with increments in insulin secretion preceding those of leptin by 6h. A temporal relationship between leptin and cortisol could not be demonstrated in the state of semistarvation but emerged after a substantial weight gain; at that time, leptin increases preceded cortisol increases by 8h.. Absolute leptin, insulin and cortisol levels are profoundly changed during starvation in anorectic patients, while refeeding, paralleled by a BMI gain, reverses these changes. During refeeding the relationship between leptin and cortisol changed profoundly, showing no significant correlation in the state of starvation, whereas at T3 after refeeding a strong inverse relationship could be observed. Leptin and insulin did not correlate significantly at any of the three stages studied.

Topics: Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Circadian Rhythm; Cohort Studies; Female; Food; Humans; Hydrocortisone; Insulin; Leptin; Longitudinal Studies; Male; Reference Values; Starvation

A decreased production of leptin has been reported in women with anorexia nervosa (AN) and has been attributed merely to the patients' reduced body fat mass. The extent to which eating patterns, purging behaviors, psychopathology and endocrine changes may contribute to the genesis of leptin alterations has not been deeply investigated. Therefore, we measured plasma levels of leptin, glucose and other hormones in three groups of eating disorder patients with different body weight (BW), eating patterns and purging behaviors. Sixty-seven women, 21 with AN, 32 with bulimia nervosa (BN), 14 with binge-eating disorder (BED) and 25 healthy females volunteered for the study. We found that circulating leptin was significantly reduced in AN and BN patients, but significantly enhanced in women with BED. In anorexics, plasma glucose was decreased, whereas plasma cortisol was enhanced; blood concentrations of 17beta-estradiol and prolactin (PRL) were reduced in both AN, BN and BED patients. In all subject groups, a strong positive correlation emerged between plasma levels of leptin and the subjects' BW or body mass index, but not between leptin and psychopathological measures, plasma glucose, cortisol, PRL and 17beta-estradiol. Since leptin was reduced in both underweight anorexics and normal weight bulimics, but increased in overweight BED women, who compulsively binge without engaging in compensatory behaviors, we suggest that factors other than BW may play a role in the determination of leptin changes in eating disorders.

Topics: Adult; Anorexia Nervosa; Body Weight; Bulimia; Estradiol; Feeding Behavior; Female; Hormones; Humans; Hydrocortisone; Hyperphagia; Leptin; Obesity; Prolactin

Leptin is thought to represent a peripheral signal involved in the regulation of energy balance. Its action has been studied in animals and obese subjects. Little is known about leptin's role during negative energy balance.. The objective was to evaluate the relation between energy turnover, body composition, and plasma leptin concentrations in anorexia nervosa (AN).. Sixteen weight-stable women with AN were compared with 22 control subjects and 14 rehabilitated AN patients (R-AN). Basal metabolic rate (BMR) was measured by indirect calorimetry; fat-free mass (FFM) and fat mass (FM) were calculated according to a 4-compartment model. Plasma leptin was determined by radioimmunoassay.. The BMR of AN patients (2.73 +/- 0.37 kJ/min) was significantly lower than that of control subjects (3.45 +/- 0.34 kJ/min) (P < 0.001), even after adjustment for FFM (2.92 +/- 0.33 kJ/min in AN patients and 3.30 +/- 0.26 kJ/min in control subjects; P < 0.004). Plasma leptin concentrations in AN patients were 76% lower than in control subjects, even after body fat was controlled for. In R-AN patients, BMR was not significantly different from that of control subjects and leptin concentrations were generally close to normal. Plasma leptin concentrations correlated significantly with FM (r(2) = 0.53, P < 0.0000) and BMR, even after adjustment for FFM (r(2) = 0.21, P < 0.0003).. BMR and plasma leptin concentrations are depressed in patients with AN; this is not explained by body-composition changes. The relation between leptin and BMR suggests that leptin plays a role in the energy sparing response to exposure to chronic energy deficiency. The return of BMR to normal and the significant increase in leptin concentrations in R-AN patients suggests a full reversibility of this adaptation mechanism.

Topics: Adolescent; Adult; Anorexia Nervosa; Basal Metabolism; Body Composition; Calorimetry, Indirect; Energy Intake; Energy Metabolism; Female; Humans; Leptin; Regression Analysis

To examine changes in plasma leptin levels and resting energy expenditure (REE) during short-term refeeding of patients with anorexia nervosa (AN).. This was a longitudinal study of 21 women meeting the DSM-IV criteria for AN who were admitted to the hospital for renutrition. Height, weight, percent body fat (assessed by skin fold thickness), REE (measured by indirect calorimetry), and circulating plasma leptin concentration were assessed at the time of admission and 7 days later.. Over the course of 1 week of refeeding, body mass index (BMI) increased 0.75 +/- 0.15 kg/m(2) (p <.0001), body fat increased 0.9 +/- 0.2% (p <.0001), and REE increased 107 +/- 33 kcal/24 hr (p =.0037). The change in mean leptin levels was not statistically significant (0.45 +/- 0.44 ng/ml; p =.32).. Leptin is unlikely responsible for the increase in REE observed with short-term refeeding.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Eating; Energy Metabolism; Female; Humans; Leptin; Nutritional Support

The main objective of the study was to evaluate the endocrinological picture of anorexia. Serum leptin levels are low in untreated anorexia nervosa (AN), but studies of the exact relationship between leptin, body weight and hormones of hypothalamo-hypophyseal-thyroid axis and the impact of refeeding in anorectics are limited. The sample consistent of 15 patients with anorexia nervosa before and 1 month after partial weight recovery, and 15 age-matched control subjects. The body mass index (BMI), leptin, plasma neuropeptide Y (NPY), serotonin, thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) in serum were evaluated for each subject. The mean serum levels of leptin, T4, and T3 were significantly lower before weight recovery in 15 patients with AN than they were in control subjects. After partial weight recovery, basal T3 levels were unchanged and significantly lower than in controls. Basal T4 was even still more reduced, but we observed significantly elevated ratio of T3/T4 and reduced ratio rT3/T4 of in AN patients after gain recovery, indicating increased conversion of T4 to T3 than to rT3. The levels of serum leptin were low in AN, but after partial weight recovery slightly increased, and correlated with BMI. No differences were observed in serum NPY. Serum levels of IGF-1 and serotonin were lower in AN than in controls before and after partial weight gain. IGF-1 was slightly increased after partial weight gain. We did not find correlation between serum levels of leptin and serum T4. The low serum levels of T3 associated with chronic starvation were thought to be the result of impaired peripheral conversion of T4 to T3. However, decreased levels of T3 were still apparent even after a partial weight gain, and the concentration of T4 was even lower. The diminished serum level of TSH in AN, however, appeared to return to the level of controls. On the basis of these results, we assume that low serum levels of thyroid hormones in AN reflect a dysfunction of the HPT axis in AN patients. It is known that in man serum serotonin levels correlate positively with T3 levels. It is possible that the low serum levels of thyroid hormones in AN subjects result in low serum serotonin and its product, melatonin. While IGF-1 reflects the energy intake of the previous few weeks, the serum leptin concentration reflects the true status of the adipose stores, a fact that has useful clinical implications.

Topics: Anorexia Nervosa; Body Mass Index; Female; Humans; Hypothalamus; Insulin-Like Growth Factor I; Leptin; Neuropeptide Y; Pituitary Gland; Serotonin; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Leptin is a protein produced by the ob-ob gene which inhibits food intake. Plasma levels have previously been reported to be altered in obesity and anorexia nervosa (AN) but not bulimia nervosa (BN). We measured fasting plasma leptin levels by radioimmunoassay in 53 subjects carefully studied at NIMH, including 37 women meeting DSM-III-R criteria for BN [10 with concurrent AN (body mass index (BMI)=14.1+/-1.4), 27 without AN (BMI=20.4+/-1.6)] and 16 normal control women (NCs) (BMI=21.1+/-2.0). Patients were medication-free and abstinent from bingeing and purging for three to four weeks prior to study. Plasma leptin levels were significantly correlated to BMI (r=0.41, P<0.002), weight (kg, r=0.43, P<0.001), and percent average body weight (%ABW, r=0.45, P<0.001) in the total group. Plasma leptin levels were lower in the BN subjects (3.4+/-2.5 ng/ml) compared to the NCs (6.1+/-2.6 ng/ml, P<0.001, ANCOVA) even after controlling for BMI and weight. There was no significant difference between BN subjects with AN (n=10, 2.6+/-2.6 ng/ml) and those without AN (n=27, 3.8+/-2.4 ng/ml), despite lower BMI in BN with AN. Furthermore, leptin levels were decreased in BN without AN compared with healthy controls, even though BMI was comparable in these two subgroups. Plasma leptin concentrations were negatively correlated with baseline plasma cortisol levels (n=49, r=-0.49, P<0.001) and positively correlated with prolactin responses following L-tryptophan (n=49, r=0.37, P<0.009) and m-chlorophenylpiperazine (n=52, r=0.24, P<0.09). This is the first known report of decreased plasma leptin levels in BN. The decrement in leptin concentration is not related to BMI, body weight, or the presence or absence of BN. HPA axis activation as well as serotonin dysregulation may be related to decreased leptin levels, which may in turn contribute to disinhibited eating in BN. Although current leptin levels were not correlated with self-reported previous binge frequency, the role of leptin in the pathophysiology of BN deserves further study.

Topics: Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Bulimia; Female; Humans; Hydrocortisone; Leptin; Prolactin; Reference Values

Semi-starvation induced hyperactivity (SIH) occurs in rodents upon caloric restriction. We hypothesized that SIH is triggered by the decline in leptin secretion associated with food restriction. To test this hypothesis, rats, which had established a stable level of activity, were treated with leptin or vehicle via implanted minipumps concomitantly to initiation of food restriction for 7 days. In a second experiment treatment was initiated after SIH had already set in. In contrast to the vehicle-treated rats, which increased their baseline activity level by 300%, the development of SIH was suppressed by leptin. Furthermore, leptin was able to stop SIH, after it had set in. These results underscore the assumed major role of leptin in the adaptation to semi-starvation. Because SIH has been viewed as a model for anorexia nervosa, we also assessed subjective ratings of motor restlessness in 30 patients with this eating disorder in the emaciated state associated with hypoleptinemia and after increments in leptin secretion brought upon by therapeutically induced weight gain. Hypoleptinemic patients ranked their motor restlessness higher than upon attainment of their maximal leptin level during inpatient treatment. Thus, hypoleptinemia might also contribute to the hyperactivity frequently associated with anorexia nervosa.

Topics: Animals; Anorexia Nervosa; Appetite; Energy Intake; Energy Metabolism; Hyperkinesis; Infusion Pumps, Implantable; Leptin; Male; Neurosecretory Systems; Physical Conditioning, Animal; Rats; Rats, Wistar; Starvation; Weight Gain

The present study was conducted in order to analyze the relationship existing between leptin and insulin levels in massive weight loss and weight recovery. Thirteen patients with severe obesity, 14 patients with anorexia nervosa and 13 healthy control subjects were studied. The patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet for 12 weeks. They were evaluated prior to (body mass index [BMI] 51.2 +/- 8.8 Kg/m2) and after drastic weight loss (BMI 40.6 +/- 6.7 Kg/m2). Patients with anorexia nervosa were treated exclusively with nutritional therapy during 12 weeks, and they were evaluated at their lowest weight status (BMI 16.2 +/- 2.2 Kg/m2) and after weight recovery (BMI 17.9 +/- 2.3 Kg/m2). The BMI of the normal subjects was in the normal range of 20 to 27 Kg/m2 (average 22.8 +/- 2.6 Kg/m2). BMI, percentage of body fat, waist circumference, and serum levels of leptin, insulin, and C-peptide were determined in each patient and normal subject. In severely obese patients, serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 51.8 +/- 22.3 to 23.7 +/- 10.2 ng/ml; insulin: from 27.1 +/- 13.3 to 17.2 +/- 7.2 mU/ml). In patients with anorexia nervosa, the mean serum leptin levels were significantly higher after weight recovery (5.5 +/- 3.2 vs 7.6 +/- 6 ng/ml). Serum leptin in the severe obesity group correlated positively with BMI, percentage body fat and waist circumference before and after weight loss. In those patients suffering from anorexia nervosa, serum leptin correlated positively with the BMI, percentage of body fat, and waist circumference in the low weight state and after weight recovery. In addition, their serum insulin correlated with BMI and waist circumference after weight recovery. These data reveal that serum leptin concentration correlates significantly with the BMI and body fat content 1) in subjects with a range of weight and caloric intake, 2) in obese patients after drastic weight loss; 3) in anorexic patients after weight gain; and that hyper- or normoinsulinemia do not seem to have any influence on the leptin changes caused by weight loss or gain.

Topics: Adipose Tissue; Adolescent; Adult; Anorexia Nervosa; Anthropometry; Body Mass Index; C-Peptide; Combined Modality Therapy; Female; Gastroplasty; Humans; Hyperinsulinism; Insulin; Leptin; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Weight Gain; Weight Loss

Patients with anorexia nervosa (AN) have hyperactivity of their hypothalamic-pituitary-adrenal (HPA) axis, sometimes accompanied by elevations of cortisol. We examined whether the normal effects of short-term dexamethasone treatment upon HPA axis suppression and appetite stimulation are observed in these patients. Five young women with AN and ten healthy female controls received one week of high-dose oral dexamethasone (2 mg/m2/d) preceded and followed by hormonal evaluation of sensitivity to glucocorticoids and psychological assessments. No differences in hormone levels of the HPA axis were observed between the two groups and control groups at baseline, after dexamethasone suppression, or following ACTH stimulation testing. However, fasting insulin levels were significantly lower in the AN group, both before and after dexamethasone therapy and their serum leptin levels were also significantly lower. The AN group had significantly lower scores on the Anorexia Nervosa Subtest and the Beck Depression Inventory after dexamethasone compared to controls. On daily analog scales, AN patients had higher anxiety scores while on dexamethasone. Normal sensitivity to glucocorticoids was observed in all parameters examined except for mild abnormalities in pancreatic beta-cell function. These data suggest that AN may represent a state of partial glucocorticoid resistance, as in other states of restricted food intake. Furthermore, these pilot data, including the effects of dexamethasone upon psychological outlook in AN, suggest that glucocorticoids are not an effective therapy for these patients.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Anorexia Nervosa; Blood Glucose; Depression; Dexamethasone; Drug Administration Schedule; Female; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Leptin; Pilot Projects; Pituitary-Adrenal System; Treatment Outcome

Leptin action in peripheral tissues is enabled by an interaction with specific transmembrane receptors. Several of leptin receptor isoforms were identified, including soluble leptin receptor isoform structurally identical to extracellular domain of the the long leptin receptor isoform. The soluble receptor isoform is released to the circulation and acts probably as leptin-binding factor. The aim of our study was to measure serum concentrations of the soluble leptin receptor in patients with anorexia nervosa and in the control group of healthy women. Relationships of soluble leptin receptor levels to body mass index (BMI), body fat content, serum leptin, TNF-alpha and insulin levels were also studied.. 16 patients with anorexia nervosa and 16 age-matched lean healthy women were included into the study. All of the subjects were measured and weighed, the body fat content was estimated from the skinfold thickness measurement. The blood for the determination of leptin, soluble leptin receptor and other hormonal parameters was obtained from all subjects after the overnight fasting. BMI, body fat content, serum leptin and insulin levels in patients with anorexia nervosa were significantly lower than in the control group (BMI: 14.98 +/- 2.32 vs. 22.21 +/- 2.48, p < 0.01, % fat content: 16.43 +/- 4.56 vs. 27.19 +/- 4.59, p < 0.01, leptin: 1.37 +/- 1.85 ng.ml-1 vs. 7.19 +/- 3.49 ng.ml-1, p < 0.01, insulin: 12.97 +/- 2.89 mU.l-1 vs. 17.09 +/- 5.57 mU.l-1, p < 0.05). Serum soluble leptin receptor levels in patients with anorexia nervosa were significantly higher compared the to control group (24.67 +/- 8.3 U.ml-1 vs. 15.71 +/- 2.79 U.ml-1, p < 0.01). No significant differences in serum TNF-alpha levels between the groups studied were found. Serum leptin levels in both groups correlated positively with BMI and body fat content. Serum soluble leptin receptor levels in both groups correlated negatively with BMI only. No statistically significant relationships between serum soluble leptin receptor levels and the rest of parameters studied were found in any of the groups studied.. Serum soluble leptin receptors levels in patients with anorexia nervosa were significantly higher in comparison with the healthy subjects. Except of the negative correlation between serum soluble leptin receptor levels and BMI no statistically significant relationships between serum soluble leptin receptor and the rest of parameters studied were found.

Topics: Anorexia Nervosa; Body Mass Index; Carrier Proteins; Female; Humans; Insulin; Leptin; Receptors, Cell Surface; Receptors, Leptin; Tumor Necrosis Factor-alpha

Leptin plays an important role in reproductive function. In patients with acute anorexia nervosa, serum leptin levels have repeatedly been shown to be lower than in age-matched controls. We have previously hypothesized that the amenorrhea characteristic of anorexia nervosa is related to this low leptin secretion. In an attempt to address this hypothesis, serum levels of leptin and follicle stimulating hormone (FSH) and luteinizing hormone (LH) of 16 female inpatients with anorexia nervosa or an eating disorder not otherwise specified (atypical anorexia nervosa) were measured on a biweekly basis during weight gain. We hypothesized that a serum leptin level of 1.85 microg L(-1) would be associated with gonadotropin levels at or above the minimal level observed during the menstrual cycle in healthy adult fertile females. Our results revealed that increments of LH levels generally tracked increments of leptin levels during the first weeks of treatment. Similarly, in those patients with low referral leptin levels, FSH initially also tracked leptin levels. In contrast, a relationship between gonadotropin levels and leptin secretion was no longer discernible after LH and FSH levels had peaked. Those patients with exceedingly low leptin levels upon admission revealed a slow increase of gonadotropin levels. Our hypothesis of a threshold leptin level of 1.85 microg L(-1) was supported for LH only.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Female; Follicle Stimulating Hormone; Humans; Leptin; Luteinizing Hormone; Menstrual Cycle; Proteins; Regression Analysis; Weight Gain

This study investigated the role of leptin on eating behavior and reproductive function in eating disorders.. The subjects included 80 eating-disordered women, having different fat mass, eating behavior, and endocrine abnormalities, and 26 control women. Plasma leptin, insulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), cortisol, insulin growth factor-1 (IGF-1), free T4 levels, percent body fat, eating behavior score, and menstrual status score were evaluated for each subject.. In eating-disordered patients, log of leptin levels were significantly correlated with body fat mass, eating behavior score, menstrual status score, and insulin, LH, and FSH levels. Stepwise regression analysis showed that fat mass and eating behavior score were significant determinants of leptin levels. Furthermore, in patients undergoing recovery, leptin levels were determined by fat mass and/or eating behavior.. These results suggest that leptin may play some role in counteracting the abnormal eating behavior, reproductive function, and fat mass in these disorders.

Topics: Adipose Tissue; Adult; Analysis of Variance; Anorexia Nervosa; Female; Follicle Stimulating Hormone; Humans; Hydrocortisone; Insulin; Insulin-Like Growth Factor I; Leptin; Luteinizing Hormone; Proteins; Radioimmunoassay

Topics: Adipose Tissue; Adolescent; Adult; Anorexia Nervosa; Body Composition; Female; Humans; Leptin; Proteins; Weight Gain

To measure serum leptin concentrations in women with anorexia nervosa (AN) and to identify independent predictors of leptin levels, thereby allowing hormone levels to be modeled using regression analysis.. A cross-sectional study of 15 AN inpatients and 16 healthy control subjects. Age, height, weight, percent body fat, total caloric intake, fat intake, and fasting plasma leptin levels were recorded. Stepwise forward regression analysis was carried out to identify predictors of leptin levels.. Circulating leptin concentrations in AN were 3.5+/-0.5 versus 7.6+/-1.2 ng/ml in control subjects. Percent body fat correlated best with leptin levels in anorexic and control subjects (r =.63; p =.0002), with caloric intake showing only a moderate correlation (r = .47; p = .008). Only percent body fat was a significant predictor of plasma leptin levels in our regression model.. Leptin levels are proportionately lower in AN as compared to healthy controls. It appears that physiological regulation of plasma levels with respect to percent body fat is maintained in individuals with little body fat.

Topics: Adipose Tissue; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Cross-Sectional Studies; Energy Intake; Female; Humans; Leptin; Middle Aged

Leptin is a protein hormone produced by adipocytes that provide information about the body fat content. It was previously reported that serum leptin levels were decreased in patients with anorexia nervosa in comparison with healthy control subjects. The aim of our study was to compare serum leptin levels in patients with anorexia nervosa (n=11, initial mean BMI=15.4 kg/m2) before and after partial recovery with control age-matched subjects (n=11, mean BMI= 20.3 kg/m2) and to study the relationships of leptin levels, serum lipids and biochemical nutritional parameters. We found that serum leptin concentrations in patients with anorexia nervosa were significantly reduced in comparison with control subjects (3.61 vs 9.37 ng.ml(-1), p<0.01). Serum cholesterol, triglycerides, total protein and albumin in patients with anorexia nervosa either before or after partial recovery did not differ from the control group. After partial recovery, a significant increase in serum leptin was observed (4.83 vs 3.61 ng.ml(-1), p<0.05), but the values still remained significantly lower than in the control group (p<0.01) Leptin levels correlated positively with the body mass index in the control group and anorexia nervosa group before recovery. The correlation with BMI in the anorexia nervosa group after refeeding was not significant. No significant correlation was found between leptin concentrations and serum lipids, total protein, albumin and prealbumin, respectively. Serum leptin thus represents a sensitive parameter that reflects the nutritional status in patients with anorexia nervosa suitable for long-term follow up during refeeding therapy.

Topics: Adult; Anorexia Nervosa; Body Mass Index; Eating; Female; Humans; Leptin; Lipids

Leptin, the product of the ob-gene, is specifically released by adipocytes. In addition to its metabolic function it seems to affect the feedback-mechanisms of the hypothalamic-pituitary-gonadal-axis. We studied 13 female juvenile elite gymnasts with anorexia athletica (AA) and 9 female patients with anorexia nervosa (AN) regarding the relation between leptin, fat stores, and the reproductive hormone levels. Leptin levels in females with anorexia nervosa (Tanner stage B4 [median]; mean age: 17.8 +/- 1.7 years) were low (2.9 +/- 2.7 microg/L), and were related to body mass index (BMI) (r = 0.71; p = 0.03) and percentage body fat mass (r = 0.78; p = 0.01). Leptin levels of the elite gymnasts were even more decreased (1.2 +/- 0.8 microg/L) caused by the low amount of fat stores. Leptin correlated with BMI (r= 0.77; p = 0.004) and the percentage body fat mass (r = 0.6; p = 0.04). In elite gymnasts leptin levels correlated with CA showing an age-dependent increase (r= 0.59; p = 0.04). Oestradiol was secreted at a low level in both groups (AN: 25.6 +/- 17.4 microg/L; AA: 24.4 +/- 13.5 microg/L). A delay in menarche and a retarded bone maturation occurred in AA. Our results clearly show that leptin levels are low in restrained eaters. Leptin levels represent the fat stores in the body and play a permissive role for female pubertal development. There is evidence that the mechanisms leading to a dysregulation of the reproductive-axis in patients with AN are comparable with those leading to delayed puberty in juvenile elite gymnasts with AA. This implies that AN and AA are overlapping groups and AA can lead to the development of AN.

Topics: Adolescent; Amenorrhea; Anorexia Nervosa; Body Composition; Body Mass Index; Child; Estradiol; Feeding Behavior; Female; Gymnastics; Humans; Leptin; Puberty

Osteopenia is a frequent, often persistent, complication of anorexia nervosa (AN) in adolescent girls and occurs during a critical time in bone development. Little is known about bone metabolism in this patient population. Therefore, we measured bone density (BMD) and body composition by dual energy x-ray absorptiometry, nutritional status, bone turnover, calcium, and hormonal status in 19 adolescent girls with AN (mean +/- SEM, 16.0+/-0.4 yr) and 19 bone age-matched controls. The mean duration of AN was 19+/-5 months. Spinal (L1-L4) osteopenia was common in AN. Lumbar anterioposterior BMD was more than 1 SD below the mean in 42% of patients, and lateral spine BMD was more than 1 SD below in 63% of patients compared with controls. Lean body mass significantly predicted lumbar bone mineral content (r = 0.75; P < 0.0001) in controls only. In AN, duration of illness was the most significant predictor of spinal BMD (lumbar: r = -0.44; P = 0.06; lateral: r = -0.59; P = 0.008). AN adolescents with mature BA (15 yr and greater) were hypogonadal [estradiol, 16.2+/-1.9 vs. 23.3+/-1.6 pg/mL (P = 0.01); free testosterone, 0.70+/-0.17 vs. 1.36+/-0.14 pg/mL (P = 0.01)] although dehydroepiandrosterone sulfate and urinary free cortisol levels did not differ. Leptin levels were reduced in AN (2.9+/-2.1 vs. 16.5+/-1.8 ng/mL; P < 0.0001). Insulin-like growth factor I (IGF-I) was reduced in AN to 50% of control levels (219+/-41 vs. 511+/-35 ng/mL; P < 0.0001) and correlated with all measures of nutritional status, particularly leptin (r = 0.80; P < 0.0001). Surrogate markers of bone formation, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP), were significantly (P = 0.02) reduced in AN vs. controls (OC, 39.1+/-6.4 vs. 59.2+/-5.2 ng/mL; BSAP, 27.9+/-4.0 vs. 40.6+/-3.4 U/L). The majority of the variation in bone formation in AN was due to IGF-I levels (OC: r2 = 0.72; P = 0.002; BSAP: r2 = 0.53; P = 0.01) in stepwise regression analyses. Bone resorption was comparable in patients and controls. These data demonstrate that bone formation is reduced and uncoupled to bone resorption in mature adolescents with AN in association with low bone density. Lean body mass was a significant predictor of BMD in controls, but not AN patients. The major correlate of bone formation in AN was the nutritionally dependent bone trophic factor, IGF-I. Reduced IGF-I during the critical period of bone mineral accumulation may be an important factor in the development of osteopenia

Topics: Absorptiometry, Photon; Adolescent; Alkaline Phosphatase; Anorexia Nervosa; Body Composition; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Calcium; Estradiol; Female; Humans; Leptin; Lumbar Vertebrae; Nutritional Status; Osteocalcin; Spine; Testosterone

Serum leptin levels and resting energy expenditure are significantly decreased in patients with anorexia nervosa compared to healthy subjects. Partial realimentation of patients with anorexia nervosa increases both these parameters. However, there so far are no data concerning the relationship of serum leptin levels and resting energy expenditure in patients with anorexia nervosa. The aim of our study was to follow the relationship of serum leptin levels and resting energy expenditure in patients with anorexia nervosa before and after refeeding.. It was found that serum leptin levels in patients with anorexia nervosa both before and after partial realimentation were significantly lower compared to healthy subjects (0.86 +/- 0.9 ng.ml-1 and 1.77 +/- 1.9 ng.ml-1 vs 6.85 +/- 3.0 ng.ml-1, p < 0.05). The total resting energy expenditure in patients with anorexia nervosa both before and after realimentation were significantly lower than in the control group (4973 +/- 979 and 5263 +/- 899 vs 6401 +/- 827 kJ/day, p < 0.05). When expressed per body weight the resting energy expenditure in patients with anorexia nervosa was significantly higher in comparison with the control group (122.3 +/- 20.6 and 121.5 +/- 14.2 vs 104.2 +/- 14.6 kJ/day, p < 0.05). The differences in resting energy expenditure in patients with anorexia nervosa before and after refeeding did not reach statistical significance. The body mass and the body fat content increased significantly after realimentation index (14.5 +/- 1.4 vs 15.6 +/- 1.5 kg.(m2)-1 and 14.9 +/- 3.4 vs 16.6 +/- 3.7, p < 0.05) but remained still below of those of control group (BMI 22.3 +/- 2.7, body fat content 26.9 +/- 4.2).. Our study confirmed the reduced serum leptin levels and the total resting energy expenditure in patients with anorexia nervosa compared to healthy age-matched subjects. No statistically significant relationships were found between serum leptin levels and resting energy expenditure either in healthy subjects or in patients with anorexia nervosa before or after partial realimentation respectively.

Topics: Adolescent; Adult; Anorexia Nervosa; Basal Metabolism; Eating; Female; Humans; Leptin

Serum leptin levels are low in untreated anorexia nervosa, but studies of the exact relationship between leptin and body weight and the impact of refeeding in anorectics are limited. Therefore, we studied serum leptin, insulin-like growth factor I, and other endocrine parameters in female anorectics before and after gaining weight and in female normal body weight controls. Leptin levels in untreated anorectics were significantly lower than those in normal body weight controls (3.6 +/- 1.6 vs. 12.0 +/- 6.9 ng/mL; P < 0.001), and they uncoupled from body weight in a nonlinear relationship, suggesting a threshold effect at lowest body weights. Leptin increased significantly with refeeding (5.6 +/- 3.8 ng/mL; P < 0.01). The significant linear correlations of leptin with body mass index in the anorectics after weight gain and in normal body weight controls (r = 0.69; P < 0.001 and r = 0.76; P < 0.001, respectively) are consistent with a normal physiological increase in leptin with weight gain. Leptin and insulin-like growth factor I were highly correlated, even after controlling for body weight (r = 0.63; P = 0.001) during starvation, but were no longer significantly correlated after body weight gain in the anorectics or the normal body weight controls. Further studies are necessary to elucidate the relationship of leptin to neuroendrocrine abnormalities seen in starvation and to determine a possible contribution of leptin to difficulties with weight restoration in anorexia nervosa.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Bulimia; Female; Hormones; Humans; Leptin; Proteins; Reference Values

Leptin is a protein encoded by the ob gene that is expressed in adipocytes and regulates eating behavior via neuroendocrine mechanisms. Plasma leptin levels have been shown to correlate with weight and body fat in normal, obese and anorexic subjects. In the last of these populations, the dynamic profile of plasma leptin levels during short-term refeeding has never been assessed. We thus investigated basal plasma leptin levels in 29 female patients with anorexia nervosa (AN) (age 21.9 +/- 1.4 years, body mass index (BMI) 15.2 +/- 0.3 kg/m2) and in 80 normal female controls (age 21.2 +/- 0.2 years, BMI 20.3 +/- 0.3 kg/m2, mean +/- S.E.M.). Basal plasma leptin levels in AN were decreased by 77% compared with controls (2.5 +/- 0.2 vs 11.1 +/- 0.7 ng/ml, P < 0.0001). In both AN subjects and controls, plasma leptin levels correlated significantly with BMI (r2 = 0.448, P < 0.0001 and r2 = 0.339, P < 0.0001 respectively). Five AN patients (four female, one male, age 22.0 +/- 4.7 years, BMI 14.2 +/- 0.4 kg/m2, body fat 4.3 +/- 0.9 kg or 11.0 +/- 1.9% of body weight, basal metabolic rate (BMR) 958 +/- 122 kcal/day) were studied during a 3-day refeeding period and compared with eight control subjects (two male, six female, age 25.7 +/- 1.2 years, BMI 21.3 +/- 0.8 kg/m2, body fat 15.1 +/- 0.9 kg or 24.6 +/- 1.7%, BMR 1455 +/- 78 kcal/day) submitted to 36-h fasting. The amount of calories administered was based on BMR + 20% (carbohydrate 60%, protein 17%, fat 23%). In contrast to the rise in leptin levels that occurred during refeeding after a prolonged fast period in normal subjects, plasma leptin levels remained low and unchanged throughout the 3 days of renutrition in AN patients. The circadian rhythm of leptin was also completely abolished. This contrasted with the preserved circadian variations of cortisol, whose mean levels were increased. In conclusion, we confirmed that plasma leptin levels are low in AN and correlate with body weight. We further demonstrated that plasma leptin levels do not respond to short-term refeeding in anorexic patients in whom circadian variations are not restored, which suggests that the acute regulation of leptin by positive changes in energy balance is not preserved under a critical threshold of body fat.

Topics: Adult; Analysis of Variance; Anorexia Nervosa; Case-Control Studies; Circadian Rhythm; Female; Humans; Hydrocortisone; Leptin; Male; Proteins; Secretory Rate; Thyrotropin

The aim of this work was to assess the relationship between GH-binding protein (GHBP) and leptin. Both peptides are nutritionally regulated, but the recent implication of a role for leptin in the GH axis requires further study. To avoid the sexual dimorphism in leptin values, we performed leptin standardization according to gender (SD score-leptin). The relationship between SD score-leptin and GHBP was studied in 128 adults with different nutritional status [8 groups according to body mass index (BMI)], ranging from severely underweight anorexia nervosa to highly morbid obesity. Both GHBP and SD score-leptin significantly increased according to BMI within the range from 18-27 kg/m2, whereas no significant differences were found among underweight groups (BMI, < 18 kg/m2) or among obesity grades (BMI, > 27 kg/m2). We found a strong correlation between GHBP and SD score-leptin (r = 0.8; P < 0.0001). Multiple regression analysis revealed SD score-leptin to be a significant determinant of GHBP, accounting for 64% of the variation, whereas BMI did not contribute further to explaining changes in GHBP. This suggests a physiological pathway involving both GHBP (the soluble fraction of GH receptor) and leptin. Thus, we might speculate that leptin could be the signal that induces the related nutritional changes observed in GHBP/GH receptor expression.

Topics: Adolescent; Adult; Aged; Anorexia Nervosa; Body Mass Index; Carrier Proteins; Female; Humans; Leptin; Male; Middle Aged; Nutritional Status; Obesity, Morbid; Proteins; Regression Analysis

In rodents, leptin is involved in regulating eating behaviour, fat storage, and reproductive function. In humans, the serum leptin concentration in obese and normal weight subjects correlates with body mass index, reflecting the body fat store. The serum leptin exhibit diurnal variation, however, this has been reported to be absent in normal weighted amenorrheic athletes. Anorexia nervosa is associated with multiple endocrine abnormalities. Hypothalamic amenorrhoea often precedes the weight loss and may persist after weight recovery. We hypothesized that leptin could be involved in the regulation of eating behaviour and gonadal function in anorexia nervosa.. We measured the concentration of leptin in serum samples taken after an overnight fast in 18 female anorexia nervosa patients and 11 controls. To study diurnal variation, eight patients and 11 controls were hospitalized for 24 h and had a standardized diet at regular times. Seven blood samples were obtained at 4 h intervals from each subject.. The patients fulfilled the DSM-IV criteria for anorexia nervosa. The mean body mass index for the patients was 14.2 +/- 2.3 kg/m2 and for controls 20.3 +/- 1.7 kg/m2.. The mean fasting leptin concentration as well as the 24 h mean concentration were significantly lower in the anorectic group than in the control group (2.5 +/- 0.9 vs 10.1 +/- 6.1 micrograms/l, P < 0.01 and 2.7 +/- 1.5 vs 10.6 +/- 7.1 micrograms/l, P < 0.01 respectively). In the whole group of subjects (n = 28) a significant positive correlation between the leptin level and body mass index was found (r = 0.63, P < 0.001). In the anorectic group it was found that the leptin level correlated better with body fat percentage than with body mass index. In normalized data the time course of the mean leptin levels showed a monophasic variation with nadir and zenith at about 0900 and 0100 h respectively. However, the individual coefficients of variance were significantly lower in the anorectic group compared to the group of healthy women.. In patients with anorexia nervosa the leptin level is low, reflecting the low body fat mass, and the relative diurnal variation is strikingly reduced. The similarity to that of normal weighted women with hypothalamic amenorrhoea suggest that altered leptin oscillations may be of particular significance in the hypothalamic regulation of reproductive function.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Composition; Body Mass Index; Case-Control Studies; Circadian Rhythm; Female; Humans; Leptin; Proteins

Topics: Animals; Anorexia Nervosa; Female; Infertility, Female; Leptin; Mice; Pheromones; Proteins; Religion and Medicine

A new, sensitive ELISA for human leptin in plasma and cerebrospinal fluid (CSF) was developed, using monoclonal antibodies. The lower limit of detection of this ELISA was 0.78 pg/assay. Both intra- and interassay imprecision values were <7%. The dilution curves of plasma and CSF showed good linearity, and the recovery was 83.2-95.6%. There was good correlation between plasma leptin concentrations by the ELISA and a commercially available RIA (r = 0.99). Our ELISA is advantageous because it does not require radioisotopes, it produces results in hours rather than days, and more importantly, it improves on the detection limit and plasma interference of the RIA kit. The new ELISA enables measurement of low concentrations of leptin, as are seen in CSF and in plasma of patients with anorexia nervosa.

Topics: Adipose Tissue; Animals; Anorexia Nervosa; Antibodies, Monoclonal; Cerebrospinal Fluid; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Mice; Mice, Inbred C57BL; Proteins; Radioimmunoassay; Recombinant Proteins; Sensitivity and Specificity

In anorexia nervosa, underweight results from a loss of body mass due to a restricted energy intake. Circulating leptin levels have been shown to be low in the acute stage of the disorder. We studied diurnal secretion characteristics of leptin, insulin and cortisol in a study group of anorectic patients prior to refeeding, a second study group of anorectic patients after initiation of refeeding and study groups of healthy underweight and normal-weight controls. Spontaneous secretion of leptin, insulin and cortisol was measured by drawing blood samples every 2 h for 24 h. The temporal relationships between the diurnal secretion patterns of the three hormones were assessed by cross-correlation analysis in every study group. Plasma levels of leptin and cortisol were secreted with a specific circadian rhythmicity and displayed an intricate temporal relationship in anorectic patients. Semistarvation in the non-refed patients was associated with (1) exceedingly low plasma leptin levels, (2) a qualitative alteration in the circadian rhythm of leptin and cortisol levels and (3) an alteration in the temporal coupling between cortisol and leptin. In contrast, in the patients who had gained weight, leptin levels were higher; furthermore, the diurnal pattern of leptin and the temporal relationship between leptin and cortisol were similar to controls. Increments in insulin secretion preceded those of leptin by 4-6 h in both anorectic patients and in controls. Leptin levels increased 4 h prior to those of cortisol in controls and in refed patients, whereas in the non-refed patients cortisol increased prior to leptin. Thus, anorexia nervosa leads to pronounced, albeit reversible changes in the secretion dynamics of leptin and cortisol.

Topics: Adult; Anorexia Nervosa; Circadian Rhythm; Female; Humans; Hydrocortisone; Insulin; Insulin Secretion; Leptin; Male; Proteins

Topics: Adolescent; Adult; Animals; Anorexia Nervosa; Child; Humans; Leptin; Mice; Mice, Obese; Obesity; Proteins

Serum levels of leptin are decreased in underweight AN patients and increase with weight restoration. To assess the relationship of decreased leptin levels with other hormonal abnormalities in AN and to evaluate the possible role of increasing leptin levels, alone or in combination with other hormones, in the resumption of menses that accompanies weight gain, we studied cross-sectionally sixty-five consecutively enrolled AN patients. Subjects were divided in three groups: (I) underweight and amenorrheic; (II) weight-recovered but still amenorrheic; and (III) weight-recovered and eumenorrheic women. Patients in group I had decreased BMI, serum leptin, estradiol (E2), insulin-like growth factor 1 (IGF-1) and urinary growth hormone (GH) levels and increased sex hormone-binding globulin (SHBG) levels, compared to AN patients in groups II and III. Moreover, although no differences in leptin levels or BMI were observed between amenorrheic and eumenorrheic weight-recovered patients (groups II and III), free E2 and GH levels were higher (P<0.02) in weight-recovered, eumenorrheic women. Thus, it appears that leptin is a necessary, but not a sufficient, factor for the resumption of menses in AN patients.

Topics: Adult; Amenorrhea; Anorexia Nervosa; Body Mass Index; Estradiol; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Menstrual Cycle; Proteins; Sex Hormone-Binding Globulin; Weight Gain

Mutations in the leptin gene can result in profound obesity in both rodents and humans. In humans, serum leptin levels correlate with body mass index (BMI: kg m(-2)). However, in patients with anorexia nervosa (AN) leptin levels are lower than in BMI-matched healthy controls. We had previously argued that genes involved in weight regulation should be considered as candidate genes for AN. To investigate this hypothesis we screened the coding region of the leptin gene and part of the leptin gene linked upstream region (LEGLUR) in 49 patients with AN and 315 children and adolescents with extreme obesity. Two novel mutations in the coding region (Ser-91-Ser; Glu-126-Gln), each found in a single proband, and a novel polymorphism in the LEGLUR (position -1387 G/A; frequency of both alleles approximately 0.50) were identified. Tests for association of LEGLUR polymorphism alleles were negative by comparing allele frequencies between 115 AN patients, 71 bulimia nervosa patients, 315 extremely obese children and adolescents, 141 healthy underweights and 50 controls that were not selected for body weight. Tests for transmission disequilibrium were also negative. Hence, an influence of variations in the leptin gene on eating disorders or extreme early onset obesity could not be detected.

Topics: Adolescent; Age of Onset; Amino Acid Substitution; Anorexia Nervosa; Body Mass Index; Body Weight; Bulimia; Child; Gene Frequency; Genotype; Humans; Leptin; Linkage Disequilibrium; Nuclear Family; Obesity; Point Mutation; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Proteins; Reference Values; Regulatory Sequences, Nucleic Acid; Thinness

From a metabolic point of view, anorexia nervosa may be viewed as a mirror image of obesity. We compared insulin secretion, clearance and action on glucose metabolism during an intravenous glucose tolerance test in nine women with anorexia nervosa and in nine age-matched normal-weight controls. Insulin secretion (ISR) was derived by deconvolution of plasma C-peptide levels, insulin clearance (MCR(I)) was obtained by dividing the area under the curve (AUC(0-180 min)) of ISR by the corresponding AUC of plasma insulin levels, insulin sensitivity (S(I)) and glucose effectiveness index (S(G)) were calculated by Bergman's minimal model. The anorectic women had markedly lower BMI values (13.7+/-0.6 vs 23.2+/-0.8 kg/m2, p<0.0001) and serum basal leptin levels (2.8+/-0.6 vs 8.9+/-1.8 ng/mL, p=0.005) than control women. The anorectic women exhibited clear-cut lower fasting and post-glucose plasma insulin levels but similar corresponding plasma C-peptide concentrations when compared to controls. Consequently, ISR was similar in both groups while MCR(I) was significantly increased in anorexia nervosa (MCR(I): 3320+/-881 vs 822+/-79 mL x min(-1) x m(-2), p<0.02). The index S(I) tended to be higher in anorectic women than in normal-weight subjects, but without reaching the level of statistical significance because of a high between-subject variability (20.2+/-5.7 vs 12.5+/-2.2 10(-5) x min(-1)/pmol x L(-1), NS). The index S(G) was similar in both groups (0.022+/-0.004 vs 0.018+/-0.002 min(-1), NS). In conclusion, low plasma insulin levels observed in women with anorexia nervosa result from high MCR(I) rather than from depressed insulin secretion. Insulin sensitivity is not systematically increased and glucose effectiveness is unchanged in anorectic women when compared to normal-weight controls.

Topics: Adult; Anorexia Nervosa; Body Mass Index; C-Peptide; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Leptin

Topics: Adolescent; Adult; Amenorrhea; Animals; Anorexia Nervosa; Estradiol; Female; Humans; Leptin; Menstruation; Osteoporosis; 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

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 besides that little is known about the physiological actions of leptin in humans. In order to understand the role of leptin in severe malnutrition, in the present work 10 patients recently diagnosed with anorexia nervosa were studied both before and 2 months later, after partial weight recovery, and were compared with 18 normal-weight women as controls. Leptin was measured by a newly developed radioimmunoassay and both IGF-I and IGFBP-3 were measured by commercial radioimmunoassays. The mean (+/-SE) serum leptin concentrations (in microgram/liter) were 18.1 +/- 2.0 in control women with BMI of 21.1 +/- 0.3, significantly higher (P < 0.01) than that in the anorexia nervosa patients at diagnosis (2.2 +/- 0.1, BMI 15.3 +/- 0.6). These differences were also observed in IGF-I values (microgram/liter) that were 228.0 +/- 14.6 in controls and 157.4 +/- 28.7 in anorexia nervosa patients (P < 0.02). No differences were observed in IGF-BP3. After treatment, patients with anorexia nervosa experienced an increase in BMI (17.1 +/- 0.5, P < 0.0001 vs before) although they were still underweight. The partial recovery in weight led to a complete normalization of IGF-I levels (214.0 +/- 21.0 micrograms/liter) and to an enhancement in leptin levels (3.3 +/- 0.5 micrograms/liter; P < 0.03 vs before treatment), though still lower than those in normal-weight women (P < 0.05). Individually analyzed, a large dispersion was observed in control subjects, with leptin levels ranging from 5.5 to 38.7 micrograms/liter, while in all anorexia nervosa patients leptin levels were under 3 micrograms/liter. A treatment-induced increase in body weight led to an increase in leptin levels in 7 out of the 10 anorexia nervosa patients studied and the 3 patients with no increase in leptin were all initially under the 14.5 BMI. In conclusion, leptin levels are severely reduced in anorexia nervosa patients with severe malnutrition, and a significant rise occurred after partial weight recovery. There seems to be a level of BMI below which leptin levels do not drop further but also do not increase despite weight gain. While IGF-I reflects the energy intake of the previous few weeks, the serum leptin concentration reflects the true status of the adipose stores, a fact that has useful clinical implications.

Topics: Adult; Anorexia Nervosa; Body Mass Index; Case-Control Studies; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Proteins; Weight Gain

Studies in rodents have shown that leptin acts in the central nervous system to modulate food intake and energy metabolism. To evaluate the possible role of leptin in the weight loss of anorexia nervosa, this study compared cerebrospinal fluid (CSF) and plasma leptin concentrations in anorexic patients and controls. Subjects included 11 female patients with anorexia nervosa studied at low weight and after treatment, and 15 healthy female controls. Concentrations of leptin in blood and CSF were measured by RIA. Patients with anorexia nervosa, compared to controls, had decreased concentrations of leptin in CSF (98 +/- 26 vs. 160 +/- 58 pg/mL; P < 0.0005) and plasma (1.75 +/- 0.46 vs. 7.01 +/- 3.92 ng/mL; P < 0.005). The CSF to plasma leptin ratio, however, was higher for patients (0.060 +/- 0.023) than for controls (0.025 +/- 0.007; P < 0.0001). At posttreatment testing, although patients had not yet reached normal body weight, CSF and plasma leptin concentrations had increased to normal levels. These results demonstrate the dynamic changes in plasma and CSF leptin during positive energy balance in anorexia nervosa. The results further suggest that normalization of CSF leptin levels before full weight restoration during treatment of anorexic patients could contribute to resistance to weight gain and/or incomplete weight recovery.

Topics: Adult; Anorexia Nervosa; Female; Humans; Hydroxyindoleacetic Acid; Leptin; Nutritional Status; Proteins; Reference Values; Weight Gain

Circulating leptin concentrations are known to be low in acute anorexia nervosa (AN), which is characterized by low weight, amenorrhea and specific psychopathological features. In this study plasma leptin concentrations were determined during inpatient treatment of 23 adolescent females with AN using a sensitive radioimmunoassay (RIA) and set into relationship to leptin levels of females matched for age, body mass index (BMI; kg m-2) and/or percent body fat. At referral patients had leptin concentrations well below the female controls. Weight gains led to steep increases of leptin levels which peaked at values well in excess of those observed in controls matched for BMI. In patients who reached the final treatment stage and who were followed-up after discharge, levels subsequently fluctuated and finally dropped into or below the control range. The low leptin levels at referral are likely to be involved in the pathogenesis of amenorrhea and the reduced metabolic state of acutely ill patients. Peak leptin levels reached after weight gain are possibly the cause of increased energy expenditure during this stage of the disorder.

Topics: Adolescent; Anorexia Nervosa; Female; Humans; Leptin; Obesity; Proteins; Weight Gain; Weight Loss

Evidence that leptin plays an important role in reproductive function is accumulating rapidly. We hypothesized that low leptin synthesis is associated with amenorrhea. We therefore determined serum leptin levels in 43 underweight female students, who were screened for lifetime occurrence of amenorrhea. We assessed the predictive value of leptin, body mass index (BMI), fat mass and percent body fat, respectively, for lifetime occurrence of amenorrea. Factors predicting amenorrhea were tested for their capability to predict current amenorrhea in a second cohort of 63 inpatients with anorexia nervosa (AN) or bulimia nervosa (BN). Furthermore, the relationships between serum leptin levels and of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone, respectively, were evaluated. Only leptin predicted lifetime occurrence of amenorrhea in the student cohort. The critical leptin level was in the range of 1.85 micrograms L-1. This level served to largely separate anorectic from bulimic patients. In patients with AN mean serum log10 leptin levels over the first 4 weeks of inpatient treatment were correlated with mean FSH, LH and estradiol levels, respectively. Evidently, a critical leptin level is needed to maintain menstruation. In affluent populations eating disorders are likely to be a major cause of a low leptin synthesis.

Topics: Adolescent; Adult; Amenorrhea; Anorexia Nervosa; Body Mass Index; Cohort Studies; Contraceptives, Oral; Estradiol; Female; Follicle Stimulating Hormone; Humans; Leptin; Luteinizing Hormone; Obesity; Progesterone; Proteins; Weight Loss

The study objective was to determine circulating levels of the appetite-controlling neuropeptides, neuropeptide Y (NPY), galanin, and leptin, in subjects with eating disorders. The study group consisted of 48 obese women aged 19 to 45 years, 15 women with anorexia nervosa aged 18 to 23 years, and 19 lean healthy women aged 18 to 42 years (control group). The obese women were divided into four groups: (A) body mass index (BMI) = 25 to 30 kg/m2, n = 9 (overweight); (B) BMI = 31 to 40 kg/m2, n = 23 (moderate obesity); (C) BMI greater than 40 kg/m2, n = 9 (severe obesity); and (D) BMI = 31 to 40 kg/m2, n = 7 (moderate obesity + non-insulin-dependent diabetes mellitus [NIDDM]). Plasma NPY, galanin, and leptin concentrations were measured in peripheral blood samples with radioimmunoassay methods. Plasma NPY levels in obese women (groups A, B, C, and D) were significantly higher as compared with the control group (P < .01, P < .001, P < .001, and P < .001, respectively). The highest plasma NPY concentrations were observed in obese women with NIDDM. Plasma galanin levels were significantly higher in groups B, C, and D (P < .001, P < .001, and P < .001, respectively). Plasma leptin concentrations were significantly higher in groups C and D as compared with the control group (P < .001 and P < .001, respectively). Plasma NPY and galanin concentrations in women with anorexia nervosa did not differ from the levels in the control group. However, plasma leptin concentrations were significantly lower in anorectic women than in the control group (P < .01). Our results indicate that inappropriate plasma concentrations of NPY, galanin, and leptin in obese women may be a consequence of their weight status, or could be one of many factors involved in the pathogenesis of obesity.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Galanin; Humans; Leptin; Neuropeptide Y; Obesity; Proteins; Radioimmunoassay

Topics: Anorexia Nervosa; Eating; Humans; Hypothalamic Hormones; Leptin; Proteins

Leptin is a protein encoded by the ob gene that is expressed in adipocytes and regulates eating behavior via central neuroendocrine mechanisms. Serum leptin levels have been shown to correlate with weight and percent body fat in normal and obese individuals; however, it is not known whether the regulation of leptin is normal below a critical threshold of body fat in chronic undernutrition. We investigated serum leptin levels in 22 women, aged 23 +/- 4 yr, with anorexia nervosa. Duration of disease, weight, BMI, percent body fat, and serum leptin levels were determined for each patient. Nutritional status was assessed further by caloric intake and measurement of insulin and insulin-like growth factor I (IGF-I) levels. Twenty-three healthy women, aged 23 +/- 4 yr, taking no medications, with normal menstrual function and body mass index (BMI) between 20-26 kg/m2 (mean, 23.7 +/- 1.7 kg/m2), served as a control population for comparison of leptin levels. Subjects with anorexia nervosa were low weight (BMI, 16.3 +/- 1.6 kg/m2; normal, 20-26 kg/m2) and exhibited a striking reduction in percent body fat (7 +/- 2%; normal, 20-30%). The mean serum leptin level was significantly decreased in subjects with anorexia nervosa compared with that in age- and sex-matched controls of normal body weight (5.6 +/- 3.7 vs. 19.1 +/- 8.1 ng/mL; P < 0.0001). Serum leptin levels were correlated highly with weight, as expressed either BMI (r = 0.66; P = 0.002) or percent ideal body weight (r = 0.68; P = 0.0005), body fat (r = 0.70; P = 0.0003), and IGF-I (r = 0.64; P = 0.001), but not with caloric intake or serum levels of estradiol or insulin in subjects with anorexia nervosa. The correlation between leptin and body fat was linear, with progressively lower, but detectable, leptin levels measured even in patients with less than 5% body fat, but was not significant when the effects of weight were taken into account. In contrast, the correlation between leptin and IGF-I remained significant when the effects of weight, body fat, and caloric intake were taken into account. In normal controls, leptin correlated with BMI (r = 0.55; P = 0.007) and IGF-I (r = 0.44; P < 0.05), but not with fat mass. These data demonstrate that serum leptin levels are reduced in association with low weight and percent body fat in subjects with anorexia nervosa compared to normal controls. Leptin levels correlate highly with weight, percent body fat, and IGF-I in subjects with anorexia nervosa, suggesting tha

Topics: Adipose Tissue; Adolescent; Adult; Anorexia Nervosa; Body Mass Index; Body Weight; Case-Control Studies; Energy Intake; Female; Humans; Insulin-Like Growth Factor I; Leptin; Proteins

Topics: Adolescent; Adult; Animals; Anorexia Nervosa; Blood Proteins; Body Mass Index; Female; Humans; Leptin; Male; Mice; Obesity; Proteins