neuropeptide-y and Anorexia-Nervosa

The vast majority of new neuropeptides feature unique biochemical properties as well as awide spectrum of physiological activity applied in numerous neuronal pathways, including hypothalamus and the limbic system. Special interest should be paid to nesfatin-1 - the relatively recently discovered and still intensively studied regulatory factor and a potential modulator of eating behaviors. New information about it now allows to consider this neuropeptide as a potentially important factor involved in the pathogenesis of many different mental disorders. The considered pharmacomodulation of nesfatinergic signaling may be potentially helpful in the future treatment of some neuropsychiatric and metabolic disorders including anorexia nervosa. Although the results of some basic and clinical tests seem to be promising, all possible applications of the aforementioned neuropeptides, together with their agonists and antagonists still remain in the area of speculation. The intensive search of selective modulators of their known receptors may facilitate the opening of a promising chapter in the eating disorders therapy. This paper provides a review of recent scientific reports regarding the hypothetical role of nesfatin-1 in the neuronal pathways related to pathophysiology of anorexia nervosa.

Topics: Anorexia Nervosa; Appetite Regulation; Feeding and Eating Disorders; Humans; Hypothalamus; Immunohistochemistry; Nervous System Physiological Phenomena; Neurochemistry; Neuropeptide Y; Neuropeptides; Nucleobindins

Complex mechanisms have evolved that control feeding and energy homeostasis in mammals. Centrally, particularly in the hypothalamus, numerous neurotransmitters have been identified that regulate appetite and energy homeostasis. On the other hand, hormones released from the gut signal states of hunger and satiety to the brain. From the large number of players involved in this interplay, peptides from the neuropeptide Y (NPY) family are unique, with the predominantly neuronally expressed NPY being one of the most strongly stimulating agents for food intake while its two other closely related family members peptide YY (PYY) and pancreatic polypeptide (PP) released from the gut induce satiety. Another major player in this circuitry is ghrelin, which is released from the stomach and is the only known hormone that signals hunger to the brain. It is doing this by stimulating hypothalamic NPY production and release, subsequently leading to increased appetite and feeding behaviour. Deregulation of these processes can lead to either the development of obesity or the other extreme, anorexia. The aim of this review is to summarize the recent literature on NPY and ghrelin and its involvement in anorexia nervosa.

Topics: Animals; Anorexia Nervosa; Appetite Regulation; Bone and Bones; Energy Metabolism; Ghrelin; Homeostasis; Humans; Neurons; Neuropeptide Y; Osteoporosis; Pancreatic Polypeptide; Peptide YY; Protein Precursors; Receptors, Ghrelin; Receptors, Neuropeptide Y; Signal Transduction

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

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

Outcome in anorexia nervosa remains poor and a new way of looking at this condition is therefore needed. To this aim, we review the effects of food restriction and starvation in humans. It is suggested that body weight remains stable and relatively low when the access to food requires a considerable amount of physical activity. In this condition, the human homeostatic phenotype, body fat content is also low and as a consequence, the synthesis and release of brain neurotransmitters are modified. As an example, the role of neuropeptide Y is analyzed in rat models of this state. It is suggested that the normal behavioral role of neuropeptide Y is to facilitate the search for food and switch attention from sexual stimuli to food. Descriptive neuroendocrine studies on patients with anorexia nervosa have not contributed to the management of the patients and the few studies in which hormones have been administered have, at best, reversed an endocrine consequence secondary to starvation. In a modified framework for understanding the etiology and treatment of anorexia nervosa it is suggested that the condition emerges because neural mechanisms of reward and attention are engaged. The neural neuropeptide Y receptor system may be involved in the maintenance of the behavior of eating disorder patients because the localization of these receptors overlaps with the neural systems engaged in cue-conditioned eating in limbic and cortical areas. The eating behavior of patients with anorexia nervosa, and other eating disorders as well, is viewed as a cause of the psychological changes of the patients. Patients are trained to re-learn normal eating habits using external support and as they do, their symptoms, including the psychological symptoms, dissolve.

Topics: Animals; Anorexia Nervosa; Body Mass Index; Body Weight; Eating; Feeding Behavior; Homeostasis; Humans; Motor Activity; Neuroendocrinology; Neuropeptide Y; Starvation

Anorexia nervosa (AN) is an eating disorder affecting mostly young people which could lead to serious complications and consequences. There are ethnical and gender differences in the incidence and prevalence of AN, but the influence of urbanization has not yet been proved. The relationship of genetic background to the risk of AN is still being investigated. In this review we summarize current knowledge about the relationship between AN and polymorphism of substances known to be regulating eating behaviour or metabolic pathways e.g. serotonin, ghrelin, catechol-O-methyl transferase, neuropeptide Y, brain-derived neurotrophic factor and adipokines.

Topics: Adipokines; Anorexia Nervosa; Catechol O-Methyltransferase; Genetic Predisposition to Disease; Ghrelin; Humans; Neuropeptide Y; Polymorphism, Genetic; Risk Factors; Serotonin

Topics: Adrenal Gland Neoplasms; Alzheimer Disease; Anorexia Nervosa; Autonomic Nervous System Diseases; Biomarkers; Humans; Hypertension; Immunoradiometric Assay; Neuroblastoma; Neuropeptide Y; Pheochromocytoma; Radioimmunoassay; Reference Values

Topics: Animals; Anorexia Nervosa; Biomarkers; Eating; Energy Metabolism; Ghrelin; Humans; Neuropeptide Y; Peptide Hormones; Postprandial Period

The role of neuropeptide Y (NPY) in feeding behavior and zinc deficiency-induced anorexia has been controversial because hypothalamic NPY levels are elevated in both zinc deficiency and food restriction. A recent report shows that while NPY is released from terminals in the paraventricular nucleus of the hypothalamus of food-restricted animals, this release is significantly impaired in zinc-deficient animals. Zinc deficiency may therefore cause anorexia by inhibiting the release of NPY that is required for receptor activation.

Topics: Adolescent; Adult; Animals; Anorexia Nervosa; Eating; Female; Humans; Male; Neuropeptide Y; Rats; Zinc

The eating disorders anorexia nervosa and bulimia nervosa are best conceptualized as syndromes and are classified on the basis of the clusters of symptoms they present. According to the multidimensional model, eating disorders begin with dieting, which is propelled into a full-blown disorder by antecedent conditions of biological vulnerability and genetics, premorbid psychological characteristics, family interactions, and social climate. The medical abnormalities present in individuals with eating disorders are due to starvation conditions and purging behaviors and will resolve with nutritional rehabilitation and the cessation of purging. Comorbid psychiatric conditions such as affective disorders, anxiety disorders, substance abuse, and personality disorders are frequently present. For anorexia nervosa, the most effective strategy is multidimensional treatment, consisting of nutritional rehabilitation, medical attention, individual cognitive psychotherapy, and family counseling or therapy if the patient is younger than age 18 years. For bulimia nervosa, the treatment of choice is cognitive-behavioral therapy with directions in a manual for therapists. A second choice for treatment is an antidepressant, beginning with fluoxetine.

Topics: Anorexia Nervosa; Bulimia; Cholecystokinin; Dopamine; Female; Humans; Neuropeptide Y; Serotonin

Topics: Anorexia Nervosa; Body Image; Bulimia; Cognitive Behavioral Therapy; Family; Homovanillic Acid; Humans; Hypothalamus; Neuropeptide Y; Neurotransmitter Agents; Psychiatric Status Rating Scales; Research

Starvation-induced alterations of neuropeptide activity probably contribute to neuroendocrine dysfunctions in anorexia nervosa. For example, CRH alterations contribute to hypercortisolemia and NPY alterations may contribute to amenorrhea. Alterations of these peptides as well as opioids, vasopressin, and oxytocin activity could contribute to other characteristic psychophysiological disturbances, such as reduced feeding, in acutely ill anorexics. Such neuropeptide disturbances could contribute to the vicious cycle that has been hypothesized to occur in anorexia nervosa. That is, the consequences of malnutrition perpetuate pathological behavior.

Topics: Anorexia Nervosa; Corticotropin-Releasing Hormone; Feeding Behavior; Humans; Neuropeptide Y; Neuropeptides; Neurosecretory Systems; Opioid Peptides; Oxytocin; Starvation; Vasopressins

Patients with anorexia nervosa have neuroendocrine and behavioral alterations that starvation and weight loss are thought to cause, or contribute to, since they are reversed by weight restoration. We have found that anorexics have starvation-related disturbances of neuropeptide Y (NPY), corticotropin-releasing hormone (CRH), and beta-endorphin, as determined by their measurements in cerebrospinal fluid. The relationship between these neuropeptides and several symptoms in anorexia, together with findings in experimental animals, raise a possibility that changes in the activity of these neuropeptides contribute to neuroendocrine and behavioral alterations in anorexia. Specifically, a disturbance of central nervous system CRH activity is likely to be responsible for hypercortisolemia, while a disturbance of central nervous system NPY may contribute to amenorrhea. In addition, disturbances of these neuropeptides could contribute to other symptoms such as increased physical activity, hypotension, reduced sexual interest, depression, and pathological feeding behavior.

Topics: Adult; Anorexia Nervosa; beta-Endorphin; Corticotropin-Releasing Hormone; Female; Humans; Neuropeptide Y; Neuropeptides

Ghrelin, a peptide found in the stomach, increases appetite and fat-free mass while suppressing energy expenditure. Ghrelin requires modification by medium-chain triglycerides (MCTs) to exert its physiological effects. In this study, we investigated ghrelin activation and the resulting physiological changes following MCT administration.. Thirty participants were selected from among inpatients diagnosed with anorexia nervosa (AN). The patients were randomly divided into three groups by the MCT content of their nutritional supplement: (1) 'MCT high' (>6 g/day), (2) 'MCT moderate' (1-6 g/day), and (3) 'MCT low' (<1 g/day). Physical factors such as body weight and composition, as well as levels of nutrition-related serum factors such as acylated (active form) and desacyl (inactive form) ghrelin, leptin, growth hormone, insulin-like growth factor, and neuropeptide Y (NPY) were measured at weeks 0, 2, 4, and 6 of the treatment protocol.. Significantly higher ghrelin activation was found in the 'MCT high' than in the 'MCT low' group (P < 0.05). The amount of consumed MCT had a curvilinear relationship with the active ghrelin level (P = 0.00). NPY levels in the 'MCT high' group were significantly more elevated than in the 'MCT low' group (P < 0.05). MCT administration did not significantly affect the remaining factors.. This study clearly demonstrated that MCT activates ghrelin and increases NPY, suggesting that nutritional supplementation with MCT may be effective for the treatment of AN patients in an emaciated state.

Topics: Adolescent; Adult; Anorexia Nervosa; Biomarkers; Body Composition; Enteral Nutrition; Female; Ghrelin; Humans; Japan; Neuropeptide Y; Nutrition Assessment; Time Factors; Treatment Outcome; Triglycerides; Up-Regulation; Weight Gain; Young Adult

Neuropeptide Y (NPY) and peptide YY (PYY) are involved in metabolic regulation. The purpose of the study was to assess the serum levels of NPY and PYY in adolescents with anorexia nervosa (AN) or obesity (OB), as well as in a healthy control group (CG). The effects of potential confounders on their concentrations were also analysed. Eighty-nine adolescents were included in this study (AN = 30, OB = 30, and CG = 29). Anthropometric measurements and psychometric assessment of depressive symptoms, eating behaviours, body attitudes, and fasting serum levels of NPY and PYY were analysed. The AN group presented severe depressive symptoms, while the OB group held different attitudes towards the body. The levels of NPY were lower in the AN and OB groups as compared with the CG. The PYY levels were higher in the OB group than in the AN group and the CG. The severity of eating disorder symptoms predicted fasting serum concentrations of NPY. Lower levels of NPY in AN, as well as in OB suggests the need to look for a common link in the mechanism of this effect. Higher level of PYY in OB may be important in explaining complex etiopathogenesis of the disease. The psychopathological symptoms may have an influence on the neurohormones regulating metabolism.

Topics: Adolescent; Anorexia Nervosa; Blood Glucose; Body Mass Index; Child; Depression; Fasting; Feeding Behavior; Female; Humans; Insulin; Male; Neuropeptide Y; Obesity; Peptide YY

Anorexia nervosa (AN) presents an adaptive appetite regulating profile including high levels of ghrelin and 26RFa (orexigenic) and low levels of leptin and PYY (anorexigenic). However, this adaptive mechanism is not effective in promoting food intake. The NPY/proopiomelanocortin (POMC) system plays a crucial role in the regulation of feeding behavior as NPY is the most potent orexigenic neuropeptide identified so far and as the POMC-derived peptide α-MSH drastically reduces food intake, and this peptidergic system has not been thoroughly studied in AN.. The aim of the present study was thus to investigate whether a dysfunction of the NPY/POMC occurs in two populations with low body weight, AN and constitutional thinness (CT).. This was a cross-sectional study performed in an endocrinological unit and in an academic laboratory.. Three groups of age-matched young women were studied: 23 with AN (AN), 22 CT and 14 normal weight controls.. Twelve-point circadian profiles of plasma NPY and α-MSH levels were measured in the three groups of investigated subjects.. No significant circadian variation of NPY was detected between the three groups. Plasma α-MSH levels were significantly lower in AN (vs controls) all over the day. The CT group, compared to controls, presented lower levels of α-MSH in the morning and the evening, and an important rise during lunchtime.. In AN patients, the NPY system is not up-regulated under chronic undernutrition suggesting that this may play a role in the inability of anorectic women to adapt food intake to their energy demand. In contrast, low circadian α-MSH levels integrate the adaptive profile of appetite regulation of this disease. Finally, in CT women, the important α-MSH peak detected during lunchtime could explain why these patients are rapidly food satisfied.

Topics: Adolescent; Adult; alpha-MSH; Anorexia Nervosa; Body Composition; Body Mass Index; Body Weight; Circadian Rhythm; Cross-Sectional Studies; Female; Hormones; Humans; Neuropeptide Y; Thinness; Young Adult

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

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

Peptides ghrelin, obestatin and neuropeptide Y (NPY) play an important role in regulation of energy homeostasis, the imbalance of which is associated with eating disorders anorexia (AN) and bulimia nervosa (BN). The changes in ghrelin, obestatin and NPY plasma levels were investigated in AN and BN patients after administration of a high-carbohydrate breakfast (1604 kJ). Eight AN women (aged 25.4+/-1.9, BMI: 15.8+/-0.5), thirteen BN women (aged 22.0+/-1.05, BMI: 20.1+/-0.41) and eleven healthy women (aged 25.1+/-1.16, BMI: 20.9+/-0.40) were recruited for the study. We demonstrated increased fasting ghrelin in AN, but not in BN patients, while fasting obestatin and NPY were increased in both AN and BN patients compared to the controls. Administration of high-carbohydrate breakfast induced a similar relative decrease in ghrelin and obestatin plasma levels in all groups, while NPY remained increased in postprandial period in both patient groups. Ghrelin/obestatin ratio was lower in AN and BN compared to the controls. In conclusions, increased plasma levels of fasting NPY and its unchanged levels after breakfast indicate that NPY is an important marker of eating disorders AN and BN. Different fasting ghrelin and obestatin levels in AN and BN could demonstrate their diverse functions in appetite and eating suppression.

Topics: Anorexia Nervosa; Body Composition; Body Mass Index; Bulimia Nervosa; Dietary Carbohydrates; Eating; Female; Ghrelin; Humans; Neuropeptide Y; Postprandial Period

Genetic factors likely contribute to the biological vulnerability of eating disorders.. Case-control association study on one neuropeptide Y gene (Leu7Pro) polymorphism and three ghrelin gene (Arg51Gln, Leu72Met and Gln90Leu) polymorphisms.. 114 eating disorder patients (46 with anorexia nervosa, 30 with bulimia nervosa, 38 with binge eating disorder) and 164 healthy controls were genotyped.. No differences were detected between patients and controls for any of the four polymorphisms in allele frequency and genotype distribution (P > 0.05). Allele frequencies and genotypes had no significant influence on body mass index (P > 0.05) in eating disorder patients.. Positive findings of former case-control studies of associations between ghrelin gene polymorphisms and eating disorders could not be replicated. Neuropeptide Y gene polymorphisms have not been investigated in eating disorders before.

Topics: Adolescent; Adult; Anorexia Nervosa; Binge-Eating Disorder; Body Mass Index; Bulimia Nervosa; Case-Control Studies; Feeding and Eating Disorders; Female; Gene Frequency; Genetic Association Studies; Genotype; Ghrelin; Humans; Male; Middle Aged; Neuropeptide Y; Polymorphism, Single Nucleotide; Young Adult

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

The hypothesis that treatment with neuropeptide Y (NPY) can increase running activity and decrease food intake and body weight was tested. Female rats with a running wheel lost more weight than sedentary rats and ran progressively more as the availability of food was gradually reduced. When food was available for only 1h/day, the rats lost control over body weight. Correlatively, the level of NPY mRNA was increased in the hypothalamic arcuate nucleus. This phenomenon, activity-based-anorexia, was enhanced by intracerebroventricular infusion of NPY in rats which had food available during 2h/day. By contrast, NPY stimulated food intake but not wheel running in rats which had food available continuously. These findings are inconsistent with the prevailing theory of the role of the hypothalamus in the regulation of body weight according to which food intake is a homeostatic process controlled by "orexigenic" and "anorexigenic" neural networks. However, the finding that treatment with NPY, generally considered an "orexigen", can increase physical activity and decrease food intake and cause a loss of body weight is in line with the clinical observation that patients with anorexia nervosa are physically hyperactive and eat only little food despite having depleted body fat and up-regulated hypothalamic "orexigenic" peptides.

Topics: Adaptation, Physiological; Animals; Anorexia Nervosa; Appetite Regulation; Arcuate Nucleus of Hypothalamus; Body Weight; Disease Models, Animal; Eating; Female; Motor Activity; Neuropeptide Y; Rats; Rats, Wistar; RNA, Messenger

Topics: Adolescent; Anorexia Nervosa; Feeding Behavior; Female; Humans; Neuropeptide Y; Peptide YY; Weight Loss

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

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

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

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

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

Disturbances of leptin, neuropeptide Y (NPY), and peptide YY (PYY) have been found in women who are ill with anorexia or bulimia nervosa. It is not certain whether peptide disturbances are cause or consequence of eating disorders.. Plasma leptin and cerebrospinal fluid leptin, NPY, and PYY concentrations were measured in women who were recovered from anorexia or bulimia nervosa to determine whether alterations persisted after recovery.. NPY, PYY, and leptin concentrations were similar across all diagnostic groups.. Alterations in NPY, PYY, and serum leptin concentrations are probably secondary to pathological eating behaviors. Alterations of these peptides are unlikely to be trait-related disturbances that contribute to the etiology of eating disorders.

Topics: Adipose Tissue; Adult; Anorexia Nervosa; Body Image; Body Mass Index; Bulimia; Convalescence; Female; Humans; Neuropeptide Y; Peptide YY; Proteins; Severity of Illness Index; Spinal Puncture

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

Studies were performed to determine the effects of intracerebroventricular norepinephrine (NE) or neuropeptide Y (NPY) on the ovine hypothalamic-pituitary-adrenal (HPA) axis. NE (50 micrograms) increased mean hypophysial-portal corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) levels (1 h, 1.3- and 2.9-fold; 4 h, 2.2- and 5.7-fold) and caused acute and sustained increases in mean plasma ACTH and cortisol. NPY (50 microgram) also increased mean CRF and AVP levels (1 h, 1.4- and 4.2-fold; 4 h, 1.1- and 1.9-fold), increased pituitary-adrenal activity at 1 h, and caused ACTH hypersecretion at 4 h. When added to cultured ovine anterior pituitary cells, NPY neither increased basal ACTH release nor augmented CRF- or AVP-induced ACTH release. We conclude that: (a) activation of either the central noradrenergic or NPY pathways causes an acute and sustained stimulation of the ovine HPA axis; (b) such activation increases the AVP/CRF ratio, suggesting a dominant role for AVP in the ovine stress response; and (c) the central noradrenergic or NPY systems may cause sustained HPA activation by attenuating or disrupting the glucocorticoid negative feedback on those brain areas concerned with regulation of the HPA axis. The possible roles of the central noradrenergic and NPY systems in the etiology of the hypercortisolemia of endogenous depression and anorexia nervosa are discussed.

Topics: Animals; Anorexia Nervosa; Arginine Vasopressin; Corticotropin-Releasing Hormone; Cushing Syndrome; Depression; Female; Hypothalamo-Hypophyseal System; Neuropeptide Y; Norepinephrine; Pituitary-Adrenal System; Sheep; Sodium Chloride

The related central nervous system peptides neuropeptide Y and peptide YY have been found to be among the most potent endogenous stimulants of feeding behavior. We measured these neuropeptides in cerebrospinal fluid to determine whether they contributed to the pathophysiologic characteristics of anorexia and bulimia nervosa. Cerebrospinal fluid neuropeptide Y concentrations were significantly elevated in underweight anorectic patients and in many of the anorectic patients studied at intervals after weight restoration. These levels normalized in long-term weight-restored anorectic patients who had a return of normal menstrual cycles. Increased neuropeptide Y activity may contribute to several characteristic disturbances in anorexia, including menstrual dysregulation. Cerebrospinal fluid peptide YY concentrations were significantly elevated in normal-weight bulimic patients abstinent from pathological eating behavior for a month compared with themselves when actively bingeing and vomiting or compared with healthy volunteers. Increased peptide YY activity may contribute to a drive to overfeed in normal-weight bulimic patients.

Topics: Adult; Anorexia Nervosa; Body Weight; Bulimia; Drive; Eating; Female; Gastrointestinal Hormones; Humans; Menstrual Cycle; Neuropeptide Y; Peptide YY; Peptides