neuropeptide-y and Feeding-and-Eating-Disorders

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

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

The 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

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

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

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

Neuropeptide Y is the most potent physiological appetite transducer known. The NPY network is the conductor of the hypothalamic appetite regulating orchestra in the arcuate nucleus-paraventricular nucleus (ARC-PVN) of the hypothalamus. NPY and cohorts, AgrP, GABA and adrenergic transmitters, initiate appetitive drive directly through Y1, Y5, GABAA and alpha1 receptors, co-expressed in the magnocellular PVN (mPVN) and ARC neurons and by simultaneously repressing anorexigenic melanocortin signaling in the ARC-PVN axis. The circadian and ultradian rhythmicities in NPY secretion imprint the daily circadian and episodic feeding patterns. Although a number of afferent hormonal signals from the periphery can directly modulate NPYergic signaling, the reciprocal circadian and ultradian rhythmicities of anorexigenic leptin from adipocytes and orexigenic ghrelin from stomach, encode a corresponding pattern of NPY discharge for daily meal patterning. Subtle and progressive derangements produced by environmental and genetic factors in this exquisitely intricate temporal relationship between the two opposing humoral signals and the NPY network promote hyperphagia and abnormal rate of weight gain culminating in obesity and attendant metabolic disorders. Newer insights at cellular and molecular levels demonstrate that a breakdown of the integrated circuit due both to high and low abundance of NPY at target sites, underlies hyperphagia and increased adiposity. Consequently, interruption of NPYergic signaling at a single locus with NPY receptor antagonists may not be the most efficacious therapy to suppress hyperphagia and obesity. Central leptin gene therapy in rodents has been shown to subjugate, i.e. bring under homeostatic control, NPYergic signaling and suppress the age-related and dietary obesity for extended periods and thus shows promise as a newer treatment modality to curb the pandemic of obesity and metabolic syndrome.

Topics: Animals; Appetite; Arcuate Nucleus of Hypothalamus; Circadian Rhythm; Feeding and Eating Disorders; Genetic Therapy; Metabolic Syndrome; Neuropeptide Y; Obesity; Paraventricular Hypothalamic Nucleus; Receptors, Neuropeptide Y; Signal Transduction

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

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

Neuropeptide Y (NPY), a 36-amino-acid neuropeptide is the most potent physiological appetite transducer known. Episodic NPY neurosecretion in hypothalamic target sites is temporally linked with onset of the daily feeding pattern. Upregulation of NPY signaling in the arcuate nucleus-paraventricular nucleus (ARC-PVN) neural axis is responsible for the hyperphagia evoked by dieting, fasting, hormonal and genetic factors, and disruption in intrahypothalamic signaling. Clusters of NPY-producing neurons in the ARC that coexpress gamma- amino butyric acid and agouti-related peptide, and those in the brain stem (BS) that coexpress catecholamines and galanin, participate in disparate manners to regulate appetitive behavior. NPY receptors, Y1, Y2, and Y5, expressed by various components of the NPY network, mediate NPY-induced feeding. Imbalance in NPY signaling due either to high or low abundance of NPY at target sites elicits hyperphagia leading to increased fat accretion and obesity. Recent studies show that intermittent, feedback action of opposing afferent hormonal signals-leptin from adipose tissue and ghrelin from stomach-regulate the episodic secretion of orexigenic NPY in the PVN-ARC. Apparently, the hypothalamic NPY network is the primary common pathway intimately involved in genesis of appetite- stimulating impulses.

Topics: Animals; Appetite; Appetite Stimulants; Feeding and Eating Disorders; Humans; Neuropeptide Y; Obesity

Neuropeptide Y (NPY) family of hormones exhibits a wide spectrum of central and peripheral activities mediated by six G-protein coupled receptor subtypes denoted as Y1, Y2, Y3, Y4, Y5, and y6. Investigations to date have implicated NPY in the pathophysiology of a number of diseases including feeding disorders, seizures, anxiety, diabetes, hypertension, congestive heart failure and intestinal disorders. These observations suggest that long-acting, potent NPY receptor selective agonists and antagonists developed could be used to treat a variety of diseases. These possibilities are discussed in this paper.

Topics: Feeding and Eating Disorders; Heart Failure; Humans; Malabsorption Syndromes; Neuropeptide Y; Receptors, Neuropeptide Y; Seizures

Topics: Animals; Appetite; Energy Metabolism; Feeding and Eating Disorders; Feeding Behavior; Humans; Neuropeptide Y

Topics: Animals; Biogenic Monoamines; Epinephrine; Feeding and Eating Disorders; Feeding Behavior; Galanin; Humans; Hypothalamus; Neuropeptide Y; Neuropeptides; Norepinephrine; Peptides; Rats

A number of common pathological features have been observed in obsessive‑compulsive disorder (OCD) and eating disorders (EDs). The present study examined the association between OCD and EDs at the genetic level in order to gain an improved understanding of the shared genetic basis of the diseases and identify novel potential risk genes for the two diseases. An integrated analysis using large‑scale disease‑gene association data and gene expression data was conducted. Disease‑gene association data were acquired from the Pathway Studio Mammalian database. Gene expression data were acquired from samples of 133 subjects, including 15 ED cases, 16 OCD cases and 102 normal controls. Genes associated with OCD and ED presented significant overlap (21 genes, P=6.70x10‑34), serving roles within multiple common genetic pathways (top 10 pathway enrichment P<4.30x10‑7) that were implicated in the two diseases. A genetic network of 17 genes was constructed, through which OCD and ED were observed to influence each other. Expression analysis revealed four novel common significant genes for OCD and ED (oxytocin receptor, glutamate decarboxylase 2, neuropeptide Y and glutamate ionotropic receptor kainate type subunit 3). These genes demonstrated a strong functional association with the two diseases. The results of the present study supported the presence of complex genetic associations between OCD and ED. Genes associated with one disease are worthy of further investigation as potential risk factors for the other. The findings of the present study may provide novel insights into the understanding of the pathogenesis of OCD and ED.

Topics: Feeding and Eating Disorders; Gene Expression; Gene Regulatory Networks; Genetic Association Studies; Genetic Predisposition to Disease; Glutamate Decarboxylase; Humans; Neuropeptide Y; Obsessive-Compulsive Disorder; Receptors, Oxytocin

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

Amphetamine (AMPH) releases monoamines, transiently stimulates locomotion, and inhibits feeding. Using a genetic approach, we show that mice lacking dopamine (DA-deficient, or DD, mice) are resistant to the hypophagic effects of a moderate dose of AMPH (2 microg/g) but manifest normal AMPH-induced hypophagia after restoration of DA signaling in the caudate putamen by viral gene therapy. By contrast, AMPH-induced hypophagia in response to the same dose of AMPH is not blunted in mice lacking the ability to make norepinephrine and epinephrine (Dbh(-/-)), dopamine D(2) receptors (D2r(-/-)), dopamine D(1) receptors (D1r(-/-)), serotonin 2C receptors (Htr2c(-/Y)), neuropeptide Y (Npy(-/-)), and in mice with compromised melanocortin signaling (A(y)). We suggest that, at this moderate dose of AMPH, dysregulation of striatal DA is the primary cause of AMPH-induced hypophagia and that regulated striatal dopaminergic signaling may be necessary for normal feeding behaviors.

Topics: Amphetamine; Analysis of Variance; Animals; Behavior, Animal; Corpus Striatum; Dopamine; Dopamine beta-Hydroxylase; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Eating; Feeding and Eating Disorders; Feeding Behavior; Genetic Therapy; Hunger; Levodopa; Locomotion; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuropeptide Y; Receptor, Serotonin, 5-HT2C; Receptors, Dopamine D1; Receptors, Dopamine D2; Time Factors; Tyrosine 3-Monooxygenase