Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) conjugated with a ribosomal inactivating toxin, saporin (SAP), is a toxin that targets NPY receptor-expressing cells. Injection of NPY-SAP into the rat arcuate nucleus (Arc) and basomedial hypothalamus (BMH) destroys two populations of NPY-receptor-expressing neurons important for the control of food intake and body weight, NPY and pro-opiomelanocortin (POMC) and cocaine and amphetamine related transcript (CART) neurons, and produces profound hyperphagia and obesity. Here, we investigated the contribution of lateral hypothalamus (LHA) orexigenic peptides, orexins and melanocortin concentrating hormone (MCH), to these lesion effects. We microinjected NPY-SAP into two sites on each side of the Arc, causing a loss of NPY and POMC/CART neurons that was limited to the Arc. Lesioned rats rapidly became hyperphagic and obese. However, MCH and prepro-orexin mRNA expression were not increased in the LHA in the lesioned rats, but were decreased at some levels of the LHA or were unchanged. NPY-SAP-induced obesity therefore differs from dietary obesity and from obesity associated with leptin or leptin receptor deficiency in which MCH gene expression is increased. The Arc NPY-SAP lesion produces obesity and hyperphagia that does not require overexpression of hypothalamic neuropeptides currently considered to provide major stimulatory drive for food intake: NPY, agouti gene-related protein, MCH or orexins. The source of the seemingly unregulated stimulatory drive for feeding in these animals has not been identified, but may be associated with hindbrain or endocrine mechanisms.
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PMID:Hyperphagia and obesity produced by arcuate injection of NPY-saporin do not require upregulation of lateral hypothalamic orexigenic peptide genes. 1857 7

We investigated the role of neuropeptide Y Y(1) receptors in acute, chronic and withdrawal effects of nicotine with reference to feeding behavior. Rats were administered with nicotine, neuropeptide Y, neuropeptide Y Y(1) receptor agonist [Leu(31),Pro(34)]neuropeptide Y or antagonist BIBP3226 (N(2)-diphenylacetyl)-N-[(4-hydroxy-phenyl)-methyl]-D-arginine amide) via i.c.v. route, and food intake was measured at 2 and 6 h post-injection time-points. While acute nicotine or BIBP3226 reduced food intake, increase was observed following neuropeptide Y or [Leu(31),Pro(34)]neuropeptide Y. Nicotine-induced anorexia was antagonized by pre-treatment with neuropeptide Y or [Leu(31),Pro(34)]neuropeptide Y, and potentiated by BIBP3226. Furthermore, effects of chronic nicotine (i.p.) and its withdrawal, alone and in combination with BIBP3226 were evaluated with reference to feeding and body weight. Concurrent administration of BIBP3226 with nicotine prevented the development of tolerance to nicotine-induced anorexia, and withdrawal hyperphagia and weight gain. Moreover, acute BIBP3226 attenuated the hyperphagia following nicotine termination. Additionally, immunocytochemical profile of neuropeptide Y in the hypothalamus was studied following differential nicotine treatments. Acute nicotine treatment dramatically reduced neuropeptide Y immunoreactivity in the arcuate and paraventricular nuclei. Chronic nicotine administration decreased neuropeptide Y immunoreactivity in arcuate, but not in paraventricular nucleus. Nicotine withdrawal resulted in significant increase in the neuropeptide Y immunoreactivity in both the nuclei. Neuropeptide Y immunoreactivity in the lateral hypothalamus did not change following any of the treatments. The results suggest that neuropeptide Y in the arcuate and paraventricular nuclei of hypothalamus may be involved in acute, chronic and withdrawal effects of nicotine on the feeding behavior, possibly via neuropeptide Y Y(1) receptors.
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PMID:Involvement of neuropeptide Y Y(1) receptors in the acute, chronic and withdrawal effects of nicotine on feeding and body weight in rats. 1928 64

Neuropeptide Y (NPY) Y1 receptors are implicated in CNS regulation of food intake, but their role in hypoglycemic hyperphagia remains unclear. The present studies utilized a pharmacological approach to investigate the hypothesis that NPY acts via Y1 receptor-dependent mechanisms to regulate feeding and blood glucose profiles during intermediate insulin-induced hypoglycemia. Groups of ovariectomized, estradiol benzoate-treated female rats were injected subcutaneously with one or four doses of neutral protamine Hagedorn insulin (NPH), on as many days, or with diluent alone. Before final treatments on day four, the animals were pretreated by intracerebroventricular (icv) delivery of the NPY Y1 receptor antagonist, 1229U91, or the vehicle, artificial cerebrospinal fluid (acsf). Food intake during acute hypoglycemia was significantly diminished between t(o) and +2 h in animals pretreated with the Y1 receptor antagonist versus vehicle. Administration of 1229U91 prior to the fourth of four NPH doses suppressed hypoglycemic hyperphagia over a relatively longer interval, e.g. 4 h, after t(o) relative to the acute insulin group. Blood glucose levels after a single NPH injection were similar in acsf- and antagonist-pretreated rats at +2, +4, and +6 h, but were lower at +9 h in the latter group. Pretreatment with 1229U91 did not modify glucose profiles between +2 and +9 h after multiple dosing with NPH, but prevented recovery from hypoglycemia at +12 h. The present results show that central NPY Y1 receptor antagonism inhibits hypoglycemic hyperphagia, and that this suppressive effect on feeding was of greater duration during recurring hypoglycemia. The data also show that Y1 receptor blockade decreases glycemic responses to both single and serial NPH dosing, albeit at different post-injection time points. The current studies support the view that NPY Y1 receptors function within central neural pathways that govern feeding and glycemic responses to intermediate-acting insulin, and that Y1 receptor-mediated stimulation of food intake may habituate in a positive manner to repetitive insulin-induced hypoglycemia. Further research is needed to evaluate the impact of chronic insulin-induced hypoglycemia on neuropeptide Y neurotransmission and Y1 receptor expression within regulatory circuitries that control food intake and glucostasis.
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PMID:Effects of intracerebroventricular administration of the NPY-Y1 receptor antagonist, 1229U91, on hyperphagic and glycemic responses to acute and chronic intermediate insulin-induced hypoglycemia in female rats. 1961 44

The Dorsomedial Nucleus of the Hypothalamus (DMH) is known to play important roles in ingestive behavior and body weight homeostasis. The DMH contains neurons expressing Neuropeptide Y (NPY) during specific physiological conditions of hyperphagia and obesity, however, the role of DMH-NPY neurons has yet to be characterized. In contrast to the DMH-NPY neurons, NPY expressing neurons have been best characterized in the Arcuate Nucleus of the Hypothalamus (ARH). The purpose of this study is to characterize the chemical phenotype of DMH-NPY neurons by comparing the gene expression profiles of NPY neurons in the DMH and ARH isolated from postnatal NPY-hrGFP mice by microarray analysis. Twenty genes were differentially expressed in the DMH-NPY neurons compared to the ARH. Among them, there were several transcriptional factors that play important roles in the regulation of energy balance. DMH-NPY neurons expressed Glutamic Acid Decarboxylase (GAD) 65 and 67, suggesting that they may be GABAergic, similar to ARH-NPY neurons. While ARH-NPY neurons expressed leptin receptor (ObRb) and displayed the activation of STAT3 in response to leptin administration, DMH-NPY neurons showed neither. These findings strongly suggest that DMH-NPY neurons could play a distinct role in the control of energy homeostasis and are differentially regulated from ARH-NPY neurons through afferent inputs and transcriptional regulators.
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PMID:Differential gene expression between neuropeptide Y expressing neurons of the dorsomedial nucleus of the hypothalamus and the arcuate nucleus: microarray analysis study. 2038 Aug 14

Neuropeptide Y (NPY) and agouti-related peptide (AGRP) can produce hyperphagia, reduce energy expenditure, and promote triglyceride deposition in adipose depots. As these two neuropeptides are coexpressed within the hypothalamic arcuate nucleus and mediate a major portion of the obesity caused by leptin signaling deficiency, we sought to determine whether the two neuropeptides mediated identical or complementary actions. Because of separate neuropeptide receptors and signal transduction mechanisms, there is a possibility of distinct encoding systems for the feeding and energy expenditure aspects of leptin-regulated metabolism. We have genetically added NPY deficiency and/or AGRP deficiency to LEPR deficiency isolated to AGRP cells. Our results indicate that the obesity of LEPR deficiency in AGRP/NPY neurons can produce obesity with either AGRP or NPY alone with AGRP producing hyperphagia while NPY promotes reduced energy expenditure. The absence of both NPY and AGRP prevents the development of obesity attributable to isolated LEPR deficiency in AGRP/NPY neurons. Operant behavioral testing indicated that there were no alterations in the reward for a food pellet from the AGRP-specific LEPR deficiency.
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PMID:Neuropeptide Y and agouti-related peptide mediate complementary functions of hyperphagia and reduced energy expenditure in leptin receptor deficiency. 2128 24

The genetically obese Zucker rat is a well characterized model of early onset human obesity. Many of the endocrine and metabolic abnormalities of obese animals are common to other strains of genetically obese animals as well as morbidly obese humans. Neuropeptide Y (NPY), a potent orexigenic agent, was recently found to be elevated in adult obese animals compared to their lean littermates. In this study we first examined hypothalamic expression of preproNPY mRNA, using solution hybridization/ nuclease protection analysis, in phenotypically-matched, i.e. lean or obese, immature (5-week-old) and mature (33-week-old) animals. Although changes were not statistically different, a trend toward decreased hypothalamic preproNPY mRNA levels was detected in both lean and obese mature animals. We next compared hypothalamic preproNPY mRNA levels between age-matched lean and obese animals at 5, 14 and 33 weeks of age and found elevated preproNPY mRNA levels in obese rats at all three ages. These data suggest that increased levels of hypothalamic NPY are an early manifestation of the obese phenotype and may, therefore, contribute to hyperphagia and increased weight gain in obese Zucker rats.
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PMID:Developmental aspect of differences in hypothalamic preproneuropeptide y messenger ribonucleic Acid content in lean and genetically obese zucker rats. 2155 17

Many animals hoard food, including humans, but despite its pervasiveness, little is known about the physiological mechanisms underlying this appetitive behavior. We summarize studies of food hoarding in humans and rodents with an emphasis on mechanistic laboratory studies of species where this behavior importantly impacts their energy balance (hamsters), but include laboratory rat studies although their wild counterparts do not hoard food. The photoperiod and cold can affect food hoarding, but food availability is the most significant environmental factor affecting food hoarding. Food-deprived/restricted hamsters and humans exhibit large increases in food hoarding compared with their fed counterparts, both doing so without overeating. Some of the peripheral and central peptides involved in food intake also affect food hoarding, although many have not been tested. Ad libitum-fed hamsters given systemic injections of ghrelin, the peripheral orexigenic hormone that increases with fasting, mimics food deprivation-induced increases in food hoarding. Neuropeptide Y or agouti-related protein, brain peptides stimulated by ghrelin, given centrally to ad libitum-fed hamsters, duplicates the early and prolonged postfood deprivation increases in food hoarding, whereas central melanocortin receptor agonism tends to inhibit food deprivation and ghrelin stimulation of hoarding. Central or peripheral leptin injection or peripheral cholecystokinin-33, known satiety peptides, inhibit food hoarding. Food hoarding markedly increases with pregnancy and lactation. Because fasted and/or obese humans hoard more food in general, and more high-density/high-fat foods specifically, than nonfasted and/or nonobese humans, understanding the mechanisms underlying food hoarding could provide another target for behavioral/pharmacological approaches to curb obesity.
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PMID:Neural and hormonal control of food hoarding. 2165 77

Neuropeptide Y (NPY) produced by arcuate nucleus (ARC) neurons has a strong orexigenic effect on target neurons. Hypothalamic NPY levels undergo wide-ranging oscillations during the circadian cycle and in response to fasting and peripheral hormones (from 0.25 to 10-fold change). The aim of the present study was to evaluate the impact of a moderate long-term modulation of NPY within the ARC neurons on food consumption, body weight gain and hypothalamic neuropeptides. We achieved a physiological overexpression (3.6-fold increase) and down-regulation (0.5-fold decrease) of NPY in the rat ARC by injection of AAV vectors expressing NPY and synthetic microRNA that target the NPY, respectively. Our work shows that a moderate overexpression of NPY was sufficient to induce diurnal over-feeding, sustained body weight gain and severe obesity in adult rats. Additionally, the circulating levels of leptin were elevated but the immunoreactivity (ir) of ARC neuropeptides was not in accordance (POMC-ir was unchanged and AGRP-ir increased), suggesting a disruption in the ability of ARC neurons to response to peripheral metabolic alterations. Furthermore, a dysfunction in adipocytes phenotype was observed in these obese rats. In addition, moderate down-regulation of NPY did not affect basal feeding or normal body weight gain but the response to food deprivation was compromised since fasting-induced hyperphagia was inhibited and fasting-induced decrease in locomotor activity was absent.These results highlight the importance of the physiological ARC NPY levels oscillations on feeding regulation, fasting response and body weight preservation, and are important for the design of therapeutic interventions for obesity that include the NPY.
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PMID:Moderate long-term modulation of neuropeptide Y in hypothalamic arcuate nucleus induces energy balance alterations in adult rats. 2179 27

Neuropeptide Y (NPY) acting in the hypothalamus is one of the most powerful orexigenic agents known. Of the five known Y receptors, hypothalamic Y1 and Y5 have been most strongly implicated in mediating hyperphagic effects. However, knockout of individual Y1 or Y5 receptors induces late-onset obesity--and Y5 receptor knockout also induces hyperphagia, possibly due to redundancy in functions of these genes. Here we show that food intake in mice requires the combined actions of both Y1 and Y5 receptors. Germline Y1Y5 ablation in Y1Y5(-/-) mice results in hypophagia, an effect that is at least partially mediated by the hypothalamus, since mice with adult-onset Y1Y5 receptor dual ablation targeted to the paraventricular nucleus (PVN) of the hypothalamus (Y1Y5(Hyp/Hyp)) also exhibit reduced spontaneous or fasting-induced food intake when fed a high fat diet. Interestingly, despite hypophagia, mice with germline or hypothalamus-specific Y1Y5 deficiency exhibited increased body weight and/or increased adiposity, possibly due to compensatory responses to gene deletion, such as the decreased energy expenditure observed in male Y1Y5(-/-) animals relative to wildtype values. While Y1 and Y5 receptors expressed in other hypothalamic areas besides the PVN--such as the dorsomedial nucleus and the ventromedial hypothalamus--cannot be excluded from having a role in the regulation of food intake, these studies demonstrate the pivotal, combined role of both Y1 and Y5 receptors in the mediation of food intake.
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PMID:Y1 and Y5 receptors are both required for the regulation of food intake and energy homeostasis in mice. 2276 53

Neuropeptide Y (NPY) is a potent hypothalamic orexigenic peptide. Within the hypothalamus, Npy is primarily expressed in the arcuate nucleus (ARC) and the dorsomedial hypothalamus (DMH). While the actions of ARC NPY in energy balance control have been well studied, a role for DMH NPY is still being unraveled. In contrast to ARC NPY that serves as one of downstream mediators of actions of leptin in maintaining energy homeostasis, DMH NPY is not under the control of leptin. Npy gene expression in the DMH is regulated by brain cholecystokinin (CCK) and other yet to be identified molecules. The findings of DMH NPY overexpression or induction in animals with increased energy demands and in certain rodent models of obesity implicate a role for DMH NPY in maintaining energy homeostasis. In support of this view, adeno-associated virus (AAV)-mediated overexpression of NPY in the DMH causes increases in food intake and body weight and exacerbates high-fat diet-induced hyperphagia and obesity. Knockdown of NPY in the DMH via AAV-mediated RNAi ameliorates hyperphagia, obesity and glucose intolerance of Otsuka Long-Evans Tokushima Fatty rats in which DMH NPY overexpression has been proposed to play a causal role. NPY knockdown in the DMH also prevents high-fat diet-induced hyperphagia, obesity and impaired glucose homeostasis. A detailed examination of actions of DMH NPY reveals that DMH NPY specifically affects nocturnal meal size and produces an inhibitory action on within meal satiety signals. In addition, DMH NPY modulates energy expenditure likely through affecting brown adipocyte formation and thermogenic activity. Overall, the recent findings provide clear evidence demonstrating critical roles for DMH NPY in energy balance control, and also imply a potential role for DMH NPY in maintaining glucose homeostasis.
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PMID:Dorsomedial hypothalamic NPY and energy balance control. 2308 63


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