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)

An enhanced production of hypothalamic neuropeptide Y (NPY) now appears to underlie a number of hyperphagia syndromes. However, the role of NPY in the hyperphagia induced by hypothalamic lesions has not yet been explored. Here, hypothalamic lesions were induced in mice by administration of goldthioglucose (GTG) and brain sections were stained immunocytochemically for NPY without pretreatment with colchicine. NPY-immunoreactive somas were visible in the hypothalamus of only one of eight control mice but were identified in the hypothalami of six of seven mice with GTG lesions. This suggests that GTG lesions cause an enhanced production of NPY, perhaps due to interruption of fibers from arcuate dopaminergic neurons that normally inhibit NPY+ cells. Thus, hypothalamic lesions may provoke hyperphagia by stimulating the production of NPY.
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PMID:Hypothalamic lesions increase neuronal immunoreactivity for neuropeptide Y. 139 10

Untreated insulin-deficient diabetes causes hyperphagia and neuroendocrine disturbances that may be partly mediated by increased hypothalamic activity of neuropeptide Y (NPY), a potent central appetite stimulant. The metabolic signal that stimulates hypothalamic NPY is unknown. This study aimed to determine whether insulin deficiency or hyperglycemia was responsible. Regional hypothalamic NPY concentrations were compared in streptozocin-diabetic (STZ-D) rats rendered nearly normoglycemic by either insulin replacement or food restriction. Untreated STZ-D rats were hyperphagic and showed significantly increased (p less than 0.01) hypothalamic NPY concentrations in the arcuate nucleus and lateral hypothalamic area. Once-daily ultralente insulin injections corrected hypoinsulinemia and hyperglycemia, abolished hyperphagia, and normalized NPY concentrations in all hypothalamic regions. By contrast, food restriction effectively lowered glycemia without raising insulin levels. In these underfed diabetic rats, NPY concentrations rose further and were significantly higher than nondiabetic and untreated diabetic levels in most hypothalamic regions. We conclude that insulin deficiency is a major stimulus to hypothalamic NPY in STZ-D, whereas hyperglycemia may exert an inhibitory influence. These findings support the hypothesis that hypothalamic NPY responds to specific metabolic cues and is involved in regulating energy balance and conserving body weight.
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PMID:Insulin deficiency is a specific stimulus to hypothalamic neuropeptide Y: a comparison of the effects of insulin replacement and food restriction in streptozocin-diabetic rats. 143 14

We tested the hypothesis that the hyperphagia observed in streptozotocin (STZ)-induced diabetic rats is due to increased release of neuropeptide Y (NPY) in the paraventricular nucleus (PVN) of the hypothalamus. In the first experiment, male rats were injected with STZ or vehicle (control) via the tail vein and 18-20 days later, NPY levels in seven hypothalamic sites and release in vitro from selected hypothalamic sites were evaluated. The results showed that in association with STZ-produced marked hyperglycemia and hyperphagia, NPY concentrations were increased in four hypothalamic sites, including the PVN. Evaluation of NPY release in vitro showed that both basal and KCl-induced release was significantly higher from the micro-dissected PVN of STZ-treated than control rats. A similar augmentation in the NPY efflux in vitro was detected from the median eminence arcuate nucleus, but not from the neighboring ventromedial nucleus of STZ-treated rats. In the second experiment, rats were treated with STZ or vehicle and received permanent push-pull cannula (PPC) in the PVN for evaluation of NPY release in vivo 18-21 days after STZ treatment. The results showed that mean NPY levels in the perfusates collected from the PVN of diabetic rats were significantly higher as compared to control rats. Since NPY is the most potent naturally occurring orexigenic signal and the PVN is an important initial site of NPY action in the stimulatory pathway regulating feeding, our findings of augmented PVN NPY release in vivo and in vitro are in accord with the hypothesis that increased NPY secretion in the PVN may be responsible for hyperphagia in diabetic rats.
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PMID:Neuropeptide Y release from the paraventricular nucleus increases in association with hyperphagia in streptozotocin-induced diabetic rats. 144 35

Previous work has characterized an anorexic action for endogenous, central nervous system corticotropin-releasing factor (CRF). Central injection of CRF decreases food intake induced pharmacologically by various appetite stimulants and a CRF antagonist attenuates restraint stress anorexia. Also, stressful physiological stimuli that are relevant to ingestive regulation, such as glucoprivation and protein nutrient deficiency, activate CRF systems. The present experiments examined the effects of exogenously administered CRF and a CRF antagonist, alpha-helical CRF(9-41), on spontaneous feeding induced by neuropeptide Y (NPY) and by a tail-pinch stressor. Pretreatment with a low dose of the CRF antagonist (1 microgram ICV) enhanced the hyperphagia induced by NPY while reducing the latency to begin feeding and increasing the duration of eating during tail pinch. Higher doses of alpha-hel CRF (5 and 25 micrograms ICV) exhibited diminishing or opposite effects. In contrast, CRF pretreatment (0.02, 0.1, and 0.5 microgram ICV) blocked the acquisition of tail-pinch feeding. Hence, while CRF administration impairs intake in these and other feeding paradigms, alpha-hel CRF actually facilitated dose dependently the intensity of the feeding response to NPY and tail pinch. These results suggest that endogenous CRF systems may play a role in modulating excessive feeding under conditions of evoked appetite and that brain CRF systems regulate feeding when excessive intake threatens to compromise the performance of other noningestive behaviors.
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PMID:Endogenous corticotropin-releasing factor modulates feeding induced by neuropeptide Y or a tail-pinch stressor. 148 May 13

Regional hypothalamic neuropeptide Y (NPY) concentrations were compared between cp/cp JCR:LA corpulent rats, which were grossly obese, hyperphagic, and hyperinsulinemic, and lean (+/+) controls. In freely fed cp/cp rats, NPY levels in the arcuate nucleus (ARC) were 31% higher than in lean rats (p less than 0.001). In lean rats, chronic food restriction significantly raised NPY levels by 22% in the ARC (p less than 0.05) and by 44% in the dorsomedial nucleus (DMH; p less than 0.05). By contrast, food-restricted cp/cp rats showed no change in the ARC, but NPY levels rose in the DMH (by 36%; p less than 0.05) and ventromedial nucleus (31%; p less than 0.05). Increased NPY levels in the ARC, the major site of hypothalamic NPY synthesis, suggests increased NPYergic activity in cp/cp rats; given the central actions of NPY, this could contribute to hyperphagia, obesity, and hyperinsulinemia in this syndrome. Abnormal NPY responses to food deprivation further suggest dysregulation of NPY in cp/cp rats.
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PMID:Hypothalamic neuropeptide Y disturbances in the obese (cp/cp) JCR:LA corpulent rat. 152 65

Elevated levels of immunoreactive hypothalamic neuropeptide Y have recently been reported both in streptozotocin-induced diabetic rats and in the spontaneously diabetic BB rat. We have measured the levels of neuropeptide Y encoding messenger ribonucleic acid (mRNA) in both of these rat models to determine whether an increase in neuropeptide Y gene expression is a contributory factor to the increases in hypothalamic neuropeptide Y immunoreactive peptide content. In the hypothalami of both the spontaneously diabetic BB/E and the streptozotocin-diabetic animals, neuropeptide Y mRNA showed significant elevations (to 204 +/- 13% (+/- SE) and 387 +/- 48% of control values, respectively, p less than 0.01 for both). Our results demonstrate that two models of insulin-deficient diabetes in the rat are associated with increased hypothalamic neuropeptide Y mRNA. Taken with the known effects of neuropeptide Y on food intake these results suggest that increased neuropeptide Y synthesis in the hypothalamus may be related to the hyperphagia seen in the diabetic condition.
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PMID:Increased hypothalamic neuropeptide Y messenger RNA levels in two rat models of diabetes. 155 14

Hyperphagia in the obese Zucker rat is characterized by the early modification of the dark/light (D/L) rhythm of food intake. This rhythm is mainly driven by the suprachiasmatic nucleus (SCN) and, more controversially, by the ventromedian nucleus (VMN). In the SCN of adult obese Zucker rat, the concentrations of neuropeptide Y (NPY), a potent stimulator of food intake, are increased whereas those of neurotensin (NT), an anorexigenic peptide, are decreased. However, nothing is actually known about the synchronicity of the dysregulation of the D/L rhythm and variations of these peptides. That is why we measured NPY and NT in the microdissected SCN and VMN of lean (n = 16) and obese (n = 15) Zucker rats before the occurrence of hyperphagia (day 16 of age) and a few days after weaning (day 30 of age) when the modifications are apparent. For NPY, there was a very significant effect of age (P less than 0.001) for both nuclei and a significant effect of genotype (P less than 0.02) for the SCN only. NPY concentrations increased between 16 and 30 days in both nuclei (+74% (SCN) and +70% (VMN) in the obese rat; +57% (SCN) and +67% (VMN) in the lean rat; P less than 0.001). NPY in the SCN was not different at 16 days of age between lean and obese rats but significantly increased at 30 days in the obese rat (22.6 +/- 1.2 vs. 18.6 +/- 1.5 ng/mg protein; P less than 0.05). NT was not detected in the SCN of either group at 16 days or at 30 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early modification of neuropeptide Y but not of neurotensin in the suprachiasmatic nucleus of the obese Zucker rat. 164 Nov 88

Increased hypothalamic neuropeptide Y levels have previously been demonstrated in several hypothalamic nuclei of the (fa/fa) Zucker rat. This study set out to characterise hypothalamic NPY receptors in both genotypres and to study the effect of exogenous NPY on feeding behavior in these rats. Spontaneous daytime food intake was raised in the obese rat (p less than 0.05). Total hypothalamic receptor density (Bmax) was reduced in the obese rat compared with the lean rat (by 56%, p less than 0.005), but affinity remained unaltered. The lowest dose of NPY tested (23.5 pmol) stimulated daytime feeding in lean rats after 1, 2 and 3 hours but was inaffective in the obese rat (p less than 0.05). At two higher doses (235 pmol and 2.35 nmol), NPY was equipotent in both genotypes over 1 and 2 hours but NPY-induced feeding was attenuated over 3 hours in the obese rat. These results suggest an overactive endogenous NPYergic system in the obese (fa/fa) rat which might contribute to hyperphagia and obesity in this strain.
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PMID:Hypothalamic neuropeptide Y receptor characteristics and NPY-induced feeding responses in lean and obese Zucker rats. 165 13

D-myo-Inositol-1,2,6-trisphosphate (PP56) is a novel experimental drug which is structurally related to the intracellular second messenger IP3. Among other pharmacological effects, PP56 has been shown to antagonize neuropeptide Y (NPY) induced vasoconstriction with a high degree of specificity. We examined the effects of i.c.v. PP56 on locomotor activity and food intake in rats, and on the hypoactivity and hyperphagia induced by NPY. In the open field, PP56 given alone increased locomotor activity by up to 85%. It did not prevent NPY induced hypoactivity to any extent. PP56 given alone did not affect food intake except for a small increase after the highest dose tested (200 nmol). When NPY was given after pretreatment with PP56, NPY induced hyperphagia was significantly reduced. A similar effect, however, was seen with regard to the hyperphagia produced by another orexigenic peptide, galanin. PP56 did not affect the binding of 125I-NPY to brain membranes in vitro, or to cells of two different neuroblastoma cell lines which selectively express NPY Y1 or Y2 receptors. In summary, PP56 acted as a locomotor stimulant per se. Only one of the two tested central effects of NPY could be antagonized by PP56, and then only partially and in a non-specific manner. The central effects of PP56 do not seem to be produced at the level of NPY receptors.
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PMID:Effects of intracerebroventricular D-myo-inositol-1,2,6-trisphosphate (PP56), a proposed neuropeptide Y (NPY) antagonist, on locomotor activity, food intake, central effects of NPY and NPY-receptor binding. 166 39

Central and lateral hypothalamic concentrations of 9 regulatory peptides implicated in the control of feeding behaviour were measured in corpulent (cp/cp) JCR:LA-cp rats which develop spontaneous obesity, hyperinsulinaemia and hyperlipidaemia, and in lean (+/?) controls. In female cp/cp rats, central hypothalamic levels of neuropeptide Y (NPY), neurotensin, somatostatin and substance P were significantly lower (p less than 0.02) than in lean female controls. Following food restriction with a 16% reduction in body weight, these differences were apparently reversed and there were also significant rises in the lateral hypothalamic concentrations of neurotensin and of galanin. The other 4 peptides examined (bombesin, calcitonin gene-related peptide, neuromedin B and vasoactive intestinal peptide) did not differ significantly between cp/cp and lean females, either fed freely or food-restricted. Male cp/cp rats showed no significant differences from lean males in central or lateral hypothalamic concentrations of any of the 9 peptides. NPY and galanin are powerful and specific central appetite stimulants, whereas neurotensin, substance P and somatostatin inhibit feeding when injected centrally. Disturbances in these putative appetite-regulating peptides may be involved in the hyperphagia and other hypothalamic abnormalities in this spontaneous obesity syndrome. The apparent absence of differences between the male corpulent and lean groups may relate to sexual dimorphism of the syndrome, which is more marked in the females.
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PMID:Hypothalamic regulatory peptide disturbances in the spontaneously obese JCR: LA-corpulent rat. 172 Mar 64


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