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)

A central dysregulation of several neuropeptides could be at the origin of the marked hyperphagia of the obese Zucker rat, a well-known animal model used for the study of obesity. Neuropeptide Y (NPY), which strongly stimulates food intake and increases early in life in obese rats, plays a major role in the development of this hyperphagia. The aim of our experiment was to measure the feeding responses of lean (n = 8) and obese (n = 17) male Zucker rats to several doses of exogenous NPY injected in the lateral brain ventricle. We analyzed the microstructure of the rats' feeding behavior with an automatic device for 8 h post-injection. NPY stimulated food intake both in the lean and obese rats in a dose-dependent manner (P < 0.001). However, the minimal effective dose was always 3-4 times greater in the obese rats than in the lean ones (range: 0.43-0.53 vs. 0.12-0.18 microgram/brain; P < 0.001). Meal size, meal duration and time spent eating significantly increased in the lean rats (P < 0.05 or less). The last two parameters also increased in the obese rats but with the highest dose (5 micrograms) only. The obese Zucker rats were therefore less sensitive to NPY than the lean ones, probably because of their already high endogenous NPY levels. The modifications in the eating behavior indicate that NPY could overcome the satiety signals.
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PMID:Increased threshold concentrations of neuropeptide Y for a stimulatory effect on food intake in obese Zucker rats--changes in the microstructure of the feeding behavior. 782 94

A central dysregulation of several neuropeptides could be at the origin of the marked hyperphagia of the obese Zucker rat, a well-known animal model used for the study of obesity. Neuropeptide Y (NPY), which stimulates food intake and increases early in life in obese rats, plays a major role in the development of this hyperphagia. The aim of our experiment was to test a proposed NPY antagonist namely PYX-2 in obese hyperphagic Zucker rats in order to know if it could be an interesting drug for limiting their food intakes. Four doses of PYX-2 (50-1000 pmol) were injected in a counterbalanced order in the lateral brain ventricles of 10 adult male Zucker rats. Food intake was recorded 0.5, 1, 2, 3, 6, and 23 h after PYX-2 injection and compared either to the rat's spontaneous food intake or to the food intake following injection of artificial CSF (vehicle) only. It was not modified by any dose of PYX-2 whatever the time considered (1 h after injection: 4.3 +/- 0.5 (1000 pmol) vs 4.6 +/- 0.8 (CSF) g; 23 h period: 27.0 +/- 1.9 (1000 pmol) vs 26.6 +/- 2.9 (CSF) g; N.S.). Thus, PYX-2, the putative NPY antagonist, totally failed to inhibit food intake in the obese rats. The absence of effect of PYX-2 on food intake can be explained by the structure of PYX-2, a modified 27-36 amino acid sequence that may not be recognized by the Y1-type NPY receptors which are involved in the regulation of feeding behavior.
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PMID:Putative neuropeptide Y antagonist failed to decrease overeating in obese Zucker rats. 789 51

Lactation is accompanied by hyperphagia and a reduction in brown adipose tissue (BAT) thermogenesis, which are unexplained. Neuropeptide Y (NPY) powerfully stimulates feeding and inhibits BAT thermogenesis when injected into the paraventricular nucleus and other specific regions of the rat hypothalamus. We have tested the hypothesis that hypothalamic NPY activity is increased in lactating rats. Lactating rats consumed over four times as much food as nonlactating controls (n = 10; p < 0.001). Final plasma insulin concentrations in lactating rats were lower than in controls (6.8 +/- 0.8 vs. 11.7 +/- 2.1 pmol/l; p < 0.05) although plasma glucose and corticosterone concentrations were comparable (p > 0.05). Lactating rats showed significantly higher NPY levels than controls in specific hypothalamic regions, namely the arcuate nucleus-median eminence complex (a 41% rise; p < 0.001), paraventricular nucleus (35%; p < 0.001), ventromedial nucleus (66%; p = 0.003), and dorsomedial nucleus (78%; p < 0.001). Other hypothalamic regions showed no significant differences between groups. Increased NPY concentrations in specific hypothalamic regions, particularly the arcuate nucleus where NPY is synthesized, suggest increased activity of the hypothalamic NPYergic system in lactation. Neuropeptide Y may mediate hyperphagia and reduced BAT thermogenesis in lactation. Hypoinsulinemia may be a stimulus to hypothalamic NPY in lactation, as has been postulated in other conditions of negative energy balance.
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PMID:Increased neuropeptide Y concentrations in specific hypothalamic regions of lactating rats: possible relationship to hyperphagia and adaptive changes in energy balance. 801 84

Neuropeptide Y (NPY) is a 36 amino acid peptide belonging to the pancreatic polypeptide family of neuroendocrine hormones. It is the most abundant peptide yet discovered in the mammalian brain and is widely expressed by neurons in the central and peripheral nervous systems as well as adrenal medullary cells. Recently, a large number of studies have focussed on the potential roles played by NPY within the hypothalamus and pituitary with respect to the control of food intake and energy homeostasis. It is now clear that NPY is a potent stimulator of food intake in models of hyperphagia, that hypothalamic NPY also regulates sympathetic neural activity and it appears that NPY may also influence the glucocorticoid, growth hormone and thyroid hormone axes. Taken together, current data suggest that hypothalamic and pituitary NPY-expressing cells represent an important and critical site of integration of peripheral hormonal signals with regulation of energy homeostasis.
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PMID:Neuropeptide Y: a central regulator of energy homeostasis. 813 18

Neuropeptide Y (NPY) is a potent central appetite stimulant found in hypothalamic neurons that have close anatomical associations with neurons containing serotonin, a powerful anorectic agent. To determine whether the two neurotransmitters interact functionally, we have studied the effects on regional hypothalamic NPY concentrations of acute and chronic administration of methysergide, a 5-HT1BC/serotonin receptor antagonist. Chronic methysergide treatment (10 mg/kg/day) was given by subcutaneously implanted osmotic minipumps (n = 8). Acute effects of methysergide were determined 4 h after a single injection (10 mg/kg) in a separate group (n = 8). Controls (n = 8) had implanted minipumps delivering saline, and also received a saline injection 4 h before sacrifice. Food intake was significantly increased (p < 0.01) by both acute and chronic methysergide treatment. In the chronically treated rats, NPY levels were significantly increased over controls in the arcuate nucleus (ARC; by 41%, p = 0.02) and paraventricular nucleus (PVN; by 40%, p < 0.01). Acute methysergide treatment also increased NPY concentrations in the ARC (by 81%, p < 0.01) and PVN (by 30%, p < 0.01). Methysergide administration, which stimulated feeding, therefore raised NPY concentrations in the ARC, where NPY is synthesized, and in the PVN, a major site of NPY release where NPY injection induces hyperphagia. These findings suggest that NPYergic and serotoninergic innervations in the hypothalamus interact to regulate food intake, and raise the possibility that increased NPY release may mediate the hyperphagic effect of serotoninergic 5-HT1BC/receptor blockade.
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PMID:Increased neuropeptide Y concentrations in specific hypothalamic nuclei of the rat following treatment with methysergide: evidence that NPY may mediate serotonin's effects on food intake. 823 27

Neuropeptide Y (NPY) injected into the hypothalamus stimulates feeding and affects pituitary secretion. Insulin-deficient diabetes and food deprivation markedly increase hypothalamic NPY and NPY mRNA levels, suggesting increased activity of NPYergic pathways in the hypothalamus, which could account for hyperphagia and neuroendocrine changes in these conditions. To clarify these changes, NPY receptor characteristics were compared amongst rats with 3-weeks' untreated streptozotocin diabetes, insulin-treated normoglycemic diabetics, and non-diabetics, and also in food-deprived (72 h), food-deprived then refed, and in freely fed rats. Hypothalamic tissue homogenates (pooled from 3 rats; n = 9 per group) in Tris/HCl buffer were incubated with 30 pM [125I]porcine NPY and unlabeled NPY (range, 1 pM to 1 microM) for 1 h. Bound and free fractions were separated by vacuum filtration. Scatchard analysis revealed both high-affinity (Kd 0.3-0.8 nM) and low-affinity (Kd 14-40 nM) NPY receptor populations. Compared with nondiabetics, diabetic rats showed significantly reduced numbers (Bmax) of both high-affinity receptors (10 +/- 2 vs. 57 +/- 2 pmol/mg protein; p < 0.001) and low-affinity receptors (113 +/- 25 vs. 544 +/- 48 pmol/mg protein; p < 0.001). Insulin treatment partially restored Bmax of both high- and low-affinity receptors (24 +/- 1 and 334 +/- 60 pmol/mg protein, respectively; p < 0.01 vs. both other groups). Food deprivation also reduced Bmax of high-affinity (36 +/- 2 vs. 56 +/- 7 pmol/mg protein in freely fed; p < 0.05) and low-affinity receptors (288 +/- 6 vs. 457 +/- 17 pmol/mg protein; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide Y receptor numbers are reduced in the hypothalamus of streptozotocin-diabetic and food-deprived rats: further evidence of increased activity of hypothalamic NPY-containing pathways. 828 70

Neuropeptide Y (NPY) mediates feeding behavior through a local hypothalamic network formed by the arcuate and paraventricular nuclei (the AP axis). In the hypothalamus, NPY is mainly synthesized in neurons of the arcuate nucleus. These neurons project to the paraventricular nucleus, the site where NPY has the strongest stimulatory effects on food intake of Sprague-Dawley rats. In the adult Zucker fatty rat (a genetic model of obesity with a well-established hyperphagia), NPY concentrations in these nuclei are higher than in its lean counterpart. We measured hypothalamic NPY before the appearance of altered eating behavior, e.g., in very young (16-d-old) lean and obese Zucker pups, and in pups at an age when overeating had begun, e.g., a few days after weaning at 30 d. At 30 d, NPY concentrations were significantly higher in obese than in lean rats in the arcuate nucleus (14.2 +/- 0.7 vs. 11.6 +/- 0.5 pmol/mg protein, P < 0.01). This difference was not observed at 16 d. A 160% increase was noted in the paraventricular nuclei of obese rats between 16 and 30 d of life compared with a 100% increase in the lean rats (P < 0.001). Neuropeptide Y concentration was greater in 30-d-old rats than in 16-d-old rats in other areas involved in the regulation of feeding behavior, such as the dorsomedian nuclei and lateral hypothalamus, but the values did not differ between genotypes. Higher NPY concentration was therefore detected early in young obese rats in the main hypothalamic site of NPY synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevated neuropeptide Y in the arcuate nucleus of young obese Zucker rats may contribute to the development of their overeating. 850 77

Neuropeptide Y (NPY) neurones in the arcuate nucleus of the rodent hypothalamus may play a key role in responding to reductions in body energy stores with appropriate changes in energy homeostasis, namely an increase in food-seeking behaviour and hyperphagia, together with a reduction in heat production by brown adipose tissue. These adaptive responses are mimicked by the injection of NPY into the main sites of projection of the NPY neurones, and animals that are threatened by energy deficits (e.g. through starvation or insulin-deficient diabetes) show increased activity of these neurones. Genetically obese rodents also show hyperactivity of the NPY neurones, which is inappropriate to their energy needs and may contribute to their hyperphagia, reduced energy expenditure and excessive weight gain. The NPY neurones may be inhibited by insulin and leptin, which may both serve as signals of peripheral fat mass. Ultimately, characterization of the specific "feeding' receptors which mediate NPY's central effects on energy homeostasis may provide opportunities for designing drugs to manipulate and appetite and energy balance in man, notably obesity and the cachexia commonly associated with malignancy and chronic infection.
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PMID:Neuropeptide Y, the hypothalamus and the regulation of energy homeostasis. 887 Nov 82

Neuropeptide Y (NPY) is synthesized in arcuate (ARC) neurons which project principally to the paraventricular nucleus (PVN). NPY injected into the PVN causes hyperphagia, reduced energy expenditure and eventually obesity, effects which are opposed by nicotine. We aimed to investigate whether nicotine's effects on energy balance might be mediated by inhibition of hypothalamic NPYergic neurons. Nicotine or saline was given for 1 or 12 days using osmotic minipumps, and additional groups of rats were food-restricted to the intake of the nicotine-treated groups to allow for the effects of hypophagia on hypothalamic NPY. One day's nicotine treatment (12 mg/kg/day) reduced food intake by 30% (P < 0.001) and body weight by 2% (P < 0.01 vs. controls). NPY mRNA levels were significantly reduced by 40% (P < 0.05) and NPY concentrations fell significantly by 33% in the ARC and PVN (both P < 0.01). Matched food restriction also reduced NPY levels significantly in the ARC and PVN (P < 0.02 vs. controls) but had no effect on NPY mRNA. 12 days' nicotine treatment (12 mg/kg/day) lowered cumulative food intake by 8% (P = 0.02) and body weight by 10% (P < 0.05). NPY mRNA levels rose by 40% (P < 0.05), while NPY levels again fell in the ARC and PVN (both P < 0.05). Food restriction, which induced weight loss comparable with that during nicotine treatment, increased NPY mRNA to levels that were 100% above controls (P < 0.01) and also significantly higher than in the nicotine-treated group (P < 0.05). Food restriction also reduced NPY peptide levels in the PVN (P < 0.02), but did not affect those in the ARC. In addition, 12 days' nicotine treatment significantly reduced plasma insulin levels compared with controls (P < 0.05). We suggest that nicotine may inhibit NPY synthesis in the hypothalamus, independently of any effects due to altered energy balance. Reduced activity of NPYergic neurons in the ARC-PVN projection may mediate the effects of nicotine on energy balance.
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PMID:Nicotine administration reduces neuropeptide Y and neuropeptide Y mRNA concentrations in the rat hypothalamus: NPY may mediate nicotine's effects on energy balance. 897 38

Neuropeptide Y (NPY) in the hypothalamus plays an important role in the regulation of food intake and body weight and seems to be implicated in the etiology of obesity. When intracerebroventricularly (ICV) infused for 6 days in normal rats, NPY resulted in hyperphagia, increased body weight gain, hyperinsulinemia, hypercorticosteronemia, and hypertriglyceridemia compared with vehicle-infused control rats. NPY infusion also resulted in an insulin-resistant state in muscles and in a state of insulin hyperresponsiveness in white adipose tissue, as assessed by the measurement of the in vivo glucose utilization index of these tissues during euglycemic-hyperinsulinemic clamps. All of these hormono-metabolic effects produced by chronic central NPY infusion were completely prevented when rats were adrenalectomized before NPY administration. Adrenalectomy per se had no effect on any of the parameters mentioned above. The levels of mRNA for the obese gene were increased in white adipose tissue after 6 days of ICV NPY infusion in normal rats, and white adipose tissue weight was also increased. These effects of ICV NPY infusion were markedly decreased by prior adrenalectomy, although NPY infusion was able to somewhat enhance the low white adipose tissue obese mRNA levels and tissue weight of adrenalectomized rats. In conclusion, intact adrenal glands, and probably circulating corticosterone in particular, are necessary for the establishment of most of the hormonal and metabolic effects induced by chronic ICV infusion of NPY in normal rats.
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PMID:Adrenalectomy prevents the obesity syndrome produced by chronic central neuropeptide Y infusion in normal rats. 900 Jun 96


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