Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 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 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

Neuropeptide Y increases blood pressure and appetite, disorders of which have a genetic component. The present study examined the neuropeptide-Y Y1 receptor gene (NPYY1R) for involvement in essential hypertension (HT) and obesity. Frequency of alleles of the only known variant, involving a point mutation in intron 1, was determined by PCR and PstI digestion. Minor allele frequency was 0.37 in 75 HT offspring of two HT parents, compared with 0.35 in 86 normotensives (NTs) ( chi 2 = 0.11; P = 0.73). In obese and lean HTs frequency was 0.40 and 0.35 (chi 2 = 0.51; P = 0.46); and was 0.38 and 0.34 in obese and lean NTs (chi 2 = 0.16; P = 0.69). In conclusion, variant(s) in linkage disequilibrium with the NPYY1R RFLP are not involved in HT or obesity.
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PMID:Neuropeptide-Y Y1 receptor gene polymorphism: cross-sectional analyses in essential hypertension and obesity. 790 88

Neuropeptide Y (NPY) induces a robust feeding response when it is injected in the hypothalamus. It stimulates both carbohydrate and fat intakes. Diets rich in either macronutrient are known to induce obesity and to modify feeding behavior. The aim of the present study was to determine the effects of long-term ingestion of these diets on hypothalamic NPY in relation with food intake and body weight gain and composition. For this purpose, three groups of weanling Long-Evans rats were fed either a well-balanced diet, a high-carbohydrate (HC) diet (high starch plus 25% sucrose solution), or a high-fat (HF) diet during 14 weeks. Body weight and food intake were recorded during this period. At the end of the experiment, NPY was measured in several microdissected brain areas, and some adipose tissues (AT) depots were sampled. HF rats weighed significantly more than the two other groups (p < 0.02). They were also fattier (+ 30-50% in AT weights; p < 0.01). Energy intake (EI) of the HC rats was significantly greater than that of the control (+ 15%; p < 0.02) and HF rats (+ 34%; p < 0.01) during the week preceding killing. EI of HF rats over the whole experiment was lower than that of the two groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Macronutrient type independently of energy intake modulates hypothalamic neuropeptide Y in Long-Evans rats. 804 91

Neuropeptide Y (NPY) is a potent orexigenic peptide. Structure-activity studies have revealed that nearly the entire sequence of NPY is required to elicit feeding responses. Therefore, in order to develop antagonistic peptides for NPY-induced feeding, we synthesized full-length analogs of NPY, substituting D-Trp in the C-terminal receptor binding region, and screened their activity in rat hypothalamus. Although [D-Trp36]NPY and [D-Trp34]NPY inhibited isoproterenol-stimulated hypothalamic membrane adenylate cyclase activity, [D-Trp32]NPY exhibited no intrinsic activity. Furthermore, [D-Trp32]NPY inhibited [125I]NPY binding to rat hypothalamic membranes with a potency comparable to that of NPY. The presence of 30 and 300 nM concentrations of [D-Trp32]NPY shifted the inhibitory dose-response curve of NPY on isoproterenol-stimulated hypothalamic membrane adenylate cyclase activity parallel to the right with comparable KB values. Moreover, in vivo experiments in rats revealed that [D-Trp32]NPY (10 micrograms) significantly attenuated the 1-h feeding response induced by NPY (1 microgram). Several other substitutions at position 32 including 2-D-Nal resulted in agonist activity, suggesting that there are strict structural requirements to induce the antagonistic property in NPY. These findings confirm that [D-Trp32]NPY is a competitive antagonist of NPY in both in vitro and in vivo systems. Analogs based on [D-Trp32]NPY may have potential clinical application, since NPY has been implicated in the pathophysiology of a number of feeding disorders including obesity, anorexia, and bulimia.
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PMID:[D-TRP32]neuropeptide Y: a competitive antagonist of NPY in rat hypothalamus. 814 32

Neuropeptide Y (NPY) is a 36 amino-acid peptide. It is localized within the brain but is also present peripherally. It is a well substantiated orexigenic peptide with several other endocrine and behavioural effects. In this study NPY mRNA levels were measured, using the polymerase chain reaction amplification technique, in the hypothalamus of pre-obese (unweaned 13-day-old), young (weaned 28-day-old) and adult (11-week-old) obese fa/fa rats and compared to those of lean age-matched controls. Before weaning, pre-obese pups had the same NPY mRNA levels as controls. After weaning NPY mRNA levels were increased 2-fold in young 28-day-old and 4-fold in adult obese rats, relative to corresponding controls. When adult obese rats were intracerebroventricularly-treated with ovine corticotropin-releasing hormone (oCRF) for 7 days, they stopped gaining body weight relative to vehicle-infused obese controls. Upon measuring NPY mRNA levels in the hypothalamus of these two groups of animals, it was shown that the high NPY mRNA levels of vehicle-treated (control) obese rats were decreased by 3-fold following the intracerebroventricular oCRF administration. It is proposed that: 1) hypothalamic NPY may play a role in the establishment and maintenance of the genetic obesity syndrome of the fa/fa rat, and 2) maintenance of the genetic obesity syndrome of the fa/fa rat, and 2) hypothalamic NPY could be partly regulated by central CRF.
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PMID:Hypothalamic neuropeptide Y messenger ribonucleic acid levels in pre-obese and genetically obese (fa/fa) rats; potential regulation thereof by corticotropin-releasing factor. 840 61

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) is a powerful stimulant of food intake and is proposed to activate a hypothalamic 'feeding' receptor distinct from previously cloned Y-type receptors. This receptor was first suggested to explain a feeding response to NPY and related peptides, including NPY2-36, that differed from their activities at the Y1 receptor. Here we report the expression cloning of a novel Y-type receptor from rat hypothalamus, which we name Y5. The complementary DNA encodes a 456-amino-acid protein with less than 35% overall identity to known Y-type receptors. The messenger RNA is found primarily in the central nervous system, including the paraventricular nucleus of the hypothalamus. The extent to which selected peptides can inhibit adenylate cyclase through the Y5 receptor and stimulate food intake in rats correspond well. Our data support the idea that the Y5 receptor is the postulated 'feeding' receptor, and may provide a new method for the study and treatment of obesity and eating disorders.
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PMID:A receptor subtype involved in neuropeptide-Y-induced food intake. 870 Jan 97

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

The obesity syndrome of ob/ob mice results from lack of leptin, a hormone released by fat cells that acts in the brain to suppress feeding and stimulate metabolism. Neuropeptide Y (NPY) is a neuromodulator implicated in the control of energy balance and is overproduced in the hypothalamus of ob/ob mice. To determine the role of NPY in the response to leptin deficiency, ob/ob mice deficient for NPY were generated. In the absence of NPY, ob/ob mice are less obese because of reduced food intake and increased energy expenditure, and are less severely affected by diabetes, sterility, and somatotropic defects. These results suggest that NPY is a central effector of leptin deficiency.
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PMID:Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. 917 44

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


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