The pharmacology of neuropeptide Y (NPY) receptor-mediated feeding in rats characterizes better Y5 than Y1, but not Y2 or Y4 subtypes

Wyss, P; Stricker–Krongrad, Alain; Brunner, L; Miller, John W.; Crossthwaite, Andrew J.; Whitebread, Steven; Criscione, Leoluca

doi:10.1016/s0167-0115(98)00089-5

Cited by 78 publications

(45 citation statements)

References 39 publications

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“…The obesity in our Npy Ϫ/Ϫ mice was associated with a small but statistically significant increase in total body fat as well as a decrease in lean body mass, leading to an alteration in the ratio of lean body mass to fat body mass. It should be noted that a similar increase in weight with no apparent change in food intake was also reported for Y1r-and Y5r-null mice (21,29,42). Thus the absence of either NPY ligand or its cognate receptors may lead to mild obesity.…”

Section: Discussionsupporting

confidence: 65%

NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting

Segal-Lieberman

Trombly

Juthani

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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Neuropeptide Y (NPY) is an orexigenic (appetite-stimulating) peptide that plays an important role in regulating energy balance. When administered directly into the central nervous system, animals exhibit an immediate increase in feeding behavior, and repetitive injections or chronic infusions lead to obesity. Surprisingly, initial studies of Npy−/− mice on a mixed genetic background did not reveal deficits in energy balance, with the exception of an attenuation in obesity seen in ob/ob mice in which the NPY gene was also deleted. Here, we show that, on a C57BL/6 background, NPY ablation is associated with an increase in body weight and adiposity and a significant defect in refeeding after a fast. This impaired refeeding response in Npy−/− mice resulted in a deficit in weight gain in these animals after 24 h of refeeding. These data indicate that genetic background must be taken into account when the biological role of NPY is evaluated. When examined on a C57BL/6 background, NPY is important for the normal refeeding response after starvation, and its absence promotes mild obesity.

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Section: Discussionsupporting

confidence: 65%

NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting

Segal-Lieberman

Trombly

Juthani

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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“…This was not supported by recent observations on food intake and body weight of mice null for NPY or the Y-5R (32,33), although the effects of NPY absence can be observed in older mice and in leptin-deficient mice (34,35). Pharmacological studies suggest a partial involvement of the Y-1 receptor in NPY-induced feeding (20,36), but studies with Y-1 antisense oligonucleotides are currently inconclusive (15,(37)(38)(39). Whereas NPY Y-1R deficiency attenuates the stimulation of food intake by NPY and the rise in NPY during fasting, mice null for the receptor display a similar increase in body weight with age as do Y-5R knock-out mice (35).…”

Section: Discussionmentioning

confidence: 58%

“…The orexigenic activity of NPY is thought to be mediated through the Y5 receptor subtype because spontaneous NPY-and fasting-induced food intake are blocked by both Y-5 antagonists and Y-5 antisense oligonucleotide (16 -19). However, other data implicate the Y-1 receptor subtype as a possible mediator of NPY-induced food intake (20).…”

Section: Introductionmentioning

confidence: 99%

Effects of a High‐Fat Diet and Strain on Hypothalamic Gene Expression in Rats

et al. 2002

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Effects of a high-fat diet and strain on hypothalamic gene expression in rats. Obes Res. 2002;10:1188 -1196. Objective: This study was designed to investigate whether dietary fat and genetic background might differentially alter the expression of hypothalamic genes involved in food intake. Research Methods and Procedures: Three-month-old Osborne-Mendel (OM) and S5B/Pl rats were fed either a high-fat or a low-fat diet for 14 days. mRNA for neuropeptide Y (NPY), corticotrophin-releasing hormone, NPY Y-1 receptor and Y-5 receptor, and serotonin 2c (5-HT2c) receptors were measured using Northern blotting or ribonuclease protection assays. Results: OM rats showed an increased expression of NPY and corticotrophin-releasing hormone compared with S5B/Pl rats. The expression of NPY-Y1 and -Y5 receptor mRNA was significantly higher in the hypothalamus of OM rats compared with S5B/Pl rats. The expression of 5HT-2c receptor mRNA was significantly reduced in both strains of rats eating a high-fat diet when compared with the animals eating the low-fat diet. Discussion: These data suggest that over activity of the NPY system may contribute to the development of obesity in OM rats and that expression of the 5HT-2c receptor gene may be modulated by dietary fat.

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“…8 Correlation studies indicate that the stimulation of food intake induced by a range of NPY analogs is closely linked to their af®nity for the NPY Y 1 and particularly the NPY Y 5 receptor subtype. 9 Further evidence in favor of the NPY Y 1 receptor subtype is mixed since blockade of this receptor lowers food intake while antisense oligonucleotides directed against the NPY Y 1 receptor paradoxically increase food intake. 10 ± 12 The evidence supporting a role for the NPY Y 5 receptor appears more consistent since antisense oligonucleotides directed against the NPY Y 5 receptor and a selective NPY Y 5 antagonist, CGP 71683A reduce food intake in free-feeding and energy deprived lean rats.…”

Section: Introductionmentioning

confidence: 99%

Reduced food intake in response to CGP 71683A may be due to mechanisms other than NPY Y5 receptor blockade

et al. 2001

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INTRODUCTION:The purpose of this study was to test the continuing validity of the hypothesis that neuropeptide Y (NPY) produced in the brain controls food intake through an interaction with the NPY Y 5 receptor subtype.METHODS: The hypothesis was tested using CGP 71683A a potent and highly selective non-peptide antagonist of the NPY Y 5 receptor which was administered into the right lateral ventricle of obese Zucker faafa rats. RESULTS: Intraventricular injection of 3.4 nmolakg NPY increased food intake during a 2 h test period. Doses of CGP 71683A in excess of 15 nmolakg (i.cv.) resulted in blockade of the increase in food intake produced by NPY. Repeated daily injection of CGP 71683A (30 ± 300 nmolakg, i.cv.) immediately before the dark phase produced a dose-dependent and slowly developing decrease in food intake. CGP 71683A has a low af®nity for NPY Y 1 , Y 2 and Y 4 receptors but a very high af®nity for the NPY Y 5 receptor (Ki, 1.4 nM). Surprisingly, CGP 71683A had similarly high af®nity for muscarinic receptors (Ki, 2.7 nM) and for the serotonin uptake recognition site (Ki, 6.2 nM) in rat brain. Anatomic analysis of the brain after treatment with CGP 71683A demonstrated an in¯ammatory response associated with the fall in food intake. CONCLUSIONS: While the fall in food intake in response to CGP 71683A may have a Y 5 component, interactions with other receptors or in¯ammatory mediators may also play a role. It is concluded that CGP 71683A is an imprecise tool for investigating the role of the NPY Y 5 receptor in the control of physiological processes including food intake. International Journal of Obesity (2001) 25, 84 ± 94

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The pharmacology of neuropeptide Y (NPY) receptor-mediated feeding in rats characterizes better Y5 than Y1, but not Y2 or Y4 subtypes

Cited by 78 publications

References 39 publications

NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting

NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting

Effects of a High‐Fat Diet and Strain on Hypothalamic Gene Expression in Rats

Reduced food intake in response to CGP 71683A may be due to mechanisms other than NPY Y5 receptor blockade

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