Role of the Y5 neuropeptide Y receptor in feeding and obesity

Marsh, Donald J.; Hollopeter, Gunther; Kafer, Kathy E.; Palmiter, Richard D.

doi:10.1038/nm0698-718

Cited by 390 publications

(213 citation statements)

References 21 publications

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“…Results from diverse molecular and genetic paradigms are consistent with the implication that NPY, in concert with co-expressed orexigenic AgrP, GABA and adrenergic transmitters, constitutes an obligatory orexigenic signaling modality that is intimately involved in propagation of the timely appetitive drive under the direction of photoperiodic and hormonal cues (7,11,(27)(28)(29)47,(49)(50)(51)54,(56)(57)(58)(59). Additional recent disclosures that the hard wiring for the timely operation of this interplay is established during postnatal development have put the notion that NPY is a physiological appetite transducer on firm footing (11,(28)(29)(30)49,64).…”

Section: Is Npy a Naturally Occurring Appetite Transducer?supporting

confidence: 56%

To subjugate NPY is to improve the quality of life and live longer

Kalra

2007

Peptides

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The interactive network of Neuropeptide Y (NPY) and cohorts is necessary for integrating the hypothalamic regulation of appetite and energy expenditure with the endocrine and neuroendocrine systems on a daily basis. Genetic and environmental factors that produce an insufficiency of leptin restraint on NPY and cognate receptors deregulate the homeostasis to engender various lifethreatening risk factors. Recent studies from our laboratory show that neurotherapy consisting of a single central administration of recombinant adeno-associated virus vector encoding the leptin gene can repress the hypothalamic NPY system for the lifetime of rodents. A major benefit of this stable tonic restraint is deceleration of pathophysiologic sequalae that shorten life span. These include suppression of weight gain, fat accumulation, circulating adipokines, amelioration of major symptoms of metabolic syndrome, improved reproduction and bone health. Thus, sustained repression of NPY signaling in the hypothalamus by leptin transgene expression can improve the quality of life and extend longevity.

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Section: Is Npy a Naturally Occurring Appetite Transducer?supporting

confidence: 56%

To subjugate NPY is to improve the quality of life and live longer

Kalra

2007

Peptides

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“…Even though NPY is one of the most potent orexigenic peptides (Salton et al 2000), NPY knockout mice have normal levels of food intake and body weight (Erickson et al 1996). Furthermore, deletion of either the NPY Y1 (Pedrazzini et al 1998) or the Y5 (Marsh et al 1998) receptor resulted in the paradoxical induction of obesity. Thus, the genetic studies exploring the role of NPY in body weight regulation were inconsistent with the pharmacologic studies.…”

Section: Animal Models Of Obesitymentioning

confidence: 99%

Relevance of animal models to human eating disorders and obesity

2008

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Background and rationale This review addresses the role animal models play in contributing to our knowledge about the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) and obesity. Objectives Explore the usefulness of animal models in complex biobehavioral familial conditions, such as AN, BN, and obesity, that involve interactions among genetic, physiologic, psychological, and cultural factors. Results and conclusionsThe most promising animal model to mimic AN is the activity-based anorexia rodent model leading to pathological weight loss. The paradigm incorporates reward elements of the drive for activity in the presence of an appetite and allows the use of genetically modified animals. For BN, the sham-feeding preparation in rodents equipped with a gastric fistula appears to be best suited to reproduce the postprandial emesis and the defects in satiety. Animal models that incorporate genes linked to behavior and mood may clarify biobehavioral processes underlying AN and BN. By contrast, a relative abundance of animal models has contributed to our understanding of human obesity. Both environmental and genetic determinants of obesity have been modeled in rodents. Here, we consider single gene mutant obesity models, along with models of obesigenic environmental conditions. The contributions of animal models to obesity research are illustrated by their utility for identifying genes linked to human obesity, for elucidating the pathways that regulate body weight and for the identification of potential therapeutic targets. The utility of these models may be further improved by exploring the impact of experimental manipulations on the behavioral determinants of energy balance.

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“…These peptides bind with differing affinities to receptors of the Y-receptor family (Y1, Y2, Y3, Y4, and Y5 in humans, plus y6 in rodents) [10]. Whereas Y1 and Y5 receptors are believed to primarily mediate feeding behavior [11,12], studies of Y2 and Y4 receptors suggest a role in controlling BMD [3,4]. Y2 receptors are expressed on NPY-secreting neurons in the arcuate nucleus and are believed to act as autoreceptors to decrease the release of NPY [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Peptide YY (PYY) levels and bone mineral density (BMD) in women with anorexia nervosa

Utz¹,

Lawson²,

Misra³

et al. 2008

Bone

105

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Introduction-Anorexia nervosa is a psychiatric illness that results in significant bone loss. Studies examining the neuroendocrine dysregulation that occurs in AN may increase understanding of endocrine systems that regulate bone mass. PYY is an anorexigenic peptide derived primarily from the intestine, with actions mediated via activation of Y-receptors. We have previously shown that PYY levels are elevated in adolescents with AN. Y2 receptor knockout mice have increased bone mineral density (BMD) and thus PYY may play a role in regulating bone mass. We hypothesized that PYY levels would be inversely associated with BMD in women with AN.

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Role of the Y5 neuropeptide Y receptor in feeding and obesity

Cited by 390 publications

References 21 publications

To subjugate NPY is to improve the quality of life and live longer

To subjugate NPY is to improve the quality of life and live longer

Relevance of animal models to human eating disorders and obesity

Peptide YY (PYY) levels and bone mineral density (BMD) in women with anorexia nervosa

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