Normal feeding behavior, body weight and leptin response require the neuropeptide Y Y2 receptor

Naveilhan, Philippe; Hassani, Hessameh; Canals, Josep M.; Ekstrand, A. Jonas; Larefalk, Åsa; Chhajlani, Vijay; Arenas, Ernest; Gedda, Karin; Svensson, Lennart; Thorén, Peter; Ernfors, Patrik

doi:10.1038/13514

Cited by 258 publications

(158 citation statements)

References 28 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

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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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“…From the literature it has been demonstrated that NPY2R is a crucial receptor in appetite regulation. NPY2R knock-outs have been shown to increase food intake, weight and adiposity [25]. Furthermore, in other mouse models, it has been observed that NPY2R regulates production of NPY, agouti-related peptide (AgRP), proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART), and these changes are associated with functional changes in food intake [50].…”

Section: Discussionmentioning

confidence: 99%

“…It has been established that mice lacking the NPY2R gene have an increased body weight and food intake [25].…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

et al. 2007

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Aims/hypothesis Genetic variants of genes for peptide YY (PYY), neuropeptide Y2 receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for association with severe obesity. Subjects and methods The initial screening of the genes for variants was performed by sequencing in a group of severely obese subjects (n=161). Case-control analysis of the common variants was then carried out in 557 severely obese adults, 515 severely obese children and 1,163 nonobese/non-diabetic control subjects. Rare variants were genotyped in 700 obese children and the non-obese/nondiabetic control subjects (n=1,163). Results Significant association was found for a 5′ variant (rs6857715) in the NPY2R gene with both severe adult obesity (p=0.002) and childhood obesity (p=0.02). This significant association was further supported by a pooled allelic analysis of all obese cases (adults and children, n=928) vs the control subjects (n=938) (p=0.0004, odds ratio=1.3, 95% CI 1.1-1.5). Quantitative trait analysis of BMI and WHR was performed and significant association was observed for SNP rs1047214 in NPY2R with an increase in WHR in the severely obese children (codominant model p=0.005, recessive model p=0.001). Association was also observed for an intron 3 variant (rs162430) in the PYY gene with childhood obesity (p=0.04). No significant associations were observed for PPY variants. Only one rare variant in the NPY2R gene (C-5641T) was not found in lean individuals and this was found to co-segregate with obesity in one family. Conclusions/interpretation These results provide evidence of association for NPY2R and PYY gene variants with obesity and none for PPY variants. A rare variant of the NPY2R gene showed evidence of co-segregation with Diabetologia (2007)

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“…7 Peripheral administration of PYY in rodents reduces NPY mRNA levels and increases the POMC mRNA levels in the arcuate nucleus, as well as reduces food intake, but has no effect in fasted Y2R knockout mice. 7,16 However, there are redundancy or compensatory mechanisms as reflected by slightly increased body weight and generally larger food intake in full, and conditional hypothalamic, Y2R knock-out mice 33,34 and by results from studies on other NPY receptor knockouts. 35 Hung et al 18 recently reported association for Y2R 585T4C polymorphism to obesity-related parameters among 421 men representing the general population in eastern UK.…”

Section: Discussionmentioning

confidence: 99%

Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

et al. 2005

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Background: Gut hormones and their receptors are considered important in the control of feeding behavior. The gut hormone peptide-YY (PYY) has anorexic effects via the inhibitory neuropeptide Y2 receptor (Y2R) highly expressed in orexigenic NPY/ AGRP neurons within the arcuate nucleus, a major integrator of appetite control in the hypothalamus. Design: Genetic case-control association study of single nucleotide polymorphisms (SNPs) in Y2R and PYY. Subjects: Swedish Caucasians comprising 148 lean, 129 overweight/obese and 226 morbidly obese men. Measurements: Genotypes of the common, silent and conserved SNP Y2R 585T4C and the common SNP PYY Arg72Thr, as well as various obesity-related clinical parameters. Results: Obese men had a lower allele and homozygosity frequency of the common allele 585T4C:T which was particularly evident comparing morbidly obese with lean men (P ¼ 0.002), and analyzing dependence between continuous body mass index (BMI) and genotype (P ¼ 0.002). In agreement, systolic blood pressure tended to be lower in those homozygous for allele T, which was not explained by the BMI -genotype dependence. We found no association to obesity for the PYY Arg72Thr polymorphism, which is located nearby the essential carboxy terminal. Conclusion: A common and conserved variant of the PYY and NPY receptor Y2R is less prevalent among obese compared to among lean Swedish men. This suggests that the common Y2R variant is protective against obesity. Our findings further implicate Y2R in food intake regulation.

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Normal feeding behavior, body weight and leptin response require the neuropeptide Y Y2 receptor

Cited by 258 publications

References 28 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

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

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