Neuropeptide Y Deficiency Attenuates Responses to Fasting and High-Fat Diet in Obesity-Prone Mice

Hiralben R. Patel; Yong Qi; Evan J. Hawkins; Stanley M. Hileman; Joel K. Elmquist; Yumi Imai; Rexford S. Ahima

doi:10.2337/db05-0624

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Neuropeptide Y Deficiency Attenuates Responses to Fasting and High-Fat Diet in Obesity-Prone Mice

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Neuropeptide Y Deficiency Attenuates Responses to Fasting and High-Fat Diet in Obesity-Prone Mice

Hiralben R. Patel, Yong Qi, Evan J. Hawkins, Stanley M. Hileman, Joel K. Elmquist, Yumi Imai and Rexford S. Ahima

Diabetes (New York, N.Y.), Vol.55(11), pp.3091-3098

11/01/2006

DOI: 10.2337/db05-0624

PMID: 17065347

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Abstract

Neuropeptide Y (NPY) stimulates feeding and weight gain, but deletion of the NPY gene does not affect food intake and body weight in mice bred on a mixed genetic background. We reasoned that the orexigenic action of NPY would be evident in C57Bl/6J mice susceptible to obesity. NPY deficiency has no significant effect in mice fed a normal rodent diet. However, energy expenditure is elevated during fasting, and hyperphagia and weight gain are blunted during refeeding. Expression of agouti-related peptide (AGRP) in the hypothalamus is increased in NPY knockout (NPYko) than wild-type mice, but unlike wild type there is no further increase in AGRP when NPYko mice are fasted. Moreover, NPYko mice have higher oxygen consumption and uncoupling protein-1 expression in brown adipose tissue during fasting. The failure of an increase in orexigenic peptides and higher thermogenesis may contribute to attenuation of weight gain when NPYko mice are refed. C57Bl/6J mice lacking NPY are also less susceptible to diet-induced obesity (DIO) as a result of reduced feeding and increased energy expenditure. The resistance to DIO in NPYko mice is associated with a reduction in nocturnal feeding and increased expression of anorexigenic hypothalamic peptides. Insulin, leptin, and triglyceride levels increase with adiposity in both wild-type and NPYko mice.

Details

Title: Subtitle: Neuropeptide Y Deficiency Attenuates Responses to Fasting and High-Fat Diet in Obesity-Prone Mice
Creators: Hiralben R. Patel - University of Pennsylvania
Yong Qi - University of Pennsylvania
Evan J. Hawkins - University of Pennsylvania
Stanley M. Hileman - West Virginia University
Joel K. Elmquist - The University of Texas Southwestern Medical Center
Yumi Imai - University of Pennsylvania
Rexford S. Ahima - University of Pennsylvania
Resource Type: Journal article
Publication Details: Diabetes (New York, N.Y.), Vol.55(11), pp.3091-3098
DOI: 10.2337/db05-0624
PMID: 17065347
NLM abbreviation: Diabetes
ISSN: 0012-1797
eISSN: 1939-327X
Language: English
Date published: 11/01/2006
Academic Unit: Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984359569902771

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