Overexpression of neuropeptide Y in the dorsomedial hypothalamus causes hyperphagia and obesity in rats.

Abstract

We sought to determine a role for NPY overexpression in the dorsomedial hypothalamus (DMH) in obesity etiology using the rat model of adeno-associated virus (AAV)-mediated expression of NPY (AAVNPY) in the DMH. Rats received bilateral DMH injections of AAVNPY or control vector and were fed on regular chow. Five-week postviral injection, half the rats from each group were switched to access to a high-fat diet for another 11 weeks. We examined variables including body weight, food intake, energy efficiency, meal patterns, glucose tolerance, fat mass, plasma insulin, plasma leptin, and hypothalamic gene expression. Rats with DMH NPY overexpression had increased food intake and body weight and lowered metabolic efficiency. The hyperphagia was mediated through increased meal size during the dark. Although these rats had normal blood glucose, their plasma insulin levels were increased in both basal and glucose challenge conditions. While high-fat diet induced hyperphagia, obesity, and hyperinsulinemia, these effects were amplified in rats with DMH NPY overexpression. Arcuate Npy, agouti-related protein and proopiomelanocortin expression was appropriately regulated in response to positive energy balance. These results indicate that DMH NPY overexpression can cause hyperphagia and obesity and DMH NPY may have actions in glucose homeostasis.

• Authors: Fenping Zheng, Yonwook J Kim, Pei-Ting Chao, Sheng Bi
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 21 Issue 6 Pg. 1086-92 (Jun 2013) ISSN: 1930-739X [Electronic] United States
• PMID: 23526718 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 The Obesity Society.

Chemical References

• AGRP protein, rat
• Agouti-Related Protein
• Leptin
• Neuropeptide Y
• Pro-Opiomelanocortin
• Glucose

Topics

• Agouti-Related Protein (genetics, metabolism)
• Animals
• Body Weight
• Dependovirus (genetics, metabolism)
• Diet, High-Fat
• Disease Models, Animal
• Energy Metabolism
• Gene Expression Regulation
• Glucose (metabolism)
• Glucose Tolerance Test
• Homeostasis
• Hyperphagia (genetics, pathology)
• Hypothalamus (metabolism)
• Leptin (blood)
• Male
• Neuropeptide Y (genetics, metabolism)
• Obesity (genetics, pathology)
• Pro-Opiomelanocortin (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley