Overexpression of Neuropeptide Y in the Dorsomedial Hypothalamus Causes Hyperphagia and Obesity in Rats

Authors

  • Fenping Zheng,

    1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Endocrinology, The Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Yonwook J. Kim,

    1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Pei-Ting Chao,

    1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Sheng Bi

    Corresponding author
    1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Errata

This article is corrected by:

  1. Errata: Erratum: Overexpression of neuropeptide Y in the dorsomedial hypothalamus causes hyperphagia and obesity in rats Volume 24, Issue 4, 977, Article first published online: 14 March 2016

  • Disclosure: The authors have no competing interests.

  • Funding agencies: This work was supported by US National Institute of Diabetes and Digestive and Kidney Diseases Grants DK074269 and DK087888.

  • This article originally published online on 21 March 2013; the online version has since been changed. The heading was updated to Original Article on 27 January 2016.

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.

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