Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biol Psychiatry. 2010 Jun 1;67(11):1075-82. doi: 10.1016/j.biopsych.2009.12.003. Epub 2010 Jan 12.

A beta3-adrenergic-leptin-melanocortin circuit regulates behavioral and metabolic changes induced by chronic stress.

Author information

  • 1Department of Internal Medicine (Division of Hypothalamic Research), The University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Erratum in

  • Biol Psychiatry. 2010 Jul 1;68(1):112. Cui, Huixing [corrected to Cui, Huxing].

Abstract

BACKGROUND:

Obesity has been associated with an increased risk of developing several psychiatric illnesses, including major depression and posttraumatic stress disorder. Likewise, these stress-related disturbances are associated with a higher rate of obesity; yet, the neurobiological mechanisms linking obesity and stress remain incompletely understood.

METHODS:

Following exposure to chronic social defeat stress (CSDS), mice were given free access to either regular chow or a Western-style diet high in triglycerides and cholesterol. Comprehensive metabolic and behavioral testing was then conducted.

RESULTS:

Mice subjected to CSDS and then fed a high-fat diet for 30 days display severe behavioral deficits accompanied by redistribution of body fat. Stressed mice have decreased adipose tissue as well as decreased serum leptin levels compared with control mice. Pharmacological inhibition of beta(3)-adrenergic signaling during CSDS normalizes these metabolic abnormalities but worsens behavioral symptoms. Furthermore, mice subjected to CSDS display central leptin resistance including reduced expression of pro-opiomelanocortin in hypothalamus. Administration of a central melanocortin agonist worsens stress-induced behavioral deficits, while mice lacking the melanocortin-4 receptor display attenuated symptoms.

CONCLUSIONS:

These results indicate that chronic signaling through beta(3)-adrenergic receptors during social stress is an adaptive response that improves behavioral function. However, these responses come at the expense of central leptin resistance and melanocortin signaling alterations that contribute to significant and long-lasting metabolic abnormalities.

Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PMID:
20060958
[PubMed - indexed for MEDLINE]
PMCID:
PMC2868111
Free PMC Article

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk