Journal article
A β3-adrenergic-leptin-melanocortin circuit regulates behavioral and metabolic changes induced by chronic stress
Biological psychiatry (1969), Vol.67(11), pp.1075-1082
06/01/2010
DOI: 10.1016/j.biopsych.2009.12.003
PMCID: PMC2868111
PMID: 20060958
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 β3-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 β3-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.
Details
- Title: Subtitle
- A β3-adrenergic-leptin-melanocortin circuit regulates behavioral and metabolic changes induced by chronic stress
- Creators
- Jen-Chieh Chuang - Department of Internal Medicine (Division of Hypothalamic Research), The University of Texas Southwestern Medical Center, Dallas, TX, 75390Vaishnav Krishnan - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9127Hana G Yu - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9127Brittany Mason - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9127Huixing Cui - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9127Matthew B Wilkinson - Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, 10029-6574Jeffrey M Zigman - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9127Joel K Elmquist - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9127Eric J Nestler - Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, 10029-6574Michael Lutter - Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9127
- Resource Type
- Journal article
- Publication Details
- Biological psychiatry (1969), Vol.67(11), pp.1075-1082
- DOI
- 10.1016/j.biopsych.2009.12.003
- PMID
- 20060958
- PMCID
- PMC2868111
- ISSN
- 0006-3223
- eISSN
- 1873-2402
- Grant note
- name: National Alliance for Research in Schizophrenia and Depression, award: K08 MH084058-1A1, UL1-DE019584-02, R01 MH51399, R37 DK53301, R01DK071320, RL1 DK081182, 1RL1 DK081185-01, 1PL1DK081182-01, K08 DK068069-01A2, P50 MH066172; DOI: 10.13039/100004339, name: Sanofi-Aventis
- Language
- English
- Date published
- 06/01/2010
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984040487902771
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