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.
Key Words
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Article info
Publication history
Published online: January 11, 2010
Accepted:
December 1,
2009
Received in revised form:
November 20,
2009
Received:
September 10,
2009
Identification
Copyright
© 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
