A β3-Adrenergic-Leptin-Melanocortin Circuit Regulates Behavioral and Metabolic Changes Induced by Chronic Stress

Jen Chieh Chuang, Vaishnav Krishnan, Hana G. Yu, Brittany Mason, Huixing Cui, Matthew B. Wilkinson, Jeffrey M. Zigman, Joel K. Elmquist, Eric J. Nestler, Michael Lutter

Research output: Contribution to journalArticle

71 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1075-1082
Number of pages8
JournalBiological Psychiatry
Volume67
Issue number11
DOIs
StatePublished - Jun 1 2010

Fingerprint

Melanocortins
Leptin
Adrenergic Agents
Obesity
Adipose Tissue
Pro-Opiomelanocortin
Behavioral Symptoms
High Fat Diet
Post-Traumatic Stress Disorders
Adrenergic Receptors
Hypothalamus
Psychiatry
Triglycerides
Cholesterol
Pharmacology
Depression
Diet
Serum

Keywords

  • Anxiety
  • depression
  • feeding
  • hypothalamus
  • leptin
  • metabolism

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

A β3-Adrenergic-Leptin-Melanocortin Circuit Regulates Behavioral and Metabolic Changes Induced by Chronic Stress. / Chuang, Jen Chieh; Krishnan, Vaishnav; Yu, Hana G.; Mason, Brittany; Cui, Huixing; Wilkinson, Matthew B.; Zigman, Jeffrey M.; Elmquist, Joel K.; Nestler, Eric J.; Lutter, Michael.

In: Biological Psychiatry, Vol. 67, No. 11, 01.06.2010, p. 1075-1082.

Research output: Contribution to journalArticle

Chuang, Jen Chieh ; Krishnan, Vaishnav ; Yu, Hana G. ; Mason, Brittany ; Cui, Huixing ; Wilkinson, Matthew B. ; Zigman, Jeffrey M. ; Elmquist, Joel K. ; Nestler, Eric J. ; Lutter, Michael. / A β3-Adrenergic-Leptin-Melanocortin Circuit Regulates Behavioral and Metabolic Changes Induced by Chronic Stress. In: Biological Psychiatry. 2010 ; Vol. 67, No. 11. pp. 1075-1082.
@article{5cc7f4b46cbd45b7be402c7caea090d9,
title = "A β3-Adrenergic-Leptin-Melanocortin Circuit Regulates Behavioral and Metabolic Changes Induced by Chronic Stress",
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.",
keywords = "Anxiety, depression, feeding, hypothalamus, leptin, metabolism",
author = "Chuang, {Jen Chieh} and Vaishnav Krishnan and Yu, {Hana G.} and Brittany Mason and Huixing Cui and Wilkinson, {Matthew B.} and Zigman, {Jeffrey M.} and Elmquist, {Joel K.} and Nestler, {Eric J.} and Michael Lutter",
year = "2010",
month = "6",
day = "1",
doi = "10.1016/j.biopsych.2009.12.003",
language = "English (US)",
volume = "67",
pages = "1075--1082",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "11",

}

TY - JOUR

T1 - A β3-Adrenergic-Leptin-Melanocortin Circuit Regulates Behavioral and Metabolic Changes Induced by Chronic Stress

AU - Chuang, Jen Chieh

AU - Krishnan, Vaishnav

AU - Yu, Hana G.

AU - Mason, Brittany

AU - Cui, Huixing

AU - Wilkinson, Matthew B.

AU - Zigman, Jeffrey M.

AU - Elmquist, Joel K.

AU - Nestler, Eric J.

AU - Lutter, Michael

PY - 2010/6/1

Y1 - 2010/6/1

N2 - 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.

AB - 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.

KW - Anxiety

KW - depression

KW - feeding

KW - hypothalamus

KW - leptin

KW - metabolism

UR - http://www.scopus.com/inward/record.url?scp=77951878302&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951878302&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2009.12.003

DO - 10.1016/j.biopsych.2009.12.003

M3 - Article

VL - 67

SP - 1075

EP - 1082

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 11

ER -