Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity

Jing Liu, Ming Guo, Di Zhang, Shao Ying Cheng, Meilian Liu, Jun Ding, Philipp E. Scherer, Feng Liu, Xinyun Lu

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Depression is a debilitating mental illness and is often comorbidwith metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte-derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, "anhedonia," and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressant-like behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders.

Original languageEnglish (US)
Pages (from-to)12248-12253
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number30
DOIs
StatePublished - Jul 24 2012
Externally publishedYes

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Adiponectin
Antidepressive Agents
Learned Helplessness
Depression
Anhedonia
Haploinsufficiency
Obese Mice
Interpersonal Relations
Depressive Disorder
Neutralizing Antibodies
Hypoglycemic Agents
Adipocytes
Type 2 Diabetes Mellitus
Glucocorticoids
Hormones
Insulin
Diet
Weights and Measures
Injections

Keywords

  • Adipokines
  • Adipose tissue
  • Dexamethasome suppression test
  • Forced swim test
  • Tail suspension test

ASJC Scopus subject areas

  • General

Cite this

Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity. / Liu, Jing; Guo, Ming; Zhang, Di; Cheng, Shao Ying; Liu, Meilian; Ding, Jun; Scherer, Philipp E.; Liu, Feng; Lu, Xinyun.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 30, 24.07.2012, p. 12248-12253.

Research output: Contribution to journalArticle

Liu, Jing ; Guo, Ming ; Zhang, Di ; Cheng, Shao Ying ; Liu, Meilian ; Ding, Jun ; Scherer, Philipp E. ; Liu, Feng ; Lu, Xinyun. / Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 30. pp. 12248-12253.
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