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, Xin Yun Lu

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


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
Issue number30
StatePublished - Jul 24 2012


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

ASJC Scopus subject areas

  • General


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