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

作者：Jing Liu, Ming Guo, Di Zhang, Shao-Ying Cheng, Meilian Liu, Jun Ding, Philipp E. Scherer, Feng Liu, Xin‐Yun Lu · 发表于：Proceedings of the National Academy of Sciences · 年份：2012 · DOI：10.1073/pnas.1202835109 · 被引用次数：188 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Apelin-related biomedical research、Adipose Tissue and Metabolism

Depression is a debilitating mental illness and is often comorbid with 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.