Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12248-53. doi: 10.1073/pnas.1202835109. Epub 2012 Jul 9. Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity.
Liu J, Guo M, Zhang D, Cheng SY, Liu M, Ding J, Scherer PE, Liu F, Lu XY.
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
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.