Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity.
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.
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Jing
J
Liu
Ming
M
Guo
Di
D
Zhang
Shao-Ying
SY
Cheng
Meilian
M
Liu
Jun
J
Ding
Philipp E
PE
Scherer
Feng
F
Liu
Xin-Yun
XY
Lu
D015502:Absorptiometry, Photon; D052242:Adiponectin / Q000097:blood* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D059445:Anhedonia / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D001786:Blood Glucose; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D003907:Dexamethasone / Q000008:administration & dosage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005938:Glucocorticoids / Q000378:metabolism; D057895:Haploinsufficiency; D017403:In Situ Hybridization; D057967:Infusions, Intraventricular; D007328:Insulin / Q000097:blood; D016014:Linear Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011597:Psychomotor Performance / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction
D052242:Adiponectin; D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D003907:Dexamethasone; D003345:Corticosterone