Chronic social defeat stress disrupts regulation of lipid síntesis

CHUANG JC,; CUI H,; MANSON B,; BOOKOUT AL,; YU HG,; PERELLÓ M,; ELMQUIST JK,; REPA J,; ZIGMAN JM; LUTTER M

JLR PAPERS IN PRESS

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Año: 2010 p. 1344 - 1353

0022-2275

Several psychiatric disorders increase the risk of cardiovascular disease, including posttraumatic stress disorder and major depression. While the precise mechanism for this association has not yet been established, it has been shown that certain disorders promote an unfavorable lipid profi le. To study the interaction of stress and lipid dysregulation, we utilized chronic social defeat stress (CSDS), a mouse model of chronic stress with features of posttraumatic stress disorder and major depression. Following exposure to CSDS, mice were given access to either regular chow or a Western-style diet high in fat and cholesterol (HFD). The combination of social stress and HFD resulted in signifi cant perturbations in lipid regulation, including two key features of the metabolic syndrome: increased plasma levels of non–HDL cholesterol and intrahepatic accumulation of triglycerides. These effects were accompanied by a number of changes in the expression of hepatic genes involved in lipid regulation. Transcriptional activity of LXR, SREBP1c, and ChREBP were signifi cantly affected by exposure to HFD and CSDS. We present CSDS as a model of social stress induced lipid dysregulation and propose that social stress alters lipid metabolism by increasing transcriptional activity of genes involved in lipid synthesis.