Chronic social defeat stress disrupts regulation of lipid synthesis.
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 profile. 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 significant 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 significantly 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.
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jen-Chieh
JC
Chuang
Huxing
H
Cui
Brittany L
BL
Mason
Melissa
M
Mahgoub
Angie L
AL
Bookout
Hana G
HG
Yu
Mario
M
Perello
Joel K
JK
Elmquist
Joyce J
JJ
Repa
Jeffrey M
JM
Zigman
Michael
M
Lutter
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D002908:Chronic Disease; D003863:Depression / Q000378:metabolism / Q000503:physiopathology; D004041:Dietary Fats; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007333:Insulin Resistance; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism / Q000503:physiopathology; D013312:Stress, Physiological; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol