Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c

We explored the effects of bile acids on triglyceride (TG) homeostasis using a combination of molecular, cellular, and animal models. Cholic acid (CA) prevents hepatic TG accumulation, VLDL secretion, and elevated serum TG in mouse models of hypertriglyceridemia. At the molecular level, CA decreases hepatic expression of SREBP-1c and its lipogenic target genes. Through the use of mouse mutants for the short heterodimer partner (SHP) and liver X receptor (LXR) alpha and beta, we demonstrate the critical dependence of the reduction of SREBP-1c expression by either natural or synthetic farnesoid X receptor (FXR) agonists on both SHP and LXR alpha and LXR beta. These results suggest that strategies aimed at…

• HH
  Howard Hughes Medical Institute
• IN
  Institut National de la Santé et de la Recherche Médicale
• CN
  Centre National de la Recherche Scientifique
• NI
  National Institutes of Health