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

First Author  Watanabe M Year  2004
Journal  J Clin Invest Volume  113
Issue  10 Pages  1408-18
PubMed ID  15146238 Mgi Jnum  J:120199
Mgi Id  MGI:3704037 Doi  10.1172/JCI21025
Citation  Watanabe M, et al. (2004) Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest 113(10):1408-18
abstractText  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 increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia.
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