FXR, LXRα, and PPAR regulation of triglyceride metabolism

From LipidomicsWiki

Bile acid sequestrants and bile diversion are known to induce bile acid synthesis but increase serum triglyceride levels. CDCA and a FXR agonist, GW4064, reduce serum triglycerides in mice (Maloney et al. 2000). The FXR agonist reduces serum triglyceride levels by inducing ApoCII, a cofactor of LPL that hydrolyzes triglycerides carried by VLDL and CM in the epithelium of blood vessels in muscles and adipocytes (Urizar et al. 2000), and inhibiting the ApoCIII gene (Claudel et al. 2003). PPAR agonists stimulate fatty acid oxidation and reduce serum triglyceride levels by inducing ApoAI, ApoAV and LPL. ApoAV is a newly identified lipoprotein that has been shown to reduce serum triglycerides (Pennacchio et al. 2001) PARα and FXR induce ApoAV expression in the liver (Prieur et al. 2003). Interestingly, FXR induces human, but not mouse liver PPARα. It appears that FXR and PPARα may coordinately regulate triglyceride metabolism. The LXRα agonists cause hypertriglyceridemia by inducing sterol response element binding protein 1c (SREBP-1c), which stimulates the genes involved in cholesterol and triglyceride synthesis (Repa et al. 2000). Despite their adverse effects on hypertriglyceridemia, LXR agonists are potential therapeutic agents for dyslipidemia and atherosclerosis (Lund et al.

2003).