Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c
Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c
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DOI：
10.1172/jci200421025
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发表时间：
2004-05-01
影响因子：
15.9
通讯作者：
Auwerx, J
中科院分区：
文献类型：
--
作者：
Watanabe, M;Houten, SM;Auwerx, J
我们探索胆汁酸对甘油三酯（TG）稳态的影响，使用分子，细胞和动物模型的组合。胆酸（CA）可防止高胆固醇血症小鼠模型中肝脏TG蓄积、VLDL分泌和血清TG升高。在分子水平上，CA降低了SREBP-1c及其脂肪生成靶基因的肝脏表达。通过使用小鼠短异源二聚体伴侣（SHP）和肝脏X受体（LXR）α和β的突变体，我们证明了天然或合成法尼醇X受体（FXR）激动剂对SHP和LXR α和LXR β的SR-EBP-1c表达的减少的关键依赖性。这些结果表明，应探讨旨在提高FXR活性和SHP抑制作用的策略，以纠正高脂血症。
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 SR-EBP-1c expression by either natural or synthetic farnesoid X receptor (FXR) agonists on both SHP and LXRalpha and LXRbeta. These results suggest that strategies aimed at increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia.