法尼甾体X受体
小异二聚体伴侣
肝X受体
内科学
胆酸
内分泌学
高甘油三酯血症
鹅去氧胆酸
胆汁酸
胆固醇7α羟化酶
极低密度脂蛋白
微粒体甘油三酯转移蛋白
胆固醇
脂质代谢
脂肪肝
G蛋白偶联胆汁酸受体
核受体
化学
CYP8B1
甾醇调节元件结合蛋白
脂肪变性
脂肪生成
甘油三酯
脂滴
胆固醇逆向转运
脂蛋白
生物
生物化学
甾醇
医学
基因
转录因子
作者
Mitsuhiro Watanabe,Sander M. Houten,Li Wang,Antonio Moschetta,David J. Mangelsdorf,Richard A. Heyman,David Moore,Johan Auwerx
摘要
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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