法尼甾体X受体
小异二聚体伴侣
脂肪变性
内分泌学
内科学
脂肪肝
非酒精性脂肪肝
核受体
葡萄糖稳态
基因剔除小鼠
受体
过氧化物酶体增殖物激活受体
生物
脂质代谢
化学
胰岛素抵抗
生物化学
糖尿病
医学
转录因子
疾病
基因
作者
Oludemilade Akinrotimi,Ryan Riessen,Philip VanDuyne,Jung Eun Park,Yoon Kwang Lee,Lee‐Jun Wong,Ann Marie Zavacki,Kristina Schoonjans,Sayeepriyadarshini Anakk
出处
期刊:Hepatology
[Lippincott Williams & Wilkins]
日期:2017-06-06
卷期号:66 (6): 1854-1865
被引量:47
摘要
Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are important regulators of bile acid, lipid, and glucose homeostasis. Here, we show that global Fxr –/– Shp –/– double knockout (DKO) mice are refractory to weight gain, glucose intolerance, and hepatic steatosis when challenged with high‐fat diet. DKO mice display an inherently increased capacity to burn fat and suppress de novo hepatic lipid synthesis. Moreover, DKO mice were also very active and that correlated well with the observed increase in phosphoenolpyruvate carboxykinase expression, type IA fibers, and mitochondrial function in skeletal muscle. Mechanistically, we demonstrate that liver‐specific Shp deletion protects against fatty liver development by suppressing expression of peroxisome proliferator‐activated receptor gamma 2 and lipid‐droplet protein fat‐specific protein 27 beta. Conclusion : These data suggest that Fxr and Shp inactivation may be beneficial to combat diet‐induced obesity and uncover that hepatic SHP is necessary to promote fatty liver disease. (H epatology 2017;66:1854–1865)
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