27-Hydroxycholesterol Inhibits Sterol Regulatory Element-Binding Protein 1 Activation and Hepatic Lipid Accumulation in Mice

被引：29
作者：
Li, Di [1 ,2 ]
Long, Weiqing [3 ]
Huang, Rong [1 ,2 ]
Chen, Ying [1 ,2 ]
Xia, Min [1 ,2 ]
机构：
[1] Sun Yat Sen Univ, Guangdong Prov Key Lab Food Nutr & Hlth, Dept Nutr, Northern Campus, Guangzhou, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Sch Publ Hlth, Dept Nutr, Northern Campus, Guangzhou, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Clin Lab, Guangzhou, Guangdong, Peoples R China
来源：
OBESITY | 2018年 / 26卷 / 04期
基金：
中国国家自然科学基金;
关键词：
FATTY LIVER-DISEASE; INSULIN-RESISTANCE; ADIPOCYTE DIFFERENTIATION; CHOLESTEROL HOMEOSTASIS; ENDOPLASMIC-RETICULUM; APOLIPOPROTEIN-B; ACID SYNTHESIS; MESSENGER-RNA; METABOLISM; RECEPTOR;
D O I：
10.1002/oby.22130
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
ObjectiveAlthough 27-hydroxycholesterol (27-HC) has been reported as a potent regulator of lipid homeostasis, its role in hepatic lipogenesis remains obscure. The present study was designed to investigate the impact of 27-HC on sterol regulatory element-binding protein 1 (SREBP-1) and hepatic steatosis. MethodsIn this study, the 27-HC level in mice was upregulated by overexpressing CYP27A1 or treating primary hepatocytes with 27-HC, and then the hepatic lipid accumulation was detected. Results27-HC inhibited hepatic lipid accumulation and decreased the levels of the mature active form of SREBP-1. The expression of lipogenic genes, including acetyl coenzyme A carboxylase, fatty acid synthase, stearoyl-coenzyme A desaturase-1, and glycerol-3-phosphate acyltransferase, were also suppressed after 27-HC intervention. Furthermore, 27-HC induced expression of insulin-induced gene-2 (Insig-2), an endoplasmic reticulum protein that prevents SREBP activation, both in vivo and in vitro. The inhibitory effect of 27-HC on SREBP-1 activation was absent when Insig-2 was silenced. Finally, coimmunoprecipitation showed that 27-HC promoted the binding of Insig-2 to SREBP-1. ConclusionsThese studies demonstrated the suppressive effect of 27-HC on hepatic lipid accumulation and revealed a novel mechanism by which 27-HC regulates lipogenesis.
引用
收藏
页码：713 / 722
页数：10
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