Liver X receptor alpha induces 17beta-hydroxysteroid dehydrogenase-13 expression through SREBP-1c.
Liver X receptor alpha induces 17beta-hydroxysteroid dehydrogenase-13 expression through SREBP-1c.
复制标题
肝脏 X 受体 α 通过 SREBP-1c 诱导 17β-羟基类固醇脱氢酶-13 表达。
DOI：
10.1152/ajpendo.00310.2016
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Guan You-Fei
中科院分区：
文献类型：
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作者：
Su Wen;Peng Jun;Li Sha;Dai Yu-Bing;Wang Chun-Jiong;Xu Hu;Gao Min;Ruan Xiong-Zhong;Gustafsson Jan-Ake;Zhang Xiao-Yan;Guan You-Fei
Liver X receptors, including LXRα and LXRβ, are known to be master regulators of liver lipid metabolism. Activation of LXRα increases hepatic lipid storage in lipid droplets (LDs). 17β-Hydroxysteroid dehydrogenase-13 (17β-HSD13), a recently identified liver-specific LD-associated protein, has been reported to be involved in the development of nonalcoholic fatty liver disease. However, little is known about its transcriptional regulation. In the present study, we aimed at determining whether 17β-HSD13 gene transcription is controlled by LXRs. We found that treatment with T0901317, a nonspecific LXR agonist, increased both 17β-HSD13 mRNA and protein levels in cultured hepatocytes. It also significantly upregulated hepatic 17β-HSD13 expression in wild-type (WT) and LXRβ−/−mice but not in LXRα−/−mice. Basal expression of 17β-HSD13 in the livers of LXRα−/−mice was lower than that in the livers of WT and LXRβ−/−mice. Moreover, induction of hepatic 17β-HSD13 expression by T0901317 was almost completely abolished in SREBP-1c−/−mice. Bioinformatics analysis revealed a consensus sterol regulatory element (SRE)-binding site in the promoter region of the 17β-HSD13 gene. A 17β-HSD13 gene promoter-driven luciferase reporter and ChIP assays further confirmed that the 17β-HSD13 gene was under direct control of SREBP-1c. Collectively, these findings demonstrate that LXRα activation induces 17β-HSD13 expression in a SREBP-1c-dependent manner. 17β-HSD13 may be involved in the development of LXRα-mediated fatty liver.
