Liver X receptor α induces 17β-hydroxysteroid dehydrogenase-13 expression through SREBP-1c

Wen Su, Jun Peng, Sha Li, Yu Bing Dai, Chun Jiong Wang, Hu Xu, Min Gao, Xiong Zhong Ruan, Jan Åke Gustafsson, You Fei Guan, Xiao Yan Zhang

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E357-E367
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume312
Issue number4
DOIs
StatePublished - Apr 2017

Keywords

  • 17β-HSD13
  • Gene knockout
  • Lipid droplet
  • Nonalcoholic fatty liver disease
  • Nuclear receptor
  • SCDR9

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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