Regulation of hepatic lipogenesis by the zinc finger protein Zbtb20

Gan Liu, Luting Zhou, Hai Zhang, Rong Chen, Ye Zhang, Ling Li, Jun Yu Lu, Hui Jiang, Dong Liu, Shasha Qi, Ying Ming Jiang, Kai Yin, Zhifang Xie, Yuguang Shi, Yong Liu, Xuetao Cao, Yu Xia Chen, Dajin Zou, Weiping J. Zhang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Hepatic de novo lipogenesis (DNL) converts carbohydrates into triglycerides and is known to influence systemic lipid homoeostasis. Here, we demonstrate that the zinc finger protein Zbtb20 is required for DNL. Mice lacking Zbtb20 in the liver exhibit hypolipidemia and reduced levels of liver triglycerides, along with impaired hepatic lipogenesis. The expression of genes involved in glycolysis and DNL, including that of two ChREBP isoforms, is decreased in livers of knockout mice. Zbtb20 binds to and enhances the activity of the ChREBP-α promoter, suggesting that altered metabolic gene expression is mainly driven by ChREBP. In addition, ChREBP-β overexpression largely restores hepatic expression of genes involved in glucose and lipid metabolism, and increases plasma and liver triglyceride levels in knockout mice. Finally, we show that Zbtb20 ablation protects from diet-induced liver steatosis and improves hepatic insulin resistance. We suggest ZBTB20 is an essential regulator of hepatic lipogenesis and may be a therapeutic target for the treatment of fatty liver disease.

Original languageEnglish (US)
Article number14824
JournalNature communications
Volume8
DOIs
StatePublished - Mar 22 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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