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Publication : Regulation of hepatic lipogenesis by the zinc finger protein Zbtb20.

First Author  Liu G Year  2017
Journal  Nat Commun Volume  8
Pages  14824 PubMed ID  28327662
Mgi Jnum  J:244774 Mgi Id  MGI:5913553
Doi  10.1038/ncomms14824 Citation  Liu G, et al. (2017) Regulation of hepatic lipogenesis by the zinc finger protein Zbtb20. Nat Commun 8:14824
abstractText  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-alpha promoter, suggesting that altered metabolic gene expression is mainly driven by ChREBP. In addition, ChREBP-beta 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.
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