Regulation of hepatic lipogenesis by the zinc finger protein Zbtb20
Male
0301 basic medicine
Science
Carbohydrates
Article
03 medical and health sciences
Dietary Carbohydrates
Animals
Homeostasis
Humans
Cell Nucleus
Mice, Knockout
0303 health sciences
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Lipogenesis
Q
Nuclear Proteins
3. Good health
Fatty Liver
Mice, Inbred C57BL
Protein Transport
Glucose
Gene Expression Regulation
Liver
Insulin Resistance
Glycolysis
Gene Deletion
DOI:
10.1038/ncomms14824
Publication Date:
2017-03-22T10:50:37Z
AUTHORS (19)
ABSTRACT
AbstractHepatic 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.
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CITATIONS (51)
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