Regulation of hepatic lipogenesis by the zinc finger protein Zbtb20

被引：57

作者：

Liu, Gan ^{[1
,2
]}

Zhou, Luting ^{[1
,2
]}

Zhang, Hai ^{[1
,2
]}

Chen, Rong ^{[1
,2
,3
]}

Zhang, Ye ^{[1
,2
]}

Li, Ling ^{[1
,2
]}

Lu, Jun-Yu ^{[1
,2
]}

Jiang, Hui ^{[1
]}

Liu, Dong ^{[1
]}

Qi, Shasha ^{[1
]}

Jiang, Ying-Ming ^{[4
,5
]}

Yin, Kai ^{[2
,6
]}

Xie, Zhifang ^{[1
,2
]}

Shi, Yuguang ^{[7
]}

Liu, Yong ^{[8
]}

Cao, Xuetao ^{[4
,5
]}

Chen, Yu-Xia ^{[1
,2
]}

Zou, Dajin ^{[2
,3
]}

Zhang, Weiping J. ^{[1
,2
,4
]}

机构：

[1] Second Mil Med Univ, Dept Pathophysiol, Shanghai 200433, Peoples R China

[2] Second Mil Med Univ, Obes & Diabet Res Ctr, Shanghai 200433, Peoples R China

[3] Changhai Hosp, Dept Endocrinol, Shanghai 200433, Peoples R China

[4] Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China

[5] Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

[6] Changhai Hosp, Dept Gen Surg, Shanghai 200433, Peoples R China

[7] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA

[8] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

ELEMENT-BINDING PROTEIN; STEAROYL-COA DESATURASE-1; ALPHA-FETOPROTEIN GENE; FATTY-ACID SYNTHESIS; DE-NOVO LIPOGENESIS; X-RECEPTOR LXR; INSULIN-RESISTANCE; TRANSCRIPTION FACTOR; THYROID-HORMONE; XYLULOSE; 5-PHOSPHATE;

D O I：

10.1038/ncomms14824

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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