Regulation of hepatic lipogenesis by the zinc finger protein Zbtb20.
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.
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.|Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.
Gan
G
Liu
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.|Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.
Luting
L
Zhou
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.|Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.
Hai
H
Zhang
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.|Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.|Department of Endocrinology, Changhai Hospital, Shanghai 200433, China.
Rong
R
Chen
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.|Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.
Ye
Y
Zhang
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.|Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.
Ling
L
Li
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.|Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.
Jun-Yu
JY
Lu
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.
Hui
H
Jiang
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.
Dong
D
Liu
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.
Shasha
S
Qi
National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.|Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Ying-Ming
YM
Jiang
Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.|Department of General Surgery, Changhai Hospital, Shanghai 200433, China.
Kai
K
Yin
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.|Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.
Zhifang
Z
Xie
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245, USA.
Yuguang
Y
Shi
Institute of Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Science, Shanghai 200031, China.
Yong
Y
Liu
National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.|Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
Xuetao
X
Cao
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.|Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.
Yu-Xia
YX
Chen
Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.|Department of Endocrinology, Changhai Hospital, Shanghai 200433, China.
Dajin
D
Zou
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, China.|Obesity &Diabetes Research Center, Second Military Medical University, Shanghai 200433, China.|National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
Weiping J
0000-0003-4727-2380
WJ
Zhang
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002241:Carbohydrates / Q000737:chemistry; D002467:Cell Nucleus / Q000378:metabolism; D004040:Dietary Carbohydrates; D005234:Fatty Liver / Q000235:genetics / Q000473:pathology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D014158:Transcription, Genetic; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002241:Carbohydrates; D004040:Dietary Carbohydrates; C506001:Mlxipl protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D014280:Triglycerides; C520426:Zbtb20 protein, mouse; D005947:Glucose