The Nuclear Orphan Receptor NR2F6 Promotes Hepatic Steatosis through Upregulation of Fatty Acid Transporter CD36

Zhou, Bing1; Jia, Lijing2; Zhang, Zhijian3; Xiang, Liping1; Yuan, Youwen4; Zheng, Peilin2; Liu, Bin1; Ren, Xingxing1; Bian, Hua1; Xie, Liwei5; Li, Yao6; Lu, Jieli7; Zhang, Huijie4; Lu, Yan1

2020-09-21

10.1002/advs.202002273

Advanced Science   影响因子和分区

2198-3844

2198-3844

Nuclear receptors (NRs) are a superfamily of transcription factors which sense hormonal signals or nutrients to regulate various biological events, including development, reproduction, and metabolism. Here, this study identifies nuclear receptor subfamily 2, group F, member 6 (NR2F6), as an important regulator of hepatic triglyceride (TG) homeostasis and causal factor in the development of non-alcoholic fatty liver disease (NAFLD). Adeno-associated virus (AAV)-mediated overexpression of NR2F6 in the liver promotes TG accumulation in lean mice, while hepatic-specific suppression of NR2F6 improves obesity-associated hepatosteatosis, insulin resistance, and methionine and choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH). Mechanistically, the fatty acid translocase CD36 is identified as a transcriptional target of NR2F6 to mediate its steatotic role. NR2F6 is able to bind directly onto the CD36 promoter region in hepatocytes and increases the enrichment of nuclear receptor coactivator 1 (SRC-1) and histone acetylation at its promoter. Of pathophysiological significance, NR2F6 is significantly upregulated in the livers of obese mice and NAFLD patients. Moreover, treatment with metformin decreases NR2F6 expression in obese mice, resulting in suppression of CD36 and reduced hepatic TG contents. Therefore, these results provide evidence for an unpredicted role of NR2F6 that contributes to liver steatosis and suggest that NR2F6 antagonists may present a therapeutic strategy for reversing or treating NAFLD/NASH pathogenesis.

CD36 non-alcoholic fatty liver disease nuclear receptors obesity

SCI ; EI

英语

其他

National Key Research and Development Program[2018YFA0800400] ; National Natural Science Foundation of China[81722013][81670716][81670795] ; Natural Science Foundation of Guangdong Province[2018B030311031] ; Shenzhen Science, Technology and Innovation Commission[JCYJ20160422150209240] ; Shanghai Key Laboratory of Veterinary Biotechnology[klab201713] ; Shanghai Sailing Program[20YF1406300]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000571240800001

WILEY

Web of Science

1.Fudan Univ, Zhongshan Hosp, Key Lab Metab & Mol Med, Fudan Inst Metab Dis,Dept Endocrinol & Metab,Mini, Shanghai 230032, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Dept Endocrinol,Shenzhen Peoples Hosp,Clin Med Co, Shenzhen 518020, Guangdong, Peoples R China
3.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Endocrinol & Metab, Shanghai 201620, Peoples R China
4.Southern Med Univ, Nanfang Hosp, Dept Endocrinol & Metab, Guangzhou 510515, Guangdong, Peoples R China
5.Guangdong Acad Sci, State Key Lab Appl Microbiol Southern China, Guangdong Prov Key Lab Microbial Culture Collect, Guangdong Open Lab Appl Microbiol,Guangdong Inst, Guangzhou 510070, Guangdong, Peoples R China
6.Shanghai Jiao Tong Univ, Sch Med, Dept Lab Anim Sci, Shanghai 200025, Peoples R China
7.Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Endocrinol & Metab, Shanghai 200025, Peoples R China

Zhou, Bing,Jia, Lijing,Zhang, Zhijian,et al. The Nuclear Orphan Receptor NR2F6 Promotes Hepatic Steatosis through Upregulation of Fatty Acid Transporter CD36[J]. Advanced Science,2020,7(21).

Zhou, Bing.,Jia, Lijing.,Zhang, Zhijian.,Xiang, Liping.,Yuan, Youwen.,...&Lu, Yan.(2020).The Nuclear Orphan Receptor NR2F6 Promotes Hepatic Steatosis through Upregulation of Fatty Acid Transporter CD36.Advanced Science,7(21).

Zhou, Bing,et al."The Nuclear Orphan Receptor NR2F6 Promotes Hepatic Steatosis through Upregulation of Fatty Acid Transporter CD36".Advanced Science 7.21(2020).