FTO promotes SREBP1c maturation and enhances CIDEC transcription during lipid accumulation in HepG2 cells

Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids
Ao ChenGuoquan Liu

Abstract

The fat mass and obesity-associated (FTO) gene is tightly related to body weight and fat mass, and plays a pivotal role in regulating lipid accumulation in hepatocytes. However, the mechanisms underlying its function are poorly understood. Sterol regulatory element binding protein-1c (SREBP1c) is a transcription factor that regulates lipogenesis. Cell death-inducing DFFA (DNA fragmentation factor-α)-like effector c (CIDEC) plays a crucial role in lipid droplets (LDs) size controlling and lipid accumulation. In this report, we first observed that FTO overexpression in HepG2 cells resulted in an increase of lipogenesis and up-regulation of SREBP1c and CIDEC, two key regulatory factors in lipogenesis. In contrast, FTO knockdown in HepG2 cells resulted in a decrease of lipogenesis and down-regulation of SREBP1c and CIDEC expression. Moreover, SREBP1c knockdown resulted in a decrease of lipogenesis in HepG2 cells with FTO overexpression. In addition, FTO demethylation defect mutant presented less transcription of the key genes, and less nuclear translocation and maturation of SREBP1c. Further investigation demonstrated that overexpression of SREBP1c in HepG2 cells also promoted high CIDEC expression. Luciferase reporter assays showe...Continue Reading

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Citations

Sep 3, 2019·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Jiamin WuXiang Zhong
Oct 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lulu ZhouXiaodong Chen
Dec 18, 2019·American Journal of Physiology. Endocrinology and Metabolism·Luis V Herrera-MarcosJesús Osada
Apr 25, 2020·Journal of Hepatology·Zhicong ZhaoQiang Xia
Aug 17, 2019·Molecular and Cellular Endocrinology·Tamiris Ingrid Petito-da-SilvaSandra Barbosa-da-Silva
Sep 25, 2021·Canadian Journal of Physiology and Pharmacology·Weixiao Zhou, Dongjiang Cai

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