Affiliation:
1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science Nanjing University China
Abstract
Using a murine model of high‐fat diet (HFD)‐induced nonalcoholic fatty liver disease (NAFLD), we found that the expression of the epidermal growth factor receptor (EGFR) significantly decreased in hepatocytes. In vitro, free fatty acid influx decreased EGFR in hepatocytes. In HFD‐fed mice, ectopic expression of EGFR alleviated intrahepatic lipid accumulation and reduced serum triglyceride and cholesterol, whereas knockdown of EGFR aggravated hepatic steatosis. Notably, EGFR inhibited the induction of lipogenic genes, including Srebf1, Srebf2, Fasn, Acc1 and Ppara, both in vitro and in vivo. Mechanistically, EGFR potentiates TGF‐β/Smad signalling and augments the inhibitory effects of TGF‐β1 on lipogenic genes in hepatocytes. Our findings suggest a hitherto unknown paradigm in the pathogenesis of NAFLD, thereby providing a rational basis for future therapeutic considerations.
Funder
National Natural Science Foundation of China
Subject
Cell Biology,Genetics,Molecular Biology,Biochemistry,Structural Biology,Biophysics
Cited by
5 articles.
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