2. Academic Validation
  3. m6A Regulates Liver Metabolic Disorders and Hepatogenous Diabetes

m6A Regulates Liver Metabolic Disorders and Hepatogenous Diabetes

  • Genomics Proteomics Bioinformatics. 2020 Aug;18(4):371-383. doi: 10.1016/j.gpb.2020.06.003.
Yuhuan Li 1,  Qingyang Zhang 2,  Guanshen Cui 2,  Fang Zhao 3,  Xin Tian 3,  Bao-Fa Sun 4,  Ying Yang 5,  Wei Li 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China.
  • 2 University of Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; China National Center for Bioinformation, Beijing 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China.
  • 3 Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
  • 4 University of Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; China National Center for Bioinformation, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
  • 5 University of Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; China National Center for Bioinformation, Beijing 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: yingyang@big.ac.cn.
  • 6 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: liwei@ioz.ac.cn.
PMID: 33160098 DOI: 10.1016/j.gpb.2020.06.003
Abstract

N6-methyladenosine (m6A) is one of the most abundant modifications on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex (MTC) containing a key factor methyltransferase-like 3 (METTL3). However, the functions of METTL3 and m6A modification in hepatic lipid and glucose metabolism remain unclear. Here, we showed that both METTL3 expression and m6A level increased in the livers of mice with high fat diet (HFD)-induced metabolic disorders. Overexpression of METTL3 aggravated HFD-induced liver metabolic disorders and Insulin resistance. In contrast, hepatocyte-specific knockout of METTL3 significantly alleviated HFD-induced metabolic disorders by slowing weight gain, reducing lipid accumulation, and improving Insulin sensitivity. Mechanistically, METTL3 depletion-mediated m6A loss caused extended RNA half-lives of metabolism-related genes, which consequently protected mice against HFD-induced metabolic syndrome. Our findings reveal a critical role of Mettl3-mediated m6A in HFD-induced metabolic disorders and hepatogenous diabetes.

Keywords

High fat diet; Insulin resistance; Lpin1; Mettl3; RNA methylation.

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