m6A Regulates Liver Metabolic Disorders and Hepatogenous Diabetes
- Author:
Li YUHUAN
1
,
2
;
Zhang QINGYANG
;
Cui GUANSHEN
;
Zhao FANG
;
Tian XIN
;
Sun BAO-FA
;
Yang YING
;
Li WEI
Author Information
1. State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing100101,China
2. University of Chinese Academy of Sciences,Beijing 100101,China
- Keywords:
Mettl3;
RNA methylation;
High fat diet;
Insulin resistance;
Lpin1
- From:
Genomics, Proteomics & Bioinformatics
2020;18(4):371-383
- CountryChina
- Language:Chinese
-
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). How-ever, 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 pro-tected mice against HFD-induced metabolic syndrome. Our findings reveal a critical role of Mettl3-mediated m6A in HFD-induced metabolic disorders and hepatogenous diabetes.
