m6A Regulates Liver Metabolic Disorders and Hepatogenous Diabetes

被引:0
作者
Yuhuan Li [1 ,2 ]
Qingyang Zhang [2 ,3 ,4 ,5 ]
Guanshen Cui [2 ,3 ,4 ,5 ]
Fang Zhao [6 ]
Xin Tian [6 ]
Bao-Fa Sun [2 ,3 ,4 ,7 ]
Ying Yang [2 ,3 ,4 ,5 ,7 ]
Wei Li [1 ,7 ]
机构
[1] State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences
[2] University of Chinese Academy of Sciences
[3] 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
[4] China National Center for Bioinformation
[5] Sino-Danish College, University of Chinese Academy of Sciences
[6] Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University
[7] Institute for Stem Cell and Regeneration, Chinese Academy of Sciences
基金
中国国家自然科学基金;
关键词
Mettl3; RNA methylation; High fat diet; Insulin resistance; Lpin1;
D O I
暂无
中图分类号
R587.1 [糖尿病];
学科分类号
1002 ; 100201 ;
摘要
N6-methyladenosine(m6A) is one of the most abundant modifications on m RNAs 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 HFDinduced 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.
引用
收藏
页码:371 / 383
页数:13
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