Mettl3-mediated m6A modification plays a role in lipid metabolism disorders and progressive liver damage in mice by regulating lipid metabolism-related gene expression

作者：Dai, Guanqi; Huang, Shihao; Li, Yonglong; Tu, Xueyi; Xia, Jiawei; Zhou, Zhihao; Chen, Wanyi; Zhang, Ao; Lin, Jintao; Li, Yingchun; He, Danhua; Lin, Taoyan; Cong, Jinge; Lei, Ye; Han, Liuxin; Yao, Zhenxia; Liu, Weiwei; Zhou, Ying; Li, Qiwen; Li, Jing; Zhang, Yuqin; Wu, Aibing; Xiao, Dong^*; Wang, Wanshan^*; Zhao, Wentao^*; Jia, Junshuang^*; Lin, Xiaolin^*

来源：Aging-US, 2023, 15(12): 5550-5568.

• NAFLD
• m6A modification
• epigenetics
• lipid metabolism
• Mettl3

Aims: N6-methyladenosine (m6A), the most abundant and conserved epigenetic modification of mRNA, participates in various physiological and pathological processes. However, the roles of m6A modification in liver lipid metabolism have yet to be understood entirely. We aimed to investigate the roles of the m6A "writer" protein methyltransferase-like 3 (Mettl3) in liver lipid metabolism and the underlying mechanisms. Main Methods: We assessed the expression of Mettl3 in liver tissues of diabetes (db/db) mice, obese (ob/ob) mice, high saturated fat-, cholesterol-, and fructose-induced non-alcoholic fatty liver disease (NAFLD) mice, and alcohol abuse and alcoholism (NIAAA) mice by quantitative reverse-transcriptase PCR (qRT-PCR). Hepatocytespecific Mettl3 knockout mice were used to evaluate the effects of Mettl3 deficiency in mouse liver. The molecular mechanisms underlying the roles of Mettl3 deletion in liver lipid metabolism were explored by multiomics joint analysis of public data from the Gene Expression Omnibus database and further validated by qRTPCR and Western blot.

• 单位
  1; 南方医科大学; 6