Metformin combats obesity by targeting FTO in an m6A-YTHDF2-dependent manner

Obesity has become a health threat and hard enough to deal with. Evidences show that metformin could inhibit adipogenesis and combat obesity, while its mechanisms remain to be elucidated more comprehensively. In this study, we found that administration of metformin could combat obesity of mice induc...

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Bibliographic Details
Published in:Journal of drug targeting 2022-10, Vol.30 (9), p.983-991
Main Authors: Liao, Xing, Liu, Jiaqi, Chen, Yushi, Liu, Youhua, Chen, Wei, Zeng, Botao, Liu, Yuxi, Luo, Yaojun, Huang, Chaoqun, Guo, Guanqun, Wang, Yizhen, Wang, Xinxia
Format: Article
Language:English
Subjects:
adipogenesis
FTO
MCE
Metformin
obesity
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Summary:Obesity has become a health threat and hard enough to deal with. Evidences show that metformin could inhibit adipogenesis and combat obesity, while its mechanisms remain to be elucidated more comprehensively. In this study, we found that administration of metformin could combat obesity of mice induced by high-fat diet (HFD), indicated by strikingly decreased body weight and weight of inguinal white adipose tissue (iWAT) and epidydimal white adipose tissue (eWAT) compared with the control group. Mechanically, we revealed that metformin could inhibit protein expression of FTO, leading to increased m 6 A methylation levels of cyclin D1 (Ccnd1) and cyclin dependent kinase 2 (Cdk2), two crucial regulators in cell cycle. Ccnd1 and Cdk2 with increased m 6 A levels were recognised by YTH m 6 A RNA binding protein 2 (YTHDF2), causing an YTHDF2-dependent decay and decreased protein expressions. In consequence, mitotic clonal expansion (MCE) process was blocked and adipogenesis was inhibited.
ISSN:1061-186X
1029-2330
DOI:10.1080/1061186X.2022.2071906