Metformin combats obesity by targeting FTO in an m6A-YTHDF2-dependent manner. (6th October 2022)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of drug targeting. Volume 30:Number 9(2022)
• Page Start: 983
• Page End: 991
• Publication Date: 2022-10-06
• Subjects: Metformin -- FTO -- MCE -- adipogenesis -- obesity; Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.1080/1061186X.2022.2071906
• Languages: English
• ISSNs: 1061-186X

Abstract

Abstract: 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.