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 m6A methylation levels of cyclin D1 (Ccnd1) and cyclin dependent kinase 2 (Cdk2), two crucial regulators in cell cycle. Ccnd1 and Cdk2 with increased m6A levels were recognised by YTH m6A 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.
Keywords:
Author contributions
Xing Liao and Xinxia Wang proposed the concept of the investigation. Xing Liao and Jiaqi Liu performed the most experiments and analysed the data. Yushi Chen, Youhua Liu, Wei Chen, Botao Zeng, Yuxi Liu helped finish the partial experiments, and Yaojun Luo, Chaoqun Huang, Guanqun Guo assisted in the slaughter performance of mice and sample collections. Xing Liao, Yizhen Wang and Xinxia Wang wrote the manuscript.
Disclosure statement
The authors declare no conflicts of interest. The authors alone are responsible for the content and writing of this article.