mRNA m⁶A methylation downregulates adipogenesis in porcine adipocytes.

Fat Mass and Obesity-associated protein (FTO), associated with obesity, is proved to demethylate N6-methyladenosine (m(6)A), which raises questions regarding whether m(6)A plays vital roles in adipogenesis. To prove this, overexpression and knockdown of FTO and METTL3, as well as the chemical treatment in procine adipocytes were conducted. The results showed FTO negatively regulated m(6)A levels and positively regulated adipogenesis, while METTL3 positively correlated with m(6)A levels and negatively with adipogenesis. To remove the potential effect of FTO and METTL3 gene, chemical reagents of methylation inhibitor cycloleucine and methyl donor betaine were used to test the regulation effect of m(6)A on adipogenesis. The results showed the inverse effect of m(6)A on lipid accumulation in porcine adipocytes. These findings provide compelling evidence that m(6)A plays a critical role in the regulation of adipogenesis.