The Demethylase Activity of FTO (Fat Mass and Obesity Associated Protein) Is Required for Preadipocyte Differentiation

摘要: FTO (fat mass and obesity associated gene) was genetically identified to be with body index (BMI), presumably through functional regulation of energy homeostasis. However, the cellular molecular mechanisms by which functions remain largely unknown. Using 3T3-L1 preadipocyte as a model study role in adipogenesis, we demonstrated that is functionally required for differentiation. knock-down siRNA inhibited differentiation, whereas ectopic over-expression enhanced process. The demethylase activity Level N6-methyladenosine (m6A) decreased cells over-expressing FTO. In contrast, overexpression R96Q, missense mutant lack activity, had no effect on m6A level impeded Treatment Rosiglitazone, PPARγ agonist, could overcome differentiation inhibition imposed R96Q mutant, suggesting mediated PPARγ.