The aims of the present study were to evaluate the expression of prolyl4-hydroxylase subunit alpha 3 (P4HA3) in adipocytes and adiposetissue and to explore its effect on obesity and type 2 diabetes mellitus (T2DM).We initially demonstrated that P4HA3 was significantlyupregulated in the subcutaneous adipose tissue of obesity and T2DM patients, andits functional roles in adipocyte differentiation and insulin resistance wereinvestigated using in vitro and in vivomodels. The gene discussed is P4HA3; the disease is obesity due to melanocortin 4 receptor deficiency.