Co-IP and luciferase assays confirmed that PRDM16 regulates the transcriptional activity, expression, and interaction of PPARα and PGC-1α, while the overexpression of PPARα and PGC-1α reverses PRDM16 deficiency-induced cellular dysfunction in T2DM model. The gene discussed is PPARGC1A; the disease is type 2 diabetes mellitus.