FGF21 and obesity due to melanocortin 4 receptor deficiency: SUMO-specific protease SENP1 deficiency leads to hyper-SUMOylation of SIRT3, which can protect mice from HFD-induced obesity by increasing oxidative phosphorylation and energy expenditure.298 SENP2 deSUMOylated PPARα and promoted its ubiquitylation, which in turn inhibited FGF21 expression and fatty acid oxidation.299 Meanwhile, FGF21 null mice are lipodystrophy and have less body fat, which is associated with PPARγ SUMOylation at lysine 107.