In addition to phosphorylation, leptin-induced STAT3 methylation by protein arginine N-methyltransferase 2 (PRMT2) was also shown to occur, and PRMT2−/− mice are lean, hypophagic, have reduced serum leptin levels and are more resistant to diet-induced obesity (DIO) compared to wild-type littermates (105). Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.