LNK deficiency improved glucose metabolism and IR in obese mice, suggesting the LNK might play a pivotal role in controlling glucolipid metabolism and obesity-induced IR by regulating IRS1/PI3K/Akt/AS160 signaling and the AKT/FOXO3 pathway [15,16]. Here, SH2B3 is linked to obesity due to melanocortin 4 receptor deficiency.