INS and obesity due to melanocortin 4 receptor deficiency: Although the mechanisms underlying how obesity and FFAs-induced insulin resistance remain incompletely understood, mainstream views suggest that excessive FFAs can lead to dysfunction in gluconeogenesis and glycogen synthesis by increasing the level of intracellular phosphorylated glycogen synthase, down-regulating the phosphorylation of protein kinase B (p-AKT), reducing the expression of glycogen synthase, and inhibiting the insulin signal pathway (132, 150, 151).