INS and obesity due to melanocortin 4 receptor deficiency: In obesity, hyperplasia (cell number increase) and hypertrophy (cell size increase) of WAT is accompanied by increased levels of triglycerides and NEFA in plasma [8, 9], resulting in lipid deposition into plasma and tissues, such as liver and muscle, simultaneously triggering low-grade inflammation [10–13], reducing insulin sensitivity in adipose tissue, liver and skeletal muscle via insulin receptor substrate1 (IRS1)/AKT mediated insulin signaling [14–17], and ultimately leading to systemic insulin resistance and glucose and lipid metabolism disorders [18, 19].