INS and obesity due to melanocortin 4 receptor deficiency: Obesity induces insulin resistance, mediated by chronic low-grade inflammation including endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and hyperinsulinemia secondary to diminished insulin excretion via the kidney and the liver along with increased insulin production resulting from the increased number of pancreatic beta-cells, and weight loss is reported to attenuate or reverse obesity-induced insulin resistance [48,49].