Solid evidence has demonstrated the elevation of the UPR in the liver of patients with diabetes, obesity, and NAFLD, whereas administration of the chemical chaperones 4-phenyl butyric acid (PBA) or taurine-conjugated ursodeoxycholic acid (TUDCA) to ob/ob mice normalized blood glucose levels, improved insulin sensitivity, and reduced hepatic steatosis [59,60]. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.