Activation of FXR and of a G protein–coupled bile acid receptor (GPBAR1, i.e., TGR5) by agonists improves insulin and glucose sensitivity and stimulates energy metabolism thus preventing diabetes mellitus, obesity, and nonalcoholic fatty liver disease, which is one of the leading causes of liver diseases, because of its association with obesity, type 2 diabetes mellitus, and dyslipidemia [107,141,284]. This evidence concerns the gene NR1H4 and obesity due to melanocortin 4 receptor deficiency.