They also showed that TGR5 and CCK synergistically activate nodose neurons to reduce food intake.95 TGR5 activation induces calcium (Ca2+) responses in L-cells and stimulates their release of GLP-1,96 which regulates glucose homeostasis and feeding behavior via vagal and/or hormonal routes.97 TGR5 is also expressed in the hypothalamus, and bile acids can circulate directly to the brain and prevent diet-induced obesity.98 LCA and DCA also activate TGR5 in enteric neurons and enterochromaffin cells (EC) in the colon to control motility.99,100. This evidence concerns the gene GPBAR1 and obesity due to melanocortin 4 receptor deficiency.