Using mouse-human chimeric TGR5 revealed that three amino acid residues (Q77(ECL1), R80(ECL1), and Y89(3.29)) are important in the human TGR5-nomilin interaction, and demonstrated that four hydrophilic hydrogen-bonding interactions occur between nomilin and human TGR5 [64], which provided the structure basis for the modification of nomilin as anti-obesity drugs. This evidence concerns the gene GPBAR1 and obesity due to melanocortin 4 receptor deficiency.