The TGR5−/− obese mice exhibited high daily food/energy intake, fat mass and inflammatory status. TGR5−/− obese mice maintained an attraction for lipids. In TBCs, the fatty acid-triggered Ca2+ signaling was increased in TBC from TGR5−/− obese mice. TGR5 may modulate fat eating behavior and obesity. The gene discussed is GPBAR1; the disease is obesity due to melanocortin 4 receptor deficiency.