On macrophages and Kupffer cells, activation of TGR5 dampens NF-κB-mediated cytokine expression, modulates immune signals of Treg and TH17, and regulates immunity and inflammation.100,135 TGR5 on brown adipose tissue activates cAMP-dependent iodothyronine deiodinase 2 which converts inactive thyroxine into active thyroid hormone and regulates energy homeostasis.136 TGR5 on hepatic stellate cells promotes the formation of liver fibrosis.137 Besides, TGR5 on cholangiocytes regulates resorptive and secretory mediators, and modulates bile flow and composition138 (Fig. 6c). Here, GPBAR1 is linked to Hepatic fibrosis.