TGR5 and Immunometabolism: Insights from Physiology and Pharmacology

In the past decade substantial progress has been made in understanding how the insurgence of chronic low-grade inflammation influences the physiology of several metabolic diseases. Tissue-resident immune cells have been identified as central players in these processes, linking inflammation to metabolism. The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and its activation mediates potent anti-inflammatory effects. Herein, we summarize recent advances in TGR5 research, focusing on the downstream effector pathways that are modulated by TGR5 activators, and on its therapeutic potential in inflammatory and metabolic diseases.

TrendsLow-grade chronic inflammation, characterized by elevated proinflammatory gene expression, confers susceptibility to metabolic diseases and promotes metabolic syndrome.Bile acids, initially discovered as lipid solubilizers, are now recognized as signaling molecules with an anti-inflammatory action.TGR5 activation blocks inflammation by reducing macrophage activation, thereby preserving metabolic function.TGR5 agonists have therapeutic potential to treat immunometabolic disorders, including atherosclerosis and diet-induced obesity.