TGR5related

TGR5-related refers to biology associated with the G protein-coupled bile acid receptor known as TGR5, or GPBAR1 (G protein-coupled bile acid receptor 1). TGR5 is a cell-surface receptor activated by several bile acids, with signaling primarily via Gs proteins that increase intracellular cyclic AMP (cAMP). In some contexts, TGR5 can influence other pathways as well, but the canonical response is cAMP-mediated.

Tissue distribution and signaling effects are diverse. TGR5 is expressed in enteroendocrine cells of the intestine, cholangiocytes, liver macrophages, adipose tissue, and various other cell types. Activation leads to elevated cAMP, triggering downstream effects such as PKA signaling and CREB activation. In humans and animals, TGR5 contributes to multiple physiological processes, including regulation of energy expenditure, glucose metabolism, and inflammatory responses.

Functional roles include promoting GLP-1 secretion from intestinal L-cells, which can influence insulin release and glucose homeostasis. In brown adipose tissue, TGR5 activation can induce type 2 iodothyronine deiodinase (DIO2), increasing local T3 production and thermogenesis. Anti-inflammatory effects have been observed in macrophages, where TGR5 signaling can dampen pro-inflammatory pathways. TGR5 also participates in bile duct function and gallbladder motility, reflecting its role in bile acid physiology.

Clinical relevance and research are focused on TGR5 as a therapeutic target for metabolic diseases such as obesity, type 2 diabetes, and nonalcoholic fatty liver disease. Several selective TGR5 agonists have shown promise in preclinical models, but clinical development faces challenges including potential adverse effects and tissue-specific responses. As of now, TGR5-targeted therapies are investigational and not approved for standard clinical use.