Ffar3, also known as GPR41, is a G protein-coupled receptor activated by short-chain fatty acids (SCFAs), mainly acetate, butyrate, and propionate. It is involved in multiple biological processes such as metabolism and immune regulation. SCFAs, produced by gut microbial fermentation of dietary fiber, bind to Ffar3, which is part of the signaling pathways related to gut-brain axis, energy metabolism, and immune functions [2,3,4,5].

In a study, young mice with intestine-specific loss of FFAR2/3 exhibited gut and brain abnormalities similar to those in older mice. This indicates that reduced Ffar3 signaling due to a decline in butyrate-producing bacteria in aged gut microbiota leads to low butyrate levels, which in turn results in suppressed mucin formation, increased gut permeability, inflammation, and brain dysfunction [1]. In another study, islets from global knockout FFAR3 (Ffar3(-/-)) mice secreted more insulin in a glucose-dependent manner compared to wild-type islets, suggesting that Ffar3 signaling mediates glucose-stimulated insulin secretion through a Gαi/o sensitive pathway [6].

In conclusion, Ffar3 plays a crucial role in maintaining gut and brain health, as well as in insulin secretion regulation. The use of Ffar3 knockout mouse models has been instrumental in revealing its functions in age-related gut-brain axis disorders and in pancreatic islet biology, providing insights into potential therapeutic strategies for related diseases.