Ffar3, also known as GPR41, is a G protein-coupled receptor activated by short-chain fatty acids (SCFAs), mainly acetate, butyrate, and propionate [2]. It is involved in multiple physiological functions such as metabolism and immune response regulation, and is part of the microbiota-gut-brain axis [2,3].

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 FFAR2/3 signaling, including that of Ffar3, due to low butyrate levels caused by a decline in butyrate-producing bacteria in aged gut microbiota, leads to increased gut permeability, inflammation, and brain abnormalities [1]. In another study, global knockout FFAR3 (Ffar3(-/-)) mouse islets secreted more insulin in a glucose-dependent manner compared to wild-type islets, suggesting that FFAR3 signaling inhibits glucose-dependent insulin secretion through a Gαi/o pathway [4].

In conclusion, Ffar3 plays a crucial role in maintaining gut-brain health and regulating insulin secretion. The use of Ffar3 knockout mouse models has revealed its significance in age-related cognitive decline and metabolic regulation, providing insights into potential therapeutic strategies for age-associated diseases and diabetes [1,4].

References:

1. Mishra, Sidharth P, Jain, Shalini, Wang, Bo, Rane, Sushil G, Yadav, Hariom. 2024. Abnormalities in microbiota/butyrate/FFAR3 signaling in aging gut impair brain function. In JCI insight, 9, . doi:10.1172/jci.insight.168443. https://pubmed.ncbi.nlm.nih.gov/38329121/

2. Kimura, Ikuo, Ichimura, Atsuhiko, Ohue-Kitano, Ryuji, Igarashi, Miki. 2019. Free Fatty Acid Receptors in Health and Disease. In Physiological reviews, 100, 171-210. doi:10.1152/physrev.00041.2018. https://pubmed.ncbi.nlm.nih.gov/31487233/

3. Stilling, Roman M, van de Wouw, Marcel, Clarke, Gerard, Dinan, Timothy G, Cryan, John F. 2016. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? In Neurochemistry international, 99, 110-132. doi:10.1016/j.neuint.2016.06.011. https://pubmed.ncbi.nlm.nih.gov/27346602/

4. Priyadarshini, Medha, Layden, Brian T. 2015. FFAR3 modulates insulin secretion and global gene expression in mouse islets. In Islets, 7, e1045182. doi:10.1080/19382014.2015.1045182. https://pubmed.ncbi.nlm.nih.gov/26091414/