FFAR3 (GPR41) is a G protein-coupled receptor activated by short-chain fatty acids (SCFAs)—primarily propionate, butyrate, and pentanoate—produced by gut microbiota fermenting dietary fiber 1. Upon SCFA activation, FFAR3 couples to pertussis toxin-sensitive G(i/o)-alpha proteins, triggering calcium mobilization, MAPK/ERK phosphorylation, and cAMP inhibition to regulate whole-body energy homeostasis 2. The receptor modulates sympathetic nervous system activity and may regulate blood pressure, gut hormone secretion (PYY, leptin), and intestinal gluconeogenesis 3. FFAR3 signaling also promotes IL-22 production by immune cells through HDAC inhibition and AhR/HIF1α pathways, maintaining intestinal barrier integrity and mucosal immunity 4. Dysbiosis-associated SCFA deficiency impairs FFAR3 signaling in inflammatory bowel diseases, suggesting therapeutic potential through SCFA supplementation or microbiota restoration 5. Additionally, FFAR3 activation by butyrate demonstrates neuroprotective effects in neurological disorders including Alzheimer's disease through reduced neuroinflammation and enhanced histone acetylation 6. Human monocytes express FFAR3 and display anti-inflammatory responses to SCFA-mediated activation, distinguishing human from murine immune regulation 7.