FFAR3

FFAR3 (free fatty acid receptor 3, or GPR41) is a G protein-coupled receptor (GPCR) primarily activated by gut microbiota-derived short-chain fatty acids (SCFAs)—such as propionate, butyrate, and acetate—thereby linking dietary fiber metabolism to host physiological regulation^[1][2]. Functioning as a nutrient-sensing receptor, FFAR3 participates in energy homeostasis, gastrointestinal signaling, and metabolic regulation via SCFA-dependent signaling pathways^[1][3]. Mechanistically, FFAR3 mediates cellular responses to microbial metabolites and is involved in sympathetic nervous system activation, hormonal regulation, and adipocyte-related metabolic processes^[2][3]. In experimental models, alterations in FFAR3 signaling influence body fat composition, energy expenditure, and metabolic phenotypes, indicating its association with obesity, diabetes, and other metabolic diseases^[2][4][5]. Although FFAR3 responds to SCFAs similarly to the closely related FFAR2 (GPR43), distinct differences exist regarding ligand selectivity, signal transduction characteristics, tissue distribution, and physiological functions, suggesting that the two receptors play non-redundant roles in host metabolic regulation^[1][3][5]. This distinction is particularly significant for elucidating microbiota-host communication and the biological effects mediated by SCFAs^[3][6]. In research applications, FFAR3 can be activated by endogenous SCFAs and selective synthetic agonists, whereas β-hydroxybutyrate and certain research compounds have been reported to antagonize or modulate its activity, thereby providing pharmacological tools for investigating metabolic and neurophysiological signaling pathways^[5].

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