FFAR4

FFAR4 (free fatty acid receptor 4, also known as GPR120) is a lipid-sensing G protein-coupled receptor (GPCR) activated by long-chain fatty acids—particularly omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)—that plays a crucial role in regulating metabolic and immune homeostasis^[1][2]. Mechanistically, FFAR4 activation induces β-arrestin-2-dependent signaling, thereby interfering with inflammatory signaling cascades and exerting anti-inflammatory effects; it also participates in the regulation of glucose homeostasis, fat accumulation, gastrointestinal hormone secretion, and insulin sensitivity^[1][3]。Consequently, FFAR4 is regarded as a key nutrient-sensing receptor linking fatty acid signaling to metabolic-inflammatory pathways, and it is closely associated with obesity, insulin resistance, and related cardiometabolic diseases^[2][3][4]。In disease models, FFAR4 activation ameliorates metabolic abnormalities and alleviates insulin resistance, underscoring its value as an experimental target in research on metabolic diseases and inflammation^[4][5]。Compared to FFAR1—a related receptor that also responds to long-chain fatty acids—FFAR4 exhibits distinct signaling characteristics and tissue-specific functions; furthermore, human FFAR4 exists as both long and short splice isoforms, whereas only the short isoform has been identified in rodents to date^[1][6]。In experimental studies, selective FFAR4 agonists such as TUG-891 and GSK137647A are widely used to elucidate receptor-mediated metabolic and anti-inflammatory effects, while the negative allosteric modulator AH-7614 is frequently employed to inhibit FFAR4 signaling pathways^[7][8]。

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