Li Yang, Liu Qiao, Pan Chuan-Ying, Lan Xian-Yong
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
Department of Pathology, Tangdu Hospital, Air Force Medical University, 710038, China.
Pharmacol Ther. 2025 Aug;272:108878. doi: 10.1016/j.pharmthera.2025.108878. Epub 2025 May 16.
Free Fatty Acid Receptor 2 (FFA2), also known as GPR43, is a receptor activated by short-chain fatty acids (SCFAs) with fewer than six carbons in their aliphatic chains. This receptor is expressed in immune cells, adipose tissue, the gastrointestinal tract, and pancreatic islet cells, where it plays a crucial role in the modulation of inflammation, lipid metabolism, insulin secretion, and appetite regulation. Extensive research has been conducted to elucidate the structural attributes and physiological functions of FFA2. Furthermore, several synthetic agonists have been developed for FFA2 that can preferentially activate certain G-proteins, demonstrating potential pharmacological advantages in both in vivo and in vitro studies. Herein, we review the structure and physiological functions of FFA2 and its synthetic ligands, discussing the structural basis of FFA2's biased signaling and the potential role of biased ligands targeting this receptor in the treatment of metabolic and neurodegenerative diseases.
游离脂肪酸受体2（FFA2），也称为GPR43，是一种由脂肪链中碳原子数少于六个的短链脂肪酸（SCFA）激活的受体。该受体在免疫细胞、脂肪组织、胃肠道和胰岛细胞中表达，在调节炎症、脂质代谢、胰岛素分泌和食欲方面发挥着关键作用。人们已经进行了广泛的研究来阐明FFA2的结构特性和生理功能。此外，还开发了几种针对FFA2的合成激动剂，它们可以优先激活某些G蛋白，在体内和体外研究中都显示出潜在的药理学优势。在此，我们综述FFA2及其合成配体的结构和生理功能，讨论FFA2偏向性信号传导的结构基础以及靶向该受体的偏向性配体在治疗代谢性疾病和神经退行性疾病中的潜在作用。
