3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a metabolite produced by the gut microbiota through the conversion of 4-hydroxy-3-methoxycinnamic acid (HMCA), which is a widely distributed hydroxycinnamic acid-derived metabolite found abundantly in plants. Several beneficial effects of HMPA have been suggested, such as antidiabetic properties, anticancer activities, and cognitive function improvement, in animal models and human studies. However, the intricate molecular mechanisms underlying the bioaccessibility and bioavailability profile following HMPA intake and the substantial modulation of metabolic homeostasis by HMPA require further elucidation. In this study, we effectively identified and characterized HMPA-specific GPR41 receptor, with greater affinity than HMCA. The activation of this receptor plays a crucial role in the anti-obesity effects and improvement of hepatic steatosis by stimulating the lipid catabolism pathway. For the improvement of metabolic disorders, our results provide insights into the development of functional foods, including HMPA, and preventive pharmaceuticals targeting GPR41.

3-(4-羟基-3-甲氧基苯基)丙酸 (HMPA) 是肠道微生物群通过 4-羟基-3-甲氧基肉桂酸 (HMCA) 转化产生的代谢物，HMCA 是一种广泛分布的羟基肉桂酸衍生代谢物大量存在于植物中。在动物模型和人体研究中，HMPA 具有多种有益作用，例如抗糖尿病特性、抗癌活性和认知功能改善。然而，HMPA 摄入后的生物可及性和生物利用度概况以及 HMPA 对代谢稳态的实质性调节背后的复杂分子机制需要进一步阐明。在这项研究中，我们有效地鉴定和表征了 HMPA 特异性 GPR41 受体，其亲和力比 HMCA 更高。该受体的激活通过刺激脂质分解代谢途径，在抗肥胖作用和改善肝脂肪变性中发挥着至关重要的作用。为了改善代谢紊乱，我们的研究结果为开发功能性食品（包括 HMPA）和针对 GPR41 的预防性药物提供了见解。