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Abstract
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.
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Details
1 Kyoto University, Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033); Kyoto University, Laboratory of Molecular Endocrinology, Graduate School of Pharmaceutical Sciences, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033); Kyoto University, Center for Living Systems Information Science (CeLiSIS), Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033)
2 Kyoto University, Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033)
3 Kyoto University, Laboratory of Molecular Endocrinology, Graduate School of Pharmaceutical Sciences, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033)
4 Maruzen Pharmaceuticals Co., Ltd., Research Center, Fukuyama, Japan (GRID:grid.258799.8)
5 Kyoto University, Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033); Kyoto University, Laboratory of Molecular Endocrinology, Graduate School of Pharmaceutical Sciences, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033); Tokyo University of Agriculture and Technology, Department of Applied Biological Science, Graduate School of Agriculture, Fuchu, Japan (GRID:grid.136594.c) (ISNI:0000 0001 0689 5974)