| 论文作者 |
Lin, J; Nie, QX; Cheng, J; Zhong, YN; Zhang, TY; Zhang, XY; Ge, XY; Ding, Y; Niu, CY; Gao, YH; Wang, K; Gao, MX; Wang, XM; Chen, WX; Yun, CY; Ye, C; Xu, JK; Shaoyong, W; Zhang, LJ; Shang, P; Luo, X; Zhang, ZW; Zheng, X; Sha, XY; Zhang, JX; Nie, SP; Zhang, XG; Ren, FZ; Liu, HY; Dong, ER; Yu, X; Ji, LN; Pang, YL; Sun, JP; Jiang, CT |
| 摘要 |
Recently, microbial amino-acid-conjugated bile acids (MABAs) have been found to be prevalent in human samples. However, their physiological significance is still unclear. Here, we identify tryptophan-conjugated cholic acid (Trp-CA) as the most significantly decreased MABA in patients with type 2 diabetes (T2D), and its abundance is negatively correlated with clinical glycemic markers. We further demonstrate that Trp-CA improves glucose tolerance in diabetic mice. Mechanistically, we find that Trp-CA is a ligand of the orphan G protein-coupled receptor (GPCR) Mas-related G protein-coupled receptor family member E (MRGPRE) and determine the binding mode between the two. Both MRGPRE-Gs-cyclic AMP (cAMP) and MRGPRE-beta-arrestin-1-aldolase A (ALDOA) signaling pathways contribute to the metabolic benefits of Trp-CA. Additionally, we find that the bacterial bile salt hydrolase/transferase of Bifidobacterium is responsible for the production of Trp-CA. Together, our findings pave the way for further research on MABAs and offer additional therapeutic targets for the treatment of T2D. |
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