Abstract：
With exercise, muscle and bone produce factors with beneficial effects on brain, fat, and other organs. Exercise in mice increased fibroblast growth factor 23 (FGF23), urine phosphate, and the muscle metabolite L-β-aminoisobutyric acid (L-BAIBA), suggesting that L-BAIBA may play a role in phosphate metabolism. Here, we show that L-BAIBA increases in serum with exercise and elevates Fgf23 in osteocytes. The D enantiomer, described to be elevated with exercise in humans, can also induce Fgf23 but through a delayed, indirect process via sclerostin. The two enantiomers both signal through the same receptor, Mas-related G-protein-coupled receptor type D, but activate distinct signaling pathways; L-BAIBA increases Fgf23 through Gαs/cAMP/PKA/CBP/β-catenin and Gαq/PKC/CREB, whereas D-BAIBA increases Fgf23 indirectly through sclerostin via Gαi/NF-κB. In vivo, both enantiomers increased Fgf23 in bone in parallel with elevated urinary phosphate excretion. Thus, exercise-induced increases in BAIBA and FGF23 work together to maintain phosphate homeostasis.
摘要：
有了锻炼,肌肉和骨骼产生对大脑有益的因子，脂肪，和其他器官。小鼠的运动增加成纤维细胞生长因子23（FGF23），尿磷酸盐,和肌肉代谢产物L-β-氨基异丁酸（L-BAIBA），提示L-BAIBA可能在磷酸盐代谢中发挥作用。这里,我们显示，L-BAIBA在血清中随着运动而增加，并升高骨细胞中的Fgf23。D对映体，被描述为随着人类的锻炼而升高，也可以诱导Fgf23，但通过延迟，通过硬化素间接过程。两种对映体都通过相同的受体发出信号，Mas相关G蛋白偶联受体D型,但激活不同的信号通路；L-BAIBA通过Gαs/cAMP/PKA/CBP/β-catenin和Gαq/PKC/CREB增加Fgf23，而D-BAIBA通过Gαi/NF-κB通过硬化蛋白间接增加Fgf23。在体内,两种对映体都增加了骨骼中的Fgf23，同时尿磷酸盐排泄增加。因此，运动诱导的BAIBA和FGF23增加共同作用以维持磷酸盐稳态。
