1. Microbiota-derived 3-phenylpropionic acid promotes myotube hypertrophy by Foxo3/NAD+ signaling pathway.
- Author
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Li, Penglin, Feng, Xiaohua, Ma, Zewei, Yuan, Yexian, Jiang, Hongfeng, Xu, Guli, Zhu, Yunlong, Yang, Xue, Wang, Yujun, Zhu, Canjun, Wang, Songbo, Gao, Ping, Jiang, Qingyan, and Shu, Gang
- Subjects
KREBS cycle ,BLOOD circulation ,CELLULAR signal transduction ,MUSCLE mass ,SKELETAL muscle ,MICROBIAL metabolites ,PROTEOLYSIS ,PHENYLALANINE ,MUSCLE growth - Abstract
Background: Gut microbiota and their metabolites play a regulatory role in skeletal muscle growth and development, which be known as gut-muscle axis. 3-phenylpropionic acid (3-PPA), a metabolite produced by colonic microorganisms from phenylalanine in the gut, presents in large quantities in the blood circulation. But few study revealed its function in skeletal muscle development. Results: Here, we demonstrated the beneficial effects of 3-PPA on muscle mass increase and myotubes hypertrophy both in vivo and vitro. Further, we discovered the 3-PPA effectively inhibited protein degradation and promoted protein acetylation in C2C12 and chick embryo primary skeletal muscle myotubes. Mechanistically, we supported that 3-PPA reduced NAD
+ synthesis and subsequently suppressed tricarboxylic acid cycle and the mRNA expression of SIRT1/3, thus promoting the acetylation of total protein and Foxo3. Moreover, 3-PPA may inhibit Foxo3 activity by directly binding. Conclusions: This study firstly revealed the effect of 3-PPA on skeletal muscle growth and development, and newly discovered the interaction between 3-PPA and Foxo3/NAD+ which mechanically promote myotubes hypertrophy. These results expand new understanding for the regulation of gut microbiota metabolites on skeletal muscle growth and development. [ABSTRACT FROM AUTHOR]- Published
- 2024
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