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  • Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-β1 and p38 MAPK Signaling Pathway.

Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-β1 and p38 MAPK Signaling Pathway.

International journal of molecular sciences (2023-07-29)
Xiaomao Luo, Huiling Zhang, Xiaorui Cao, Ding Yang, Yi Yan, Jiayin Lu, Xiaonan Wang, Haidong Wang
ABSTRACT

Fgf21 has been identified as playing a regulatory role in muscle growth and function. Although the mechanisms through which endurance training regulates skeletal muscle have been widely studied, the contribution of Fgf21 remains poorly understood. Here, muscle size and function were measured, and markers of fiber type were evaluated using immunohistochemistry, immunoblots, or qPCR in endurance-exercise-trained wild-type and Fgf21 KO mice. We also investigated Fgf21-induced fiber conversion in C2C12 cells, which were incubated with lentivirus and/or pathway inhibitors. We found that endurance exercise training enhanced the Fgf21 levels of liver and GAS muscle and exercise capacity and decreased the distribution of skeletal muscle fiber size, and fast-twitch fibers were observed converting to slow-twitch fibers in the GAS muscle of mice. Fgf21 promoted the markers of fiber-type transition and eMyHC-positive myotubes by inhibiting the TGF-β1 signaling axis and activating the p38 MAPK signaling pathway without apparent crosstalk. Our findings suggest that the transformation and function of skeletal muscle fiber types in response to endurance training could be mediated by Fgf21 and its downstream signaling pathways. Our results illuminate the mechanisms of Fgf21 in endurance-exercise-induced fiber-type conversion and suggest a potential use of Fgf21 in improving muscle health and combating fatigue.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
SB 203580, solid, ≥98% (HPLC)
Sigma-Aldrich
Anti-α-Tubulin antibody, Mouse monoclonal, clone DM1A, purified from hybridoma cell culture
Millipore
Protease Inhibitor Cocktail Set VI, The Protease Inhibitor Cocktail Set VI controls the activity of Protease. This small molecule/inhibitor is primarily used for Protease Inhibitors applications.