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

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 ma...

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Detalles Bibliográficos
Autores principales: Luo, Xiaomao, Zhang, Huiling, Cao, Xiaorui, Yang, Ding, Yan, Yi, Lu, Jiayin, Wang, Xiaonan, Wang, Haidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10379449/
https://www.ncbi.nlm.nih.gov/pubmed/37511159
http://dx.doi.org/10.3390/ijms241411401
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author Luo, Xiaomao
Zhang, Huiling
Cao, Xiaorui
Yang, Ding
Yan, Yi
Lu, Jiayin
Wang, Xiaonan
Wang, Haidong
author_facet Luo, Xiaomao
Zhang, Huiling
Cao, Xiaorui
Yang, Ding
Yan, Yi
Lu, Jiayin
Wang, Xiaonan
Wang, Haidong
author_sort Luo, Xiaomao
collection PubMed
description 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.
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spelling pubmed-103794492023-07-29 Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-β1 and p38 MAPK Signaling Pathway Luo, Xiaomao Zhang, Huiling Cao, Xiaorui Yang, Ding Yan, Yi Lu, Jiayin Wang, Xiaonan Wang, Haidong Int J Mol Sci Article 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. MDPI 2023-07-13 /pmc/articles/PMC10379449/ /pubmed/37511159 http://dx.doi.org/10.3390/ijms241411401 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Luo, Xiaomao
Zhang, Huiling
Cao, Xiaorui
Yang, Ding
Yan, Yi
Lu, Jiayin
Wang, Xiaonan
Wang, Haidong
Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-β1 and p38 MAPK Signaling Pathway
title Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-β1 and p38 MAPK Signaling Pathway
title_full Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-β1 and p38 MAPK Signaling Pathway
title_fullStr Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-β1 and p38 MAPK Signaling Pathway
title_full_unstemmed Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-β1 and p38 MAPK Signaling Pathway
title_short Endurance Exercise-Induced Fgf21 Promotes Skeletal Muscle Fiber Conversion through TGF-β1 and p38 MAPK Signaling Pathway
title_sort endurance exercise-induced fgf21 promotes skeletal muscle fiber conversion through tgf-β1 and p38 mapk signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10379449/
https://www.ncbi.nlm.nih.gov/pubmed/37511159
http://dx.doi.org/10.3390/ijms241411401
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