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Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1α
The conversion of skeletal muscle fiber from fast-twitch to slow-twitch is crucial for sustained contractile and stretchable events, energy homeostasis, and anti-fatigue ability. The purpose of our study was to explore the mechanism and effects of garcinol on the regulation of skeletal muscle fiber...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916769/ https://www.ncbi.nlm.nih.gov/pubmed/36769025 http://dx.doi.org/10.3390/ijms24032702 |
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author | Yao, Weilei Guo, Baoyin Jin, Taimin Bao, Zhengxi Wang, Tongxin Wen, Shu Huang, Feiruo |
author_facet | Yao, Weilei Guo, Baoyin Jin, Taimin Bao, Zhengxi Wang, Tongxin Wen, Shu Huang, Feiruo |
author_sort | Yao, Weilei |
collection | PubMed |
description | The conversion of skeletal muscle fiber from fast-twitch to slow-twitch is crucial for sustained contractile and stretchable events, energy homeostasis, and anti-fatigue ability. The purpose of our study was to explore the mechanism and effects of garcinol on the regulation of skeletal muscle fiber type transformation. Forty 21-day-old male C57/BL6J mice (n = 10/diet) were fed a control diet or a control diet plus garcinol at 100 mg/kg (Low Gar), 300 mg/kg (Mid Gar), or 500 mg/kg (High Gar) for 12 weeks. The tibialis anterior (TA) and soleus muscles were collected for protein and immunoprecipitation analyses. Dietary garcinol significantly downregulated (p < 0.05) fast myosin heavy chain (MyHC) expression and upregulated (p < 0.05) slow MyHC expression in the TA and soleus muscles. Garcinol significantly increased (p < 0.05) the activity of peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) and markedly decreased (p < 0.05) the acetylation of PGC-1α. In vitro and in vivo experiments showed that garcinol decreased (p < 0.05) lactate dehydrogenase activity and increased (p < 0.05) the activities of malate dehydrogenase and succinic dehydrogenase. In addition, the results of C2C12 myotubes showed that garcinol treatment increased (p < 0.05) the transformation of glycolytic muscle fiber to oxidative muscle fiber by 45.9%. Garcinol treatment and p300 interference reduced (p < 0.05) the expression of fast MyHC but increased (p < 0.05) the expression of slow MyHC in vitro. Moreover, the acetylation of PGC-1α was significantly decreased (p < 0.05). Garcinol promotes the transformation of skeletal muscle fibers from the fast-glycolytic type to the slow-oxidative type through the p300/PGC-1α signaling pathway in C2C12 myotubes. |
format | Online Article Text |
id | pubmed-9916769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99167692023-02-11 Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1α Yao, Weilei Guo, Baoyin Jin, Taimin Bao, Zhengxi Wang, Tongxin Wen, Shu Huang, Feiruo Int J Mol Sci Article The conversion of skeletal muscle fiber from fast-twitch to slow-twitch is crucial for sustained contractile and stretchable events, energy homeostasis, and anti-fatigue ability. The purpose of our study was to explore the mechanism and effects of garcinol on the regulation of skeletal muscle fiber type transformation. Forty 21-day-old male C57/BL6J mice (n = 10/diet) were fed a control diet or a control diet plus garcinol at 100 mg/kg (Low Gar), 300 mg/kg (Mid Gar), or 500 mg/kg (High Gar) for 12 weeks. The tibialis anterior (TA) and soleus muscles were collected for protein and immunoprecipitation analyses. Dietary garcinol significantly downregulated (p < 0.05) fast myosin heavy chain (MyHC) expression and upregulated (p < 0.05) slow MyHC expression in the TA and soleus muscles. Garcinol significantly increased (p < 0.05) the activity of peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) and markedly decreased (p < 0.05) the acetylation of PGC-1α. In vitro and in vivo experiments showed that garcinol decreased (p < 0.05) lactate dehydrogenase activity and increased (p < 0.05) the activities of malate dehydrogenase and succinic dehydrogenase. In addition, the results of C2C12 myotubes showed that garcinol treatment increased (p < 0.05) the transformation of glycolytic muscle fiber to oxidative muscle fiber by 45.9%. Garcinol treatment and p300 interference reduced (p < 0.05) the expression of fast MyHC but increased (p < 0.05) the expression of slow MyHC in vitro. Moreover, the acetylation of PGC-1α was significantly decreased (p < 0.05). Garcinol promotes the transformation of skeletal muscle fibers from the fast-glycolytic type to the slow-oxidative type through the p300/PGC-1α signaling pathway in C2C12 myotubes. MDPI 2023-01-31 /pmc/articles/PMC9916769/ /pubmed/36769025 http://dx.doi.org/10.3390/ijms24032702 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 Yao, Weilei Guo, Baoyin Jin, Taimin Bao, Zhengxi Wang, Tongxin Wen, Shu Huang, Feiruo Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1α |
title | Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1α |
title_full | Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1α |
title_fullStr | Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1α |
title_full_unstemmed | Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1α |
title_short | Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1α |
title_sort | garcinol promotes the formation of slow-twitch muscle fibers by inhibiting p300-dependent acetylation of pgc-1α |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916769/ https://www.ncbi.nlm.nih.gov/pubmed/36769025 http://dx.doi.org/10.3390/ijms24032702 |
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