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...

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Main Authors: Weilei Yao, Baoyin Guo, Taimin Jin, Zhengxi Bao, Tongxin Wang, Shu Wen, Feiruo Huang
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/3/2702
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author Weilei Yao
Baoyin Guo
Taimin Jin
Zhengxi Bao
Tongxin Wang
Shu Wen
Feiruo Huang
author_facet Weilei Yao
Baoyin Guo
Taimin Jin
Zhengxi Bao
Tongxin Wang
Shu Wen
Feiruo Huang
author_sort Weilei Yao
collection DOAJ
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 (<i>p</i> < 0.05) fast myosin heavy chain (MyHC) expression and upregulated (<i>p</i> < 0.05) slow MyHC expression in the TA and soleus muscles. Garcinol significantly increased (<i>p</i> < 0.05) the activity of peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) and markedly decreased (<i>p</i> < 0.05) the acetylation of PGC-1α. In vitro and in vivo experiments showed that garcinol decreased (<i>p</i> < 0.05) lactate dehydrogenase activity and increased (<i>p</i> < 0.05) the activities of malate dehydrogenase and succinic dehydrogenase. In addition, the results of C2C12 myotubes showed that garcinol treatment increased (<i>p</i> < 0.05) the transformation of glycolytic muscle fiber to oxidative muscle fiber by 45.9%. Garcinol treatment and p300 interference reduced (<i>p</i> < 0.05) the expression of fast MyHC but increased (<i>p</i> < 0.05) the expression of slow MyHC in vitro. Moreover, the acetylation of PGC-1α was significantly decreased (<i>p</i> < 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.
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spelling doaj.art-0daca088d8964816ae87d359ba57a1ae2023-11-16T17:01:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243270210.3390/ijms24032702Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1αWeilei Yao0Baoyin Guo1Taimin Jin2Zhengxi Bao3Tongxin Wang4Shu Wen5Feiruo Huang6Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, ChinaThe 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 (<i>p</i> < 0.05) fast myosin heavy chain (MyHC) expression and upregulated (<i>p</i> < 0.05) slow MyHC expression in the TA and soleus muscles. Garcinol significantly increased (<i>p</i> < 0.05) the activity of peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) and markedly decreased (<i>p</i> < 0.05) the acetylation of PGC-1α. In vitro and in vivo experiments showed that garcinol decreased (<i>p</i> < 0.05) lactate dehydrogenase activity and increased (<i>p</i> < 0.05) the activities of malate dehydrogenase and succinic dehydrogenase. In addition, the results of C2C12 myotubes showed that garcinol treatment increased (<i>p</i> < 0.05) the transformation of glycolytic muscle fiber to oxidative muscle fiber by 45.9%. Garcinol treatment and p300 interference reduced (<i>p</i> < 0.05) the expression of fast MyHC but increased (<i>p</i> < 0.05) the expression of slow MyHC in vitro. Moreover, the acetylation of PGC-1α was significantly decreased (<i>p</i> < 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.https://www.mdpi.com/1422-0067/24/3/2702skeletal musclefiber typegarcinolp300PGC-1α
spellingShingle Weilei Yao
Baoyin Guo
Taimin Jin
Zhengxi Bao
Tongxin Wang
Shu Wen
Feiruo Huang
Garcinol Promotes the Formation of Slow-Twitch Muscle Fibers by Inhibiting p300-Dependent Acetylation of PGC-1α
International Journal of Molecular Sciences
skeletal muscle
fiber type
garcinol
p300
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 skeletal muscle
fiber type
garcinol
p300
PGC-1α
url https://www.mdpi.com/1422-0067/24/3/2702
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