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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/3/2702 |
| Summary: | 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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| ISSN: | 1661-6596 1422-0067 |