Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
Int J Mol Sci. 2023 Jan 31;24(3):2702. doi: 10.3390/ijms24032702.
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 ( < 0.05) fast myosin heavy chain (MyHC) expression and upregulated ( < 0.05) slow MyHC expression in the TA and soleus muscles. Garcinol significantly increased ( < 0.05) the activity of peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) and markedly decreased ( < 0.05) the acetylation of PGC-1α. In vitro and in vivo experiments showed that garcinol decreased ( < 0.05) lactate dehydrogenase activity and increased ( < 0.05) the activities of malate dehydrogenase and succinic dehydrogenase. In addition, the results of C2C12 myotubes showed that garcinol treatment increased ( < 0.05) the transformation of glycolytic muscle fiber to oxidative muscle fiber by 45.9%. Garcinol treatment and p300 interference reduced ( < 0.05) the expression of fast MyHC but increased ( < 0.05) the expression of slow MyHC in vitro. Moreover, the acetylation of PGC-1α was significantly decreased ( < 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.
肌纤维由快肌向慢肌的转化对于持续的收缩和伸展事件、能量稳态和抗疲劳能力至关重要。我们的研究目的是探讨 Garcinol 调节骨骼肌纤维类型转化的机制和效果。将 40 只 21 日龄雄性 C57/BL6J 小鼠（n = 10/饮食）分为对照组和对照组加 Garcinol 组（100mg/kg，低浓度 Garcinol；300mg/kg，中浓度 Garcinol；500mg/kg，高浓度 Garcinol），喂养 12 周。收集比目鱼肌和胫骨前肌进行蛋白质和免疫沉淀分析。饮食 Garcinol 显著下调（<0.05）比目鱼肌和胫骨前肌中的快肌肌球蛋白重链（MyHC）表达，而上调（<0.05）慢肌 MyHC 表达。Garcinol 显著增加（<0.05）过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）的活性，并显著降低（<0.05）PGC-1α 的乙酰化。体内外实验表明，Garcinol 降低（<0.05）乳酸脱氢酶活性，增加（<0.05）苹果酸脱氢酶和琥珀酸脱氢酶活性。此外，C2C12 肌管的结果表明，Garcinol 处理使糖酵解肌纤维向氧化肌纤维的转化增加了 45.9%。Garcinol 处理和 p300 干扰降低（<0.05）了快肌 MyHC 的表达，但增加（<0.05）了体外慢肌 MyHC 的表达。此外，PGC-1α 的乙酰化明显降低（<0.05）。Garcinol 通过 C2C12 肌管中的 p300/PGC-1α 信号通路促进骨骼肌纤维从快糖酵解型向慢氧化型的转化。
