Transformation of skeletal muscle fiber type from fast twitch to slow twitch has significances for sustained contractile and stretchable events, energy homeostasis and antifatigue ability. However, the regulation of skeletal muscle fiber type transformation through nutritional intervention is still not fully spelled out. Grape seed proanthocyanidin extract (GSPE) has been widely reported to play a broader role in many aspects of diseases with its various pharmacological and health-promoting effects. In this study, we found that GSPE significantly improved the fatigue resistance in mice. GSPE up-regulated slow myosin heavy chain (MyHC) and down-regulated fast MyHC, accompanied by increases in activities of succinic dehydrogenase and malate dehydrogenase and by decreased lactate dehydrogenase activity in muscle of mice and in C2C12 myotubes. The AMP-activated protein kinase (AMPK) signaling can be activated by GSPE. Several upstream and downstream factors of AMPK signaling such as liver kinase B1, nuclear respiratory factor 1, calcium calmodulin-dependent protein kinase kinase β, sirtuin1 and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) were also up-regulated by GSPE. Specific inhibition of AMPK signaling by AMPK inhibitor compound C or by AMPKα1 siRNA significantly abolished the GSPE-induced the activation of AMPK and the increase of PGC-1α, and attenuated the GSPE-induced increase of slow MyHC and decrease of fast MyHC in C2C12 myotubes. Taken together, we revealed that GSPE promotes skeletal muscle fiber type transformation from fast twitch to slow twitch through AMPK signaling pathway, and this GSPE-induced fiber type transformation may contribute to increased fatigue resistance.

骨骼肌纤维类型从快速抽搐向缓慢抽搐的转变对于持续的收缩和伸展事件，能量稳态和抗疲劳能力具有重要意义。然而，通过营养干预对骨骼肌纤维类型转化的调控仍未完全阐明。据报道，葡萄籽原花青素提取物（GSPE）具有多种药理作用和促进健康的作用，在疾病的许多方面起着更广泛的作用。在这项研究中，我们发现GSPE可以显着改善小鼠的抗疲劳性。GSPE上调缓慢的肌球蛋白重链（MyHC）和下调快速的MyHC，伴随着琥珀酸脱氢酶和苹果酸脱氢酶活性的增加，以及小鼠肌肉和C2C12肌管中乳酸脱氢酶活性的降低。GSPE可以激活AMP激活的蛋白激酶（AMPK）信号。AMPK信号的一些上游和下游因素，例如肝激酶B1，核呼吸因子1，钙调蛋白依赖性蛋白激酶激酶β，sirtuin1和过氧化物酶体增殖物激活受体-γ共激活因子-1α（PGC-1α）也被上调。 GSPE。AMPK抑制剂化合物C或AMPKα1siRNA对AMPK信号的特异性抑制，显着消除了GSPE诱导的AMPK活化和PGC-1α的增加，并减弱了GSPE诱导的C2C12肌管慢MyHC的增加和快MyHC的减少。 。综上所述，我们发现GSPE通过AMPK信号传导途径促进骨骼肌纤维类型从快速抽搐转变为缓慢抽搐，