Grape seed proanthocyanidin extract promotes skeletal muscle fiber type transformation via AMPK signaling pathway

Abstract Transformation of skeletal muscle fiber type from fast-twitch to slow-twitch has significances for sustained contractile and stretchable events, energy homeostasis, and anti-fatigue 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 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 AMPK signaling can be activated by GSPE. Several upstream and downstream factors of AMPK signaling such as liver kinase B1 (LKB1), nuclear respiratory factor 1 (NRF1), calcium calmodulin-dependent protein kinase kinase β (CaMKKβ), sirtuin1 (Sirt1) 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 (si-AMPKα1) 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.