Epigallocatechin Gallate Reduces Slow-Twitch Muscle Fiber Formation and Mitochondrial Biosynthesis in C2C12 Cells by Repressing AMPK Activity and PGC-1α Expression.

Abstract

Epigallocatechin gallate (EGCG) is a major active compound in green tea polyphenols. EGCG acts as an antioxidant to prevent the cell damage caused by free radicals and their derivatives. In skeletal muscle, exercise causes the accumulation of intracellular reactive oxygen species (ROS) and promotes the formation of slow-type muscle fiber. To determine whether EGCG, as a ROS scavenger, has any effect on skeletal muscle fiber type, we applied different concentrations (0, 5, 25, and 50 μM) of EGCG in the culture medium of differentiated C2C12 cells for 2 days. The fiber-type composition, mitochondrial biogenesis-related gene expression, antioxidant and glucose metabolism enzyme activity, and ROS levels in C2C12 cells were then detected. According to our results, 5 μM EGCG significantly decreased the cellular activity of SDH, 25 μM EGCG significantly downregulated the MyHC I, PGC-1α, NRF-1, and p-AMPK levels and SDH activity while enhancing the CAT and GSH-Px activity and decreasing the intracellular ROS levels, and 50 μM EGCG significantly downregulated MyHC I, PGC-1α, and NRF-1 expression and HK and SDH activity while increasing LDH activity. Furthermore, 300 μM H2O2 and 0.5 mM AMPK agonist (AICAR) improved the expression of MyHC I, PGC-1α, and p-AMPK, which were all reversed by 25 μM EGCG. In conclusion, the effect of EGCG on C2C12 cells may occur through the reduction of the ROS level, thereby decreasing both AMPK activity and PGC-1α expression and eventually reducing slow-twitch muscle fiber formation and mitochondrial biosynthesis.