Luteolin increases slow muscle fibers via FLCN-AMPK-PGC-1α signaling pathway

While the regulating mechanisms of slow myofibers have been gradually explored, there are currently a lack of effective means to increase slow myofibers proportion. Here, we have showed that luteolin could markedly improve endurance exercise performance and increase body oxygen consumption of mice, and activate aerobic enzyme activity and slow myofibers related genes and proteins expression in mice's skeletal muscle. Meanwhile, folliculin (FLCN)-AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) pathway was activated by treatment luteolin in the tissues. Furthermore, by in vitro investigation and FLCN lentivirus infection, we have found that the over-expression of FLCN significantly reduces the effects of luteolin on slow myofibers expression and AMPK-PGC-1 alpha axis activation. Together, our results indicate that luteolin can increase the proportion of slow myofibers probably by FLCN-AMPK-PGC-1 alpha pathway. These findings provide a novel approach to increase slow muscle fibers proportion and improve skeletal muscle fitness.