Two weeks of high-intensity interval training increases skeletal muscle mitochondrial respiration via complex-specific remodeling in sedentary humans.

Abstract

Aerobic training remodels the quantity and quality (function per unit) of skeletal muscle mitochondria to promote substrate oxidation, however, there remain key gaps in understanding the underlying mechanisms during initial training adaptations. We used short-term high-intensity interval training (HIIT) to determine changes to mitochondrial respiration and regulatory pathways that occur early in remodeling. Fifteen normal-weight sedentary adults started seven sessions of HIIT over fourteen days and fourteen participants completed the intervention. We collected vastus lateralis biopsies before and 48-hours after HIIT to determine mitochondrial respiration, RNA sequencing, and western blotting for proteins of mitochondrial respiration and degradation via autophagy. HIIT increased respiration per mitochondrial protein for lipid (+23% P=0.020), complex I (+18%, P=0.0015), complex I+II (+14%, P<0.0001) and complex II (+24% P<0.0001). Transcripts that increased with HIIT identified several gene sets of mitochondrial respiration, particularly for complex I, while transcripts that decreased identified pathways of DNA and chromatin remodeling. HIIT lowered protein abundance of autophagy markers for p62 (-19%, P=0.012) and LC3 II/I (-20%, P=0.004) in whole-tissue lysates but not isolated mitochondria. Meal tolerance testing revealed HIIT increased the change in whole-body respiratory exchange ratio and lowered cumulative plasma insulin concentrations. Gene transcripts and respiratory function indicate remodeling of mitochondria within 2 weeks of HIIT. Overall changes are consistent with increased protein quality driving rapid improvements in substrate oxidation.