Translational Metabolism Research Laboratory

INTRODUCTION: Evidence from model systems implicates long-chain acyl-CoA synthetases (ACSLs) as key regulators of skeletal muscle fat oxidation and fat storage; however, such roles remain underexplored in humans.

PURPOSE: We sought to determine protein expression of ACSL isoforms in skeletal muscle at rest and in response to acute exercise, and identify relationships between skeletal muscle ACSLs and measures of fat metabolism in humans.

METHODS: Sedentary adults (n=14 [4M/10F], BMI 22.2±2.1 kg/m, VO2max 32.2±4.5 ml/kg/min) completed two study visits. Trials were identical other than completing 1 hour of cycling exercise (65% VO2max) or remaining sedentary. Vastus lateralis biopsies were obtained 15-minutes post-exercise (or rest) and 2-hours post-exercise to determine ACSL protein abundance. Whole-body fat oxidation was assessed at rest and during exercise using indirect calorimetry. Skeletal muscle triacylglycerol (TAG) was measured via lipidomic analysis.

RESULTS: We detected protein expression for 4 of the 5 known ACSL isoforms in human skeletal muscle. ACSL protein abundances were largely unaltered in the hours following exercise aside from a transient increase in ACSL5 15-minutes post-exercise (P=0.01 vs. Rest). Skeletal muscle ACSL1 protein abundance tended to be positively related with whole-body fat oxidation during exercise (P=0.07, r=0.53), when skeletal muscle accounts for the majority of energy expenditure. No such relationship between ACSL1 and fat oxidation was observed at rest. Skeletal muscle ACSL6 protein abundance was positively associated with muscle TAG content at rest (P=0.05, r=0.57).

CONCLUSION: Most ACSL protein isoforms can be detected in human skeletal muscle, with minimal changes in abundance following acute exercise. Our findings agree with those from model systems implicating ACSL1 and ACSL6 as possible determinants of fat oxidation and fat storage within skeletal muscle.