John A. Hawley

Autophagy and Metabolic Signaling in Human Skeletal Muscle after Acute Low-Intensity Exercise Cycling with Blood Flow Restriction.

Autophagy is an intracellular degradative system sensitive to hypoxia and exercise-induced perturbations to cellular bioenergetics. However, the effects of low-intensity endurance-based exercise performed with blood flow restriction (BFR) on cell signaling adaptive responses regulating autophagy and substrate metabolism in human skeletal muscle are unknown. In a randomized cross-over design, 9 young, healthy but physically inactive males completed three experimental trials consisting of either a resistance exercise bout (REX: 4 × 10 leg press repetitions, 70% 1-RM), endurance exercise (END: 30 min cycling, 70% VO2peak), or low-intensity cycling with BFR (15 min, 40% VO2peak). A resting muscle biopsy was obtained from the vastus lateralis two weeks prior to the first exercise trial and 3 h after each exercise bout. END increased ULK1Ser757 phosphorylation above rest and BFR (~37-51%, P<0.05). Following REX there were significant elevations compared to rest (~348%) and BFR (~973%) for p38 MAPKThr180/Tyr182 phosphorylation (P<0.05). Parkin content was lower following BFR-cycling compared to REX (~20%, P<0.05). There were no exercise-induced changes in select markers of autophagy following BFR. Genes implicated in substrate metabolism (HK2 and PDK4) were increased above rest (~143-338%) and BFR-cycling (~212517%) with END (P<0.001). We conclude that a single bout of low-intensity cycling with BFR is insufficient to induce intracellular “stress” responses (e.g., high rates of substrate turnover, local hypoxia) necessary to activate skeletal muscle autophagy signaling.