Abstract
Unc51 like autophagy activating kinase 1 (Ulk1), the primary autophagy regulator, has been linked to metabolic adaptation in skeletal muscle to exercise training. Here we compared the roles of Ulk1 and homologous Ulk2 in skeletal muscle insulin action following exercise training to gain more mechanistic insights. Inducible, skeletal muscle-specific Ulk1 knock-out (Ulk1-iMKO) mice and global Ulk2 knock-out (Ulk2–/–) mice were subjected to voluntary wheel running for 6 weeks followed by assessment of exercise capacity, glucose tolerance, and insulin signaling in skeletal muscle after a bolus injection of insulin. Both Ulk1-iMKO and Ulk2–/– mice had improved endurance exercise capacity post-exercise. Ulk1-iMKO did not improve glucose clearance during glucose tolerance test, while Ulk2–/– had only marginal improvement. However, exercise training-induced improvement of insulin action in skeletal muscle, indicated by Akt-S473 phosphorylation, was only impaired in Ulk1-iMKO. These data suggest that Ulk1, but not Ulk2, is required for exercise training-induced improvement of insulin action in skeletal muscle, implicating crosstalk between catabolic and anabolic signaling as integral to metabolic adaptation to energetic stress.
Highlights
Regular exercise is the most robust and reproducible means for promotion of whole-body health (Drake et al, 2016)
Endurance exercise capacity post-exercise training increased in a subset of both Unc51 like autophagy activating kinase 1 (Ulk1)-iMKO and WT mice (Figures 1D,E), as we have shown previously (Laker et al, 2017)
We have previously demonstrated that an essential mitophagy initiator, Ulk1, was required for improved glucose tolerance following exercise training (Laker et al, 2017)
Summary
Regular exercise is the most robust and reproducible means for promotion of whole-body health (Drake et al, 2016). Skeletal muscle is integral to the metabolic benefits of regular exercise as it is the primary tissue for the use and storage of glucose. Regular exercise prevents development of metabolic diseases, such as Type II Diabetes, but can reverse the pathology in. Improved mitochondrial quality (i.e., overall functionality) within skeletal muscle is one result of exercise training that promotes metabolic heath (Laker et al, 2014; Drake et al, 2016). While all aspects of mitochondrial quality control are sensitive to nutrient status and exercise-induced energetic stress (Drake et al, 2016), the degree to which impairment in mitochondrial quality control contributes to the etiology of metabolic pathologies (e.g., insulin resistance, type II diabetes, etc.) is debated
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