H.D. Stierwalt, S.E. Ehrlicher, M.M. Robinson, S.A. Newsom

Oregon State University, Corvallis, OR

Both obesity and aerobic exercise training influence partitioning of lipids within skeletal muscle (e.g., toward oxidation or storage). Long-chain acyl-CoA synthetases (ACSL) are implicated in such partitioning; however, to what extent skeletal muscle ACSLs are regulated by diet and exercise remains unknown. PURPOSE: To determine regulation of skeletal muscle ACSL1 and ACSL6 by diet and exercise. METHODS: Male C57BL/6J mice consumed a 60% high-fat diet (HFD) for 12 weeks to induce obesity compared to low-fat diet (LFD). At week 4, mice either began aerobic exercise (50 min/day, 5 days/week; EX-Tr) or remained sedentary (SED) for an additional 8 weeks (n=10/group). At week 12, tissues were collected in the fasted condition 36 hours post-exercise (or SED). ACSL1 and ACSL6 protein content was measured in gastrocnemius muscles via western blot. Following an acclimation period, in-cage substrate oxidation with ad-libitum access to food and water was assessed in 12 hour “light” and “dark” cycles using indirect calorimetry. RESULTS: ACSL1 is known to partition fatty acids toward oxidation. Skeletal muscle ACSL1 protein content was not changed with HFD (P=0.25 vs. LFD) and tended to decrease with EX-Tr (P=0.06 main effect EX-Tr vs. SED). Nevertheless, in-cage lipid oxidation was increased with HFD (P<0.01 vs. LFD) and tended to increase with exercise training in LFD mice (P=0.07 for EX-Tr vs. SED). ACSL6 is known to partition fatty acids toward storage. Skeletal muscle ACSL6 protein content was increased with HFD (P<0.01 vs. LFD) in SED mice but not different between diet conditions following EX-Tr (P=0.17; LFD vs. HFD EX-Tr). Such findings are in agreement with greater skeletal muscle lipid storage following HFD and with aerobic exercise training. CONCLUSION: Our results indicate skeletal muscle ACSLs undergo regulation by diet and exercise, with decreased ACSL1 following exercise training and increased ACSL6 in response to high fat feeding. Such findings suggest skeletal muscle ACSL1 content is unlikely to limit lipid oxidation whereas skeletal muscle ACSL6 may be a critical regulator of lipid storage.

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