Mitochondrial biogenesis and PGC-1α deacetylation by chronic treadmill exercise: differential response in cardiac and skeletal muscle
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- Li, L., Mühlfeld, C., Niemann, B. et al. Basic Res Cardiol (2011) 106: 1221. doi:10.1007/s00395-011-0213-9
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Posttranslational modifications of the transcriptional coactivator PGC-1α by the deacetylase SIRT1 and the kinase AMPK are involved in exercise-induced mitochondrial biogenesis in skeletal muscle. However, similar investigations have not been performed in the left ventricle (LV). Here, we tested whether treadmill training (12 weeks) modifies PGC-1α and mitochondrial biogenesis in gastrocnemius muscle and LV of C57BL/6 J wild-type mice and IL-6-deficient mice with a reported impairment in muscular AMPK activation similarly. Physical activity lowered the plasma insulin and glucose in both mouse strains, suggesting improved insulin sensitivity. The gastrocnemius muscle of IL-6-deficient mice showed reduced mitochondrial respiration and enzyme activity, which was partially normalized after training. Chronic exercise enhanced the mitochondrial biogenesis in gastrocnemius muscle as indicated by increased mRNA or protein expression of primary mitochondrial transcripts, higher mtDNA content and increased citrate synthase activity. Parallel to these changes, we observed AMPK activation, SIRT1 induction and PGC-1α deacetylation. Chronic treadmill training resulted in a mild cardiac hypertrophy in both mouse strains. However, none of these changes observed in skeletal muscle were detected in the LV (both mouse strains) with the exception of AMPK activation and a mildly increased succinate-dependent respiration. Thus, chronic endurance training induces a sustained mitochondrial biogenic response in mouse gastrocnemius muscle but not in the LV. Although AMPK activation occurs in both muscular organs, the absence of SIRT1-dependent PGC-1α deacetylation may be responsible for this significant difference. AMPK activation by IL-6 appears to be dispensable for the mitochondrial biogenic responses to chronic treadmill exercise.