Basic Research in Cardiology

, Volume 106, Issue 6, pp 1221–1234 | Cite as

Mitochondrial biogenesis and PGC-1α deacetylation by chronic treadmill exercise: differential response in cardiac and skeletal muscle

  • Ling Li
  • Christian Mühlfeld
  • Bernd Niemann
  • Ruping Pan
  • Rong Li
  • Denise Hilfiker-Kleiner
  • Ying Chen
  • Susanne RohrbachEmail author
Original Contribution


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.


Exercise Hypertrophy Mitochondrial biogenesis Heart 



We appreciate the technical assistance of R. Gall, B. Heinze and N. Woitasky. We would also like to thank Gerhard Kripp for his expert technical assistance in the electron microscopic work. This study was supported by the DFG (RO 2328/2-1) and Deutsche Stiftung für Herzforschung (F/05/05).

Supplementary material

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Supplementary material 1 (PDF 4,165 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ling Li
    • 1
  • Christian Mühlfeld
    • 2
  • Bernd Niemann
    • 3
  • Ruping Pan
    • 1
  • Rong Li
    • 4
  • Denise Hilfiker-Kleiner
    • 5
  • Ying Chen
    • 4
  • Susanne Rohrbach
    • 1
    • 4
    Email author
  1. 1.Institute of PhysiologyJustus Liebig University GiessenGiessenGermany
  2. 2.Institute of Anatomy and Cell BiologyJustus Liebig University GiessenGiessenGermany
  3. 3.Department of Cardiac and Vascular SurgeryJustus Liebig University GiessenGiessenGermany
  4. 4.Institute of PathophysiologyMartin Luther University Halle-WittenbergHalleGermany
  5. 5.Department of Cardiology and AngiologyMedical School HannoverHannoverGermany

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