Resistance exercise enhances the molecular signaling of mitochondrial biogenesis induced by endurance exercise in human skeletal muscle.

Combining endurance and strength training (concurrent training) may change the adaptation compared with single mode training. However, the site of interaction and the mechanisms are unclear. We have investigated the hypothesis that molecular signaling of mitochondrial biogenesis after endurance exercise is impaired by resistance exercise. Ten healthy subjects performed either only endurance exercise (E; 1-h cycling at ∼65% of maximal oxygen uptake), or endurance exercise followed by resistance exercise (ER; 1-h cycling + 6 sets of leg press at 70-80% of 1 repetition maximum) in a randomized cross-over design. Muscle biopsies were obtained before and after exercise (1 and 3 h postcycling). The mRNA of genes related to mitochondrial biogenesis [(peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1)α, PGC-1-related coactivator (PRC)] related coactivator) and substrate regulation (pyruvate dehydrogenase kinase-4) increased after both E and ER, but the mRNA levels were about twofold higher after ER (P < 0.01). Phosphorylation of proteins involved in the signaling cascade of protein synthesis [mammalian target of rapamycin (mTOR), ribosomal S6 kinase 1, and eukaryotic elongation factor 2] was altered after ER but not after E. Moreover, ER induced a larger increase in mRNA of genes associated with positive mTOR signaling (cMyc and Rheb). Phosphorylation of AMP-activated protein kinase, acetyl-CoA carboxylase, and Akt increased similarly at 1 h postcycling (P < 0.01) after both types of exercise. Contrary to our hypothesis, the results demonstrate that ER, performed after E, amplifies the adaptive signaling response of mitochondrial biogenesis compared with single-mode endurance exercise. The mechanism may relate to a cross talk between signaling pathways mediated by mTOR. The results suggest that concurrent training may be beneficial for the adaptation of muscle oxidative capacity.

[1]  A. Jeukendrup,et al.  The effects of replacing a portion of endurance training by explosive strength training on performance in trained cyclists , 2001, European Journal of Applied Physiology.

[2]  L. Goodyear,et al.  Exercise, MAPK, and NF-κB signaling in skeletal muscle , 2007 .

[3]  P. Aagaard,et al.  Effects of strength training on endurance capacity in top‐level endurance athletes , 2010, Scandinavian journal of medicine & science in sports.

[4]  M. Hall,et al.  TOR Signaling in Growth and Metabolism , 2006, Cell.

[5]  R. Scarpulla,et al.  PGC-1-Related Coactivator, a Novel, Serum-Inducible Coactivator of Nuclear Respiratory Factor 1-Dependent Transcription in Mammalian Cells , 2001, Molecular and Cellular Biology.

[6]  L. Goodyear,et al.  Exercise, MAPK, and NF-kappaB signaling in skeletal muscle. , 2007, Journal of applied physiology.

[7]  D. Bishop,et al.  The effects of strength training on endurance performance and muscle characteristics. , 1999, Medicine and science in sports and exercise.

[8]  C. Foster,et al.  Potential for strength and endurance training to amplify endurance performance. , 1988, Journal of applied physiology.

[9]  A. Bigard,et al.  Interaction between signalling pathways involved in skeletal muscle responses to endurance exercise , 2006, Pflügers Archiv.

[10]  A. Bonen,et al.  PGC-1alpha-mediated regulation of gene expression and metabolism: implications for nutrition and exercise prescriptions. , 2008, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[11]  G. Dimitriadis,et al.  Acute and chronic effects of strenuous exercise on glucose metabolism in isolated, incubated soleus muscle of exercise-trained rats. , 1989, Acta physiologica Scandinavica.

[12]  D. Chinkes,et al.  Resistance exercise increases AMPK activity and reduces 4E‐BP1 phosphorylation and protein synthesis in human skeletal muscle , 2006, The Journal of physiology.

[13]  S. Chien,et al.  Mechanical stimuli and nutrients regulate rapamycin‐sensitive signaling through distinct mechanisms in skeletal muscle , 2006, Journal of cellular biochemistry.

[14]  K. Sahlin,et al.  Erratum to: Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise , 2010, European Journal of Applied Physiology.

[15]  K. Häkkinen,et al.  Explosive‐strength training improves 5‐km running time by improving running economy and muscle power , 1999, Journal of applied physiology.

[16]  Ronald J. Gutmann,et al.  Recombination processes in doubly capped antimonide-based quaternary thin films , 1999 .

[17]  S. B. Wilkinson,et al.  Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle , 2008, The Journal of physiology.

[18]  W. Kraus,et al.  PGC-1α mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle , 2004 .

[19]  P. Neufer,et al.  Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise. , 2005, Metabolism: clinical and experimental.

[20]  G. Shulman,et al.  The role of AMP‐activated protein kinase in mitochondrial biogenesis , 2006, The Journal of physiology.

[21]  J. Hawley,et al.  Consecutive bouts of diverse contractile activity alter acute responses in human skeletal muscle. , 2009, Journal of applied physiology.

[22]  K. Sahlin,et al.  Similar expression of oxidative genes after interval and continuous exercise. , 2009, Medicine and science in sports and exercise.

[23]  Anthony Shield,et al.  Early signaling responses to divergent exercise stimuli in skeletal muscle from well‐trained humans , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[24]  Jiandie D. Lin,et al.  Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators , 2006, Cell.

[25]  I. Vogiatzis,et al.  Resistance exercise-induced increase in muscle mass correlates with p70S6 kinase phosphorylation in human subjects , 2007, European Journal of Applied Physiology.

[26]  J. Babraj,et al.  Selective activation of AMPK‐PGC‐1α or PKB‐TSC2‐mTOR signaling can explain specific adaptive responses to endurance or resistance training‐like electrical muscle stimulation , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[27]  Psilander Niklas,et al.  Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise , 2010, European Journal of Applied Physiology.

[28]  D. O'Gorman,et al.  Exercise intensity‐dependent regulation of peroxisome proliferator‐activated receptor γ coactivator‐1α mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle , 2010, The Journal of physiology.

[29]  J. P. McCoy,et al.  The Mammalian Target of Rapamycin (mTOR) Pathway Regulates Mitochondrial Oxygen Consumption and Oxidative Capacity* , 2006, Journal of Biological Chemistry.

[30]  W. Kraus,et al.  PGC-1alpha mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle. , 2004, Journal of applied physiology.

[31]  V. Mootha,et al.  mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex , 2007, Nature.

[32]  P. Laursen,et al.  Effect of Concurrent Resistance and Endurance Training on Physiologic and Performance Parameters of Well-Trained Endurance Cyclists , 2009, Journal of strength and conditioning research.

[33]  J. Hawley Molecular responses to strength and endurance training: are they incompatible? , 2009, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[34]  George A. Brooks,et al.  Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[35]  F. Kadi,et al.  The biology of satellite cells and telomeres in human skeletal muscle: effects of aging and physical activity , 2010, Scandinavian journal of medicine & science in sports.

[36]  C. Lundby,et al.  Relative workload determines exercise-induced increases in PGC-1alpha mRNA. , 2010, Medicine and science in sports and exercise.

[37]  M. Gibala,et al.  Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle. , 2009, Journal of applied physiology.

[38]  J. Helgerud,et al.  Maximal strength training improves running economy in distance runners. , 2008, Medicine and science in sports and exercise.

[39]  D G Sale,et al.  Interaction between concurrent strength and endurance training. , 1990, Journal of applied physiology.

[40]  Y. Hellsten,et al.  Calcium signalling in the regulation of PGC-1α, PDK4 and HKII mRNA expression , 2007, Biological chemistry.

[41]  A. de Haan,et al.  The muscle fiber type–fiber size paradox: hypertrophy or oxidative metabolism? , 2010, European Journal of Applied Physiology.

[42]  K. Baar Training for endurance and strength: lessons from cell signaling. , 2006, Medicine and science in sports and exercise.

[43]  B. Spiegelman,et al.  Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1α transcription and mitochondrial biogenesis in muscle cells , 2006, Proceedings of the National Academy of Sciences.

[44]  J. Blenis,et al.  Inactivation of the Tuberous Sclerosis Complex-1 and -2 Gene Products Occurs by Phosphoinositide 3-Kinase/Akt-dependent and -independent Phosphorylation of Tuberin* , 2003, Journal of Biological Chemistry.

[45]  J. Bergstrom Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. , 1975, Scandinavian journal of clinical and laboratory investigation.