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mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle
1 Department of Physiology and Pharmacology, Section of Molecular Exercise Physiology, Karolinska Institutet, Stockholm, Sweden; Departmant of Laboratory Medicine, Division of Clinical Physiology, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden
2 Department of Physiology and Pharmacology, Section of Molecular Exercise Physiology, Karolinska Institutet, Stockholm, Sweden
3 Department of Physiology and Pharmacology, Section of Molecular Exercise Physiology, Karolinska Institutet, Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
4 Department of Medicine, Duke University, NC, USA
5 Departmant of Laboratory Medicine, Division of Clinical Physiology, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden
* To whom correspondence should be addressed. E-mail: jessica.norrbom{at}fyfa.ki.se.
Endurance training leads to many adaptational changes in several tissues. In skeletal muscle, fatty acid usage is enhanced and mitochondrial content is increased. The exact molecular mechanisms regulating these functional and structural changes remain to be elucidated. Contractile activity induced metabolic perturbation has repeatedly been shown to be important for the induction of mitochondrial biogenesis. Recent reports suggest that the PGC-1/Tfam pathway is involved in exercise-induced mitochondrial biogenesis. In the present study, nine healthy males performed two 45-min bouts of one-legged knee extension exercise. One bout with restricted blood flow and the other with non-restricted blood flow to the working muscle. Muscle biopsies were obtained from the vastus lateralis muscle, before exercise and at 0, 30, 120 and 360 min after the exercise bout. The biopsies were analysed for whole muscle, as well as fiber-type specific, mRNA expression of MCIP1, PGC-1
and downstream mitochondrial transcription factors. A novel finding was that, in human skeletal muscle PGC-1 mRNA increased more after exercise with restricted blood flow than in the non-restricted condition. No changes were observed for the mRNA of NRF-1, Tfam, TFB1M and TFB2M. Muscle fiber type I and type II did not differ in the basal PGC-1 mRNA levels or in the expression increase following ischemic training. Another novel finding was that there was no difference between the restricted and non-restricted exercise conditions in the increase of MCIP1 mRNA, a marker for calcineurin activation. This strengthens the notion that calcineurin may play a role in PGC-1 transcription activation in human skeletal muscle.
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