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and PGC-1
have both similar and distinct effects upon myofiber switching towards an oxidative phenotype
1 Department of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Muscle Physiology, Rigshospitalet, Copenhagen, Denmark
2 Department of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen, Denmark
3 Department of Molecular Muscle Physiology, Rigshospitalet, Copenhagen, Denmark
4 Department of Diabetes Biology, Novo Nordisk A/S, Maaloev, Denmark
* To whom correspondence should be addressed. E-mail: grunnet{at}imbg.ku.dk.
Peroxisome proliferator-activated receptor 
coactivator-1
and 1
(PGC-1 and PGC-1) were overexpressed by adenovirus mediated gene transfer in cultures of primary rat skeletal muscle cells derived from neonatal myoblasts. Effects upon muscle fiber type transition and metabolism were studied from day 5 to 22 of culture. PGC-1 and PGC-1 overexpression caused a 3-4 fold increase in mRNA level and a doubling of enzymatic activity of citrate synthase, a slight increase in short chain acyl-CoA dehydrogenase mRNA, and a doubling of the mRNA level and a 30-50 % increase in enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase. Lactate dehydrogenase or creatine kinase activity was unchanged. PGC-1 enhanced glycogen build-up two-fold at 5 mM or 25 mM glucose, whereas PGC-1 caused a decrease. Both PGC-1 and PGC-1 overexpression caused a faster maturation of myotubes, as seen by mRNA downregulation of the immature MHC isoforms, MHCemb and MHCperi. PGC-1 or PGC-1 overexpression enhanced mRNA of the slow-oxidative associated MHC isoform, MHCIb and downregulated mRNA levels of the fast-glycolytic associated MHC isoforms, MHCIIX and MHCIIB. Only PGC-1 overexpression caused an increase in mRNA of the intermediary fast-oxidative associated MHC isoform, MHCIIA. PGC-1 or PGC-1 overexpression upregulated GLUT4 mRNA and downregulated Myocyte Enhancer Factor 2C (MEF2C) transcription factor mRNA; only PGC-1 overexpression caused an increase in the mRNA expression of TRB3, a negative regulator of insulin signalling. These results show that both PGC-1 and PGC-1 are involved in the regulation of skeletal muscle fiber transition and metabolism, and that they have both overlapping and differing effects.
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