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To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1113/jphysiol.2007.133025 Byline: Ida G. Lunde (1), Merete Ekmark (1), Zaheer A. Rana (12), Andres Buonanno (2), Kristian Gundersen (1) Abstract: The effects of exercise on skeletal muscle are mediated by a coupling between muscle electrical activity and gene expression. Several activity correlates, such as intracellular Ca.sup.2+, hypoxia and metabolites like free fatty acids (FFAs), might initiate signalling pathways regulating fibre-type-specific genes. FFAs can be sensed by lipid-dependent transcription factors of the peroxisome proliferator-activated receptor (PPAR) family. We found that the mRNA for the predominant muscle isoform, PPAR[delta], was three-fold higher in the slow/oxidative soleus compared to the fast/glycolytic extensor digitorum longus (EDL) muscle. In histological sections of the soleus, the most oxidative fibres display the highest levels of PPAR[delta] protein. When the soleus muscle was stimulated electrically by a pattern mimicking fast/glycolytic IIb motor units, the mRNA level of PPAR[delta] was reduced to less than half within 24 h. In the EDL, a three-fold increase was observed after slow type I-like electrical stimulation. When a constitutively active form of PPAR[delta] was overexpressed for 14 days in normally active adult fibres after somatic gene transfer, the number of I/IIa hybrids in the EDL more than tripled, IIa fibres increased from 14% to 25%, and IIb fibres decreased from 55% to 45%. The level of succinate dehydrogenase activity increased and size decreased, also when compared to normal fibres of the same type. Thus PPAR[delta] can change myosin heavy chain, oxidative enzymes and size locally in muscle cells in the absence of general exercise. Previous studies on PPAR[delta] in muscle have been performed in transgenic animals where the transgene has been present during muscle development. Our data suggest that PPAR[delta] can mediate activity effects acutely in pre-existing adult fibres, and thus is an important link in excitation-transcription coupling. Author Affiliation: (1)Department of Molecular Biosciences, University of Oslo, Oslo, Norway (2)National Institute of Health, Section of Molecular Neurobiology, NICHD, Bethesda, MD, USA Article History: (Received 21 March 2007; accepted after revision 20 April 2007; first published online 26 April 2007) Article note: Corresponding author K. Gundersen: Department of Molecular Biosciences, University of Oslo, PO Box 1041, Blindern, N-0316 Oslo, Norway. Email: kgunder@imbv.uio.no