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Am J Physiol Endocrinol Metab (December 11, 2007). doi:10.1152/ajpendo.00666.2007
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Submitted on October 18, 2007
Accepted on December 6, 2007

PGC-1{alpha} is not mandatory for exercise- and training-induced adaptive gene responsens in mouse skeletal muscle

Lotte Leick1*, Jorgen F.P. Wojtaszewski2, Sune Troels Johansen3, Kristian Kiilerich3, Gemma Comes4, Ylva Hellsten2, Juan Hidalgo4, and Henriette Pilegaard3

1 Molecular biology, Copenhagen University, Copenhagen, Denmark; , Denmark
2 Department of exercise and Sport Sciences, Copenhagen University, Copenhagen, Denmark
3 Department of Molecular Biology, Copenhagen University, Copenhagen, Denmark
4 Unidad de Fisiologia Animal, Universidad Autonoma de Barcelona, Bellaterra, Barcelona 08193, Spain

* To whom correspondence should be addressed. E-mail: lleick{at}aki.ku.dk.

The aim of the present study was to test the hypothesis that peroxisome proliferator activated receptor {gamma} co-activator (PGC)-1{alpha} is required for exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC-1{alpha}knock-out (KO) and littermate wild-type (WT) mice performed a single treadmill running exercise bout. Soleus and white gastrocnemius (WG) were obtained immediately, 2h or 6h after exercise. Another group of PGC-1{alpha}-KO and WT mice performed 5 weeks exercise training. Soleus, WG and quadriceps were obtained ~37 hours after the last training session. Resting muscles of the PGC-1{alpha}-KO mice had lower (~ 20%) cytochrome c (cyt c), cytochrome oxidase (COX)I and aminolevulinate synthase (ALAS)1 mRNA and protein levels than WT, but similar levels of AMP activated protein kinase (AMPK){alpha}1, AMPK{alpha}2 and hexokinase (HK) II compared with WT mice. A single exercise bout increased phosphorylation of AMPK and acetyl-CoA carboxylase-{beta} and the level of HKII mRNA similarly in KO and WT. In contrast cyt c mRNA in soleus was up regulated in WT muscles only. Exercise training increased cyt c, COXI, ALAS1 and HKII mRNA and protein levels equally in WT and KO animals, but cyt c, COXI and ALAS1 expression remained ~20% lower in KO animals. In conclusion, lack of PGC-1{alpha} reduced resting expression of cyt c, COXI and ALAS1 and exercise-induced cyt c mRNA expression. However PGC-1{alpha} is not mandatory for training-induced increases in ALAS1, COXI and cyt c expression showing that other factors than PGC-1{alpha} can exert these adaptations.




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