PGC-1alpha is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle.
The aim of the present study was to test the hypothesis that peroxisome proliferator activated receptor-gamma coactivator (PGC) 1alpha is required for exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC-1alpha knockout (KO) and littermate wild-type (WT) mice performed a single treadmill-running exercise bout. Soleus and white gastrocnemius (WG) were obtained immediately, 2 h, or 6 h after exercise. Another group of PGC-1alpha KO and WT mice performed 5-wk exercise training. Soleus, WG, and quadriceps were obtained approximately 37 h after the last training session. Resting muscles of the PGC-1alpha KO mice had lower ( approximately 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) alpha1, AMPKalpha2, 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 WG of KO and WT. In contrast, cyt c mRNA in soleus was upregulated 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 approximately 20% lower in KO animals. In conclusion, lack of PGC-1alpha reduced resting expression of cyt c, COXI, and ALAS1 and exercise-induced cyt c mRNA expression. However, PGC-1alpha is not mandatory for training-induced increases in ALAS1, COXI, and cyt c expression, showing that factors other than PGC-1alpha can exert these adaptations.
Leick
Lotte
L
Centre of Inflammation and Metabolism, and Copenhagen Muscle Research Centre, Department of Molecular Biology, Institute of Exercise and Sport Sciences, University of Copenhagen, Universitetsparken 13, Copenhagen, Denmark. lleick@aki.ku.dk
Wojtaszewski
Jørgen F P
JF
Johansen
Sune T
ST
Kiilerich
Kristian
K
Comes
Gemma
G
Hellsten
Ylva
Y
Hidalgo
Juan
J
Pilegaard
Henriette
H
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000222:Adaptation, Physiological / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D045304:Cytochromes c / Q000096:biosynthesis / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000502:physiology*; D006003:Glycogen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000502:physiology*; D009211:Myoglobin / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D014157:Transcription Factors
D009124:Muscle Proteins; D009211:Myoglobin; D009711:Nucleotides; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D006003:Glycogen; D045304:Cytochromes c; D051545:Cyclooxygenase 1; D000624:5-Aminolevulinate Synthetase; D017868:Cyclic AMP-Dependent Protein Kinases