PGC-1α is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle

Abstract

The aim of the present study was to test the hypothesis that peroxisome proliferator activated receptor-γ coactivator (PGC) 1α is required for exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC-1α 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-1α KO and WT mice performed 5-wk exercise training. Soleus, WG, and quadriceps were obtained ∼37 h after the last training session. Resting muscles of the PGC-1α 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) α1, AMPKα2, and hexokinase (HK) II compared with WT mice. A single exercise bout increased phosphorylation of AMPK and acetyl-CoA carboxylase-β 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 ∼20% lower in KO animals. In conclusion, lack of PGC-1α reduced resting expression of cyt c, COXI, and ALAS1 and exercise-induced cyt c mRNA expression. However, PGC-1α is not mandatory for training-induced increases in ALAS1, COXI, and cyt c expression, showing that factors other than PGC-1α can exert these adaptations.