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Centre of Inflammation and Metabolism (CIM)


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83Role of PGC-1alpha in exercise and fasting-induced adaptations in mouse liver.
Haase TN; Ringholm S; Leick L; Bienso RS; Kiilerich K; Johansen S; Nielsen MM; Wojtaszewski JF; Hidalgo J; Pedersen PA; Pilegaard H
Am J Physiol Regul Integr Comp Physiol 2011; 301(5): R1501-9
PubMed ID: 21832205

The transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1alpha plays a role in regulation of several metabolic pathways. By use of whole body PGC-1alpha knockout (KO) mice, we investigated the role of PGC-1alpha in fasting, acute exercise and exercise training-induced regulation of key proteins in gluconeogenesis and metabolism in the liver. In both wild-type (WT) and PGC-1alpha KO mice liver, the mRNA content of the gluconeogenic proteins glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) was upregulated during fasting. Pyruvate carboxylase (PC) remained unchanged after fasting in WT mice, but it was upregulated in PGC-1alpha KO mice. In response to a single exercise bout, G6Pase mRNA was upregulated in both genotypes, whereas no significant changes were detected in PEPCK or PC mRNA. While G6Pase and PC protein remained unchanged, liver PEPCK protein content was higher in trained than untrained mice of both genotypes. The mRNA content of the mitochondrial proteins cytochrome c (Cyt c) and cytochrome oxidase (COX) subunit I was unchanged in response to fasting. The mRNA and protein content of Cyt c and COXI increased in the liver in response to a single exercise bout and prolonged exercise training, respectively, in WT mice, but not in PGC-1alpha KO mice. Neither fasting nor exercise affected the mRNA expression of antioxidant enzymes in the liver, and knockout of PGC-1alpha had no effect. In conclusion, these results suggest that PGC-1alpha plays a pivotal role in regulation of Cyt c and COXI expression in the liver in response to a single exercise bout and prolonged exercise training, which implies that exercise training-induced improvements in oxidative capacity of the liver is regulated by PGC-1alpha.

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