title: Role of PGC-1α in exercise and fasting-induced adaptations in mouse liver.
abstract: The transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α plays a role in regulation of several metabolic pathways. By use of whole body PGC-1α knockout (KO) mice, we investigated the role of PGC-1α 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-1α 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-1α 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-1α KO mice. Neither fasting nor exercise affected the mRNA expression of antioxidant enzymes in the liver, and knockout of PGC-1α had no effect. In conclusion, these results suggest that PGC-1α 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-1α.
authors.affiliation: Centre of Inflammation and Metabolism and Copenhagen Muscle Research Centre, Section of Molecular and Integrative Physiology, Dept. of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tobias Nørresø
authors.initials: TN
authors.lastname: Haase
authors.forename: Stine
authors.initials: S
authors.lastname: Ringholm
authors.forename: Lotte
authors.initials: L
authors.lastname: Leick
authors.forename: Rasmus Sjørup
authors.initials: RS
authors.lastname: Biensø
authors.forename: Kristian
authors.initials: K
authors.lastname: Kiilerich
authors.forename: Sune
authors.initials: S
authors.lastname: Johansen
authors.forename: Maja Munk
authors.initials: MM
authors.lastname: Nielsen
authors.forename: Jørgen Fp
authors.initials: JF
authors.lastname: Wojtaszewski
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
authors.forename: Per Amstrup
authors.initials: PA
authors.lastname: Pedersen
authors.forename: Henriette
authors.initials: H
authors.lastname: Pilegaard
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000222:Adaptation, Physiological; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005215:Fasting / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005943:Gluconeogenesis / Q000235:genetics; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D005082:Physical Exertion; D011766:Pyruvate Carboxylase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2
chemical_list: D055372:AMP-Activated Protein Kinases; D000975:Antioxidants; D001786:Blood Glucose; D045304:Cytochromes c; D003576:Electron Transport Complex IV; D005952:Glucose-6-Phosphatase; D006003:Glycogen; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D011766:Pyruvate Carboxylase; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D015534:Trans-Activators; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C485290:Ppargc1a protein, mouse