Role of PGC-1{alpha} in exercise and fasting induced adaptations in mouse liver
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Role of PGC-1{alpha} in exercise and fasting induced adaptations in mouse liver. / Haase, Tobias Nørresø; Jørgensen, Stine Ringholm; Leick, Lotte; Biensø, Rasmus S; Kiilerich, Kristian; Johansen, Sune; Nielsen, Maja Munk; Wojtaszewski, Jorgen F P; Hidalgo, Juan; Pedersen, Per Amstrup; Pilegaard, Henriette.
In: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, Vol. 301, No. 5, 2011, p. R1501-R1509.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Role of PGC-1{alpha} in exercise and fasting induced adaptations in mouse liver
AU - Haase, Tobias Nørresø
AU - Jørgensen, Stine Ringholm
AU - Leick, Lotte
AU - Biensø, Rasmus S
AU - Kiilerich, Kristian
AU - Johansen, Sune
AU - Nielsen, Maja Munk
AU - Wojtaszewski, Jorgen F P
AU - Hidalgo, Juan
AU - Pedersen, Per Amstrup
AU - Pilegaard, Henriette
N1 - CURIS 2011 5200 095
PY - 2011
Y1 - 2011
N2 - The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)-¿ coactivator (PGC)-1a plays a role in regulation of several metabolic pathways. By use of whole body PGC-1a knockout (KO) mice we investigated the role of PGC-1a 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-1a 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 was upregulated in PGC-1a 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) 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-1a KO mice. Neither fasting nor exercise affected the mRNA expression of antioxidant enzymes in the liver and knockout of PGC-1a had no effect. In conclusion, these results suggest that PGC-1a 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-1a.
AB - The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)-¿ coactivator (PGC)-1a plays a role in regulation of several metabolic pathways. By use of whole body PGC-1a knockout (KO) mice we investigated the role of PGC-1a 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-1a 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 was upregulated in PGC-1a 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) 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-1a KO mice. Neither fasting nor exercise affected the mRNA expression of antioxidant enzymes in the liver and knockout of PGC-1a had no effect. In conclusion, these results suggest that PGC-1a 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-1a.
U2 - 10.1152/ajpregu.00775.2010
DO - 10.1152/ajpregu.00775.2010
M3 - Journal article
C2 - 21832205
VL - 301
SP - R1501-R1509
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 5
ER -
ID: 34325743