Role of PGC-1{alpha} in exercise and fasting induced adaptations in mouse liver

Tobias Nørresø Haase; Stine Ringholm Jørgensen; Lotte Leick; Rasmus S Biensø; Kristian Kiilerich; Sune Johansen; Maja Munk Nielsen; Jorgen F P Wojtaszewski; Juan Hidalgo; Per Amstrup Pedersen; Henriette Pilegaard

doi:10.1152/ajpregu.00775.2010

Role of PGC-1{alpha} in exercise and fasting induced adaptations in mouse liver

Tobias Nørresø Haase, Stine Ringholm Jørgensen, Lotte Leick, Rasmus S Biensø, Kristian Kiilerich, Sune Johansen, Maja Munk Nielsen, Jorgen F P Wojtaszewski, Juan Hidalgo, Per Amstrup Pedersen, Henriette Pilegaard

Molecular Integrative Physiology

45 Citations (Scopus)

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 traininginduced 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.

Original language	English
Journal	American Journal of Physiology: Regulatory, Integrative and Comparative Physiology
Volume	301
Issue number	5
Pages (from-to)	R1501-R1509
Number of pages	9
ISSN	0363-6119
DOIs	https://doi.org/10.1152/ajpregu.00775.2010
Publication status	Published - Nov 2011

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10.1152/ajpregu.00775.2010

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Haase, T. N., Jørgensen, S. R., Leick, L., Biensø, R. S., Kiilerich, K., Johansen, S., Nielsen, M. M., Wojtaszewski, J. F. P., Hidalgo, J., Pedersen, P. A., & Pilegaard, H. (2011). Role of PGC-1{alpha} in exercise and fasting induced adaptations in mouse liver. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 301(5), R1501-R1509. https://doi.org/10.1152/ajpregu.00775.2010

Role of PGC-1{alpha} in exercise and fasting induced adaptations in mouse liver. / Haase, Tobias Nørresø; Jørgensen, Stine Ringholm; Leick, Lotte et al.
In: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, Vol. 301, No. 5, 11.2011, p. R1501-R1509.

Research output: Contribution to journal › Journal article › Research › peer-review

Haase, TN, Jørgensen, SR, Leick, L, Biensø, RS, Kiilerich, K, Johansen, S, Nielsen, MM, Wojtaszewski, JFP, Hidalgo, J, Pedersen, PA & Pilegaard, H 2011, 'Role of PGC-1{alpha} in exercise and fasting induced adaptations in mouse liver', American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, vol. 301, no. 5, pp. R1501-R1509. https://doi.org/10.1152/ajpregu.00775.2010

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title = "Role of PGC-1{alpha} 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 traininginduced 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.",

author = "Haase, {Tobias N{\o}rres{\o}} and J{\o}rgensen, {Stine Ringholm} and Lotte Leick and Biens{\o}, {Rasmus S} and Kristian Kiilerich and Sune Johansen and Nielsen, {Maja Munk} and Wojtaszewski, {Jorgen F P} and Juan Hidalgo and Pedersen, {Per Amstrup} and Henriette Pilegaard",

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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 - 2011/11

Y1 - 2011/11

N2 - 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 traininginduced 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.

AB - 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 traininginduced 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.

U2 - 10.1152/ajpregu.00775.2010

DO - 10.1152/ajpregu.00775.2010

M3 - Journal article

C2 - 21832205

SN - 0363-6119

VL - 301

SP - R1501-R1509

JO - American Journal of Physiology: Regulatory, Integrative and Comparative Physiology

JF - American Journal of Physiology: Regulatory, Integrative and Comparative Physiology

IS - 5

ER -

Role of PGC-1{alpha} in exercise and fasting induced adaptations in mouse liver

Abstract

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