Metabolomic analysis of the skeletal muscle mice overexpressing PGC-1α

Yukino Hatazawa, Nanami Senoo, Miki Tadaishi, Yoshihiro Ogawa, Osamu Ezaki, Yasutomi Kamei, Shinji Miura

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors whose expression increases in the skeletal muscle during exercise. We have previously made transgenic mice overexpressing PGC-1α in the skeletal muscle (PGC-1α-Tg mice). PGC-1α upregulates the expression of genes associated with red fibers, mitochondrial function, fatty acid oxidation, and branched chain amino acid (BCAA) degradation. However, global analyses of the actual metabolic products have not been investigated. In this study, we conducted metabolomic analysis of the skeletal muscle in PGC-1α-Tg mice by capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry. Principal component analysis and hierarchical cluster analysis showed clearly distinguishable changes in the metabolites between PGC-1α-Tg and wild-type control mice. Changes were observed in metabolite levels of various metabolic pathways such as the TCA cycle, pentose phosphate pathway, nucleotide synthesis, purine nucleotide cycle, and amino acid metabolism, including BCAA and β-alanine. Namely, metabolic products of the TCA cycle increased in PGC-1α-Tg mice, with increased levels of citrate (2.3-fold), succinate (2.2-fold), fumarate (2.8-fold), and malate (2.3-fold) observed. Metabolic products associated with the pentose phosphate pathway and nucleotide biosynthesis also increased in PGC-1α-Tg mice. Meanwhile, BCAA levels decreased (Val, 0.7-fold; Leu, 0.8-fold; and Ile, 0.7-fold), and Glu (3.1-fold) and Asp (2.2-fold) levels increased. Levels of β-alanine and related metabolites were markedly decreased in PGC-1α-Tg mice. Coordinated regulation of the TCA cycle and amino acid metabolism, including BCAA, suggests that PGC-1α plays important roles in energy metabolism. Moreover, our metabolomics data showing the activation of the purine nucleotide pathway, malate-aspartate shuttle, as well as creatine metabolism, which are known to be active during exercise, further suggests that PGC-1α regulates metabolism in exercise. Thus, we demonstrated the roles of PGC-1α in the skeletal muscle at the metabolite level.

Original languageEnglish
Article numbere0129084
JournalPloS one
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 26 2015
Externally publishedYes

Fingerprint

Branched Chain Amino Acids
Metabolomics
metabolomics
Metabolites
Metabolism
Muscle
skeletal muscle
Skeletal Muscle
branched chain amino acids
Purine Nucleotides
Pentoses
mice
tricarboxylic acid cycle
Alanine
Pentose Phosphate Pathway
purine nucleotides
Nuclear Receptor Coactivators
metabolites
Nucleotides
Phosphates

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hatazawa, Y., Senoo, N., Tadaishi, M., Ogawa, Y., Ezaki, O., Kamei, Y., & Miura, S. (2015). Metabolomic analysis of the skeletal muscle mice overexpressing PGC-1α. PloS one, 10(6), [e0129084]. https://doi.org/10.1371/journal.pone.0129084

Metabolomic analysis of the skeletal muscle mice overexpressing PGC-1α. / Hatazawa, Yukino; Senoo, Nanami; Tadaishi, Miki; Ogawa, Yoshihiro; Ezaki, Osamu; Kamei, Yasutomi; Miura, Shinji.

In: PloS one, Vol. 10, No. 6, e0129084, 26.06.2015.

Research output: Contribution to journalArticle

Hatazawa, Y, Senoo, N, Tadaishi, M, Ogawa, Y, Ezaki, O, Kamei, Y & Miura, S 2015, 'Metabolomic analysis of the skeletal muscle mice overexpressing PGC-1α', PloS one, vol. 10, no. 6, e0129084. https://doi.org/10.1371/journal.pone.0129084
Hatazawa Y, Senoo N, Tadaishi M, Ogawa Y, Ezaki O, Kamei Y et al. Metabolomic analysis of the skeletal muscle mice overexpressing PGC-1α. PloS one. 2015 Jun 26;10(6). e0129084. https://doi.org/10.1371/journal.pone.0129084
Hatazawa, Yukino ; Senoo, Nanami ; Tadaishi, Miki ; Ogawa, Yoshihiro ; Ezaki, Osamu ; Kamei, Yasutomi ; Miura, Shinji. / Metabolomic analysis of the skeletal muscle mice overexpressing PGC-1α. In: PloS one. 2015 ; Vol. 10, No. 6.
@article{1baf200b49d64cce951b38c0ce7e0663,
title = "Metabolomic analysis of the skeletal muscle mice overexpressing PGC-1α",
abstract = "Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors whose expression increases in the skeletal muscle during exercise. We have previously made transgenic mice overexpressing PGC-1α in the skeletal muscle (PGC-1α-Tg mice). PGC-1α upregulates the expression of genes associated with red fibers, mitochondrial function, fatty acid oxidation, and branched chain amino acid (BCAA) degradation. However, global analyses of the actual metabolic products have not been investigated. In this study, we conducted metabolomic analysis of the skeletal muscle in PGC-1α-Tg mice by capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry. Principal component analysis and hierarchical cluster analysis showed clearly distinguishable changes in the metabolites between PGC-1α-Tg and wild-type control mice. Changes were observed in metabolite levels of various metabolic pathways such as the TCA cycle, pentose phosphate pathway, nucleotide synthesis, purine nucleotide cycle, and amino acid metabolism, including BCAA and β-alanine. Namely, metabolic products of the TCA cycle increased in PGC-1α-Tg mice, with increased levels of citrate (2.3-fold), succinate (2.2-fold), fumarate (2.8-fold), and malate (2.3-fold) observed. Metabolic products associated with the pentose phosphate pathway and nucleotide biosynthesis also increased in PGC-1α-Tg mice. Meanwhile, BCAA levels decreased (Val, 0.7-fold; Leu, 0.8-fold; and Ile, 0.7-fold), and Glu (3.1-fold) and Asp (2.2-fold) levels increased. Levels of β-alanine and related metabolites were markedly decreased in PGC-1α-Tg mice. Coordinated regulation of the TCA cycle and amino acid metabolism, including BCAA, suggests that PGC-1α plays important roles in energy metabolism. Moreover, our metabolomics data showing the activation of the purine nucleotide pathway, malate-aspartate shuttle, as well as creatine metabolism, which are known to be active during exercise, further suggests that PGC-1α regulates metabolism in exercise. Thus, we demonstrated the roles of PGC-1α in the skeletal muscle at the metabolite level.",
author = "Yukino Hatazawa and Nanami Senoo and Miki Tadaishi and Yoshihiro Ogawa and Osamu Ezaki and Yasutomi Kamei and Shinji Miura",
year = "2015",
month = "6",
day = "26",
doi = "10.1371/journal.pone.0129084",
language = "English",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Metabolomic analysis of the skeletal muscle mice overexpressing PGC-1α

AU - Hatazawa, Yukino

AU - Senoo, Nanami

AU - Tadaishi, Miki

AU - Ogawa, Yoshihiro

AU - Ezaki, Osamu

AU - Kamei, Yasutomi

AU - Miura, Shinji

PY - 2015/6/26

Y1 - 2015/6/26

N2 - Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors whose expression increases in the skeletal muscle during exercise. We have previously made transgenic mice overexpressing PGC-1α in the skeletal muscle (PGC-1α-Tg mice). PGC-1α upregulates the expression of genes associated with red fibers, mitochondrial function, fatty acid oxidation, and branched chain amino acid (BCAA) degradation. However, global analyses of the actual metabolic products have not been investigated. In this study, we conducted metabolomic analysis of the skeletal muscle in PGC-1α-Tg mice by capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry. Principal component analysis and hierarchical cluster analysis showed clearly distinguishable changes in the metabolites between PGC-1α-Tg and wild-type control mice. Changes were observed in metabolite levels of various metabolic pathways such as the TCA cycle, pentose phosphate pathway, nucleotide synthesis, purine nucleotide cycle, and amino acid metabolism, including BCAA and β-alanine. Namely, metabolic products of the TCA cycle increased in PGC-1α-Tg mice, with increased levels of citrate (2.3-fold), succinate (2.2-fold), fumarate (2.8-fold), and malate (2.3-fold) observed. Metabolic products associated with the pentose phosphate pathway and nucleotide biosynthesis also increased in PGC-1α-Tg mice. Meanwhile, BCAA levels decreased (Val, 0.7-fold; Leu, 0.8-fold; and Ile, 0.7-fold), and Glu (3.1-fold) and Asp (2.2-fold) levels increased. Levels of β-alanine and related metabolites were markedly decreased in PGC-1α-Tg mice. Coordinated regulation of the TCA cycle and amino acid metabolism, including BCAA, suggests that PGC-1α plays important roles in energy metabolism. Moreover, our metabolomics data showing the activation of the purine nucleotide pathway, malate-aspartate shuttle, as well as creatine metabolism, which are known to be active during exercise, further suggests that PGC-1α regulates metabolism in exercise. Thus, we demonstrated the roles of PGC-1α in the skeletal muscle at the metabolite level.

AB - Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors whose expression increases in the skeletal muscle during exercise. We have previously made transgenic mice overexpressing PGC-1α in the skeletal muscle (PGC-1α-Tg mice). PGC-1α upregulates the expression of genes associated with red fibers, mitochondrial function, fatty acid oxidation, and branched chain amino acid (BCAA) degradation. However, global analyses of the actual metabolic products have not been investigated. In this study, we conducted metabolomic analysis of the skeletal muscle in PGC-1α-Tg mice by capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry. Principal component analysis and hierarchical cluster analysis showed clearly distinguishable changes in the metabolites between PGC-1α-Tg and wild-type control mice. Changes were observed in metabolite levels of various metabolic pathways such as the TCA cycle, pentose phosphate pathway, nucleotide synthesis, purine nucleotide cycle, and amino acid metabolism, including BCAA and β-alanine. Namely, metabolic products of the TCA cycle increased in PGC-1α-Tg mice, with increased levels of citrate (2.3-fold), succinate (2.2-fold), fumarate (2.8-fold), and malate (2.3-fold) observed. Metabolic products associated with the pentose phosphate pathway and nucleotide biosynthesis also increased in PGC-1α-Tg mice. Meanwhile, BCAA levels decreased (Val, 0.7-fold; Leu, 0.8-fold; and Ile, 0.7-fold), and Glu (3.1-fold) and Asp (2.2-fold) levels increased. Levels of β-alanine and related metabolites were markedly decreased in PGC-1α-Tg mice. Coordinated regulation of the TCA cycle and amino acid metabolism, including BCAA, suggests that PGC-1α plays important roles in energy metabolism. Moreover, our metabolomics data showing the activation of the purine nucleotide pathway, malate-aspartate shuttle, as well as creatine metabolism, which are known to be active during exercise, further suggests that PGC-1α regulates metabolism in exercise. Thus, we demonstrated the roles of PGC-1α in the skeletal muscle at the metabolite level.

UR - http://www.scopus.com/inward/record.url?scp=84938651968&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938651968&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0129084

DO - 10.1371/journal.pone.0129084

M3 - Article

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e0129084

ER -