Dataset Information

Metabolomic Analysis of Skeletal Muscle in Aged Mice.

ABSTRACT: Sarcopenia is the age-induced, progressive loss of skeletal muscle mass and function. To better understand changes in skeletal muscle during sarcopenia, we performed a metabolomic analysis of skeletal muscle in young (8-week-old) and aged (28-month-old) mice by using capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry. Principal component analysis showed clear changes in metabolites between young and aged mice. Glucose metabolism products were decreased in aged mice, specifically fructose 1,6-diphosphate (0.4-fold) and dihydroxyacetone phosphate (0.6-fold), possibly from decreased glycolytic muscle fibers. Multiple metabolic products associated with phospholipid metabolism were significantly changed in aged mice, which may reflect changes in cell membrane phospholipids of skeletal muscle. Products of polyamine metabolism, which are known to increase nucleic acid and protein synthesis, decreased in spermine (0.5-fold) and spermidine (0.6-fold) levels. By contrast, neurotransmitter levels were increased in skeletal muscle of aged mice, including acetylcholine (1.8-fold), histamine (2.6-fold), and serotonin (1.7-fold). The increase in acetylcholine might compensate for age-associated dropout of neuromuscular junctions, whereas the increases in histamine and serotonin might be due to muscle injury associated with aging. Further analysis focusing on the altered metabolites observed in this study will provide essential data for understanding aging muscles.

SUBMITTER: Uchitomi R

PROVIDER: S-EPMC6639307 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Metabolomic Analysis of Skeletal Muscle in Aged Mice.

Uchitomi Ran R Hatazawa Yukino Y Senoo Nanami N Yoshioka Kiyoshi K Fujita Mariko M Shimizu Takahiko T Miura Shinji S Ono Yusuke Y Kamei Yasutomi Y

Scientific reports 20190718 1

Sarcopenia is the age-induced, progressive loss of skeletal muscle mass and function. To better understand changes in skeletal muscle during sarcopenia, we performed a metabolomic analysis of skeletal muscle in young (8-week-old) and aged (28-month-old) mice by using capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry. Principal component analysis showed clear changes in metabolites between young and aged mice. Glucose metabolism products were decreased in age ...[more]

PMID: 31320689

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Project description: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.

Dataset Information

Metabolomic Analysis of Skeletal Muscle in Aged Mice.

Publications

Metabolomic Analysis of Skeletal Muscle in Aged Mice.

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