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Transcriptional regulator PGC1α regulates amino acid metabolism activated by exercise in skeletal muscles
Author(s) -
Hatazawa Yukino,
Miura Shinji,
Kamei Yasutomi
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1083.4
Subject(s) - medicine , coactivator , endocrinology , skeletal muscle , peroxisome proliferator activated receptor , chemistry , metabolism , citric acid cycle , biology , biochemistry , receptor , transcription factor , gene
Skeletal muscles play important roles not only in exercise and nutrition metabolism, but also in human health. Peroxisome proliferator‐activated receptor (PPAR) γ coactivator 1α (PGC1α) is a coactivator of various nuclear receptors and other transcription factors, whose expression increases in the skeletal muscles during exercise. We have previously made transgenic mice overexpressing PGC1α in skeletal muscles (PGC1α‐Tg mice). PGC1α Tg mice showed increased red fiber and capacity for longer treadmill running. In this study, we analyzed metabolic changes of skeletal muscles in PGC1α‐Tg mice by global gene expression (microarray) and metabolomic analyses. Microarray data indicated that branched chain amino acid (BCAA) metabolism was activated in skeletal muscles of PGC1α‐Tg mice. Moreover, we observed that gene and protein expression of BCAA metabolism‐related enzymes were increased in PGC1α‐Tg mice (Hatazawa et al. PLOS ONE. 2014). Then, we examined low molecular weight compounds, especially water‐soluble metabolites, in skeletal muscles of PGC1α‐Tg mice by metabolomic analyses. Metabolic products of the TCA cycle increased in PGC1α‐Tg mice. Levels of β‐alanine and related metabolites, which may serve as a substrate for the TCA cycle, were markedly decreased in PGC1α‐Tg mice. Moreover, our metabolomics data showed the activation of the purine nucleotide pathway, malate–aspartate shuttle, and creatine metabolism, which are known to be active during exercise. Expression of these genes related with these pathways was increased in PGC1α‐Tg mice. Thus, the data suggests that PGC1α provide an energy source during exercise by using amino acids, including BCAA, as a substrate for the TCA cycle and activating the cycle. Meanwhile, PGC1α overexpression in skeletal muscles increased the muscle content of gamma‐aminobutyric acid (GABA), gamma‐aminoisobutyric acid (BAIBA) and serotonin, suggesting that these amino acid‐related molecules might act as secretory bioactive molecules (myokines) that have effects on other organs. Namely, this may be a new mechanism that explains the interaction of multiple organ networks in lifestyle diseases affected by exercise (Hatazawa et al. PLOS ONE. 2015).