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Publication : PGC-1α regulates alanine metabolism in muscle cells.

First Author  Hatazawa Y Year  2018
Journal  PLoS One Volume  13
Issue  1 Pages  e0190904
PubMed ID  29315328 Mgi Jnum  J:258379
Mgi Id  MGI:6113124 Doi  10.1371/journal.pone.0190904
Citation  Hatazawa Y, et al. (2018) PGC-1alpha regulates alanine metabolism in muscle cells. PLoS One 13(1):e0190904
abstractText  The skeletal muscle is the largest organ in the human body, depositing energy as protein/amino acids, which are degraded in catabolic conditions such as fasting. Alanine is synthesized and secreted from the skeletal muscle that is used as substrates of gluconeogenesis in the liver. During fasting, the expression of PGC-1alpha, a transcriptional coactivator of nuclear receptors, is increased in the liver and regulates gluconeogenesis. In the present study, we observed increased mRNA expression of PGC-1alpha and alanine aminotransferase 2 (ALT2) in the skeletal muscle during fasting. In C2C12 myoblast cells overexpressing PGC-1alpha, ALT2 expression was increased concomitant with an increased alanine level in the cells and medium. In addition, PGC-1alpha, along with nuclear receptor ERR, dose-dependently enhanced the ALT2 promoter activity in reporter assay using C2C12 cells. In the absence of glucose in the culture medium, mRNA levels of PGC-1alpha and ALT2 increased. Endogenous PGC-1alpha knockdown in C2C12 cells reduced ALT2 gene expression level, induced by the no-glucose medium. Taken together, in the skeletal muscle, PGC-1alpha activates ALT2 gene expression, and alanine production may play roles in adaptation to fasting.
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