PublisherPublic Library of Science
MetadataShow full item record
Abstracthe 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-1α, 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-1α and alanine aminotransferase 2 (ALT2) in the skeletal muscle during fasting. In C2C12 myoblast cells overexpressing PGC-1α, ALT2 expression was increased concomitant with an increased alanine level in the cells and medium. In addition, PGC-1α, 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-1α and ALT2 increased. Endogenous PGC-1α knockdown in C2C12 cells reduced ALT2 gene expression level, induced by the no-glucose medium. Taken together, in the skeletal muscle, PGC-1α activates ALT2 gene expression, and alanine production may play roles in adaptation to fasting.
Gene Expression Regulation
MiceMice, Inbred C57BL
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Promoter Regions, Genetic
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85040245015&doi=10.1371%2fjournal.pone.0190904&partnerID=40&md5=dd614656d29c36ba08d463e0b256ad7c; http://hdl.handle.net/10713/9039
- Isoform-specific increases in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to beta2-adrenergic receptor activation and exercise.
- Authors: Miura S, Kai Y, Kamei Y, Ezaki O
- Issue date: 2008 Sep
- An increase in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to exercise is mediated by beta-adrenergic receptor activation.
- Authors: Miura S, Kawanaka K, Kai Y, Tamura M, Goto M, Shiuchi T, Minokoshi Y, Ezaki O
- Issue date: 2007 Jul
- Regulation of PGC-1α expression by a GSK-3β-TFEB signaling axis in skeletal muscle.
- Authors: Theeuwes WF, Gosker HR, Schols AMWJ, Langen RCJ, Remels AHV
- Issue date: 2020 Feb
- Metabolomic Analysis of the Skeletal Muscle of Mice Overexpressing PGC-1α.
- Authors: Hatazawa Y, Senoo N, Tadaishi M, Ogawa Y, Ezaki O, Kamei Y, Miura S
- Issue date: 2015
- Whole body overexpression of PGC-1alpha has opposite effects on hepatic and muscle insulin sensitivity.
- Authors: Liang H, Balas B, Tantiwong P, Dube J, Goodpaster BH, O'Doherty RM, DeFronzo RA, Richardson A, Musi N, Ward WF
- Issue date: 2009 Apr