title: Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes.
abstract: Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5'-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α. DHEA exposure increased glucose uptake but not the phosphorylation levels of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4. Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms.
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Yokokawa
authors.affiliation: Graduate School of Sport & Health Science, Ritsumeikan University, Shiga, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Sato
authors.affiliation: The Graduate School of Science and Engineering, Ritsumeikan University, Shiga, Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Iwanaka
authors.affiliation: Graduate School of Sport & Health Science, Ritsumeikan University, Shiga, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Honda
authors.affiliation: Faculty of Sport Science, Waseda University, Saitama, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Higashida
authors.affiliation: Graduate School of Sport & Health Science, Ritsumeikan University, Shiga, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Iemitsu
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Graduate School of Sport & Health Science, Ritsumeikan University, Shiga, Japan. Electronic address: thashimo@fc.ritsumei.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation; D000099293:Protein Kinase C-lambda
chemical_list: D055372:AMP-Activated Protein Kinases; D003687:Dehydroepiandrosterone; D005947:Glucose; D051275:Glucose Transporter Type 4; D007527:Isoenzymes; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; D000099293:Protein Kinase C-lambda; C485290:Ppargc1a protein, mouse; C495693:Slc2a4 protein, mouse
keywords: Ageing; Diabetes; Exercise; Glucose metabolism; Obesity