Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 299, Issue 5, Pages R1350-R1359Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00400.2010
Keywords
pyruvate dehydrogenase kinase
Categories
Funding
- Lundbaek Foundation, Denmark
- Danish Medical Research Council, Denmark
- Danish National Research Foundation [02-512-55]
- Capital Region of Denmark
- Danish Ministry of Science, Technology and Innovation
- European Commission
- Lundbeck Foundation [R31-2008-2490] Funding Source: researchfish
Ask authors/readers for more resources
Kiilerich K, Adser H, Jakobsen AH, Pedersen PA, Hardie DG, Wojtaszewski JFP, Pilegaard H. PGC-1 alpha increases PDH content but does not change acute PDH regulation in mouse skeletal muscle. Am J Physiol Regul Integr Comp Physiol 299: R1350-R1359, 2010. First published August 18, 2010; doi:10.1152/ajpregu.00400.2010.- The aim of this study was to test whether the transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)1 alpha regulates the content of pyruvate dehydrogenase (PDH)-E1 alpha and influences PDH activity through regulation of pyruvate dehydrogenase kinase-4 (PDK4) expression and subsequently PDH phosphorylation. PGC-1 alpha whole body knockout (KO), muscle-specific PGC-1 alpha overexpressing mice (MCK PGC-1 alpha), and littermate wild-type (WT) mice underwent two interventions known to affect PDH. Quadriceps muscles were removed from fed and 24-h fasted mice as well as at 6 h of recovery after 1-h running and from mice that did not run acutely. PDH-E1 alpha protein content and PDH-E1 alpha phosphorylation were lower in PGC-1 alpha KO and higher in MCK PGC-1 alpha mice at rest, but, while MCK PGC-1 alpha had higher PDK4 protein content, KO of PGC-1 alpha had no effect on PDK4 protein content. The differences in phosphorylation partly vanished when expressing phosphorylation relative to the PDH-E1 alpha content with only a maintained elevated phosphorylation in MCK PGC-1 alpha mice. Fasting upregulated PDK4 protein in PGC-1 alpha KO, MCK PGC-1 alpha and WT mice, but this was not consistently associated with increased PDH-E1 alpha phosphorylation. Downregulation of the activity of PDH in the active form (PDHa) at 6-h recovery from exercise in both the PGC-1 alpha KO and MCK PGC-1 alpha mice and the association between PDH-E1 alpha phosphorylation and PDHa activity in PGC-1 alpha KO mice indicate that PGC-1 alpha is not required for these responses. In conclusion, PGC-1 alpha regulates PDH-E1 alpha protein content in parallel with mitochondrial oxidative proteins, but does not seem to influence PDH regulation in mouse skeletal muscle in response to fasting and in recovery from exercise.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available