Format

Send to

Choose Destination
Am J Physiol Regul Integr Comp Physiol. 2010 Nov;299(5):R1350-9. doi: 10.1152/ajpregu.00400.2010. Epub 2010 Aug 18.

PGC-1alpha increases PDH content but does not change acute PDH regulation in mouse skeletal muscle.

Author information

1
Centre of Inflammation and Metabolism, August Krogh Bldg., Dept. of Biology, Universitetsparken 13, 2100 Copenhagen, Denmark. kkiilerich@bio.ku.dk

Abstract

The aim of this study was to test whether the transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)1α regulates the content of pyruvate dehydrogenase (PDH)-E1α and influences PDH activity through regulation of pyruvate dehydrogenase kinase-4 (PDK4) expression and subsequently PDH phosphorylation. PGC-1α whole body knockout (KO), muscle-specific PGC-1α overexpressing mice (MCK PGC-1α), 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-E1α protein content and PDH-E1α phosphorylation were lower in PGC-1α KO and higher in MCK PGC-1α mice at rest, but, while MCK PGC-1α had higher PDK4 protein content, KO of PGC-1α had no effect on PDK4 protein content. The differences in phosphorylation partly vanished when expressing phosphorylation relative to the PDH-E1α content with only a maintained elevated phosphorylation in MCK PGC-1α mice. Fasting upregulated PDK4 protein in PGC-1α KO, MCK PGC-1α and WT mice, but this was not consistently associated with increased PDH-E1α phosphorylation. Downregulation of the activity of PDH in the active form (PDHa) at 6-h recovery from exercise in both the PGC-1α KO and MCK PGC-1α mice and the association between PDH-E1α phosphorylation and PDHa activity in PGC-1α KO mice indicate that PGC-1α is not required for these responses. In conclusion, PGC-1α regulates PDH-E1α 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.

PMID:
20720174
DOI:
10.1152/ajpregu.00400.2010
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center