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

Kristian Kiilerich, Helle Adser, Anne H. Jakobsen, Per A. Pedersen, D. Grahame Hardie, Jorgen F. P. Wojtaszewski, Henriette Pilegaard

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)R1350-R1359
    Number of pages10
    JournalAmerican Journal of Physiology: Regulatory Integrative and Comparative Physiology
    Volume299
    Issue number5
    DOIs
    Publication statusPublished - Nov 2010

    Keywords

    • pyruvate dehydrogenase kinase
    • PYRUVATE-DEHYDROGENASE COMPLEX
    • TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA
    • GENE-EXPRESSION
    • METABOLIC GENES
    • KINASE-ACTIVITY
    • ISOFORM EXPRESSION
    • ENERGY-METABOLISM
    • CARBOHYDRATE DIET
    • EXERCISE
    • PHOSPHORYLATION

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