Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet

Sandra J. Peters, Robert A. Harris, Pengfei Wu, Tanya L. Pehleman, George J.F. Heigenhauser, Lawrence L. Spriet

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126 Scopus citations


The increase in skeletal muscle pyruvate dehydrogenase kinase (PDK) activity was measured in skeletal muscle of six healthy males after a eucaloric highfat/low-carbohydrate (HF/LC; 5% carbohydrate, 73% fat, and 22% protein of total energy intake) diet compared with a standardized prediet (50% carbohdyrate, 30% fat, and 21% protein). Biopsies were obtained from the vastus lateralis muscle after 3 days on the prediet (day 0) and after 1, 2, and 3 days of the HF/LC diet. Intact mitchondria were extracted from fresh muscle and analyzed for PDK activity and Western blotting of PDK2 and PDK4 protein. A second biopsy was taken at each time point and frozen for Northern blot analysis of PDK2 and PDK4 mRNAs. PDK activity increased in a linear fashion over the 3-day HF/LC diet and was significantly higher than control by 1 day. PDK activity was 0.09 ± 0.03, 0.18 ± 0.05, 0.30 ± 0.07, and 0.37 ± 0.09 min-1 at 0, 1, 2, and 3 days, respectively. PDK4 protein and mRNA increased maximally by day 1, and PDK2 protein and mRNA were unaffected by the HF/LC diet. Resting respiratory exchange ratios decreased after I day of the HF/LC diet (from 0.79 ± 0.02 to 0.72 ± 0.02) and remained depressed throughout the 3-day dietary intervention (0.68 ± 0.01). The immediate shift to fat utilization was accompanied by increased blood glycerol, β-hydroxybutyrate, and plasma free fatty acid concentrations. These results suggest that the continuing increase in PDK activity over the 3-day HF/LC diet is not due to increasing PDK protein beyond 1 day. This could be due to the contribution of another isoform to the total PDK activity or to a continual increase in PDK4 or PDK2 specific activity.

Original languageEnglish (US)
Pages (from-to)E1151-E1158
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number6 44-6
StatePublished - 2001


  • Mitochondria
  • Pyruvate dehydrogenase activity
  • Pyruvate dehydrogenase kinase 2
  • Pyruvate dehydrogenase kinase 4
  • Respiratory exchange ratio

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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