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1 Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
2 School of Health Sciences, Deakin University, Burwood, Victoria, Australia
* To whom correspondence should be addressed. E-mail: rtunstal{at}uoguelph.ca.
Fasting forces adaptive changes in whole body and skeletal muscle metabolism that increase fat oxidation and decrease the oxidation of carbohydrate. We tested the hypothesis that 40 h of fasting would decrease pyruvate dehydrogenase (PDH) activity and increase PDH kinase isoform (PDK1-4) mRNA expression in human skeletal muscle. The putative transcriptional activators of PDK isozymes, peroxisome proliferator-activated receptor alpha (PPAR
) protein and forkhead homolog in rhabdomyosarcoma (FKHR) mRNA were also measured. Eleven healthy adults fasted following a standard meal (25% fat, 60% carbohydrate, 15% protein) with blood and skeletal muscle samples taken at 3, 15, and 40 h post prandial. Fasting increased plasma free fatty acid, glycerol and 
-hydroxybutyrate concentrations and decreased glucose and insulin concentrations. PDH activation decreased from 0.88 ± 0.11 mmol acetyl-CoA/min/kg wet muscle at 3 h to 0.62 ± 0.10 (NS) and 0.39 ± 0.06 (p<0.05) mmol/min/kg wet mass following 15 and 40 h of fasting. While all four PDK isoforms were expressed in human skeletal muscle, PDK2 and 4 mRNA were the most abundant. PDK1 and 3 mRNA abundance was ~ 1% and 15% of the PDK2 and PDK4 levels, respectively. The 40 h fast had no effect on PDK1, 2 and 3 mRNA expression. PDK4 mRNA was significantly increased ~3-fold after 15 h and ~14-fold after 40 h of fasting. Skeletal muscle PPAR protein and FKHR mRNA abundance were unaffected by the fast. The results suggest that decreased PDH activation following 40 h of fasting may have been a function of the large increase in PDK4 mRNA expression and possible subsequent increase in PDK protein and activity. The changes in PDK4 expression and PDH activity did not coincide with increases in the transcriptional activators, PPAR and FKHR.
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