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Physiol. Genomics 8: 5-13, 2002. First published November 27, 2001; doi:10.1152/physiolgenomics.00076.2001
1094-8341/02 $5.00
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Received 4 September 2001; accepted in final form 12 November 2001.
Physiological Genomics 8:5-13 (2002)
1094-8341/02 $5.00 © 2002 American Physiological Society

Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a hibernating mammal

MICHAEL J. BUCK1, TERESA L. SQUIRE1 and MATTHEW T. ANDREWS2

1 Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695-7614
2 Department of Biology, University of Minnesota Duluth, Duluth, Minnesota 55812

Hibernation in mammals requires a metabolic shift away from the oxidation of carbohydrates and toward the combustion of stored fatty acids as the primary source of energy during torpor. A key element involved in this fuel selection is pyruvate dehydrogenase kinase isoenzyme 4 (PDK4). PDK4 inhibits pyruvate dehydrogenase and thus minimizes carbohydrate oxidation by preventing the flow of glycolytic products into the tricarboxylic acid cycle. This paper examines expression of the PDK4 gene during hibernation in heart, skeletal muscle, and white adipose tissue (WAT) of the 13-lined ground squirrel, Spermophilus tridecemlineatus. During hibernation PDK4 mRNA levels increase 5-fold in skeletal muscle and 15-fold in WAT compared with summer-active levels. Similarly, PDK4 protein is increased threefold in heart, fivefold in skeletal muscle, and eightfold in WAT. High levels of serum insulin, likely to have an inhibitory effect on PDK4 gene expression, are seen during fall when PDK4 mRNA levels are low. Coordinate upregulation of PDK4 in three distinct tissues suggests a common signal that regulates PDK4 expression and fuel selection during hibernation.

hibernation; pyruvate dehydrogenase kinase isoenzyme 4; insulin; peroxisome proliferator-activated receptor-{alpha}; Spermophilus tridecemlineatus




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