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Articles in PresS, published online ahead of print November 27, 2001
Physiol Genomics, 10.1152/physiolgenomics.00076.2001
Submitted on September 4, 2001
Accepted on November 12, 2001
1 Genetics, North Carolina State University, Raleigh, NC, USA
2 Biology, University of Minnesota Duluth, Duluth, MN, USA
* To whom correspondence should be addressed. E-mail: mandrews{at}d.umn.edu.
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 TCA cycle. This paper examines expression of the PDK4 gene during hibernation in heart, skeletal muscle, and white adipose tissue (WAT) of the thirteen-lined ground squirrel, Spermophilus tridecemlineatus. During hibernation PDK4 mRNA levels increase 5-fold in skeletal muscle and 15-fold in WAT compared to summer-active levels. Similarly, PDK4 protein is increased 3-fold in heart, 5-fold in skeletal muscle, and 8-fold 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 up-regulation of PDK4 in three distinct tissues suggests a common signal that regulates PDK4 expression and fuel selection during hibernation.
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