Genetic control of carbon utilization during hibernation: Mechanistic considerations

During hibernation, mammals rely heavily on lipid stores to provide the fue l necessary to survive the winter. Pyruvate dehydrogenase kinase isozyme 4 (PDK-4) plays a key role in gating carbohydrate catabolism and allowing the switch to lipid metabolism. Earlier we reported that PDK-4 was up-regulate d in the heart of the thirteen-lined ground squirrel during hibernation (An drews et al., 1998). A similar induction of PDK-4 was seen in rat skeletal muscle after administration or WY-14,643, a known peroxisome proliferator a nd ligand for peroxisome proliferator-activated receptor subtype alpha (PPA R alpha; Wu er al., 1999). In light of this evidence that PPAR alpha may ac tivate PDK-4 expression, we review the role that PPARs play in lipid metabo lism and thermogenesis and discuss their potential as regulators of metabol ism during hibernation.