Genetic Control of Carbon Utilization During Hibernation: Mechanistic Considerations
During hibernation, mammals rely heavily on lipid stores to provide the fuel 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-regulated in the heart of the thirteen-lined ground squirrel during hibernation (Andrews et al., 1998). A similar induction of PDK-4 was seen in rat skeletal muscle after administration of WY-14,643, a known peroxisome proliferator and ligand for peroxisome proliferator-activated receptor subtype alpha (PPARoc; Wu et al., 1999). In light of this evidence that PPARα may activate PDK-4 expression, we review the role that PPARs play in lipid metabolism and thermogenesis and discuss their potential as regulators of metabolism during hibernation.
KeywordsBrown Adipose Tissue White Adipose Tissue Ground Squirrel Peroxisome Proliferator Fatty Acid Transport Protein
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- Boyer BB, Barnes BM, Lowell BB, Grujic D (1998) Differential regulation of uncoupling protein gene homologues in multiple tissues of hibernating ground squirrels. Am J Physiol 275 (Regulatory Integrative Comp Physiol 44): R1232-R1238Google Scholar
- Brun S, Carmona MC, Mampel T, Vinas O, Giralt M, Iglesias R, Villarroya F (1999) Activators of peroxisome proliferator-activated receptor-alpha induce the expression of the uncoupling protein-3 gene in skeletal muscle: a potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 expression at birth. Diabetes 48: 1217–1222PubMedCrossRefGoogle Scholar
- Devine JH, Eubank DW, Clouthier DE, Tontonoz P, Spiegelman BM, Hammer RE, Beale EG (1999) Adipose expression of the phosphoenolpyruvate carboxykinase promoter requires peroxisome proliferator-activated receptor gamma and 9-cis-retinoic acid receptor binding to an adipocyte-specific enhancer in vivo. J Biol Chem 274: 13604–12PubMedCrossRefGoogle Scholar
- Gunning P, Ponte P, Okayama H, Engel J, Blau H, Kedes L (1983) Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol 3: 787–795PubMedGoogle Scholar
- Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, Lehmann JM (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and y. Proc Natl Acad Sci USA 94: 4318–4323PubMedCrossRefGoogle Scholar
- Lyman CP, Willis JS, Malan A, Wang LCH (1982) Hibernation and torpor in mammals and birds. Academic Press, New YorkGoogle Scholar
- Schoonjans K, Watanabe M, Suzuki H, Mahfoudi A, Krey G, Wahli W, Grimaldi P, Staels B, Yamamoto T, Auwerx J (1995) Induction of the acyl-CoA synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter. J Biol Chem 270: 19269–19276PubMedCrossRefGoogle Scholar
- Wilson BE, Deeb S, Florant GL (1992) Seasonal changes in hormone-sensitive and lipoprotein lipase mRNA concentrations in marmot white adipose tissue. Am J Physiol 262: R177–R181.Google Scholar