Evaluation of the role of AMP-activated protein kinase and its downstream targets in mammalian hibernation.
Mammalian hibernation requires an extensive reorganization of metabolism that typically includes a greater than 95% reduction in metabolic rate, selective inhibition of many ATP-consuming metabolic activities and a change in fuel use to a primary dependence on the oxidation of lipid reserves. We investigated whether the AMP-activated protein kinase (AMPK) could play a regulatory role in this reorganization. AMPK activity and the phosphorylation state of multiple downstream targets were assessed in five organs of thirteen-lined ground squirrels (Spermophilus tridecemlineatus) comparing euthermic animals with squirrels in deep torpor. AMPK activity was increased 3-fold in white adipose tissue from hibernating ground squirrels compared with euthermic controls, but activation was not seen in liver, skeletal muscle, brown adipose tissue or brain. Immunoblotting with phospho-specific antibodies revealed an increase in phosphorylation of eukaryotic elongation factor-2 at the inactivating Thr56 site in white adipose tissue, liver and brain of hibernators, but not in other tissues. Acetyl-CoA carboxylase phosphorylation at the inactivating Ser79 site was markedly increased in brown adipose tissue from hibernators, but no change was seen in white adipose tissue. No change was seen in the level of phosphorylation of the Ser565 AMPK site of hormone-sensitive lipase in adipose tissues of hibernating animals. In conclusion, AMPK does not appear to participate in the metabolic re-organization and/or the metabolic rate depression that occurs during ground squirrel hibernation.
Horman
Sandrine
S
Hormone and Metabolic Research Unit, Christian de Duve Institute of Cellular Pathology and University of Louvain Medical School, Avenue Hippocrate, 75, B-1200 Brussels, Belgium.
Hussain
Nusrat
N
Dilworth
Stephen M
SM
Storey
Kenneth B
KB
Rider
Mark H
MH
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D006006:Glycogen Synthase / Q000276:immunology / Q000378:metabolism; D006605:Hibernation / Q000235:genetics / Q000502:physiology*; D009097:Multienzyme Complexes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D020652:Peptide Elongation Factor 2 / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D012589:Sciuridae / Q000502:physiology*; D012694:Serine / Q000378:metabolism; D002787:Sterol Esterase / Q000276:immunology / Q000378:metabolism; D013696:Temperature; D013912:Threonine / Q000378:metabolism
D009097:Multienzyme Complexes; D020652:Peptide Elongation Factor 2; D013912:Threonine; D012694:Serine; D006006:Glycogen Synthase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D002787:Sterol Esterase; D000103:Acetyl-CoA Carboxylase