Horman, S., Hussain,
N., Dilworth, S.M., Storey, K.B. and Rider, M.H. 2005. Evaluation of the role of AMP-activated
protein kinase and its downstream targets in mammalian hibernation.
Comp. Biochem. Physiol. B 142, 374-382.
Evaluation
of the role of AMP-activated protein kinase and its downstream targets in
mammalian hibernation
Sandrine Horman, Nusrat Hussain, Stephen M. Dilworth,
Kenneth B. Storey, and Mark H. Rider
Abstract
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