Analysis of the hibernation cycle using LC-MS-based metabolomics in ground squirrel liver

Nelson CJ, Otis JP, Martin SL, Carey HV. Analysis of the hibernation cycle using LC-MS-based metabolomics in ground squirrel liver. Physiol Genomics 37: 43-51, 2009. First published December 23, 2008; doi: 10.1152/physiolgenomics.90323.2008. - A hallmark of hibernation in mammals is metabolic flexibility, which is typified by reversible bouts of metabolic depression ( torpor) and the seasonal shift from predominantly carbohydrate to lipid metabolism from summer to winter. To provide new insight into the control and consequences of hibernation, we used LC/MS-based metabolomics to measure differences in small molecules in ground squirrel liver in five activity states: summer, entering torpor, late torpor, arousing from torpor, and interbout arousal. There were significant alterations both seasonally and within torpor-arousal cycles in enzyme cofactor metabolism, amino acid catabolism, and purine and pyrimidine metabolism, with observed metabolites reduced during torpor and increased upon arousal. Multiple lipids also changed, including 1-oleoyllyso-phosphatidylcholine, cholesterol sulfate, and sphingosine, which tended to be lowest during torpor, and hexadecanedioic acid, which accumulated during a torpor bout. The results reveal the dramatic alterations that occur in several classes of metabolites, highlighting the value of metabolomic analyses in deciphering the hibernation phenotype.