Final Progress Report Differential Gene Expression in Mammalian Liver during Hibernation

Hibernation is an adaptive strategy employed by some mammals to escape the cold. During hibernation, heart, respiratory and metabolic rates plummet, and core body temperatures can approach freezing. Hibernators spontaneously arouse using only endogenously-generated heat. Our long-range goal is to understand the molecular underpinnings of this phenotype in the context of the entire organism. Our efforts focussed upon liver because of its key role in metabolic and other aspects of physiological homeostasis. Specifically, our goals were to: 1) Determine whether there is a reversible inhibition of the oxidative phosphorylation apparatus during torpor (and, if so, whether this inhibition can explain the metabolic changes that accompany entrance and arousal from torpor), and 2) Isolate and analyze hibernation-induced genes. State 3 respiration is reversibly suppressed during torpor. However, this suppression was not found to be causally linked to entrance and arousal. Our other studies identified serum amyloid P as differentially expressed during hibernation. Both it and alpha-2-macroglobulin (also demonstrated to be upregulated during hibernation) apparently play a role in lowering the efficiency of blood clotting. Reduced clotting during hibernation has been recognized for many years and is thought to be critical for survival at the low heart rates that accompany hibernation.