| Mammalian hibernation is characterized by a deep reduction in basal metabolic rate and body temperature in order to maximize energy savings during times of low food availability and harsh environmental conditions. These physiological extremes are lethal to non-hibernators, yet because hibernators are broadly distributed among mammalian lineages, the genes that underlie the phenotype are hypothesized to be common to all mammals, although differentially expressed. Because of their natural phenotypic plasticity, hibernators are excellent models for identifying natural solutions to improve the human medical outcomes of a number of conditions. Hence, my research has focused on elucidating the genes that underlie the phenotype of the model hibernator, the 13-lined ground squirrel. Specifically, differential gene expression was analyzed in two organs of the hibernator, the heart and brown adipose tissue (BAT). In the heart, differential protein expression among eight dynamic seasonal and physiological stages of the hibernator's year was defined via 2D-DiGE and tandem mass-spectrometry methodology, while in BAT, differential transcript expression among 10 different seasonal and physiological states of the hibernator's year was characterized via a digital transcriptome analysis. The results of these analyses reveal that both the heart and BAT undergo a seasonal reprogramming, with gene products involved in fatty acid catabolism and the stress response increasing during the winter period of hibernation. Additionally, in heart, cofilin-2 becomes dephosphorylated during the cold body temperature and metabolically-depressed state of torpor, and this may serve as a mechanism to preserve ATP while the heart continually functions during torpor. In BAT, many of the significant transcript changes during winter hibernation exhibited an unexpected pattern -- apparently increasing despite low body temperature when transcription is suppressed during torpor and early arousal. Measurements of total, short poly(A) and long poly(A) RNA abundance in 13 candidate genes by RT-qPCR revealed three patterns of BAT RNA dynamics in hibernation. The results have led to the generation of a new hypothesis, which proposes that while most transcripts degrade during torpor, a subset involved in BAT function are stabilized via lengthened poly(A) tails, so that they are prioritized for rapid translation during the highly metabolically active period of arousal. |
