Mammalian Hibernation: Physiology, Cell Signaling, and Gene Controls on Metabolic Rate Depression

During the hibernating season, small mammals may suppress their metabolic rate during cyclic periods of deep torpor by as much as 99% as compared with normothermia. Endocrine regulation of metabolic depression is still poorly understood but recent studies suggest involvement of hormones including iodothyronamine, leptin, and ghrelin. At the intracellular level, suppression of many metabolic functions is achieved via reversible protein phosphorylation of metabolic enzymes, protein synthesis translation factors, and ion pumps. Potential roles for signaling enzymes such as the AMP-activated protein kinase in the coordination of metabolic suppression have been analyzed. Recent advances in the control of global gene expression have identified participating mechanisms including histone modifications that affect chromatin structure, SUMOylation to suppress transcription factor action, and differential regulation of mRNA transcripts by interaction with microRNA species. However, despite global transcriptional suppression, selected transcription factors are active during torpor bouts triggering the up-regulation of specific genes that serve the hibernation phenotype.