Variation, regulation, and conservation of metabolic signaling across hibernating mammals

Abstract Hibernation involves complex metabolic and physiological shifts that enable diverse mammalian species to survive prolonged periods of resource scarcity. These species are able to cope with prolonged periods of fasting, rapid weight gain and loss, periods of insulin resistance, and other physiological stresses that are associated with metabolic disease or dysfunction in non-hibernating mammals, including humans. This project investigates the mechanisms underlying metabolic innovation in mammals. To complete its objectives, this research project will use comparative and functional genomic approaches to investigate the mechanisms and evolution of hibernation across the mammalian tree, reveal detailed regulatory mechanisms underlying hibernation gene regulation in the brown bear, which is a particularly unique and valuable hibernation model system, and directly test the translational potential of bear serum factors for the modulation of human adipocyte metabolism. This work will advance our understanding of the mechanisms governing hibernation in mammals and identify specific genes, transcription factors, and signaling pathways with conserved or divergent function in hibernators compared to humans. This research will identify specific genes and regulatory mechanisms that can be targeted in the treatment of human metabolic diseases.