Metabolic Adaptation in Hibernating American Black Bears: Exploring Immobilization Protection with Mass Spectral Data and Computational Methods

American black bears (Ursus americanus) have adapted the ability to maintain homeostasis during a 4–6-month hibernation period and emerge from their dens without experiencing thrombosis, muscle loss, and other physiological detriments typically seen in immobile humans. Metabolomics has been shown to be a driver for other omic pathways and a reliable biomarker in observing physiological shifts occurring in critically ill patients and individuals with metabolic disease. Thus, understanding the hibernating bears’ metabolic regulation may have translational interest in clinical settings for patients whose conditions are exacerbated by immobility. Blood samples were collected from bears in the northern Minnesota region during three time periods: summer (July), early-denning (December), and late-denning (March). Biocrates MxP Quant 500 kit-based assay monitored for 630 metabolites and lipids for a targeted metabolic profiling dataset of 75 bear plasma samples. To identify metabolites influencing seasonal modulations, a sparse partial least squares discrimination analysis (sPLS-DA) model was utilized to produce sample plots in conjunction with correlation circles plots. We focused on the seasonal differences between 34 metabolites processed using liquid-chromatography (LC) methods and significances were confirmed using Kruskal-Wallis statistical tests. We identified 22 key metabolites, many of which are involved in protein synthesis and the metabolizing of lipids that could be driving homeostasis between summer and winter and between early- and late-denning. These key metabolites provide a baseline for discovering which pathways could influence the black bears’ ability to modulate their metabolisms for winter. Future works should analyze other metabolite classes, especially those of similar function or within the same pathways of the ones identified here to understand the specific dynamics of the biosynthetic pathways driving homeostasis.