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J Biol Chem. 2016 Oct 21;291(43):22509-22523. Epub 2016 Sep 8.

Biochemical Foundations of Health and Energy Conservation in Hibernating Free-ranging Subadult Brown Bear Ursus arctos.

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From the Department of Chemistry and Bioscience, Section of Biotechnology, Aalborg University, Fredrik Bajers Vej 7H, 9220 Aalborg East, Denmark,
From the Department of Chemistry and Bioscience, Section of Biotechnology, Aalborg University, Fredrik Bajers Vej 7H, 9220 Aalborg East, Denmark.
the Departments of Metabolomics and.
Proteomics, Helmholtz Centre for Environmental Research (UFZ), Permoserstrasse 15, 04318 Leipzig, Germany.
the Department of Clinical and Experimental Medicine, Linköping University, 581 85 Linköping, Sweden.
the Department of Cardiology, Faculty of Health, Örebro University, 701 85 Örebro, Sweden.
the Department of Forestry and Wildlife Management, Hedmark University College, Campus Evenstrand, 2411 Elverum, Norway.
the Department for Ecology and Natural Resource Management, Norwegian University of Life Sciences, Postbox 5014, 1432 Ås, Norway.
the Norwegian Institute for Nature Research, Tungasletta 2, N-7485 Trondheim, Norway, and.
the Department of Bioscience, Zoophysiology, Aarhus University, C.F. Møllers Allé 3, 8000 Aarhus C, Denmark.


Brown bears (Ursus arctos) hibernate for 5-7 months without eating, drinking, urinating, and defecating at a metabolic rate of only 25% of the summer activity rate. Nonetheless, they emerge healthy and alert in spring. We quantified the biochemical adaptations for hibernation by comparing the proteome, metabolome, and hematological features of blood from hibernating and active free-ranging subadult brown bears with a focus on conservation of health and energy. We found that total plasma protein concentration increased during hibernation, even though the concentrations of most individual plasma proteins decreased, as did the white blood cell types. Strikingly, antimicrobial defense proteins increased in concentration. Central functions in hibernation involving the coagulation response and protease inhibition, as well as lipid transport and metabolism, were upheld by increased levels of very few key or broad specificity proteins. The changes in coagulation factor levels matched the changes in activity measurements. A dramatic 45-fold increase in sex hormone-binding globulin levels during hibernation draws, for the first time, attention to its significant but unknown role in maintaining hibernation physiology. We propose that energy for the costly protein synthesis is reduced by three mechanisms as follows: (i) dehydration, which increases protein concentration without de novo synthesis; (ii) reduced protein degradation rates due to a 6 °C reduction in body temperature and decreased protease activity; and (iii) a marked redistribution of energy resources only increasing de novo synthesis of a few key proteins. The comprehensive global data identified novel biochemical strategies for bear adaptations to the extreme condition of hibernation and have implications for our understanding of physiology in general.


antimicrobial proteins; blood constituents; coagulation factor; complement system; hibernation physiology; metabolomics; protein turnover; proteomics; sex hormone-binding globulin (SHBG)

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