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

Abstract

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.

Blood clotting behavior is innately modulated in Ursus Americanus during early and late denning relative to summer months

“…Again, we consider that better understanding of modulations within the mechanisms of the clotting cascade in black bears may introduce opportunities for employing novel clinical mechanisms for anti-coagulation therapy and targeted treatments. It should be noted that in a very recent publication the clotting behavior in hibernating brown bears (Ursus arctos) has been described to elicit similar responses (Welinder et al, 2016).…”

Denning in brown bears

“…Brown bears hibernate for several months during which they do not eat, drink, defecate or urinate, thus reducing the use of the bladder, kidneys, and digestive tract (Folk, Folk, & Minor, 1972;Hissa, 1997;Stenvinkel, Fröbert, et al, 2013). Hibernation adaptations allow bears to overcome anuria, hyperlipidemia, and immobilization (Welinder et al, 2016), preserve muscles and bones avoiding osteoporosis or sarcopenia (Fröbert, Frøbert, Kindberg, Arnemo, & Overgaard, 2020;Vestergaard et al, 2011) and prevent diseases such as metabolic syndrome, diabetes, and cardiovascular pathologies (Arinell et al, 2012;Fröbert et al, 2020;Nelson & Robbins, 2015). The physiological modifications that occur in bears during hibernation, and which are summarized below, might be the result of ultimate factors such as metabolic dietary-related needs and energy conservation, which brown bears have to deal with to survive the winter (Table 1).…”

“…The hibernating induction trigger (HIT), a compound present in the blood, might initiate physiological and metabolic changes that lead to hibernation (Hellgren, 1998;Hissa et al, 1994;Jørgensen et al, 2014;Welinder et al, 2016), although it has also been suggested than more than a single substance could trigger all these changes (Hissa, 1997). For example, the sex hormone-binding globulin protein, which increases its concentration 45-fold during hibernation, might also help trigger hibernation (Welinder et al, 2016).…”

“…High concentrations of phospholipids and cholesterol may be due to the shrinking of the membrane of the adipocytes caused by dehydration (Welinder et al, 2016). The high concentrations of free fatty acids (FA) and glycerol might be the result of their release from adipose tissue during hibernation (Welinder et al, 2016), with short chain (easier oxidation) of FAs being released and retained in muscle and tissue adipose than long FA chains, as it occurs in other hibernating mammals (Giroud et al, 2019).…”

The brown bear as a translational model for sedentary lifestyle‐related diseases

“…Proteomes of blood, organs and tissues can be characterised by mass spectrometry (MS), which identifies proteins and determines relative protein quantities by matching the mass of peptide fragments to predicted peptide sequences from databases. The differences between the summer and winter brown bear plasma proteome have been characterised by Welinder et al [30], providing information of the biochemical adaptions for hibernation, as the bloodstream has primary functions in signalling. A number of adaptations specific to hibernation were discovered, including energy conservation by decreased levels of the majority of plasma proteins combined with maintained or moderately increased levels of a few key plasma proteins performing crucial functions in hibernation.…”