Can offsetting the energetic cost of hibernation restore an active season phenotype in grizzly bears (Ursus arctos horribilis)?

Abstract

Hibernation is characterized by depression of many physiological processes. To determine if this state is reversible in a non-food caching species, we fed hibernating grizzly bears (Ursus arctos horribilis) dextrose for 10 days to replace 53% or 100% of the estimated minimum daily energetic cost of hibernation. Feeding caused serum concentrations of glycerol and ketones (ß-hydroxybutyrate) to return to active season levels irrespective of the amount of glucose fed. By contrast, free-fatty acids and indices of metabolic rate, such as general activity, heart rate, and strength of the daily heart rate rhythm and insulin sensitivity were restored to roughly 50% of active season levels. Body temperature was unaffected by feeding. To determine the contribution of adipose to the metabolic effects observed after glucose feeding, we cultured bear adipocytes collected at the beginning and end of the feeding and performed metabolic flux analysis. We found a roughly 33% increase in energy metabolism after feeding. Moreover, basal metabolism before feeding was 40% lower in hibernation cells compared to fed cells or active cells cultured at 37°C, thereby confirming the temperature independence of metabolic rate. The partial depression of circulating FFA with feeding likely explains the incomplete restoration of insulin sensitivity and other metabolic parameters in hibernating bears. Further depression of metabolic function is likely to be an active process. Together, the results provide a highly controlled model to examine the relationship between nutrient availability and metabolism on the hibernation phenotype in bears.

Serum plays an important role in reprogramming the seasonal transcriptional profile of brown bear adipocytes

“…The transcriptional response in adipocytes to glucose feeding suggests that whereas metabolism and heart rate increase before den emergence, food consumption likely acts as a proximate cue necessary for the transitioning of adipose from a lipolytic/insulin-resistant state to one of insulin sensitivity (Jansen et al, 2021). This hypothesis is consistent with observations that bears do not restore full active season physiology immediately after exiting their dens and rely initially on the catabolism of fat for energy .…”

“…Serum in this and our previous studies ( Jansen et al., 2021 ; Rigano et al., 2017 ) had a dramatic impact on cellular phenotypes. To identify circulating proteins potentially underlying these phenotypes, we compared protein composition and abundance among hibernation, active, and post-glucose sera ( Figure 1 D).…”

“…Cultured brown bear adipocytes retain many of the bears’ physiological properties based on when they were harvested ( Jansen et al., 2021 ; Rigano et al., 2017 ). For example, cell cultures derived from hibernating or active season brown bears exhibited shifts in insulin sensitivity matching those seen in vivo when grown in matching serum ( Rigano et al., 2017 ).…”

“…These differences in gene expression between hibernation and active bear adipocytes may be driven by cellular state, serum components, or a combination of the two. To disentangle large-scale seasonal changes that may be driven by extrinsic factors, we previously fed captive brown bears glucose for a 10-day period during hibernation and collected preadipocytes and serum before and after the feeding trial ( Jansen et al., 2021 ). In the present study, we examined the roles of season, cellular state, and serum proteins on adipocyte gene expression.…”

Gene Expression and Tracer-Based Metabolic Flux Analysis Reveals Tissue-Specific Metabolic Scaling in vitro, ex vivo, and in vivo

“…These data have implications for metabolic regulation during hibernation, in which metabolic rates are reproducibly and markedly but reversibly suppressed (Jansen et al, 2021, 2019; Tøien et al, 2011). Metabolic scaling phenomena may also have medical relevance.…”