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

Fröbert, Ole; Frøbert, Anne Mette; Kindberg, Jonas; Arnemo, Jon M.; Overgaard, Michael Toft

doi:10.1111/joim.12983

Cited by 32 publications

(39 citation statements)

References 58 publications

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“…During hibernation, lower 2-AG (and AEA close to statistical threshold) tissue content and the reduction of CNR1 and CNR2 mRNA levels in muscle and adipose tissue, respectively, strongly support reduced ECS tone in both tissues. In non-hibernating mammals, pharmacological inhibition of CB1 leads to a decrease in PDK4 expression [26,67]. PDK4 is a major negative regulator of PDH activity, that in turn regulates the whole body oxidative carbohydrate metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…Strikingly, insulin resistance has been described in hibernating bears adipocytes [66]. As bears don't experience health consequences of circannual high body fat storage [67], a reduced CB2 signaling in adipose tissue could dampen adipose tissue in ammation. Lower amounts of 2-AG and AEA could also reduced CB1 signaling in adipose tissue, thus limiting lipogenesis and promoting lipolysis during hibernation in bears, as also suggested for hibernating marmots [31].…”

Section: Discussionmentioning

confidence: 99%

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Specific shifts in the endocannabinoid system in hibernating brown bears

Boyer

Cussonneau

Brun

et al. 2020

Preprint

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In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears ( Ursus arctos ), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear’s peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Specific shifts in the endocannabinoid system in hibernating brown bears

Boyer

Cussonneau

Brun

et al. 2020

Preprint

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“…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).…”

Section: Hibernation Physiology and The Potential Energetic Costsmentioning

confidence: 99%

Denning in brown bears

González-Bernardo

Russo

Valderrábano

et al. 2020

Ecology and Evolution

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Hibernation represents an adaptation for coping with unfavorable environmental conditions. For brown bears Ursus arctos, hibernation is a critical period as pronounced temporal reductions in several physiological functions occur. Here, we review the three main aspects of brown bear denning: (1) den chronology, (2) den characteristics, and (3) hibernation physiology in order to identify (a) proximate and ultimate factors of hibernation as well as (b) research gaps and conservation priorities. Den chronology, which varies by sex and reproductive status, depends on environmental factors, such as snow, temperature, food availability, and den altitude. Significant variation in hibernation across latitudes occurs for both den entry and exit. The choice of a den and its surroundings may affect individual fitness, for example, loss of offspring and excessive energy consumption. Den selection is the result of broad‐ and fine‐scale habitat selection, mainly linked to den insulation, remoteness, and availability of food in the surroundings of the den location. Hibernation is a metabolic challenge for the brown bears, in which a series of physiological adaptations in tissues and organs enable survival under nutritional deprivation, maintain high levels of lipids, preserve muscle, and bone and prevent cardiovascular pathologies such as atherosclerosis. It is important to understand: (a) proximate and ultimate factors in denning behavior and the difference between actual drivers of hibernation (i.e., factors to which bears directly respond) and their correlates; (b) how changes in climatic factors might affect the ability of bears to face global climate change and the human‐mediated changes in food availability; (c) hyperphagia (period in which brown bears accumulate fat reserves), predenning and denning periods, including for those populations in which bears do not hibernate every year; and (d) how to approach the study of bear denning merging insights from different perspectives, that is, physiology, ecology, and behavior.

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“…Hibernation is an ingenious survival strategy that evolved during evolution in certain species, such as bears, to conserve energy during long periods of nutrient–water shortage, coldness and hypoxia. Since hibernating bears are forced to maintain a careful balance between metabolic supply and demand, they are used as a model to develop novel approaches to counteract burden of lifestyle diseases, such as chronic kidney disease , obesity‐ and sedentary‐related diseases , organ preservation , ischaemic brain damage osteoporosis and muscle wasting . It is notable that many similarities exist between hibernation phenotypes and various long‐lived animal models ; that is, hibernation seems to retard biological ageing in proportion to time spent in the hibernating state .…”

Section: Physiological Magicians In the Animal Kingdom – Implicationsmentioning

confidence: 99%

Biomimetics – Nature's roadmap to insights and solutions for burden of lifestyle diseases

et al. 2019

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There are over 8 million species in this world that live in widely varying environments, from hot thermal fissures to cold arctic settings. These species have evolved over millions of years and vary markedly in how they have adapted to their environments. In the last decades, studies of how species have succeeded in surviving in different environments and with different resources have been recognized to provide not only insights into disease but also novel means for developing treatments. Here, we provide an overview of two related and overlapping approaches (biomimetics and zoobiquity), which are turning to the natural world for insights to better understand, treat and prevent human ‘burden of lifestyle’ pathologies from heart disease and cancer to degeneration and premature ageing. We suggest that expanding biomedical investigation beyond its decades old conventional practices to new approaches based on a broad awareness of the diversity of animal life and comparative physiology can accelerate innovations in health care under the motto ‘Nature knows best’.

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

Cited by 32 publications

References 58 publications

Specific shifts in the endocannabinoid system in hibernating brown bears

Specific shifts in the endocannabinoid system in hibernating brown bears

Denning in brown bears

Biomimetics – Nature's roadmap to insights and solutions for burden of lifestyle diseases

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