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Etienne Lefai
INRA Centre Clermont-Ferrand-Theix-Lyon
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3042-7801
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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.
Infographic
Keywords
Hibernation, Brown bear, Metabolism, Lipidomic, Docosahexaenoic acid, Endocannabinoid system, Cannabinoid receptor 1, Cannabinoid receptor 2, 2-arachidonoylglycerol, Anandamide, N-oleoylethanolamide
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View the published article at Frontiers in Zoology.
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Posted 03 Sep, 2020
No community comments so far
Editorial decision: Accept
On 31 Aug, 2020
Editor assigned
On 26 Aug, 2020
Submission checks complete
On 25 Aug, 2020
Editor invited
On 25 Aug, 2020
No comments provided
Editorial decision: Accept with minor revisions
On 17 Aug, 2020
Review #2 received
Received 13 Aug, 2020
Review #1 received
Received 12 Aug, 2020
Reviewers invited
Invitations sent on 31 Jul, 2020
Reviewer #1 agreed
On 31 Jul, 2020
Reviewer #2 agreed
On 31 Jul, 2020
Editor assigned
On 29 Jul, 2020
Submission checks complete
On 28 Jul, 2020
Editor invited
On 28 Jul, 2020
No comments provided
Editorial decision: Major revision
On 16 Jun, 2020
Review #2 received
Received 15 Jun, 2020
Review #3 received
Received 15 Jun, 2020
Review #1 received
Received 03 Jun, 2020
Reviewer #3 agreed
On 21 May, 2020
Reviewer #2 agreed
On 21 May, 2020
Reviewer #1 agreed
On 20 May, 2020
Reviewers invited
Invitations sent on 19 May, 2020
Editor assigned
On 18 May, 2020
Submission checks complete
On 17 May, 2020
Editor invited
On 17 May, 2020
First submitted
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Subject Areas
Animal Science
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See the published version of this preprint at Frontiers in Zoology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Etienne Lefai
INRA Centre Clermont-Ferrand-Theix-Lyon
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3042-7801
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Frontiers in Zoology.
Version 3
Posted 03 Sep, 2020
No community comments so far
Editorial decision: Accept
On 31 Aug, 2020
Editor assigned
On 26 Aug, 2020
Submission checks complete
On 25 Aug, 2020
Editor invited
On 25 Aug, 2020
No comments provided
Editorial decision: Accept with minor revisions
On 17 Aug, 2020
Review #2 received
Received 13 Aug, 2020
Review #1 received
Received 12 Aug, 2020
Reviewers invited
Invitations sent on 31 Jul, 2020
Reviewer #1 agreed
On 31 Jul, 2020
Reviewer #2 agreed
On 31 Jul, 2020
Editor assigned
On 29 Jul, 2020
Submission checks complete
On 28 Jul, 2020
Editor invited
On 28 Jul, 2020
No comments provided
Editorial decision: Major revision
On 16 Jun, 2020
Review #2 received
Received 15 Jun, 2020
Review #3 received
Received 15 Jun, 2020
Review #1 received
Received 03 Jun, 2020
Reviewer #3 agreed
On 21 May, 2020
Reviewer #2 agreed
On 21 May, 2020
Reviewer #1 agreed
On 20 May, 2020
Reviewers invited
Invitations sent on 19 May, 2020
Editor assigned
On 18 May, 2020
Submission checks complete
On 17 May, 2020
Editor invited
On 17 May, 2020
First submitted
On 16 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Animal Science
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Frontiers in Zoology.
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.
Infographic
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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