Specific shifts in the endocannabinoid system in hibernating brown bears

• Published in: Frontiers in Zoology
• Main Authors: Boyer, Christian, Cussonneau, Laura, Brun, Charlotte, Deval, Christiane, Pais de Barros, Jean-Paul, Chanon, Stéphanie, Bernoud-Hubac, Nathalie, Daira, Patricia, Evans, Alina, Arnemo, Jon, Swenson, Jon, Gauquelin-Koch, Guillemette, Simon, Chantal, Blanc, Stéphane, Combaret, Lydie, Bertile, Fabrice, Lefai, Etienne
• Other Authors: Unité de Nutrition Humaine (UNH), Université Clermont Auvergne 2017-2020 (UCA 2017-2020 )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Lipides - Nutrition - Cancer Dijon - U1231 (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Mécanique des Contacts et des Structures Villeurbanne (LaMCoS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institut Multidisciplinaire de Biochimie des Lipides (IMBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Covalab-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Inland Norway University of Applied Sciences - Høgskolen i Innlandet, Norwegian University of Life Sciences (NMBU), Centre National d’Études Spatiales Paris (CNES), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Centre National D'etudes SpatialesiSITE Challenge 3 Mobility program (UCA) Centre National de la Recherche Scientifique (CNRS)Strasbourg University (H2E project; MyoBears project of the PEPS ExoMod program)French Proteomic Infrastructure (ProFI) ANR-10-INSB-08-03 MESRI INRAE Clermont Metropole Swedish Environmental Protection Agency Norwegian Environment Agency Austrian Science Fund (FWF) Swedish Association for Hunting and Wildlife Management, ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2020
• Subjects: Hibernation; Brown bear; Metabolism; Lipidomic; Docosahexaenoic acid; Endocannabinoid system; Cannabinoid receptor 1; Cannabinoid receptor 2; 2-arachidonoylglycerol; Anandamide; N-oleoylethanolamide; [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology; Ursus arctos
• Online Access: https://hal.science/hal-03054587; https://hal.science/hal-03054587/document; https://hal.science/hal-03054587/file/2020_Boyer_Front_Zoology.pdf; https://doi.org/10.1186/s12983-020-00380-y

International audience 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.