MicroRNAs facilitate skeletal muscle maintenance and metabolic suppression in hibernating brown bears

• Published in: Journal of Cellular Physiology
• Main Authors: Luu, Bryan E., Lefai, Etienne, Giroud, Sylvain, Swenson, Jon E., Chazarin, Blandine, Gauquelin‐Koch, Guillemette, Arnemo, Jon M., Evans, Alina L., Bertile, Fabrice, Storey, Kenneth B.
• Other Authors: Biology, SAMS, McGill University = Université McGill Montréal, Canada, 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), Department of Integrative Biology and Evolution, Research Institute of Wildlife Ecology, University of Veterinary Medicine Vienna, Norwegian University of Life Sciences, Faculty of Environmental Sciences and Natural Resource Management (NMBU), Norvegian Institute for Nature Research, Centre National d’Études Spatiales Paris (CNES), 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), Forestry & Wildlife Management, Inland Norway University of Applied Sciences - Høgskolen i Innlandet, Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences (SLU), Centre National D'etudes Spatiales874Natural Sciences and Engineering Research Council of Canada6793Universite de Strasbourg Center National de la Recherche Scientifique Miljodirektoratet Naturvardsverket Svenska Jagareforbundet Austrian Science Fund (FWF) Centre National D'etudes Spatiales
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2020
• Subjects: Ursus arctos; ubiquitin ligase; atrophy; Mef2a; myomiR; noncoding RNA; [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT]; [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
• Online Access: https://hal.archives-ouvertes.fr/hal-02349938; https://hal.archives-ouvertes.fr/hal-02349938/document; https://hal.archives-ouvertes.fr/hal-02349938/file/Manuscript%20-%20J%20Cell%20Physiol.pdf; https://doi.org/10.1002/jcp.29294

Early ViewOnline Version of Record before inclusion in an issue Hibernating brown bears, Ursus arctos, undergo extended periods of inactivity and yet these large hibernators are resilient to muscle disuse atrophy. Physiological characteristics associated with atrophy resistance in bear muscle have been examined (e.g., muscle mechanics, neural activity) but roles for molecular signaling/regulatory mechanisms in the resistance to muscle wasting in bears still require investigation. Using quantitative reverse transcription PCR (RT-qPCR), the present study characterized the responses of 36 microRNAs linked with development, metabolism, and regeneration of skeletal muscle, in the vastus lateralis of brown bears comparing winter hibernating and summer active animals. Relative levels of mRNA of selected genes (mef2a, pax7, id2, prkaa1, and mstn) implicated upstream and downstream of the microRNAs were examined. Results indicated that hibernation elicited a myogenic microRNA, or "myomiR", response via MEF2A-mediated signaling. Upregulation of MEF2A-controlled miR-1 and miR-206 and respective downregulation of pax7 and id2 mRNA are suggestive of responses that promote skeletal muscle maintenance. Increased levels of metabolic microRNAs, such as miR-27, miR-29, and miR-33, may facilitate metabolic suppression during hibernation via mechanisms that decrease glucose uptake and fatty acid oxidation. This study identified myomiR-mediated mechanisms for the promotion of muscle regeneration, suppression of ubiquitin ligases, and resistance to muscle atrophy during hibernation mediated by observed increases in miR-206, miR-221, miR-31, miR-23a, and miR-29b. This was further supported by the downregulation of myomiRs associated with a muscle injury and inflammation (miR-199a and miR-223) during hibernation. The present study provides evidence of myomiR-mediated signaling pathways that are activated during hibernation to maintain skeletal muscle functionality in brown bears.