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INRAE

24, chemin de Borde Rouge -Auzeville - CS52627 31326 Castanet Tolosan cedex - France

Last update: May 2021

Etienne LEFAI

ORCID : 0000-0002-3042-7801

RESEARCHER ID: E-9615-2019

Tel : +33 (0)4 73 62 47 44

email: etienne.lefai@inra.fr

The hibernating brown bear, a model for the biomedical research

Research topics

Muscle atrophy, i.e. the progressive loss of muscle mass, occurs with lack of physical activity, in sedentary behavior, under immobilization or during natural aging. In human pathology, muscle atrophy is also observed in several chronic diseases as cancer, renal or cardiac failures, and also in neuromuscular pathologies.

Unfortunately, to face these major public health concerns and in the context of aging population, there are still no efficient therapeutic strategies to preserve muscle mass and to fight against muscle loss.

The Scandinavian brown bear (Ursus arctos) remains inactive in winter during up to seven months without arousal episodes and without eating, drinking, urinating or defecating, with only very limited loss in muscle protein content and strength, whereas muscle and fibre cross-sectional area is preserved. Hibernating bears thus exhibit a strong and unique ability to preserve muscle mass in conditions of muscle disuse and food deprivation, conditions during which muscle atrophy is observed in human.

Thanks to a collaborative network involving several European academic laboratories with access to bear samples thanks to the SBBRG (http://bear.info), we are developing a research program aiming at the characterization of the bear serum potential to impact human muscle cell physiology. We explore the mechanisms by which the bears successfully spare its muscle proteins during up to 7 months of inactivity during winter hibernation.

Twice a year, in winter and summer, all scientists meet in the Swedish boreal forest to capture free living bears and collect samples.

Underlying mechanisms have not been understood yet, but our recent demonstration of trans-species effects of bear serum controlling protein degradation in cultured human muscle cell holds promising potential. By inducing a hibernation-like phenotype in human muscle cells, winter bear serum, therefore, holds potential for developing new tools to fight human muscle atrophy and related metabolic disorders.

The project is also on screen

See the teaser of the 52' documentary " The superpower of the bears"

Teaser on Vimeo

ARTE /Le cinquieme reve (T. Robert and R. Marion Directors)

Selected recent publications

Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear. Cussonneau, L.; Boyer, C.; Brun, C.; Deval, C.; Loizon, E.; Meugnier, E.; Gueret, E.; Dubois, E.; Taillandier, D.; Polge, C.; Bechet, D.; Gauquelin-Koch, G.; Evans, AL.; Arnemo, JM.; Swenson JE.; Blanc, S.; Simon, C.; Lefai, E.; Bertile, F.; Combaret,L. Cells 2021, 10, 1873. doi.org/10.3390/cells10081873

Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction. Givre L, Crola Da Silva C, Swenson JE, Arnemo JM, Gauquelin-Koch G, Bertile F, Lefai E, Gomez L. Front Cardiovasc Med. 2021 Jul 16;8:687501. doi: 10.3389/fcvm.2021.687501.

Specific shifts in the endocannabinoid system in hibernating brown bears. Boyer C, Cussonneau L, Brun C, Deval C, Pais de Barros JP, Chanon S, Bernoud-Hubac N, Daira P, Evans AL, Arnemo JM, Swenson JE, Gauquelin-Koch G, Simon C, Blanc S, Combaret L, Bertile F, Lefai E. Front Zool. 2020 Nov 23;17(1):35. doi: 10.1186/s12983-020-00380-y.

MicroRNAs facilitate skeletal muscle maintenance and metabolic suppression in hibernating brown bears. Luu BE, Lefai E, Giroud S, Swenson JE, Chazarin B, Gauquelin-Koch G, Arnemo JM, Evans AL, Bertile F, Storey KB. J Cell Physiol. 2020 Apr;235(4):3984-3993. doi: 10.1002/jcp.29294. Epub 2019 Oct 23.

Metabolic reprogramming involving glycolysis in the hibernating brown bear skeletal muscle. Chazarin B, Storey KB, Ziemianin A, Chanon S, Plumel M, Chery I, Durand C, Evans AL, Arnemo JM, Zedrosser A, Swenson JE, Gauquelin-Koch G, Simon C, Blanc S, Lefai E, Bertile F. Front Zool. 2019 May 6;16:12. doi: 10.1186/s12983-019-0312-2. eCollection 2019. PMID: 31080489 Free PMC article.

Lipidomics Reveals Seasonal Shifts in a Large-Bodied Hibernator, the Brown Bear. Giroud S, Chery I, Bertile F, Bertrand-Michel J, Tascher G, Gauquelin-Koch G, Arnemo JM, Swenson JE, Singh NJ, Lefai E, Evans AL, Simon C, Blanc S. Front Physiol. 2019 Apr 12;10:389. doi: 10.3389/fphys.2019.00389. eCollection 2019.

Seasonal changes in eicosanoid metabolism in the brown bear. Giroud S, Evans AL, Chery I, Bertile F, Tascher G, Bertrand-Michel J, Gauquelin-Koch G, Arnemo JM, Swenson JE, Lefai E, Blanc S, Simon C. Naturwissenschaften. 2018 Sep 17;105(9-10):58. doi: 10.1007/s00114-018-1583-8. PMID: 30291454 Free PMC article.

Proteolysis inhibition by hibernating bear serum leads to increased protein content in human muscle cells. Chanon S, Chazarin B, Toubhans B, Durand C, Chery I, Robert M, Vieille-Marchiset A, Swenson JE, Zedrosser A, Evans AL, Brunberg S, Arnemo JM, Gauquelin-Koch G, Storey KB, Simon C, Blanc S, Bertile F, Lefai E. Sci Rep. 2018 Apr 3;8(1):5525. doi: 10.1038/s41598-018-23891-5.