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dc.rights.licenseopenen_US
dc.contributor.authorBRIAND, François
dc.contributor.authorMAUPOINT, Julie
dc.contributor.authorBROUSSEAU, Emmanuel
dc.contributor.authorBREYNER, Natalia
dc.contributor.authorBOUCHET, Melanie
dc.contributor.authorCOSTARD, Clement
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorLESTE-LASSERRE, Thierry
dc.contributor.authorPETITJEAN, Mathieu
dc.contributor.authorCHEN, Li
dc.contributor.authorCHABRAT, Audrey
dc.contributor.authorRICHARD, Virgile
dc.contributor.authorBURCELIN, Remy
dc.contributor.authorDUBROCA, Caroline
dc.contributor.authorSULPICE, Thierry
dc.date.accessioned2022-03-14T15:42:43Z
dc.date.available2022-03-14T15:42:43Z
dc.date.issued2021-04
dc.identifier.issn0026-0495en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/136463
dc.description.abstractEnBackground: Cardiovascular disease is the leading cause of deaths in nonalcoholic steatohepatitis (NASH) patients. Mouse models, while widely used for drug development, do not fully replicate human NASH nor integrate the associated cardiac dysfunction, i.e. heart failure with preserved ejection fraction (HFpEF). To overcome these limitations, we established a nutritional hamster model developing both NASH and HFpEF. We then evaluated the effects of the dual peroxisome proliferator activated receptor alpha/delta agonist elafibranor developed for the treatment of NASH patients. Methods: Male Golden Syrian hamsters were fed for 10 to 20 weeks with a free choice diet, which presents hamsters with a choice between control chow diet with normal drinking water or a high fat/high cholesterol diet with 10% fructose enriched drinking water. Biochemistry, histology and echocardiography analysis were performed to characterize NASH and HFpEF. Once the model was validated, elafibranor was evaluated at 15 mg/kg/day orally QD for 5 weeks. Results: Hamsters fed a free choice diet for up to 20 weeks developed NASH, including hepatocyte ballooning (as confirmed with cytokeratin-18 immunostaining), bridging fibrosis, and a severe diastolic dysfunction with restrictive profile, but preserved ejection fraction. Elafibranor resolved NASH, with significant reduction in ballooning and fibrosis scores, and improved diastolic dysfunction with significant reduction in E/A and E/E' ratios. Conclusion: Our data demonstrate that the free choice diet induced NASH hamster model replicates the human phenotype and will be useful for validating novel drug candidates for the treatment of NASH and associated HfpEF.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enDiastolic dysfunction
dc.subject.enFibrosis
dc.subject.enHamster
dc.subject.enHeart failure
dc.subject.enNonalcoholic steatohepatitis
dc.title.enElafibranor improves diet-induced nonalcoholic steatohepatitis associated with heart failure with preserved ejection fraction in Golden Syrian hamsters
dc.title.alternativeMetabolismen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.metabol.2021.154707en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed33444606en_US
bordeaux.journalMetabolismen_US
bordeaux.volume117en_US
bordeaux.hal.laboratoriesNeurocentre Magendie - UMR-S 1215en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03608393
hal.version1
hal.date.transferred2022-03-14T15:42:47Z
hal.exporttrue
dc.rights.ccCC BY-NC-NDen_US
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