{"id":64253,"date":"2023-01-26T18:24:04","date_gmt":"2023-01-26T17:24:04","guid":{"rendered":"https:\/\/cri1149.fr\/?post_type=publications&#038;p=64253"},"modified":"2025-09-11T16:47:58","modified_gmt":"2025-09-11T14:47:58","slug":"characterization-and-pharmacological-validation-of-a-preclinical-model-of-nash-in-gottingen-minipigs","status":"publish","type":"publication","link":"https:\/\/cri1149.fr\/en\/publication\/characterization-and-pharmacological-validation-of-a-preclinical-model-of-nash-in-gottingen-minipigs\/","title":{"rendered":"Characterization and Pharmacological Validation of a Preclinical Model of NASH in G\u00f6ttingen Minipigs"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false,"_EventAllDay":false,"_EventTimezone":"","_EventStartDate":"","_EventEndDate":"","_EventStartDateUTC":"","_EventEndDateUTC":"","_EventShowMap":false,"_EventShowMapLink":false,"_EventURL":"","_EventCost":"","_EventCostDescription":"","_EventCurrencySymbol":"","_EventCurrencyCode":"","_EventCurrencyPosition":"","_EventDateTimeSeparator":"","_EventTimeRangeSeparator":"","_EventOrganizerID":[],"_EventVenueID":[],"_OrganizerEmail":"","_OrganizerPhone":"","_OrganizerWebsite":"","_VenueAddress":"","_VenueCity":"","_VenueCountry":"","_VenueProvince":"","_VenueState":"","_VenueZip":"","_VenuePhone":"","_VenueURL":"","_VenueStateProvince":"","_VenueLat":"","_VenueLng":"","_VenueShowMap":false,"_VenueShowMapLink":false},"category_publication":[],"class_list":["post-64253","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"J Clin Exp Hepatol.","date_de_publication":"20220331","numero_doi":"","equipe":[121],"auteurs-liste":[{"texte_libre":true,"auteur-lien":null,"auteur-text":"Val\u00e9rie Duvivier"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"St\u00e9phanie Creusot"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Olivier Broux"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Aur\u00e9lie Helbert"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Ludovic Lesage"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Kevin Moreau"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Nicolas Lesueur"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Lindsay Gerard"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Karine Lemaitre"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Nicolas Provost"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Edwige-Ludiwyne Hubert"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Tania Baltauss"},{"texte_libre":false,"auteur-lien":14853,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Nathalie De Preville"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Julia Geronimi"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Lucie Adoux"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Franck Letourneur "},{"texte_libre":false,"auteur-lien":13254,"auteur-text":""},{"texte_libre":false,"auteur-lien":13161,"auteur-text":""},{"texte_libre":false,"auteur-lien":13135,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Philippe Delerive"}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/pubmed.ncbi.nlm.nih.gov\/35535064\/"}],"paragraphe":"[:fr]<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Background:\u00a0<\/strong>Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, which is associated with features of metabolic syndrome. NAFLD may progress in a subset of patients into nonalcoholic steatohepatitis (NASH) with liver injury resulting ultimately in cirrhosis and potentially hepatocellular carcinoma. Today, there is no approved treatment for NASH due to, at least in part, the lack of preclinical models recapitulating features of human disease. Here, we report the development of a dietary model of NASH in the G\u00f6ttingen minipig.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Methods:\u00a0<\/strong>First, we performed a longitudinal characterization of diet-induced NASH and fibrosis using biochemical, histological, and transcriptional analyses. We then evaluated the pharmacological response to Obeticholic acid (OCA) treatment for 8 weeks at 2.5mg\/kg\/d, a dose matching its active clinical exposure.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Results:\u00a0<\/strong>Serial histological examinations revealed a rapid installation of NASH driven by massive steatosis and inflammation, including evidence of ballooning. Furthermore, we found the progressive development of both perisinusoidal and portal fibrosis reaching fibrotic septa after 6 months of diet. Histological changes were mechanistically supported by well-defined gene signatures identified by RNA Seq analysis. While treatment with OCA was well tolerated throughout the study, it did not improve liver dysfunction nor NASH progression. By contrast, OCA treatment resulted in a significant reduction in diet-induced fibrosis in this model.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Conclusions:\u00a0<\/strong>These results, taken together, indicate that the diet-induced NASH in the G\u00f6ttingen minipig recapitulates most of the features of human NASH and may be a model with improved translational value to prioritize drug candidates toward clinical development.<\/p>\r\n<\/div>[:]","paragraphe_en":"[:fr]<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Background:\u00a0<\/strong>Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, which is associated with features of metabolic syndrome. NAFLD may progress in a subset of patients into nonalcoholic steatohepatitis (NASH) with liver injury resulting ultimately in cirrhosis and potentially hepatocellular carcinoma. Today, there is no approved treatment for NASH due to, at least in part, the lack of preclinical models recapitulating features of human disease. Here, we report the development of a dietary model of NASH in the G\u00f6ttingen minipig.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Methods:\u00a0<\/strong>First, we performed a longitudinal characterization of diet-induced NASH and fibrosis using biochemical, histological, and transcriptional analyses. We then evaluated the pharmacological response to Obeticholic acid (OCA) treatment for 8 weeks at 2.5mg\/kg\/d, a dose matching its active clinical exposure.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Results:\u00a0<\/strong>Serial histological examinations revealed a rapid installation of NASH driven by massive steatosis and inflammation, including evidence of ballooning. Furthermore, we found the progressive development of both perisinusoidal and portal fibrosis reaching fibrotic septa after 6 months of diet. Histological changes were mechanistically supported by well-defined gene signatures identified by RNA Seq analysis. While treatment with OCA was well tolerated throughout the study, it did not improve liver dysfunction nor NASH progression. By contrast, OCA treatment resulted in a significant reduction in diet-induced fibrosis in this model.<\/p>\r\n<p style=\"text-align: justify;\"><strong class=\"sub-title\">Conclusions:\u00a0<\/strong>These results, taken together, indicate that the diet-induced NASH in the G\u00f6ttingen minipig recapitulates most of the features of human NASH and may be a model with improved translational value to prioritize drug candidates toward clinical development.<\/p>\r\n<\/div>[:]","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Characterization and Pharmacological Validation of a Preclinical Model of NASH in G\u00f6ttingen Minipigs - CRI<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/cri1149.fr\/publication\/characterization-and-pharmacological-validation-of-a-preclinical-model-of-nash-in-gottingen-minipigs\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Characterization and Pharmacological Validation of a Preclinical Model of NASH in G\u00f6ttingen Minipigs - 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