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dc.creatorBenedé-Ubieto, R. (Raquel)-
dc.creatorEstévez-Vázquez, O. (Olga)-
dc.creatorGuo, F. (Feifei)-
dc.creatorChen, C. (Chaobo)-
dc.creatorSingh, Y. (Youvika)-
dc.creatorNakaya, H.I. (Helder I.)-
dc.creatorGómez-del-Moral, M. (Manuel)-
dc.creatorLamas-Paz, A. (Arantxa)-
dc.creatorMorán, L. (Laura)-
dc.creatorLópez-Alcántara, N. (Nuria)-
dc.creatorReissing, J. (Johanna)-
dc.creatorBruns, T. (Tony)-
dc.creatorAvila, M.A. (Matías Antonio)-
dc.creatorSantamaría, E. (Eva)-
dc.creatorMazariegos, M.S. (Marina S.)-
dc.creatorWoitok, M.M. (Marius Maximilian)-
dc.creatorHaas, U. (Ute)-
dc.creatorZheng, K. (Kang)-
dc.creatorJuárez, I. (Ignacio)-
dc.creatorMartín-Villa, J.M. (José Manuel)-
dc.creatorAsensio, I. (Iris)-
dc.creatorVaquero, J. (Javier)-
dc.creatorPeligros, M.I. (María Isabel)-
dc.creatorArgemí, J. (Josepmaria)-
dc.creatorBataller, R. (Ramón)-
dc.creatorAmpuero, J. (Javier)-
dc.creatorRomero-Gómez, M. (Manuel)-
dc.creatorTrautwein, C. (Christian)-
dc.creatorLiedtke, C. (Christian)-
dc.creatorBañares, R. (Rafael)-
dc.creatorCubero, F.J. (Francisco Javier)-
dc.creatorNevzorova, Y. (Yulia)-
dc.date.accessioned2021-10-05T09:48:24Z-
dc.date.available2021-10-05T09:48:24Z-
dc.date.issued2021-
dc.identifier.citationBenede Ubieto, R.; Estevez Vazquez, O.; Guo, F.; et al. "An experimental DUAL model of advanced liver damage". Hepatology Communications. 5 (6), 2021, 1051 - 1068es
dc.identifier.issn2471-254X-
dc.identifier.urihttps://hdl.handle.net/10171/62149-
dc.description.abstractIndividuals exhibiting an intermediate alcohol drinking pattern in conjunction with signs of metabolic risk present clinical features of both alcohol-associated and metabolic-associated fatty liver diseases. However, such combination remains an unexplored area of great interest, given the increasing number of patients affected. In the present study, we aimed to develop a preclinical DUAL (alcohol-associated liver disease plus metabolic-associated fatty liver disease) model in mice. C57BL/6 mice received 10% vol/vol alcohol in sweetened drinking water in combination with a Western diet for 10, 23, and 52 weeks (DUAL model). Animals fed with DUAL diet elicited a significant increase in body mass index accompanied by a pronounced hypertrophy of adipocytes, hypercholesterolemia, and hyperglycemia. Significant liver damage was characterized by elevated plasma alanine aminotransferase and lactate dehydrogenase levels, extensive hepatomegaly, hepatocyte enlargement, ballooning, steatosis, hepatic cell death, and compensatory proliferation. Notably, DUAL animals developed lobular inflammation and advanced hepatic fibrosis. Sequentially, bridging cirrhotic changes were frequently observed after 12 months. Bulk RNA-sequencing analysis indicated that dysregulated molecular pathways in DUAL mice were similar to those of patients with steatohepatitis. Conclusion: Our DUAL model is characterized by obesity, glucose intolerance, liver damage, prominent steatohepatitis and fibrosis, as well as inflammation and fibrosis in white adipose tissue. Altogether, the DUAL model mimics all histological, metabolic, and transcriptomic gene signatures of human advanced steatohepatitis, and therefore serves as a preclinical tool for the development of therapeutic targets.-
dc.description.sponsorshipSupported by EXOHEP-CM (S2017/BMD-3727), Ramón y Cajal (RYC-2014-15242 and RYC-2015-17438), NanoLiver-CM (Y2018/NMT-4949), COST Action (CA17112), AMMF (2018/117), ERAB (EA 18/14), MINECO Retos (SAF2016-78711 and SAF2017-87919-R), and German Research Foundation (DFG NE 2128/2-1, SFB 1382-403224013/A02, and SFB/TRR57/P04). FJC is a Gilead Research Liver Scholar. The research group belongs to the validated Research group Ref. 970935 “Liver Pathophysiology”, 920631 “Lymphocyte immunology”, 920361 “Immunogenética e inmunología de las mucosas” and IBL-6 (imas12-associated). FG and KZ are Chinese Scholarship Council (CSC) fellows. O.E.-V is supported by Beca FPI (associated to MINECO SAF2017-87919R) and R.B.-U. by Contratos predoctorales de personal investigador en formación UCM-Banco Santander (CT63/19).-
dc.language.isoen-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.subjectHigh-fat diet-
dc.subjectAdipose-tissue-
dc.subjectLipid-metabolism-
dc.subjectAlcohol-
dc.subjectDisease-
dc.subjectObesity-
dc.subjectInjury-
dc.subjectAssociation-
dc.subjectDysfunction-
dc.subjectFibrosis-
dc.titleAn experimental DUAL model of advanced liver damage-
dc.typeinfo:eu-repo/semantics/article-
dc.description.noteThis is an open access article under the terms of the Creative Commons Attribution- NonCommercial- NoDerivs License-
dc.identifier.doi10.1002/hep4.1698-
dadun.citation.endingPage1068-
dadun.citation.number6-
dadun.citation.publicationNameHepatology Communications-
dadun.citation.startingPage1051-
dadun.citation.volume5-

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