An Experimental DUAL Model of Advanced Liver Damage

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dc.contributor.authorBenede Ubieto, Raquel
dc.contributor.authorEstévez Vázquez, Olga
dc.contributor.authorGuo, Feifei
dc.contributor.authorChen, Chaobo
dc.contributor.authorGómez Del Moral Martín-Consuegra, Manuel María
dc.contributor.authorLamas Paz, Aranzazu
dc.contributor.authorMorán, Laura
dc.contributor.authorLópez Alcántara, Nuria
dc.contributor.authorS. Mazariegos, Marina
dc.contributor.authorZheng, Kang
dc.contributor.authorJuárez Martín-Delgado, Ignacio
dc.contributor.authorMartín Villa, José Manuel
dc.contributor.authorAsensio, Iris
dc.contributor.authorVaquero Martín, Francisco Javier
dc.contributor.authorPeligros Gómez, María Isabel
dc.contributor.authorRomero Gómez, Manuel
dc.contributor.authorBañares Cañizares, Rafael
dc.contributor.authorCubero Palero, Francisco Javier
dc.contributor.authorNevzorova, Yulia
dc.date.accessioned2024-01-31T13:59:17Z
dc.date.available2024-01-31T13:59:17Z
dc.date.issued2021-06
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.departmentDepto. de Inmunología, Oftalmología y ORL
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationBenedé‐Ubieto, Raquel1,2; Estévez‐Vázquez, Olga1,2,*; Guo, Feifei2,*; Chen, Chaobo2; Singh, Youvika3; Nakaya, Helder I.3,4; Gómez del Moral, Manuel5; Lamas‐Paz, Arantza2; Morán, Laura2; López‐Alcántara, Nuria2,6; Reissing, Johanna7; Bruns, Tony7; Avila, Matías A.8,9,10; Santamaría, Eva8,9; Mazariegos, Marina S.2; Woitok, Marius Maximilian7; Haas, Ute7; Zheng, Kang2,11,12; Juárez, Ignacio2; Martín‐Villa, José Manuel2,13; Asensio, Iris9,13,14; Vaquero, Javier9,13,14; Peligros, Maria Isabel15; Argemi, Josepmaria16,17,18; Bataller, Ramón16,19; Ampuero, Javier9,20; Romero Gómez, Manuel9,20; Trautwein, Christian7; Liedtke, Christian7; Bañares, Rafael2,9,13,14; Cubero, Francisco Javier2,11,**; Nevzorova, Yulia A.*,2,7,11,**. An Experimental DUAL Model of Advanced Liver Damage. Hepatology Communications 5(6):p 1051-1068, June 2021. | DOI: 10.1002/hep4.1698
dc.identifier.doi10.1002/hep4.1698
dc.identifier.issn2471-254X
dc.identifier.officialurlhttps://journals.lww.com/hepcomm/fulltext/2021/06000/an_experimental_dual_model_of_advanced_liver.12.aspx
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/34141989/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/97236
dc.issue.number6
dc.journal.titleHepatology Communications
dc.language.isoeng
dc.page.final1068
dc.page.initial1051
dc.publisherLippincott, Williams & Wilkins
dc.rights.accessRightsopen access
dc.subject.cdu612.017
dc.subject.ucmCiencias Biomédicas
dc.subject.ucmBiología
dc.subject.ucmGastroenterología y hepatología
dc.subject.unesco24 Ciencias de la Vida
dc.subject.unesco2407 Biología Celular
dc.titleAn Experimental DUAL Model of Advanced Liver Damage
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number5
dspace.entity.typePublication
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