dc.creator | Benedé-Ubieto, Raquel | es |
dc.creator | Estévez-Vázquez, Olga | es |
dc.creator | Guo, Feifei | es |
dc.creator | Chen, Chaobo | es |
dc.creator | Singh, Youvika | es |
dc.creator | Nakaya, Helder I. | es |
dc.creator | Ampuero Herrojo, Javier | es |
dc.creator | Romero Gómez, Manuel | es |
dc.creator | Nevzorova, Yulia A. | es |
dc.date.accessioned | 2022-11-09T15:56:02Z | |
dc.date.available | 2022-11-09T15:56:02Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Benedé-Ubieto, R., Estévez-Vázquez, O., Guo, F., Chen, C., Singh, Y., Nakaya, H.I.,...,Nevzorova, Y.A. (2021). An experimental DUAL model of advanced liver damage. Hepatology Communications, 5 (6), 1051-1068. https://doi.org/10.1002/hep4.1698. | |
dc.identifier.issn | 2471-254X | es |
dc.identifier.uri | https://hdl.handle.net/11441/139190 | |
dc.description.abstract | Individuals exhibiting an intermediate alcohol drinking pattern in conjunction with signs of metabolic risk present clini cal 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 he patomegaly, 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 path ways in DUAL mice were similar to those of patients with steatohepatitis. Conclusion: Our DUAL model is character ized 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. | es |
dc.format | application/pdf | es |
dc.format.extent | 18 p. | es |
dc.language.iso | eng | es |
dc.publisher | John Wiley & Sons | es |
dc.relation.ispartof | Hepatology Communications, 5 (6), 1051-1068. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Alcohol-associated liver disease | es |
dc.subject | Alanine aminotransferase | es |
dc.subject | Analysis of variance | es |
dc.subject | Cell lymphoma | es |
dc.title | An experimental DUAL model of advanced liver damage | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.publisherversion | https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep4.1698 | es |
dc.identifier.doi | 10.1002/hep4.1698 | es |
dc.journaltitle | Hepatology Communications | es |
dc.publication.volumen | 5 | es |
dc.publication.issue | 6 | es |
dc.publication.initialPage | 1051 | es |
dc.publication.endPage | 1068 | es |