RT Journal Article
T1 An Experimental DUAL Model of Advanced Liver Damage.
A1 Benede-Ubieto, Raquel
A1 Estevez-Vazquez, Olga
A1 Guo, Feifei
A1 Chen, Chaobo
A1 Singh, Youvika
A1 Nakaya, Helder I
A1 Gomez-del-Moral, Manuel
A1 Lamas-Paz, Arantza
A1 Moran, Laura
A1 Lopez-Alcantara, Nuria
A1 Reissing, Johanna
A1 Bruns, Tony
A1 Avila, Matías A
A1 Santamaría, Eva
A1 Mazariegos, Marina S
A1 Woitok, Marius Maximilian
A1 Haas, Ute
A1 Zheng, Kang
A1 Juarez, Ignacio
A1 Martin-Villa, Jose Manuel
A1 Asensio, Iris
A1 Vaquero, Javier
A1 Peligros, Maria Isabel
A1 Argemi, Josepmaria
A1 Bataller, Ramón
A1 Ampuero, Javier
A1 Romero-Gomez, Manuel
A1 Trautwein, Christian
A1 Liedtke, Christian
A1 Bañares, Rafael
A1 Cubero, Francisco Javier
A1 Nevzorova, Yulia A
K1 Drinking Water
K1 Hypercholesterolemia
K1 Glucose Intolerance
K1 Mice, Inbred C57BL
K1 Non-alcoholic Fatty Liver Disease
K1 Gene Expression Profiling
K1 Adipocytes
AB Individuals 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.
PB Wolters Kluwer Health
YR 2021
FD 2021
LK http://hdl.handle.net/10668/18016
UL http://hdl.handle.net/10668/18016
LA en
NO Benedé-Ubieto R, Estévez-Vázquez O, Guo F, Chen C, Singh Y, Nakaya HI, et al. An Experimental DUAL Model of Advanced Liver Damage. Hepatol Commun. 2021 Mar 11;5(6):1051-1068.
DS RISalud
RD Apr 17, 2025