RT Journal Article
T1 An Experimental DUAL Model of Advanced Liver Damage
A1 Benede Ubieto, Raquel
A1 Estévez Vázquez, Olga
A1 Guo, Feifei
A1 Chen, Chaobo
A1 Gómez Del Moral Martín-Consuegra, Manuel María
A1 Lamas Paz, Aranzazu
A1 Morán, Laura
A1 López Alcántara, Nuria
A1 S. Mazariegos, Marina
A1 Zheng, Kang
A1 Juárez Martín-Delgado, Ignacio
A1 Martín Villa, José Manuel
A1 Asensio, Iris
A1 Vaquero Martín, Francisco Javier
A1 Peligros Gómez, María Isabel
A1 Romero Gómez, Manuel
A1 Bañares Cañizares, Rafael
A1 Cubero Palero, Francisco Javier
A1 Nevzorova, Yulia
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 Lippincott, Williams & Wilkins
SN 2471-254X
YR 2021
FD 2021-06
LK https://hdl.handle.net/20.500.14352/97236
UL https://hdl.handle.net/20.500.14352/97236
LA eng
NO Benedé‐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
DS Docta Complutense
RD 30 sept 2024