An Experimental DUAL Model of Advanced Liver Damage
| Autor: | Manuel Romero Gómez, José Manuel Martín-Villa, Ramon Bataller, Feifei Guo, Rafael Bañares, Tony Bruns, Youvika Singh, Ute Haas, Eva Santamaría, Josepmaria Argemi, Marina S. Mazariegos, Christian Trautwein, Nuria López-Alcántara, Ignacio Juarez, Arantza Lamas-Paz, Francisco Javier Cubero, Olga Estévez-Vázquez, Helder I. Nakaya, MM Woitok, Matías A. Avila, Laura Morán, Iris Asensio, Kang Zheng, Manuel Gómez del Moral, Johanna Reissing, Christian Liedtke, Javier Ampuero, Raquel Benedé-Ubieto, Chaobo Chen, Yulia A. Nevzorova, Maria Isabel Peligros, Javier Vaquero |
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| Přispěvatelé: | Comunidad de Madrid, Ministerio de Economía y Competitividad (España), German Research Foundation, Gilead Sciences, China Scholarship Council, Universidad Complutense de Madrid, Banco Santander |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Lipid-metabolism Injury RC799-869 White adipose tissue Association Liver disease Fibrosis Internal medicine Medicine Disease Obesity Hepatology business.industry Fatty liver Original Articles Diseases of the digestive system. Gastroenterology medicine.disease Endocrinology High-fat diet Adipose-tissue Dysfunction Hepatic stellate cell Original Article Steatohepatitis Steatosis business Hepatic fibrosis Alcohol |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Hepatology Communications, Vol 5, Iss 6, Pp 1051-1068 (2021) Dadun. Depósito Académico Digital de la Universidad de Navarra Hepatology communications 5(6), 1051-1068 (2021). doi:10.1002/hep4.1698 Hepatology Communications |
| DOI: | 10.18154/rwth-conv-248505 |
| Popis: | 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. DUAL model perfectly mimics all histological, metabolic and transcriptomic gene signatures of human advanced steatohepatitis, and thus serve as a preclinical tool for the development of therapeutic targets. |
| Databáze: | OpenAIRE |
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