TY - JOUR A1 - Brol, Maximilian A1 - Georgiou, Stella A1 - Rasmussen, Ditlev Nytoft A1 - Ortiz, Cristina A1 - Klein, Sabine A1 - Schierwagen, Robert A1 - Uschner, Frank Erhard A1 - Eberle, Larissa A1 - Detlefsen, Sönke A1 - Pantazopoulou, Vasiliki I. A1 - Thiele, Maja A1 - Filippa, Vasiliki A1 - Torres Núñez, Sandra A1 - Anastasiadou, Ema A1 - Krag, Aleksander A1 - Trebicka, Jonel T1 - Effects of ethanol feeding in early-stage NAFLD mice induced by western diet T2 - Livers N2 - Background: The prevalence of metabolic liver diseases is increasing and approved pharmacological treatments are still missing. Many animal models of nonalcoholic fatty liver disease (NAFLD) show a full spectrum of fibrosis, inflammation and steatosis, which does not reflect the human situation since only up to one third of the patients develop fibrosis and nonalcoholic steatohepatitis (NASH). Methods: Seven week old C57Bl/J mice were treated with ethanol, Western diet (WD) or both. The animals’ liver phenotypes were determined through histology, immunohistochemistry, Western blotting, hepatic triglyceride content and gene expression levels. In a human cohort of 80 patients stratified by current alcohol misuse and body mass index, liver histology and gene expression analysis were performed. Results: WD diet and ethanol-treated animals showed severe steatosis, with high hepatic triglyceride content and upregulation of fatty acid synthesis. Mild fibrosis was revealed using Sirius-red stains and gene expression levels of collagen. Inflammation was detected using histology, immunohistochemistry and upregulation of proinflammatory genes. The human cohort of obese drinkers showed similar upregulation in genes related to steatosis, fibrosis and inflammation. Conclusions: We provide a novel murine model for early-stage fatty liver disease suitable for drug testing and investigation of pathophysiology. KW - ALD KW - NAFLD KW - NASH KW - metabolic liver disease KW - liver steatosis KW - animal model KW - mouse Y1 - 2021 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/60989 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-609897 SN - 2673-4389 VL - 1 IS - 1 SP - 27 EP - 39 PB - MDPI CY - Basel ER -