Effects of Ethanol Feeding in Early-Stage NAFLD Mice Induced by Western Diet

Maximilian Joseph Brol, Stella Georgiou, Ditlev Nytoft Rasmussen, Cristina Ortiz, Sabine Klein, Robert Schierwagen, Frank Erhard Uschner, Larissa Eberle, Sönke Detlefsen, I. PANTAZOPOULOU VASILIKI, Maja Thiele, Vasiliki Filippa, TORRES NÚÑEZ SANDRA, Ema Anastasiadou, Aleksander Krag, Jonel Trebicka

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Abstract

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.

OriginalsprogEngelsk
TidsskriftLivers
Vol/bind1
Udgave nummer1
Sider (fra-til)27-39
ISSN2673-4389
DOI
StatusUdgivet - feb. 2021

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