Choline-deficient Diet-induced NAFLD Animal Model Recaptures Core Human Pathophysiology With Similar Gene Co-expression Networks

• Published in: In vivo (Athens) Vol. 37; no. 4; pp. 1517 - 1531
• Main Authors: Ishigure, Tatsuya, Sasase, Tomohiko, Tohma, Marika, Uno, Kinuko, Toriniwa, Yasufumi, Saito, Tomoyuki, Saigo, Yasuka, Edamura, Koji, Miyajima, Katsuhiro, Ohta, Takeshi
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.07.2023
• Subjects: Amino Acids - metabolism; Animals; Choline - metabolism; Diet - adverse effects; Disease Models, Animal; Humans; Liver - pathology; Liver Neoplasms - pathology; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - genetics; non-alcoholic fatty liver disease (NAFLD); weighted gene co-expression network analysis (WGCNA); Choline-deficient L-amino acid-defined diet (CDAA)
• ISSN: 0258-851X; 1791-7549
• DOI: 10.21873/invivo.13237

Nonalcoholic fatty liver disease (NAFLD) is a wide spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Recently, the prevalence of NAFLD has dramatically increased, and treatment is urgently needed. Animal models are often used to understand the molecular mechanisms of disease development and progression, but their relevance to human diseases has not been fully understood. This study aimed to establish the usefulness of the animal model for preclinical research, we evaluated its relevance to human disease by gene expression analysis. We performed weighted gene co-expression network analysis of liver tissues from a choline-deficient L-amino acid-defined (CDAA) diet-induced NAFLD animal model. In addition, module preservation analysis was conducted to evaluate similarity across species. Several modules were identified to be associated with disease severity, and their gene co-expression network was found to be preserved in the human NAFLD datasets. Of note, module brown (immune cell clusters involved in inflammatory responses) was positively associated with disease severity, and its gene co-expression network was highly preserved in the human datasets. Tyrobp, Laptm5 and Lgals3 were identified as hub genes in the brown module, and their increased expression was confirmed in the human datasets. CDAA diet-induced NAFLD animal model recaptured key aspects of human pathophysiology (especially immune cell functions) and is thought to be a powerful tool for understanding the molecular mechanisms of NAFLD development and progression.