@article{Li2025, 
author = {Xinyue Li and Hong Zhang and Fan Yu and Shuting Xie and Tongyu Wang and Rong Zhang and Guangzhong Xu and Liang Wang and Yeping Huang and Cheng Hu},
title = {IRF8 aggravates nonalcoholic fatty liver disease via BMAL1/PPARγ axis},
year = {2025},
journal = {Genes & Diseases},
volume = {12},
number = {3},
pages = {101333},
keywords = {Brain and muscle ARNT-Like 1, Hepatic steatosis, Interferon regulatory factor 8, Lipogenesis, Non-alcoholic fatty liver disease, Peroxisome proliferator-activated receptor γ, Transcriptional regulation},
url = {https://www.sciopen.com/article/10.1016/j.gendis.2024.101333},
doi = {10.1016/j.gendis.2024.101333},
abstract = {Non-alcoholic fatty liver disease (NAFLD) is a hepatic metabolic syndrome arising from lipid metabolic imbalance, with its prevalence increasing globally. In this study, we observed a significant up-regulation of interferon regulatory factor 8 (IRF8) in the liver of NAFLD model mice and patients. Overexpression of IRF8 induced lipid accumulation in the mouse primary hepatocytes. Mice with adeno-associated virus-mediated IRF8 overexpression exhibited hepatic steatosis due to up-regulated peroxisome proliferator-activated receptor γ (PPARγ) expression and increased fatty acid uptake and lipogenesis. In vitro, small interfering RNA-mediated IRF8 knockdown attenuated triglyceride accumulation by dampening PPARγ expression through transcriptional inhibition of brain and muscle ARNT-like 1. The PPARγ-specific antagonist GW9662 abolished the effect of IRF8 overexpression. Furthermore, adeno-associated virus-mediated IRF8 knockdown in the mouse liver markedly alleviated hepatic steatosis and obesity-related metabolic syndrome. These findings indicate that IRF8 plays a vital role in modulating hepatic lipid metabolism in a PPARγ-dependent manner and provide a previously unknown insight into NAFLD therapeutic strategies.}
}