CYP4A11 is involved in the development of nonalcoholic fatty liver disease via ROS‑induced lipid peroxidation and inflammation

Gao,Huifang; Cao,Yaru; Xia,Hongguang; Zhu,Xiangyu; Jin,Yong

doi:10.3892/ijmm.2020.4479

CYP4A11 is involved in the development of nonalcoholic fatty liver disease via ROS‑induced lipid peroxidation and inflammation

Authors:
- Huifang Gao
- Yaru Cao
- Hongguang Xia
- Xiangyu Zhu
- Yong Jin
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Affiliations: Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: January 28, 2020 https://doi.org/10.3892/ijmm.2020.4479
Pages: 1121-1129
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is a fat metabolism disorder that occurs in liver cells. The development of NAFLD is considered to be associated with hepatic oxidative stress. The present study aimed to investigate the role of cytochrome P450 4A11 (CYP4A11) in the pathogenesis of NAFLD. The levels of plasma CYP4A11 and lipid peroxidation products levels exhibited a high correlation, and were increased significantly compared with those from normal subjects. Further in vitro studies demonstrated that the expression levels of CYP4A11 and the content of reactive oxygen species (ROS) were increased in free fatty acid (FFA)‑stimulated HepG2 cells. Clofibrate, a CYP4A11 inducer, aggravated cell damage. Opposite results were observed for the CYP4A11 inhibitor HET0016, which attenuated apoptosis in FFA‑treated cells. Furthermore, CYP4A11 gene overexpression and silencing were used to investigate the effects on inflammatory cytokine secretion. The data demonstrated that CYP4A11 promoted an increase in the mRNA expression of tumor necrosis factor α, interleukin (IL)‑1β and IL‑6 in response to FFA. In addition, western blot analysis highlighted that CYP4A11 caused an upregulation of phosphorylated p65 levels and therefore affected the NF‑κB signaling pathway. The data demonstrated that CYP4A11 may metabolize fatty acids to promote the production of ROS and accelerate the progression of NAFLD.

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