Zeaxanthin prevents ferroptosis by promoting mitochondrial function and inhibiting the p53 pathway in free fatty acid-induced HepG2 cells

Huimin Liu; Jie Yan; Fengtao Guan; Zhibo Jin; Jiahan Xie; Chongrui Wang; Meihong Liu; Jingsheng Liu

doi:10.1016/j.bbalip.2023.159287

Zeaxanthin prevents ferroptosis by promoting mitochondrial function and inhibiting the p53 pathway in free fatty acid-induced HepG2 cells

Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Apr;1868(4):159287. doi: 10.1016/j.bbalip.2023.159287. Epub 2023 Jan 21.

Authors

Huimin Liu¹, Jie Yan², Fengtao Guan², Zhibo Jin³, Jiahan Xie³, Chongrui Wang⁴, Meihong Liu³, Jingsheng Liu⁵

Affiliations

¹ College of Life Science, Jilin Agricultural University, Changchun, Jilin 130118, China; College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, China; National Engineering Research Center for Wheat and Corn Deep Processing, Changchun, Jilin 130118, China. Electronic address: liuhuimin@jlau.edu.cn.
² College of Life Science, Jilin Agricultural University, Changchun, Jilin 130118, China.
³ College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, China; National Engineering Research Center for Wheat and Corn Deep Processing, Changchun, Jilin 130118, China.
⁴ College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, China.
⁵ College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, China; National Engineering Research Center for Wheat and Corn Deep Processing, Changchun, Jilin 130118, China. Electronic address: liujingsheng@jlau.edu.cn.

PMID: 36690321
DOI: 10.1016/j.bbalip.2023.159287

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder worldwide and a risk factor for obesity and diabetes. Emerging evidence has shown that ferroptosis is involved in the progression of NAFLD. Zeaxanthin (ZEA) is a carotenoid found in human serum. It has been reported that ZEA can ameliorate obesity, prevent age-related macular degeneration, and protect against non-alcoholic steatohepatitis. However, no study has focused on the protective effects of ZEA against NAFLD. In this study, free fatty acid (FFA) induced HepG2 cells were used as a cell model for NAFLD. Our results suggest that ZEA exerts antioxidative and anti-inflammatory effects in FFA-induced HepG2 cells. Moreover, ZEA acted as a ferroptosis inhibitor, significantly reducing reactive oxygen species (ROS) generation and iron overload and improving mitochondrial dysfunction in FFA-induced HepG2 cells. In addition, ZEA downregulated the expression of p53 and modulated downstream targets, such as GPX4, SLC7A11, SAT1, and ALOX15, which contributed to the reduction in cellular lipid peroxidation. Our findings suggest that ZEA has the potential for NAFLD intervention.

Keywords: Ferroptosis; Mitochondria function; Non-alcoholic fatty liver disease; Zeaxanthin; p53 pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Fatty Acids, Nonesterified / metabolism
Ferroptosis*
Hep G2 Cells
Humans
Lipid Metabolism
Mitochondria / metabolism
Non-alcoholic Fatty Liver Disease* / metabolism
Obesity / metabolism
Tumor Suppressor Protein p53 / metabolism
Zeaxanthins / metabolism
Zeaxanthins / pharmacology

Substances

Fatty Acids, Nonesterified
Tumor Suppressor Protein p53
Zeaxanthins
TP53 protein, human