Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Fucosterol improves palmitic acid-induced oxidative stress, lipid droplet formation and insulin resistance in liver cells by mediating Keap1-Nrf2-lipocalin 13 axis

Zhekun Xiong¹, Liming Gan¹ , Chuntian Sun¹, Hui Zhang¹, Yanshan He¹, Huixia Su¹, Yiyuan Zheng², Fanglian Liao¹

¹Department of Spleen, Stomach and Hepatobiliary, Zhongshan Hospital of Traditional Chinese Medicine, Zhongshan, Guangdong Province 528401; ²Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong Province 510405, China.

For correspondence:- Liming Gan Email: ganliming1112@163.com Tel:+8676089980728

Accepted: 31 October 2022 Published: 30 November 2022

Citation: Xiong Z, Gan L, Sun C, Zhang H, He Y, Su H, et al. Fucosterol improves palmitic acid-induced oxidative stress, lipid droplet formation and insulin resistance in liver cells by mediating Keap1-Nrf2-lipocalin 13 axis. Trop J Pharm Res 2022; 21(11):2345-2351 doi: 10.4314/tjpr.v21i11.11

© 2022 The authors.
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Abstract

Purpose: To determine the possible effects of fucosterol (FST) on non-alcoholic fatty liver disease (NAFLD), and the mechanisms involved.

Methods: The NAFLD model was constructed using palmitic acid (PA) induction, and the expression of NF-E2-related factor 2 (Nrf2), lipocalin 13 (LCN13) and Keap1 were analyzed by immunoblot. The oxidative stress of hepatocytes was determined via ELISA assay. In addition, the role of FST on lipid content and metabolism were evaluated by Oil Red O staining and immunoblot, while the levels of p-AKT, p-IRS1, and p-PI3K were evaluated by immunoblot assay.

Results: The data revealed that FST significantly increased the viability of PA-induced hepatocytes, and the expression levels of Nrf2 and LCN13 (p < 0.05). Fucosterol enhanced Keap1-Nrf2 mediated LCN13 expression, and alleviated PA-induced oxidative stress by contributing to Keap1-Nrf2-LCN13 axis. In addition, it significantly reduced (p < 0.05) lipid droplet formation, promoted lipid metabolism, and lowered insulin resistance by enhancing Keap1- Nrf2-LCN13 axis.

Conclusion: Fucosterol regulates Keap1-Nrf2-mediated LCN13 to aid the ameliorate palmitic acid-induced oxidative stress, lipid droplet formation and insulin resistance in liver cells.

Keywords: Non-alcoholic fatty liver disease (NAFLD), Fucosterol (FST), Keap1-Nrf2-LCN13 axis, Insulin resistance