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

• Published in: Tropical journal of pharmaceutical research 2023-02, Vol.21 (11), p.2345-2351
• Main Authors: Xiong, Zhekun, Gan, Liming, Sun, Chuntian, Zhang, Hui, He, Yanshan, Su, Huixia, Zheng, Yiyuan, Liao, Fanglian
• Format: Article
• Language: English
• ISSN: 1596-5996; 1596-9827
• DOI: 10.4314/tjpr.v21i11.11

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.