AFB1 Triggers Lipid Metabolism Disorders through the PI3K/Akt Pathway and Mediates Apoptosis Leading to Hepatotoxicity

文献类型： 外文期刊

第一作者： Wang, Tiancai

作者： Wang, Tiancai;Li, Xiabing;Liao, Guangqin;Wang, Zishuang;Gu, Jingyi;Mu, Xiyan;Qiu, Jing;Qian, Yongzhong;Wang, Tiancai;Li, Xiabing;Liao, Guangqin;Wang, Zishuang;Gu, Jingyi;Mu, Xiyan;Qiu, Jing;Qian, Yongzhong;Han, Xiaoxu

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关键词： aflatoxin B1; hepatotoxicity; apoptosis; lipid metabolism; PI3K/Akt pathway

期刊名称：FOODS （ 影响因子：5.2； 五年影响因子：5.5 ）

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年卷期： 2024 年 13 卷 1 期

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收录情况： SCI

摘要： As the most prevalent mycotoxin in agricultural products, aflatoxin B1 not only causes significant economic losses but also poses a substantial threat to human and animal health. AFB1 has been shown to increase the risk of hepatocellular carcinoma (HCC) but the underlying mechanism is not thoroughly researched. Here, we explored the toxicity mechanism of AFB1 on human hepatocytes following low-dose exposure based on transcriptomics and lipidomics. Apoptosis-related pathways were significantly upregulated after AFB1 exposure in all three hES-Hep, HepaRG, and HepG2 hepatogenic cell lines. By conducting a comparative analysis with the TCGA-LIHC database, four biomarkers (MTCH1, PPM1D, TP53I3, and UBC) shared by AFB1 and HCC were identified (hazard ratio > 1), which can be used to monitor the degree of AFB1-induced hepatotoxicity. Simultaneously, AFB1 induced abnormal metabolism of glycerolipids, sphingolipids, and glycerophospholipids in HepG2 cells (FDR < 0.05, impact > 0.1). Furthermore, combined analysis revealed strong regulatory effects between PIK3R1 and sphingolipids (correlation coefficient > 0.9), suggesting potential mediation by the phosphatidylinositol 3 kinase (PI3K) /protein kinase B (AKT) signaling pathway within mitochondria. This study revealed the dysregulation of lipid metabolism induced by AFB1 and found novel target genes associated with AFB-induced HCC development, providing reliable evidence for elucidating the hepatotoxicity of AFB as well as assessing food safety risks.

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