脱氧雪腐镰刀菌烯醇(DON),3-乙酰脱氧雪腐镰刀菌烯醇(3-ADON)和15-乙酰脱氧雪腐镰刀菌烯醇(15-ADON)属于B型单端孢霉烯,在农产品中被广泛检测为最常见的霉菌毒素之一。在本研究中,我们旨在通过DON及其乙酰化衍生物中毒来表征正常人肝细胞中脂质代谢的变化。在验证了三种毒素的肝毒性后,DON,15-ADON,和3-ADON,mRNA表达通过转录组学测定,结果表明,DON和15-ADON对转录组具有显著的调节作用,其中甘油磷脂代谢途径和磷脂酶D信号通路在DON及其乙酰化衍生物的研究中尚未见报道。为了进一步验证,我们深入研究了脂质代谢,发现PC(15:0/16:0),PC(16:1/18:3),PC(18:1/22:6),PC(16:0/16:0),PC(16:0/16:1),PC(16:1/18:1),PC(14:0/18:2),对于所有九种脂质,PE(14:0/16:0)和PE(18:1/18:3)下调。结合转录组结果,我们发现这三种毒素诱导的肝脂肪变性,DON,15-ADON和3-ADON,与脂质氧化相关的基因表达改变有关,脂肪生成和脂肪分解,其对L-02细胞脂质代谢的影响主要通过PC-PE循环来实现。
Deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON) and 15-acetyldeoxynivalenol (15-ADON) belong to type B trichothecenes that are widely detected in agricultural products as one of the most common classes of mycotoxins. In the present study, we aimed to characterize the alteration of lipid metabolism in normal human hepatocytes by poisoning with DON and its acetylated derivatives. After verifying the hepatotoxicity of the three toxins, DON, 15-ADON, and 3-ADON, the mRNA expression was determined by transcriptomics, and the results showed that DON and 15-ADON had a significant regulatory effect on the transcriptome, in which glycerophospholipid metabolism pathway and phospholipase D signaling pathways have not been reported in studies of DON and its acetylated derivatives. For further validation, we explored lipid metabolism in depth and found that PC (15:0/16:0), PC (16:1/18:3), PC (18:1/22:6), PC (16:0/16:0), PC (16:0/16:1), PC (16:1/18:1), PC (14:0/18:2), PE (14:0/16:0) and PE (18:1/18:3) were downregulated for all nine lipids. Combined with the transcriptome results, we found that hepatic steatosis induced by the three toxins, DON, 15-ADON and 3-ADON, was associated with altered expression of genes related to lipid oxidation, lipogenesis and lipolysis, and their effects on lipid metabolism in L-02 cells were mainly realized through the PC-PE cycle.