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脱氧雪腐镰刀菌烯醇及其乙酰化衍生物对人正常肝细胞脂质代谢的影响。

Effects of Deoxynivalenol and Its Acetylated Derivatives on Lipid Metabolism in Human Normal Hepatocytes.

机构信息

College of Food Scienceand Engineering, Wuhan Polytechnic University, Wuhan 430023, China.

Key Laboratory for Deep Processing of Major Grain and Oil, Ministry of Education, Wuhan 430023, China.

出版信息

Toxins (Basel). 2024 Jun 26;16(7):294. doi: 10.3390/toxins16070294.

DOI:10.3390/toxins16070294
PMID:39057934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11281666/
Abstract

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.

摘要

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 型单端孢霉烯族化合物，是农产品中广泛检测到的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类肝细胞中脂质代谢的改变。在验证了三种毒素的肝毒性后，通过转录组学确定了 mRNA 的表达，结果表明 DON 和 15-ADON 对转录组有显著的调节作用，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报道。为了进一步验证，我们深入探讨了脂质代谢，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）、PE（14:0/16:0）和 PE（18:1/18:3）这 9 种脂质均下调。结合转录组结果，我们发现 DON、15-ADON 和 3-ADON 这三种毒素引起的肝脂肪变性与与脂质氧化、脂肪生成和脂肪分解相关基因的表达改变有关，它们对 L-02 细胞脂质代谢的影响主要是通过 PC-PE 循环实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/13ff4481ff6d/toxins-16-00294-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/45eadb44870c/toxins-16-00294-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/89db2f5d4332/toxins-16-00294-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/a681971988d1/toxins-16-00294-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/cdf0fda1ab8c/toxins-16-00294-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/8bf0a1a75f5c/toxins-16-00294-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/0f1476a3c28f/toxins-16-00294-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/a0b9a441d5b3/toxins-16-00294-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/b71dac7f30c0/toxins-16-00294-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/13ff4481ff6d/toxins-16-00294-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/45eadb44870c/toxins-16-00294-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/89db2f5d4332/toxins-16-00294-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/a681971988d1/toxins-16-00294-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/cdf0fda1ab8c/toxins-16-00294-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/8bf0a1a75f5c/toxins-16-00294-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/0f1476a3c28f/toxins-16-00294-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/a0b9a441d5b3/toxins-16-00294-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/b71dac7f30c0/toxins-16-00294-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e59/11281666/13ff4481ff6d/toxins-16-00294-g009.jpg

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