基因-代谢物相关性支持甲基睾酮诱导的中国长鼻鲶鱼幼鱼肝纤维化和代谢紊乱

IF 3.9 3区 环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yang Feng , Yongqiang Deng , Zhao Li , Zheng Wei , Zhongmeng Zhao , Han Zhao , Senyue Liu , Lu Zhang , Yuanliang Duan , Zhipeng Huang , Jun Du , Qiang Li , Jian Zhou , Chengyan Mou
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引用次数: 0

摘要

甲基睾酮(MT)是一种合成雄激素,经常用于水产养殖,以诱导性别逆转和提高生长率,但其对鱼类健康的持久影响尚未得到广泛研究。本研究采用组织病理学、转录组学和代谢组学的综合方法,系统地评估了MT对中国长鼻鲶鱼肝脏的毒性作用。鱼在30天内接受三种剂量的MT (100 ng, 200 ng和300 ng),然后对肝脏组织进行病理检查。该研究揭示了一项新发现,MT诱导了肝脏血管周围纤维化和异常蛋白质积聚,这与在人类中看到的效果惊人地相似。转录组学分析确定了主要富集于代谢途径的差异表达基因(DEGs),包括与PPAR信号、氮代谢和胆固醇代谢相关的基因。代谢组学分析进一步揭示了mt处理鱼的代谢谱,特别是脂肪酸和氨基酸代谢途径的显著破坏。通过VIP值筛选,鉴定出油酸、磷脂碱、各种脂质和氨基酸等关键差异代谢物。相关分析显示,MT通过上调纤维化相关COL6A6和疾病相关基因(F2R、ESR1、PGR)诱导肝纤维化。MT还诱导脂质合成代谢上调和氨基酸代谢抑制,将MT与鱼类nafld样肥胖联系起来。该研究提供了对MT肝毒性的全面见解,指导安全的水产养殖实践。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Gene-metabolite correlations underpin the hepatic fibrosis and metabolic disruption induced by methyltestosterone in juvenile Chinese longsnout catfish (Leiocassis longirostris)

Gene-metabolite correlations underpin the hepatic fibrosis and metabolic disruption induced by methyltestosterone in juvenile Chinese longsnout catfish (Leiocassis longirostris)
Methyltestosterone (MT), a synthetic androgen frequently employed in aquaculture to induce sex reversal and boost growth rates, has yet to be extensively examined for its enduring effects on the health of fish. This study systematically evaluated the toxic effects of MT on the liver of Chinese longsnout catfish (Leiocassis longirostris) using an integrated approach of histopathology, transcriptomics, and metabolomics. The fish were subjected to three doses of MT (100 ng, 200 ng, and 300 ng) over 30 days, followed by pathological examinations of liver tissue. The study unveiled a novel discovery that MT induced perivascular fibrosis and abnormal protein accumulation in the liver, which bore a striking resemblance to effects seen in humans. Transcriptomic analysis pinpointed differentially expressed genes (DEGs) that were predominantly enriched in metabolic pathways, including those related to PPAR signaling, nitrogen metabolism, and cholesterol metabolism. Metabolomic analysis further revealed significant disruptions in the metabolic profiles of MT-treated fish, particularly in fatty acid and amino acid metabolism pathways. Key differential metabolites, such as oleic acid, phosphocholine, and various lipids and amino acids, were identified through VIP value screening. Correlation analysis showed MT induced liver fibrosis via upregulating fibrosis-related COL6A6 and disease related genes (F2R, ESR1, PGR). MT also induced lipid anabolism upregulation and amino acid metabolism suppression, linking MT to NAFLD-like obesity in fish. This study offers comprehensive insights into MT's hepatic toxicity, guiding safe aquaculture practices.
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来源期刊
CiteScore
7.50
自引率
5.10%
发文量
206
审稿时长
30 days
期刊介绍: Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.
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