Fatty acid oxidation contributed to NLRP3 inflammasome activation caused by N-nitrosamines co-exposure

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-05-13 DOI:10.1016/j.fct.2025.115549

Hu Zhang , Chao Zhao , Guo Hong , Wen Xiong , Junpeng Xia , Ruijun Dong , Qianqian Wang , Kaiyue Zhang , Bing Wang

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Abstract

Nitrosamines, as common environmental carcinogens, are closely related to the development of esophageal inflammation (EI). Studies have revealed that NLRP3 inflammasome activation was a key event in nitrosamine-induced EI. However, the involvement of fatty acid metabolism in nitrosamine-induced NLRP3 inflammasome activation has not been reported. In this study, we used human esophageal epithelial (Het-1A) cells to investigate the underlying mechanisms of fatty acid oxidation (FAO) dysregulation caused by nitrosamines mixture commonly found in drinking water. The results showed that the activity of CPT1A, the key rate-limiting enzyme for FAO, upregulated with the increase of nitrosamine concentrations, while the level of acetyl-CoA revealed decreasing trends. The cells in nitrosamine-stained groups underwent fatty acid metabolism disorders, in which the concentrations of key fatty acids showed accelerated decomposition trends. Furthermore, our results revealed that nitrosamines promoted FAO via the AMPK/ACC/CPT1A pathway. Nitrosamines triggered the activation of NLRP3 inflammatory vesicles in a dose-dependent manner, with concomitant elevation in the expression of NLRP3 activation-associated ASC oligomer, caspase-1 and acetyl-α-tubulin. In brief, FAO involved in the activation of NLRP3 inflammatory vesicles in Het-1A cells due to nitrosamines exposure. This study revealed the new perspective on the mechanism of fatty acid metabolism disruption triggered by nitrosamines co-exposure.

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脂肪酸氧化有助于n -亚硝胺共暴露引起的NLRP3炎性体活化。

亚硝胺是常见的环境致癌物，与食道炎症（EI）的发生密切相关。研究表明NLRP3炎性体激活是亚硝胺诱导EI的关键事件。然而，脂肪酸代谢参与亚硝胺诱导的NLRP3炎性体激活尚未见报道。在这项研究中，我们使用人食管上皮细胞（Het-1A）来研究饮用水中常见的亚硝胺混合物引起脂肪酸氧化（FAO）失调的潜在机制。结果表明，随着亚硝胺浓度的增加，粮农组织关键限速酶CPT1A活性上调，而乙酰辅酶a水平呈下降趋势。亚硝胺染色组细胞脂肪酸代谢紊乱，关键脂肪酸浓度分解呈加速趋势。此外，我们的研究结果表明，亚硝胺通过AMPK/ACC/CPT1A途径促进FAO。亚硝胺以剂量依赖的方式触发NLRP3炎症囊泡的激活，同时NLRP3激活相关的ASC低聚物、caspase-1和乙酰-α-微管蛋白的表达升高。简而言之，由于亚硝胺暴露，FAO参与了ht - 1a细胞中NLRP3炎症囊泡的激活。本研究揭示了亚硝胺共暴露引起脂肪酸代谢紊乱机制的新视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.