溴化阻燃剂六溴环十二烷导致小鼠血脂中多不饱和脂肪酸掺入量的系统性变化

IF 3.4 3区 医学 Q2 TOXICOLOGY
Naomi E Kramer, Jacob Siracusa, Hannah Xu, Lillie Barnett, Morgan C Finnerty, Tai L Guo, John J Wagner, Franklin E Leach, Brian S Cummings
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引用次数: 0

摘要

许多家用产品都使用溴化阻燃剂来降低可燃性,但随着时间的推移,溴化阻燃剂往往会渗入周围环境中。六溴环十二烷(HBCD)是在全球人体血液中检测到的一种溴化阻燃剂。接触六溴环十二烷会导致神经系统问题和脂质代谢改变,但迄今为止这两者之间仍没有联系。由于脂质占大脑干重的 50%,因此脂质代谢在神经元功能和稳态中起着至关重要的作用。为了确定六溴环十二烷暴露对脑脂质代谢的影响,年轻的成年雄性 C57BL/6 小鼠每 3 天暴露于 1 毫克/千克的六溴环十二烷,持续 28 天。研究发现,各脑区的主要脂类都发生了变化,包括膜甘油脂类磷脂酰胆碱和磷脂酰乙醇胺,以及鞘脂类(如己基甘油酰胺)。此外,脑脂质种类中还富含饱和脂肪酸、单不饱和脂肪酸和多不饱和脂肪酸。为了了解脑脂质组变化的来源,我们对血液和肝脏脂质组以及盲肠微生物组进行了评估。肝脏和血液显示了多种脂质类别的变化,包括三酰甘油抑制以及酯化脂肪酸含量的改变。在盲肠微生物组中也检测到了显著的变化,其中固着菌与杆菌的比例下降,β多样性发生变化,与代谢途径和氨基酸生物合成相关的途径也发生了变化。这些数据表明,六溴环十二烷可诱导跨脑区和器官的脂质体改变,并支持微生物组在这些改变中的潜在作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Brominated Flame Retardant Hexabromocyclododecane Causes Systemic Changes in Polyunsaturated Fatty Acid Incorporation in Mouse Lipids.

Brominated flame retardants are used in many household products to reduce flammability, but often leach into the surrounding environment over time. Hexabromocyclododecane (HBCD) is one brominated flame retardant detected in human blood across the world. HBCD exposure can result in neurological problems and altered lipid metabolism, but to date the two remain unlinked. As lipids constitute ∼50% of brain dry weight, lipid metabolism plays a critical role in neuronal function and homeostasis. To determine the effect of HBCD exposure on brain lipid metabolism, young adult male C57BL/6 mice were exposed to 1 mg/kg HBCD every 3 days for 28 days. Major lipid classes were found to change across brain regions, including the membrane glycerolipids phosphatidylcholine and phosphatidylethanolamine, and sphingolipids such as hexosylceramide. In addition, saturated, monounsaturated, and polyunsaturated fatty acids were enriched within brain lipid species. To understand the source of the brain lipidomic alterations, the blood and liver lipidomes and the cecal microbiome were evaluated. The liver and blood demonstrated changes amongst multiple lipid classes, including triacylglycerol suppression, as well as altered esterified fatty acid content. Significant alterations were also detected in the cecal microbiome, with decreases in the Firmicutes to Bacteriodetes ratio, changes in beta diversity, and pathway alterations associated with metabolic pathways and amino acid biosynthesis. These data demonstrate that HBCD can induce lipidomic alterations across brain regions and organs and supports a potential role of the microbiome in these alterations.

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来源期刊
Toxicological Sciences
Toxicological Sciences 医学-毒理学
CiteScore
7.70
自引率
7.90%
发文量
118
审稿时长
1.5 months
期刊介绍: The mission of Toxicological Sciences, the official journal of the Society of Toxicology, is to publish a broad spectrum of impactful research in the field of toxicology. The primary focus of Toxicological Sciences is on original research articles. The journal also provides expert insight via contemporary and systematic reviews, as well as forum articles and editorial content that addresses important topics in the field. The scope of Toxicological Sciences is focused on a broad spectrum of impactful toxicological research that will advance the multidisciplinary field of toxicology ranging from basic research to model development and application, and decision making. Submissions will include diverse technologies and approaches including, but not limited to: bioinformatics and computational biology, biochemistry, exposure science, histopathology, mass spectrometry, molecular biology, population-based sciences, tissue and cell-based systems, and whole-animal studies. Integrative approaches that combine realistic exposure scenarios with impactful analyses that move the field forward are encouraged.
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