Postnatal exposure to DINP was associated with greater alterations of lipidomic markers for hepatic steatosis than DEHP in postweaning mice
Postnatal exposure to DINP was associated with greater alterations of lipidomic markers for hepatic steatosis than DEHP in postweaning mice
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DOI：
10.1016/j.scitotenv.2020.143631
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发表时间：
2021-01-05
影响因子：
9.8
通讯作者：
Huang, Yichao
中科院分区：
文献类型：
--
作者：
Yang, Yan;Sun, Fengjiang;Huang, Yichao
内分泌干扰物邻苯二甲酸二（2-乙基己基）酯（DEHP）的毒性因其激素失调、致肥胖作用和相关代谢疾病而被广泛研究。然而，DEHP的主要替代品邻苯二甲酸二异壬酯（DINP）虽然在全球的年产量有所增加，但需要更好地了解其对健康的影响。我们之前的工作报告了血浆脂质谱的破坏，但缺乏邻苯二甲酸酯暴露后肝脏（特别是整个肝脏脂质组）的代谢反应。应用靶向脂质组学技术，准确定量新生小鼠从出生到整个哺乳期暴露于4.8 mg/kg体重/天的日剂量后肝脏中共计363种脂质。性别之间的脂质类或亚类的每个总和的中断的独特模式是最明显的。DINP给药后，雌性幼仔的磷脂酰乙醇胺、双（单酰基甘油）磷酸盐和神经酰胺变化较大。相比之下，雄性动物基于磷酸甘油骨架的分子变化较小，而甘油和胆固醇酯受到DINP的破坏更大。然而，与DINP相比，DEHP引起的总体变化较小。这些发现突出了不同性别新生小鼠中DINP对甘油（二酰甘油和三酰甘油）和/或胆固醇（酯或游离形式）分子的主要脂质组学破坏，表明肝脂肪变性的发生早在断奶后。总的来说，这些发现质疑DINP作为安全DEHP替代品的适用性，并需要进一步研究长期暴露，以阐明其对慢性肝病的影响。(C)2020爱思唯尔B. V.保留所有权利。
The toxicity of the endocrine disruptor di(2-ethylhexyl) phthalate (DEHP) has been extensively studied for its hormonal dysregulation, obesogenic effect and associated metabolic diseases. DEHP's primary substitute di-isononyl phthalate (DINP), however, although increased in annual production globally, requires better understanding of its health effect. Our previous work reported disruptions in plasma lipid profiles, but the metabolic responses following phthalate exposure in the liver, particularly the entire hepatic lipidome, have been lacking. A targeted lipidomic technique was applied to accurately quantify a total of 363 lipid species in the liver of neonatal mice after exposure to a daily dose of 4.8 mg/kg body weight/day from birth throughout lactation. Distinct patterns of disruption for each sum of lipid classes or sub-classes between the genders were the most noticeable. Following DINP administration, female pups were subject to greater changes in phosphatidyl-ethanolamines, bis(monoacylglycero)phosphate and ceramides. In contrast, the males exhibited less changes in the phosphoglycerol backbone-based molecules, whereas glycerol and cholesterol esters were more disrupted by DINP. DEHP, however, induced less changes overall compared to DINP. These findings highlighted the predominant lipidomic disruption of DINP on glycerol (diacylglycerides and triacylglycerides) and/or cholesterol (in ester or free form) molecules in neonatal mice across genders, suggesting the genesis of hepatic steatosis occurring at as early as post weaning. Collectively, these findings question the suitability of DINP as a safe DEHP substitute and warrant further investigation on longer-term exposure to elucidate its effect on chronic liver diseases. (C) 2020 Elsevier B.V. All rights reserved.