Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue
Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue
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DOI：
10.1016/j.envres.2015.03.036
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发表时间：
2015-07-01
影响因子：
8.3
通讯作者：
Papadopoulos, Vassilios
中科院分区：
文献类型：
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作者：
Campioli, Enrico;Duong, Tam B.;Papadopoulos, Vassilios
塑料通常与增塑剂等添加剂混合，以增强其柔性、柔韧性和弹性。增塑剂很容易释放到环境中，主要通过摄入、皮肤接触和吸入吸收。增塑剂的主要类别之一邻苯二甲酸酯与内分泌和生殖疾病有关。2002年，1，2-环己烷二羧酸二异壬酯（DINCH）被引入市场，用于塑料材料和与食品接触的物品，并于2006年获得欧洲食品安全局的最终批准。目前，对DINCH及其代谢物的安全性和潜在代谢和内分泌干扰特性的了解有限。本研究旨在评价DINCH及其活性代谢产物环己烷-1，2-二羧酸（CHDA）和环己烷-1，2-二羧酸单异壬酯（MINCH）对大鼠脂肪组织原代基质血管分数（SVF）的生物学效应。DINCH及其代谢产物CHDA不能直接影响SVF分化。然而，SVF暴露于50 μ M和100 μ M浓度的MINCH影响Cebpa和Fabp 4的表达，从而诱导SVF前脂肪细胞积累脂质并完全分化为成熟脂肪细胞。MINCH的作用被特异性过氧化物酶体增殖物激活受体（PPAR）-α拮抗剂GW 6471阻断。总之，这些结果表明，MINCH是一种有效的PPAR-alpha激动剂和代谢干扰剂，能够诱导SVF前脂肪细胞分化，可能干扰哺乳动物的内分泌系统。(C)2015 Elsevier Inc. All rights reserved.
Plastics are generally mixed with additives like plasticizers to enhance their flexibility, pliability, and elasticity proprieties. Plasticizers are easily released into the environment and are absorbed mainly through ingestion, dermal contact, and inhalation. One of the main classes of plasticizers, phthalates, has been associated with endocrine and reproductive diseases. In 2002, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) was introduced in the market for use in plastic materials and articles intended to come into contact with food, and it received final approval from the European Food Safety Authority in 2006. At present, there is limited knowledge about the safety and potential metabolic and endocrine-disrupting properties of DINCH and its metabolites. The purpose of this study was to evaluate the biological effects of DINCH and its active metabolites, cyclohexane-1,2-dicarboxylic acid (CHDA) and cyclohexane-1,2-dicarboxylic acid mono isononyl ester (MINCH), on rat primary stromal vascular fraction (SVF) of adipose tissue. DINCH and its metabolite, CHDA, were not able to directly affect SVF differentiation. However, exposure of SVF to 50 mu M and 100 mu M concentrations of MINCH affected the expression of Cebpa and Fabp4, thus inducing SVF preadipocytes to accumulate lipids and fully differentiate into mature adipocytes. The effect of MINCH was blocked by the specific peroxisome proliferator-activated receptor (PPAR)-alpha antagonist, GW6471. Taken together, these results suggest that MINCH is a potent PPAR-alpha agonist and a metabolic disruptor, capable of inducing SVF preadipocyte differentiation, that may interfere with the endocrine system in mammals. (C) 2015 Elsevier Inc. All rights reserved.