Promoting differentiation and lipid metabolism are the primary effects for DINP exposure on 3T3-L1 preadipocytes
Promoting differentiation and lipid metabolism are the primary effects for DINP exposure on 3T3-L1 preadipocytes
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促进分化和脂质代谢是 DINP 暴露对 3T3-L1 前脂肪细胞的主要影响
DOI：
10.1016/j.envpol.2019.113154
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发表时间：
2019
影响因子：
8.9
通讯作者：
Sun Hongwen
中科院分区：
文献类型：
--
作者：
Zhang Lianying;Sun Weijie;Duan Xiaoyu;Duan Yishuang;Sun Hongwen
邻苯二甲酸二异辛酯(DINP)是一种高相对分子质量的邻苯二甲酸酯，近年来作为邻苯二甲酸二(2-乙基己基)酯(DEHP)的替代品被引入，广泛应用于各种塑料制品中。脂肪组织是DINP暴露的重要靶点，但对其在脂肪细胞中的毒性和作用机制却知之甚少(S)。因此，本研究旨在探讨DINP在3T3-L1前脂肪细胞成脂过程中的作用。DINP暴露10天广泛诱导3T3-L1前脂肪细胞向脂肪细胞成脂，通过脂肪积累和成脂标志物的基因表达来评估。逆转录-定量聚合酶链式反应结果显示，丹参多酚可上调PPARγ、C/EBPα和C/EBPβ的表达，而对固醇调节元件结合转录因子1(SREBF1)和C/EBPδ的表达无明显影响。选择性PPARγ拮抗剂GW9662可抑制去甲肾上腺素诱导的成脂作用。采用RNA-SEQ分析方法研究DINP对前脂肪细胞的全身毒性。在50 μM DINP作用下，3T3-L1前脂肪细胞共检测到1181个差异表达基因(Deg)，其中640个基因表达上调，541个基因表达下调。GO富集法显示“脂肪细胞分化”的GO项对代谢功能的影响最显著，KEGG途径富集法显示PPAR途径是受影响最大的途径。相互作用途径(IPATH)分析表明，改变的代谢途径主要集中在脂类代谢上。
Diisononyl phthalate (DINP) is a high-molecular-weight phthalate, and has been recently introduced as di-(2-ethyl hexyl) phthalate (DEHP) substitute and commonly used in a large variety of plastic items. The fat tissue is an important target for DINP exposure, however, very little is understood about its toxicity and mechanism(s) in adipocyte cells. Therefore, the present work aimed to investigate the role of DINP in adipogenesis using 3T3-L1 preadipocytes. DINP exposure for 10 days extensively induced adipogenesis in 3T3-L1 preadipocytes to adipocytes as assessed by lipid accumulation and gene expression of adipogenic markers. The RT-qPCR results showed that DINP could upregulate the expression of peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα) and C/EBPβ, while the expression of sterol regulatory element binding transcription factor 1 (SREBF1) and C/EBPδ was not affected. The DINP-induced adipogenesis could be inhibited by using the selective PPARγ antagonist GW9662. The RNA-seq analysis was used to study the systemic toxicities of DINP on preadipocytes. A total of 1181 differently expressed genes (DEGs) (640 genes were up-regulated, 541 genes were down-regulated) were detected in 3T3-L1 preadipocytes under 50 μM DINP. The GO enrichment showed the GO term of “fat cell differentiation” was the most significantly affected metabolic functions, and the KEGG pathway enrichment showed the PPAR pathway was the top affected pathway. The interactive pathway (iPath) analysis showed that the changed metabolic pathways were focus on the lipid metabolism.