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通讯作者:

顾爱华(1977-),女,江苏南通人,博士生导师,主要从事环境与健康研究。E-mail:aihuagu@njmu.edu.cn

中图分类号:R114,R12

文献标识码:A

文章编号:62-1218(2020)01-0056-05

DOI:10.12287/j.issn.2096-8965.20200109

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目录contents

    摘要

    双酚S (Bisphenol S,BPS) 是双酚A (Bisphenol A,BPA) 的替代品,被广泛用于制造各种聚合物。由于其广泛的使用,造成的环境污染已经严重威胁生态环境和人体健康。近年来,BPS所引起的脂质代谢紊乱逐渐引起大家的关注。 本文对BPS导致环境污染的现状及人群暴露风险进行总结,并从其对脂质合成、转运和降解基因的表达,代谢组学以及对过氧化物酶体增殖物激活受体γ (PPARγ)的作用等方面来探讨BPS所致脂质代谢异常的潜在机制。

    Abstract

    Bisphenol S (BPS), a substitute of bisphenol A (BPA), is widely used for manufacturing different polymers. Due to its wide range of applications, BPS caused pollution has seriously threatened the ecological environment and human health. In recent years, the relationship between BPS and lipid metabolism disorder has attracted more and more attention. This paper summarizes the distribution of BPS in the environment and human exposure risk, as well as the possible mechanisms of the association between BPS and dyslipidemias, including the expression of lipid synthesis, transport and degradation genes, metabolomics, and effect on peroxisome proliferator activated receptors γ (PPARγ).

  • 双酚S(Bisphenol S,BPS)作为双酚A(Bisphenol A,BPA)的替代品,目前广泛应用于聚碳酸酯、 环氧树脂等各种聚合物的生产。由于研究发现BPA暴露对人体健康的不良影响,其在某些产品中的使用已经受到限制。在欧盟内部,自2011年起就禁止在婴儿奶瓶中使用BPA,法国也禁止在所有食品塑料包装中使用BPA[1]。与BPA相比,BPS具有更高的机体负荷、生物利用度和环境稳定性[9]。因此,BPS已经成为BPA最常用的替代品[2, 3]。随着BPS的广泛使用,双酚S已经成为一种普遍存在的污染物, 地表水[4]、污泥[5]、沉积物[4]、灰尘[6] 甚至食品[7] 中都可以检测到其存在。饮食摄入是人体接触BPS的主要来源[8]。流行病学研究显示人体内各类基质及组织脏器均可检测到BPS的存在,提示它对人体具有健康风险。

  • 越来越多的研究证实,脂质代谢紊乱与环境内分泌干扰物有关,BPS的分子结构具有与自然激素相似的化学基团,能影响正常机体内分泌系统。本文概述了BPS在国内外的环境分布、人体内暴露情况及其引起脂质代谢紊乱的机制,为深入研究BPS的健康危害和环境风险提供依据。

  • 1 BPS的环境暴露情况

  • 由于双酚S通常用作生产环氧树脂和聚碳酸酯塑料的中间体,因此它广泛存在于我们的消费品中。欧洲化学品管理局报告,在欧洲经济区,年生产或进口BPS的数量高达1 000~10 000 吨。由于BPS在高温下更稳定,更耐生物降解,导致BPS在环境中的半衰期更长,暴露风险更高[10]。2007-2018年国内外关于BPS在环境中的残留情况见表1。 研究显示,BPS存在于多种环境介质当中。2016年太湖地表水中BPS的含量较2013 年有所增加,并显著高于日本江户川及韩国汉江。我国污泥、沉积物与室内灰尘的检出量与其他国家持平。此外,值得注意的是,在食品及饮用水中均检测出BPS的残留,虽然检出水平均低于欧洲食品安全局规定的每日可接受的摄入量(4 μg/kg/bw/day)。但随着BPS的广泛使用,将会严重威胁到人体健康。因此,通过对环境介质及食品中BPS进行检测,有助于更加严格管理BPS的生产和使用,对人体的健康具有重要的意义。

  • 表1 2007-2018年国内外文献报道的环境中BPS残留量

  • 注:a: 单位为ng/L;b: 单位为ng/g;c: 单位为ug/g; ND为未检出。

  • 2 BPS的人体内暴露水平

  • BPS已经广泛应用于我们的日常生活中,导致人们可以通过多种途径接触到BPS。研究数据表明,接触BPS可能对动物和人类的生殖系统、内分泌系统和神经系统产生不利影响,并可能引发氧化应激[19]。通过整理2007-2019 年国内外人体内BPS的检出情况(见表2),我们发现人体各种体液均可以检测到BPS,包括尿液、血清等。数据显示, 从2007 年到2014 年,美国成人尿液样本中BPS的检出水平从22%上升到74%[20]。尽管尿中BPS的水平仍较BPA低,但呈现上升的趋势。另有数据显示,母乳与脐带血中也能检测到BPS的残留,提示BPS可通过胎盘屏障和哺乳方式进入胎儿体内[21]。 通过检测母乳中BPS的含量,对于评估婴儿每日BPS的摄入量,以及调查接触BPS对婴儿生长(即婴儿的体重和长度) 的影响至关重要。

  • 3 BPS对脂质代谢紊乱的影响

  • 3.1 BPS对脂质合成、转运和降解基因的影响

  • 甘油三脂主要在肝脏、肠道和脂肪组织中合成,脂质的合成与分解不平衡是导致甘油三脂积累的原因。研究表明,斑马鱼胚胎从受精后4小时至第15天暴露于BPS(0,1,10,100 μg/L),可增加脂质合成基因乙酰辅酶A羧化酶(Acetyl-coA Carboxylase,ACC)和溶血磷脂酸酰基转移酶4(Lysophosphatidyl Acyltransferase 4,agpat4) 的表达,降低转运蛋白载脂蛋白E(Apolipoprotein E,ApoE) 和载脂蛋白(Apolipoprotein A1,ApoA1) 表达水平。在生命早期暴露后,对健康危害的远期效应往往在成年后才观察到[26]。另一斑马鱼的研究也提示[27],受精后2 小时到120 天持续暴露于BPS能导致成年斑马鱼肝脏脂质的积累,肝脏中甘油三脂的合成基因二酯酰甘油酰基转移酶2(Dgat2) 和agpat4 表达增加,并且调节肝脏中脂肪酸氧化基因过氧化物酶体增殖因子活化受体 α(Peroxisome Proliferators Activated Receptors, PPARα) 表达降低。Meng等[28] 研究发现围产期雄性小鼠暴露于BPS,可通过干扰其后代的脂质代谢促进肥胖的发展,其机制为BPS增加肝脏和白色脂肪脂质合成基因(Fasn Scd1 and Acc1) 以及转运蛋白CD36的表达,同时降低脂肪酸β氧化基因肉碱棕榈酰转移酶(Cpt-1α)的表达。同样的,在体外水平上,BPS能够上调HepG2细胞固醇调节元件结合蛋白(Srebp1) 表达。Srebp1表达增加导致脂质合成增加,脂质氧化降低,最终导致甘油三酯积累[29]。因此,BPS能通过影响脂质合成、转运和降解基因的表达,导致脂质蓄积。

  • 表2 2007-2019年国内外文献报道的人体内BPS残留量

  • 注a:平均数;b:中位数;c:几何均数;“—”文献数据缺失。

  • 3.2 BPS对代谢组学的影响

  • 代谢组学研究能够揭示环境污染物在细胞、 动物和人类样本中的代谢网络和交叉调节[30]。 Zhao等[31] 研究表明BPS(10-6, 10-4, 10-2 μΜ) 暴露能导致巨噬细胞释放促炎因子。代谢组学的结果显示, 鞘磷脂(SPs)、 甘油磷脂(GPs) 和甘油脂(GLs) 三个亚类在鞘磷脂-神经酰胺(SM-Cer) 信号通路中表现出显著改变。在差异SPs中,SM的丰度降低了1.4~1.6 倍,而Cer的丰度增加了2.5~2.7倍。暴露于BPS后,GPs(磷脂酰胆碱[PC]、溶血磷脂酰胆碱[LPC]、磷脂酰乙醇胺[PE]、和溶血磷脂酰乙醇胺[LPE])和GLs[二酰基甘油DAG]和TAG)富集,较对照组增加2.0~3.3 倍。此外,M1 表型组的SPs、GPs和GLs的变化规律与BPS处理组非常相似,表明BPS能诱导巨噬细胞的促炎极化并影响脂质代谢途径。为进一步直接反映BPS在代谢水平的影响, Gao等[10] 研究发现,胆碱及其代谢物甜菜碱在BPS高剂量组(5 000 μg/kg) 显著下降。由于胆碱在维持细胞膜完整性和脂肪酸代谢方面起着重要作用[32],因此,BPS暴露可能通过调节胆碱代谢途径影响脂质代谢。除此之外,BPS暴露还显著改变了与能量代谢密切相关的琥珀酸酯、 ATP和AMP以及与谷胱甘肽代谢相关的代谢物的含量,进一步干扰新陈代谢。Meng等[28] 研究发现将围产期小鼠暴露于BPS能导致子代成年小鼠5种游离脂肪酸(C16∶0,C18∶0,C20∶0,C22∶0,C20∶ 1n9)的相对含量显著增加[28]。这些结果表明BPS暴露能通过干扰脂质代谢水平,促进脂质积累。

  • 3.3 BPS对过氧化物酶体增殖物活化受体 γ(Peroxisome Proliferator Activated Receptors γ, PPARγ)信号通路的影响

  • PPARγ是配体诱导的转录因子,其调节与代谢和脂质合成相关的多个靶基因的表达。Gao等[10] 将THP-1 巨噬细胞暴露在BPS(1,10,100 μM)12 小时后发现,高剂量(100 μM) 的BPS能够上调PPARγ 及其靶基因脂肪酸结合蛋白4(FABP4)、肝脏X受体(LXRs) 和CD36的表达。其中,FABP4可增加胆固醇酯的积累,诱导泡沫细胞的形成,促进动脉粥样硬化的发展[33];CD36 参与调节氧化应激、炎症和脂质代谢[34];LXRs参与调节代谢途径,如胆固醇稳态、炎症和脂肪生成,LXRs也是调控巨噬细胞泡沫细胞形成的主要因素[35]。因此,BPS通过诱导PPARγ 的表达, 进一步引起代谢紊乱。 Boucher等[36] 研究发现BPS通过激活PPARγ 并增加其下游脂蛋白脂肪酶、脂肪细胞脂结合蛋白aP2 等脂肪细胞分化标志性分子的mRNA和蛋白表达水平诱导人前脂肪细胞脂质蓄积,该研究还发现BPS比BPA能更早影响脂质代谢相关基因的表达。

  • 随着BPA的禁用和限用,BPS的应用领域不断扩大,导致各种环境介质和人们的日常生活中都可以检测到BPS的存在,然而目前对BPS在环境及人体的暴露缺乏系统的了解,难以评估其危害。因此,系统研究BPS在环境中的水平,检测人体内BPS的残留量,追溯人体BPS暴露来源对于评估BPS的健康风险具有重要的意义。研究报道BPS能影响脂质代谢的紊乱,主要通过影响脂质合成、转运和降解基因的表达,代谢组学以及对PPARγ 作用来破坏机体脂质代谢平衡造成脂质蓄积。然而目前许多研究选择的剂量远高于环境及人体内暴露水平,未来仍需要关注BPS长期低剂量暴露的毒性效应,使研究结果更好反映环境BPS的水平对人体健康的危害,为BPS的安全性评价提供更多的科学证据。

  • 参考文献

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    • [2] BARRETT J R.Assessing the safety of a replacement chemical:nongenomic activity of bisphenol S[J].Environmental Health Perspectives,2013,121(3):A97.

    • [3] ELADAK S,GRISIN T,MOISON D,et al.A new chapter in the bisphenol A story:bisphenol S and bisphenol F are not safe /html/swyxzh/20200109/alternatives to this compound[J].Fertility and Sterility,2015,103(1):11-21.

    • [4] JIN H,ZHU L.Occurrence and partitioning of bisphenol analogues in water and sediment from Liaohe River Basin and Taihu Lake,China[J].Water Research,2016,103:343-351.

    • [5] SONG S,SONG M,ZENG L,et al.Occurrence and profiles of bisphenol analogues in municipal sewage sludge in China[J].Environmental Pollution,2014,186:14-19.

    • [6] ZHANG H,QUAN Q,ZHANG M,et al.Occurrence of bisphenol A and its /html/swyxzh/20200109/alternatives in paired urine and indoor dust from Chinese university students:implications for human exposure[J].Chemosphere,2020,247:125987.

    • [7] ZHANG H,ZHANG Y,LI J,et al.Occurrence and exposure assessment of bisphenol analogues in source water and drinking water in China[J].Sci Total Environ,2019,655:607-613.

    • [8] QIU W,ZHAN H,HU J,et al.The occurrence,potential toxicity,and toxicity mechanism of bisphenol S,a substitute of bisphenol A:a critical review of recent progress [J].Ecotoxicol Environ Saf,2019,173:192-202.

    • [9] DANZL E,SEI K,SODA S,et al.Biodegradation of bisphenol A,bisphenol F and bisphenol S in seawater[J].Int J Environ Res Public Health,2009,6(4):1472-1484.

    • [10] GAO P,WANG L,YANG N,et al.Peroxisome proliferator-activated receptor gamma(PPARgamma)activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse models[J].Environ Int,2020,134:105328.

    • [11] LIU Y,ZHANG S,SONG N,et al.Occurrence,distribution and sources of bisphenol analogues in a shallow Chinese freshwater lake(Taihu Lake):implications for ecological and human health risk[J].Sci Total Environ,2017(599/600):1090-1098.

    • [12] YAMAZAKI E,YAMASHITA N,TANIYASU S,et al.Bisphenol A and other bisphenol analogues including BPS and BPF in surface water samples from Japan,China,Korea and India[J].Ecotoxicol Environ Saf,2015,122:565-572.

    • [13] YU X,XUE J,YAO H,et al.Occurrence and estrogenic potency of eight bisphenol analogs in sewage sludge from the U.S.EPA targeted national sewage sludge survey[J].J Hazard Mater,2015,299:733-739.

    • [14] LIAO C,LIU F,MOON H B,et al.Bisphenol analogues in sediments from industrialized areas in the United States,Japan,and Korea:spatial and temporal distributions[J].Environ Sci Technol,2012,46(21):11558-11565.

    • [15] LIU M,JIA S,DONG T,et al.The occurrence of bisphenol plasticizers in paired dust and urine samples and its association with oxidative stress[J].Chemosphere,2019,216:472-478.

    • [16] LIAO C,LIU F,ALOMIRAH H,et al.Bisphenol S in urine from the United States and seven Asian countries:occurrence and human exposures[J].Environ Sci Technol,2012,46(12):6860-6866.

    • [17] LIAO C,KANNAN K.A survey of bisphenol A and other bisphenol analogues in foodstuffs from nine cities in China[J].Food Addit Contam Part A Chem Anal Control Expo Risk Assess,2014,31(2):319-329.

    • [18] LIAO C,KANNAN K.Concentrations and profiles of bisphenol A and other bisphenol analogues in foodstuffs from the United States and their implications for human exposure[J].J Agric Food Chem,2013,61(19):4655-4662.

    • [19] WU L H,ZHANG X M,WANG F,et al.Occurrence of bisphenol S in the environment and implications for human exposure:a short review[J].Sci Total Environ,2018,615:87-98.

    • [20] YE X,WONG L Y,KRAMER J,et al.Urinary concentrations of bisphenol A and three other bisphenols in convenience samples of U.S.Adults during 2000-2014[J].Environ Sci Technol,2015,49(19):11834-11839.

    • [21] LIU J,LI J,WU Y,et al.Bisphenol a metabolites and bisphenol S in paired maternal and cord serum[J].Environ Sci Technol,2017,51(4):2456-2463.

    • [22] JIN H,ZHU J,CHEN Z,et al.Occurrence and partitioning of bisphenol analogues in adults' blood from China[J].Environ Sci Technol,2018,52(2):812-820.

    • [23] LI A,ZHUANG T,SHI W,et al.Serum concentration of bisphenol analogues in pregnant women in China[J].SciTotal Environ,2020,707:136100.

    • [24] JIN H,XIE J,MAO L,et al.Bisphenol analogue concentrations in human breast milk and their associations with postnatal infant growth[J].Environmental Pollution,2020,259:113779.

    • [25] XUE J,WU Q,SAKTHIVEL S,et al.Urinary levels of endocrine-disrupting chemicals,including bisphenols,bisphenol A diglycidyl ethers,benzophenones,parabens,and triclosan in obese and non-obese Indian children[J].Environ Res,2015,137:120-128.

    • [26] SYLVIA K E,DEYOE J E,DEMAS G E.Early-life sickness may predispose Siberian hamsters to behavioral changes following alterations of the gut microbiome in adulthood[J].Brain Behav Immun,2018,73:571-583.

    • [27] WANG W,ZHANG X,QIN J,et al.Long-term bisphenol S exposure induces fat accumulation in liver of adult male zebrafish(Danio rerio)and slows yolk lipid consumption in F1 offspring[J].Chemosphere,2019,221(4):500-510.

    • [28] MENG Z,WANG D,YAN S,et al.Effects of perinatal exposure to BPA and its /html/swyxzh/20200109/alternatives(BPS,BPF and BPAF)on hepatic lipid and glucose homeostasis in female mice adolescent offspring[J].Chemosphere,2018,212(12):297-306.

    • [29] LI X,LI Y,YANG W,et al.SREBP-1c overexpression induces triglycerides accumulation through increasing lipid synthesis and decreasing lipid oxidation and VLDL assembly in bovine hepatocytes[J].J Steroid Biochem Mol Biol,2014,143:174-182.

    • [30] ZHANG Z H,VAZIRI N D,WEI F,et al.An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure[J].Sci Rep,2016,6:22151.

    • [31] ZHAO C,TANG Z,YAN J,et al.Bisphenol S exposure modulate macrophage phenotype as defined by cytokines profiling,global metabolomics and lipidomics analysis[J].Sci Total Environ,2017,592(8):357-365.

    • [32] NAM J,GREENWALD E,JACK-ROBERTS C,et al.Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity[J].J Nutr Biochem,2017,49:80-88.

    • [33] FURUHASHI M,SAITOH S,SHIMAMOTO K,et al.Fatty Acid-Binding Protein 4(FABP4):pathophysiological insights and potent clinical biomarker of metabolic and cardiovascular diseases[J].Clin Med Insights Cardiol,2014,8(3):23-33.

    • [34] CHOROMANSKA B,MYSLIWIEC P,CHOROMANSKA K,et al.The role of CD36 receptor in the pathogenesis of atherosclerosis[J].Adv Clin Exp Med,2017,26(4):717-722.

    • [35] MCLAREN J E,MICHAEL D R,ASHLIN T G,et al.Cytokines,macrophage lipid metabolism and foam cells:implications for cardiovascular disease therapy[J].Prog Lipid Res,2011,50(4):331-347.

    • [36] BOUCHER J G,AHMED S,ATLAS E.Bisphenol S induces adipogenesis in primary human preadipocy-tes from female donors[J].Endocrinology,2016,157(4):1397-1407.

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    • [9] DANZL E,SEI K,SODA S,et al.Biodegradation of bisphenol A,bisphenol F and bisphenol S in seawater[J].Int J Environ Res Public Health,2009,6(4):1472-1484.

    • [10] GAO P,WANG L,YANG N,et al.Peroxisome proliferator-activated receptor gamma(PPARgamma)activation and metabolism disturbance induced by bisphenol A and its replacement analog bisphenol S using in vitro macrophages and in vivo mouse models[J].Environ Int,2020,134:105328.

    • [11] LIU Y,ZHANG S,SONG N,et al.Occurrence,distribution and sources of bisphenol analogues in a shallow Chinese freshwater lake(Taihu Lake):implications for ecological and human health risk[J].Sci Total Environ,2017(599/600):1090-1098.

    • [12] YAMAZAKI E,YAMASHITA N,TANIYASU S,et al.Bisphenol A and other bisphenol analogues including BPS and BPF in surface water samples from Japan,China,Korea and India[J].Ecotoxicol Environ Saf,2015,122:565-572.

    • [13] YU X,XUE J,YAO H,et al.Occurrence and estrogenic potency of eight bisphenol analogs in sewage sludge from the U.S.EPA targeted national sewage sludge survey[J].J Hazard Mater,2015,299:733-739.

    • [14] LIAO C,LIU F,MOON H B,et al.Bisphenol analogues in sediments from industrialized areas in the United States,Japan,and Korea:spatial and temporal distributions[J].Environ Sci Technol,2012,46(21):11558-11565.

    • [15] LIU M,JIA S,DONG T,et al.The occurrence of bisphenol plasticizers in paired dust and urine samples and its association with oxidative stress[J].Chemosphere,2019,216:472-478.

    • [16] LIAO C,LIU F,ALOMIRAH H,et al.Bisphenol S in urine from the United States and seven Asian countries:occurrence and human exposures[J].Environ Sci Technol,2012,46(12):6860-6866.

    • [17] LIAO C,KANNAN K.A survey of bisphenol A and other bisphenol analogues in foodstuffs from nine cities in China[J].Food Addit Contam Part A Chem Anal Control Expo Risk Assess,2014,31(2):319-329.

    • [18] LIAO C,KANNAN K.Concentrations and profiles of bisphenol A and other bisphenol analogues in foodstuffs from the United States and their implications for human exposure[J].J Agric Food Chem,2013,61(19):4655-4662.

    • [19] WU L H,ZHANG X M,WANG F,et al.Occurrence of bisphenol S in the environment and implications for human exposure:a short review[J].Sci Total Environ,2018,615:87-98.

    • [20] YE X,WONG L Y,KRAMER J,et al.Urinary concentrations of bisphenol A and three other bisphenols in convenience samples of U.S.Adults during 2000-2014[J].Environ Sci Technol,2015,49(19):11834-11839.

    • [21] LIU J,LI J,WU Y,et al.Bisphenol a metabolites and bisphenol S in paired maternal and cord serum[J].Environ Sci Technol,2017,51(4):2456-2463.

    • [22] JIN H,ZHU J,CHEN Z,et al.Occurrence and partitioning of bisphenol analogues in adults' blood from China[J].Environ Sci Technol,2018,52(2):812-820.

    • [23] LI A,ZHUANG T,SHI W,et al.Serum concentration of bisphenol analogues in pregnant women in China[J].SciTotal Environ,2020,707:136100.

    • [24] JIN H,XIE J,MAO L,et al.Bisphenol analogue concentrations in human breast milk and their associations with postnatal infant growth[J].Environmental Pollution,2020,259:113779.

    • [25] XUE J,WU Q,SAKTHIVEL S,et al.Urinary levels of endocrine-disrupting chemicals,including bisphenols,bisphenol A diglycidyl ethers,benzophenones,parabens,and triclosan in obese and non-obese Indian children[J].Environ Res,2015,137:120-128.

    • [26] SYLVIA K E,DEYOE J E,DEMAS G E.Early-life sickness may predispose Siberian hamsters to behavioral changes following alterations of the gut microbiome in adulthood[J].Brain Behav Immun,2018,73:571-583.

    • [27] WANG W,ZHANG X,QIN J,et al.Long-term bisphenol S exposure induces fat accumulation in liver of adult male zebrafish(Danio rerio)and slows yolk lipid consumption in F1 offspring[J].Chemosphere,2019,221(4):500-510.

    • [28] MENG Z,WANG D,YAN S,et al.Effects of perinatal exposure to BPA and its /html/swyxzh/20200109/alternatives(BPS,BPF and BPAF)on hepatic lipid and glucose homeostasis in female mice adolescent offspring[J].Chemosphere,2018,212(12):297-306.

    • [29] LI X,LI Y,YANG W,et al.SREBP-1c overexpression induces triglycerides accumulation through increasing lipid synthesis and decreasing lipid oxidation and VLDL assembly in bovine hepatocytes[J].J Steroid Biochem Mol Biol,2014,143:174-182.

    • [30] ZHANG Z H,VAZIRI N D,WEI F,et al.An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure[J].Sci Rep,2016,6:22151.

    • [31] ZHAO C,TANG Z,YAN J,et al.Bisphenol S exposure modulate macrophage phenotype as defined by cytokines profiling,global metabolomics and lipidomics analysis[J].Sci Total Environ,2017,592(8):357-365.

    • [32] NAM J,GREENWALD E,JACK-ROBERTS C,et al.Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity[J].J Nutr Biochem,2017,49:80-88.

    • [33] FURUHASHI M,SAITOH S,SHIMAMOTO K,et al.Fatty Acid-Binding Protein 4(FABP4):pathophysiological insights and potent clinical biomarker of metabolic and cardiovascular diseases[J].Clin Med Insights Cardiol,2014,8(3):23-33.

    • [34] CHOROMANSKA B,MYSLIWIEC P,CHOROMANSKA K,et al.The role of CD36 receptor in the pathogenesis of atherosclerosis[J].Adv Clin Exp Med,2017,26(4):717-722.

    • [35] MCLAREN J E,MICHAEL D R,ASHLIN T G,et al.Cytokines,macrophage lipid metabolism and foam cells:implications for cardiovascular disease therapy[J].Prog Lipid Res,2011,50(4):331-347.

    • [36] BOUCHER J G,AHMED S,ATLAS E.Bisphenol S induces adipogenesis in primary human preadipocy-tes from female donors[J].Endocrinology,2016,157(4):1397-1407.

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