癌变·畸变·突变 ›› 2020, Vol. 32 ›› Issue (4): 245-255.doi: 10.3969/j.issn.1004-616x.2020.04.001

• 论著 •    下一篇

低剂量双酚A通过调控PPARγ致小鼠糖脂代谢紊乱的研究

龙子, 樊隽澍, 吴光源, 王欣, 海春旭   

  1. 空军军医大学军事预防医学院毒理学教研室, 特殊作业环境危害评估与防治教育部重点实验室, 陕西省自由基生物学与医学重点实验室, 陕西 西安 710032
  • 收稿日期:2019-12-10 修回日期:2020-05-21 出版日期:2020-07-31 发布日期:2020-08-01
  • 通讯作者: 王欣,E-mail:xinwang@fmmu.edu.cn;海春旭,E-mail:cx-hai@fmmu.edu.cn E-mail:xinwang@fmmu.edu.cn;cx-hai@fmmu.edu.cn
  • 作者简介:龙子,E-mail:luoze0317@126.com。
  • 基金资助:
    国家自然科学基金(21677176)

Low-dose of bisphenol A induced glucose and lipid metabolism disorders in mice by regulating PPARγ

LONG Zi, FAN Junshu, WU Guangyuan, WANG Xin, HAI Chunxu   

  1. Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Air Force Military Medical University, Xi'an 710032, Shaanxi, China
  • Received:2019-12-10 Revised:2020-05-21 Online:2020-07-31 Published:2020-08-01

摘要: 目的: 探讨双酚A(BPA)在低剂量条件下单独或联合高脂饮食(HFD)对小鼠糖脂代谢的影响及机制。方法: 60只C57BL/6J小鼠随机分为5组,建立不同浓度[1、10、100、1 000 μg/(kg·d)]BPA暴露的动物模型。确定最佳剂量后将另外60只C57BL/6J小鼠随机分为5组:对照组、HFD组、BPA组、BPA联合HFD组、BPA联合人参皂苷Rh1(Rh1)组。通过检测肝脏甘油三酯(TG)含量及葡萄糖耐量等指标评价小鼠糖脂代谢功能。结果: 形态学实验及生化测定结果显示,小鼠在10 μg/(kg·d)BPA暴露下肝脏脂质积累程度最高。与对照组相比,BPA暴露导致小鼠肝脏TG含量升高,葡萄糖耐量降低(P均 < 0.05)。与单纯HFD饲养小鼠相比,HFD饲养的BPA暴露小鼠肝脏TG含量升高,葡萄糖耐量降低(P均 < 0.05)。脂肪生成相关调控因子过氧化物酶体增殖物激活受体γ(PPARγ)、固醇调节元件结合蛋白(SREBP1)、脂肪酸合酶(FASN)和硬脂酰辅酶A去饱和酶1(SCD-1)的表达水平显著升高(P均 < 0.05)。使用Rh1处理BPA暴露小鼠,与单纯BPA暴露组相比,肝脏TG含量显著降低(P < 0.05)。结论: BPA暴露能够诱导小鼠糖脂代谢紊乱,并加重HFD诱导的糖脂代谢紊乱。BPA调控一系列脂质代谢相关基因诱导脂质积累,引起糖脂代谢紊乱的发生。使用Rh1抑制PPARγ的表达可减轻BPA诱导的糖脂代谢紊乱。因此PPARγ转录水平的表达上调可能是BPA诱导的糖脂代谢紊乱的重要原因。

关键词: 双酚A, 低剂量暴露, 高脂饮食, 过氧化物酶体增殖物激活受体γ, 糖脂代谢紊乱

Abstract: OBJECTIVE: To investigate the effect and mechanism of low doses of bisphenol A (BPA) alone or in combination with high fat diet (HFD) on glucose and lipid metabolism in mice. METHODS: Sixty C57BL/6J mice were randomly divided into five groups for exposure to BPA at different concentrations[1,10, 100,1 000 μg/(kg·d)]. After determining the optimal dose,another 60 C57BL/6J mice were randomly divided into 5 groups:control,BPA,BPA+HFD,HFD,BPA+Ginsenoside Rh1 (Rh1). The function of glucose and lipid metabolism in mice was evaluated by measuring liver triglyceride (TG) content and glucose tolerance. RESULTS: After exposure of 10 μg/(kg·d) BPA,morphological and biochemical determinations showed that these mice had the highest lipid accumulation. Compared with the control group, BPA exposure resulted in increased liver TG levels and decreased glucose tolerance (P < 0.05). Compared with HFD group,mice from the BPA + HFD group had increased liver TG content and decreased glucose tolerance (P < 0.05). Expression levels of peroxidosomal proliferator activated receptor γ (PPARγ), sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FASN) and stearyl coenzyme A desaturase 1 (SCD-1), which are related to adipogenesis, were significantly increased (P < 0.05). In BPA exposed mice treated with Rh1, liver TG levels were significantly reduced compared with the BPA exposed mice (P < 0.05). CONSLUSION: BPA exposure induced glucose and lipid metabolism disorders in mice, and aggravate HFD-induced glucose and lipid metabolism disorders. BPA regulated a series of lipid metabolism-related genes to induce lipid accumulation, leading to the disorder of glucose and lipid metabolism. Inhibition of PPARγ expression with Rh1 significantly alleviated BPA-induced disorders of glucose and lipid metabolism. Therefore, increased PPARγ transcription could be a key reason of glucose and lipid metabolism disorder induced by BPA.

Key words: bisphenol A, low dose exposure, high fat diet, PPARγ, glucose and lipid metabolic disorder

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