Real-ambient exposure to air pollution exaggerates excessive growth of adipose tissue modulated by Nrf2 signal
Real-ambient exposure to air pollution exaggerates excessive growth of adipose tissue modulated by Nrf2 signal
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真实环境暴露于空气污染会加剧由 Nrf2 信号调节的脂肪组织的过度生长
DOI：
10.1016/j.scitotenv.2020.138652
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发表时间：
2020-08-15
影响因子：
9.8
通讯作者：
Zheng, Yuxin
中科院分区：
文献类型：
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作者：
Jiang, Menghui;Li, Daochuan;Zheng, Yuxin
空气污染正成为全球性的公共健康威胁，主要由PM2.5引起的心血管疾病和肺部疾病介导。最近，观察性流行病学研究提出了PM2.5与肥胖之间的联系。同样，这种联系也得到了有限的动物研究的支持。然而，介导PM2.5有害影响的潜在机制仍然难以捉摸。在本研究中，我们采用了“真实环境暴露”系统进行实验，这是更接近的环境空气污染的状况相比，肠道滴注法和浓缩空气颗粒物（CAPs）暴露系统。核因子E2相关因子2（Nrf 2）以前曾被报道在暴露于PM2.5时可以防止炎症和氧化应激。在这里，我们报道了Nrf 2（-/-）小鼠在“真实环境暴露”于PM2.5后，与过滤空气（FA）组相比，脂肪组织过度生长。与FA组相比，PM2.5暴露组Nrf 2（-/-）小鼠皮下脂肪组织（sWAT）和性腺白色脂肪组织（gWAT）的脂肪细胞体积增大。此外，Nrf 2（-/-）小鼠血清和肝脏中高密度脂蛋白（HDL）和低密度脂蛋白（LDL）水平在PM2.5暴露组也有显著变化。重要的是，当分析脂肪生成酶的表达时，在PM2.5暴露组中，Nrf 2（-/-）小鼠脂肪组织和肝脏中相关特异性基因的水平发生改变。有趣的是，Nrf 2（-/-）小鼠肝脏中调节脂肪生成酶表达的关键转录因子，如过氧化物酶体增殖物激活受体（PPARa，PPAR.），在PM2.5暴露组中也被发现改变。总之，我们的研究模拟了环境空气污染的状况，揭示了对PM2.5暴露的不利影响的新见解，提供了空气污染与脂肪组织过度生长之间的新联系，并支持Nrf 2在介导PM2.5副作用中的重要作用。(C)2020 Elsevier B. V.保留所有权利。
Air pollution was becoming a global threat to the public health, which was primarily mediated by PM2.5 induced cardiovascular diseases and pulmonary diseases. Recently, observational epidemiologic studies proposed the link between PM2.5 and obesity. Consistently, the link was also supported by limited animal researches. However, the potential mechanism mediating the harmful effects of PM2.5 was still elusive. In this study, we applied the "real-ambient exposure" system to conduct the experiments, which was closer to the status of ambient air pollution compared with the method of intratracheal instillation and concentrated air particles (CAPs) exposure system. Nuclear factor E2-related factor 2 (Nrf2) was previously reported to protect against inflammation and oxidative stresswhen exposed to PM2.5. Here, we reported that Nrf2(-/-) mice developed overgrowth of adipose tissue after "real-ambient exposure" to PM2.5, compared to filtered air (FA) group. Consistently, compared to FA group, adipocytes from subcutaneous (sWAT) and gonadal (gWAT) white adipose tissue of Nrf2(-/-) mice exhibited enlarged cell size in PM2.5 exposure group. Furthermore, the levels of high-density lipoprotein (HDL) and lowdensity lipoprotein (LDL) in serum and liver of Nrf2(-/-) mice were also altered statistically in PM2.5 exposure group. Importantly, when the expression of lipogenic enzymes was analyzed, the levels of the related specific genes in adipose tissue and liver of Nrf2(-/-) mice were altered in PM2.5 exposure group. Interestingly, the key transcription factors modulating expression of lipogenic enzymes in liver of Nrf2(-/-) mice were also found altered in PM2.5 exposure group, such as peroxisome proliferator-activated receptor (PPARa, PPAR.). Taken together, our study mimicked the status of ambient air pollution, revealed new insights into the adverse effect of PM2.5 exposure, provided new link between air pollution and overgrowth of adipose tissue, and supported the vital role of Nrf2 in mediating the side effects of PM2.5. (C) 2020 Elsevier B.V. All rights reserved.