Inflammatory pathway genes belong to major targets of persistent organic pollutants in adipose cells.
Inflammatory pathway genes belong to major targets of persistent organic pollutants in adipose cells.
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DOI：
10.1289/ehp.1104282
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发表时间：
2012-04
影响因子：
10.4
通讯作者：
Barouki R
中科院分区：
文献类型：
--
作者：
Kim MJ;Pelloux V;Guyot E;Tordjman J;Bui LC;Chevallier A;Forest C;Benelli C;Clément K;Barouki R
背景：流行病学研究强调持久性有机污染物（POP）在肥胖和代谢综合征中的可能作用。这些污染物储存在脂肪组织（AT）中。目的：研究持久性有机污染物对人体脂肪细胞和啮齿类动物AT的影响。研究方法：利用人多能脂肪源性干细胞，我们进行了大规模的基因表达分析，以确定2，3，7，8-四氯二苯并对二恶英（TCDD），多氯联苯（PCB）同系物126（PCB-126）和PCB-153修饰的主要途径，并评估其毒性效应。TCDD对基因表达和AT组织学的影响也在小鼠中进行了评估。结果如下：在前体细胞和脂肪细胞中最显著调节的基因是那些参与炎症/免疫反应、癌症和代谢途径的基因。有趣的是，前体细胞的诱导倍数和调控基因的数量高于脂肪细胞，表明前者对污染物的影响更敏感。当细胞与污染物的组合处理，AhR配体TCDD和PCB-126的影响占主导地位相比，非二恶英样PCB-153。AhR受体拮抗剂α-萘酚酮可降低AhR配体的作用。在野生型AT中观察到炎症通路的调节，但在AhR敲除小鼠中未观察到。结论：体内外研究均表明，脂肪细胞是AhR配体的靶细胞，并提示炎症是AhR的主要调控途径之一。这些观察结果表明，污染物可能有助于低度AT炎症，伴随着代谢性疾病的发病机制。
Background: Epidemiological studies emphasize the possible role of persistent organic pollutants (POPs) in obesity and the metabolic syndrome. These pollutants are stored in adipose tissue (AT). Objectives: Our aim was to study the effects of POPs on human adipose cells and rodent AT. Methods: Using human multipotent adipose-derived stem cells, we carried out large-scale gene expression analysis to identify the major pathways modified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyl (PCB) congener 126 (PCB-126), and PCB-153 and to evaluate their toxic effects. The effects of TCDD on gene expression and AT histology were also assessed in mice. Results: The most significantly regulated genes in both precursor cells and adipocytes were those involved in the inflammatory/immune response, cancer, and metabolism pathways. Interestingly, the fold induction and the number of modulated genes were higher in precursors than in adipocytes, suggesting that the former could be more sensitive to the effect of pollutants. When cells were treated with combinations of pollutants, the effects of the AhR ligands TCDD and PCB-126 were dominant compared with those of the non-dioxin-like PCB-153. The effects of AhR ligands were reduced by the AhR antagonist α-naphthoflavone. The regulation of inflammatory pathway was observed in wild-type AT but not in AhR-knockout mice. Conclusions: Both in vitro and in vivo studies showed that adipose cells were targets of AhR ligands and suggest that inflammation is one of the main regulated pathways. These observations suggest a possible contribution of pollutants to low-grade AT inflammation that accompanies the pathogenesis of metabolic diseases.
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影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
使用基于生理学的大鼠药代动力学模型研究体脂肪量和 CYP1A2 诱导对 TCDD 药代动力学的影响。
影响因子：
10.4
作者：
Emond, Claude;Birnbaum, Linda S.;DeVito, Michael J.
通讯作者：
DeVito, Michael J.
影响因子：
4.6
作者：
Fain JN
通讯作者：
Fain JN
影响因子：
3.7
作者：
Li, Wen;Vogel, Christoph F. A.;Matsumura, Fumio
通讯作者：
Matsumura, Fumio
影响因子：
13.6
作者：
Hsu, Hsin-Fen;Tsou, Tsui-Chun;Yeh, Szu-Ching
通讯作者：
Yeh, Szu-Ching