Quizalofop-p-Ethyl Induces Adipogenesis in 3T3-L1 Adipocytes

被引:23
作者
Biserni, Martina [1 ]
Mesnage, Robin [1 ]
Ferro, Raquel [1 ]
Wozniak, Eva [2 ,3 ]
Xenakis, Theodoros [2 ,3 ]
Mein, Charles A. [2 ,3 ]
Antoniou, Michael N. [1 ]
机构
[1] Kings Coll London, Guys Hosp, Dept Med & Mol Genet, Sch Basic & Biomed Sci,Fac Life Sci & Med,Gene Ex, 8th Floor,Tower Wing, London SE1 9RT, England
[2] Barts & London Queen Marys Sch Med & Dent, Genome Ctr, London, England
[3] John Vane Sci Ctr, London EC1M 6BQ, England
关键词
quizalofop; pesticide; adipogenesis; obesogen; glyphosate; 3T3-L1; ENDOCRINE DISRUPTING CHEMICALS; OBESOGEN TRIBUTYLTIN; PRENATAL EXPOSURE; STEM-CELLS; IN-VITRO; GLYPHOSATE; TOXICITY; DIFFERENTIATION; ACTIVATION;
D O I
10.1093/toxsci/kfz097
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Exposure to endocrine disrupting chemicals is an established risk factor for obesity. The most commonly used pesticide active ingredients have never been tested in an adipogenesis assay. We tested for the first time the potential of glyphosate, 2, 4-dichlorophenoxyacetic acid, dicamba, mesotrione, isoxaflutole, and quizalofop-p-ethyl (QpE) to induce lipid accumulation in murine 3T3-L1 adipocytes. Only QpE caused a dose-dependent statistically significant triglyceride accumulation from a concentration of 5 up to 100 mu M. The QpE commercial formulation Targa Super was 100 times more cytotoxic than QpE alone. Neither the estrogen receptor antagonist ICI 182, 780 nor the glucocorticoid receptor antagonist RU486 was able to block the QpE-induced lipid accumulation. RNAseq analysis of 3T3-L1 adipocytes exposed to QpE suggests that this compound exerts its lipid accumulation effects via a peroxisome proliferator-activated receptor gamma (PPAR gamma)-mediated pathway, a nuclear receptor whose modulation influences lipid metabolism. QpE was further shown to be active in a PPAR gamma reporter gene assay at 100 mu M, reaching 4% of the maximal response produced by rosiglitazone, which acts as a positive control. This indicates that lipid accumulation induced by QpE is only in part caused by PPAR gamma activation. The lipid accumulation capability of QpE we observe suggest that this pesticide, whose use is likely to increase in coming years may have a hitherto unsuspected obesogenic property.
引用
收藏
页码:452 / 461
页数:10
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