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Toxicol Sci. 2019 Aug 1;170(2):452-461. doi: 10.1093/toxsci/kfz097.

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

Author information

1
Department of Medical and Molecular Genetics, School of Basic and Biomedical Sciences, Faculty of Life Sciences & Medicine, Gene Expression and Therapy Group, King's College London, Guy's Hospital, London SE1 9RT, UK.
2
Genome Centre, Barts and the London School of Medicine and Dentistry, London, UK.
3
John Vane Science Centre, London, EC1M 6BQ, UK.

Abstract

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 µM. 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 (PPARγ)-mediated pathway, a nuclear receptor whose modulation influences lipid metabolism. QpE was further shown to be active in a PPARγ reporter gene assay at 100 µM, 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 PPARγ 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.

KEYWORDS:

3T3-L1; adipogenesis; glyphosate; obesogen; pesticide; quizalofop

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