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 µM 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 were 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 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.
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Date of publication: 17 April 2019; Toxicological Sciences
Author information: Marina Biserni (1); Robin Mesnage (1); Raquel Ferro (1); Eva Wozniak (2); Theodoros Xenakis (2); Charles A Mein (2); & Michael N Antoniou (1)
(1) Gene Expression and Therapy Group, King’s College London, Faculty of Life Sciences & Medicine, School of Basic and Biomedical Sciences, Department of Medical and Molecular Genetics, 8th Floor, Tower Wing, Guy’s Hospital, Great Maze Pond, London SE1 9RT, United Kingdom
(2) Genome Centre, Barts and the London School of Medicine and Dentistry, John Vane Science Centre, London EC1M 6BQ, United Kingdom