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Ecotoxicol Environ Saf. 2019 Jul 6;182:109406. doi: 10.1016/j.ecoenv.2019.109406. [Epub ahead of print]

Linking chemical exposure to lipid homeostasis: A municipal waste water treatment plant influent is obesogenic for zebrafish larvae.

Author information

1
CIMAR/CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos s/n, 4450-208, Matosinhos, Portugal; FCUP-Faculty of Sciences, University of Porto, Rua Do Campo Alegre, 4169-007, Porto, Portugal; ICBAS - Institute of Biomedical Sciences Abel Salazar, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313, Porto, Portugal.
2
CIMAR/CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos s/n, 4450-208, Matosinhos, Portugal; FCUP-Faculty of Sciences, University of Porto, Rua Do Campo Alegre, 4169-007, Porto, Portugal.
3
CIMAR/CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos s/n, 4450-208, Matosinhos, Portugal; ICBAS - Institute of Biomedical Sciences Abel Salazar, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313, Porto, Portugal.
4
CIMAR/CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos s/n, 4450-208, Matosinhos, Portugal.
5
Department of Analytical Chemistry, Nutrition and Food Sciences, IIAA-Institute for Food Analysis and Research, Universidade de Santiago de Compostela, Constantino Candeira S/N, 15782, Santiago de Compostela, Spain.
6
CIMAR/CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos s/n, 4450-208, Matosinhos, Portugal; FCUP-Faculty of Sciences, University of Porto, Rua Do Campo Alegre, 4169-007, Porto, Portugal. Electronic address: santos@ciimar.up.pt.

Abstract

Obesity, a risk factor for the development of type-2 diabetes, hypertension, cardiovascular disease, hepatic steatosis and some cancers, has been ranked in the top 10 health risk in the world by the World Health Organization. Despite the growing body of literature evidencing an association between the obesity epidemic and specific chemical exposure across a wide range of animal taxa, very few studies assessed the effects of chemical mixtures and environmental samples on lipid homeostasis. Additionally, the mode of action of several chemicals reported to alter lipid homeostasis is still poorly understood. Aiming to fill some of these gaps, we combined an in vivo assay with the model species zebrafish (Danio rerio) to screen lipid accumulation and evaluate expression changes of key genes involved in lipid homeostasis, alongside with an in vitro transactivation assay using human and zebrafish nuclear receptors, retinoid X receptor α and peroxisome proliferator-activated receptor γ. Zebrafish larvae were exposed from 4 th day post-fertilization until the end of the experiment (day 18), to six different treatments: experimental control, solvent control, tributyltin at 100 ng/L Sn and 200 ng/L Sn (positive control), and wastewater treatment plant influent at 1.25% and 2.5%. Exposure to tributyltin and to 2.5% influent led to a significant accumulation of lipids, with white adipose tissue deposits concentrating in the perivisceral area. The highest in vitro tested influent concentration (10%) was able to significantly transactivate the human heterodimer PPARγ/RXRα, thus suggesting the presence in the influent of HsPPARγ/RXRα agonists. Our results demonstrate, for the first time, the ability of complex environmental samples from a municipal waste water treatment plant influent to induce lipid accumulation in zebrafish larvae.

KEYWORDS:

Endocrine disruptor; Environmental mixture; Nuclear receptor; Obesity; Obesogen

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