Dataset Information

Metabolic Effects of a Chronic Dietary Exposure to a Low-Dose Pesticide Cocktail in Mice: Sexual Dimorphism and Role of the Constitutive Androstane Receptor (Untargeted urine UPLC-MS assay)

ABSTRACT:

BACKGROUND: Epidemiological evidence suggests a link between pesticide exposure and the development of metabolic diseases. However, most experimental studies have evaluated the metabolic effects of pesticides using individual molecules, often at non relevant doses or in combination with other risk factors such as high fat diets.

OBJECTIVES: We aimed to evaluate, in mice, the metabolic consequences of chronic dietary exposure to a pesticide mixture at non-toxic doses, relevant to consumers’ risk assessment.

METHODS: A mixture of six pesticides commonly used in France i.e. boscalid, captan, chlorpyrifos, thiofanate, thiacloprid, and ziram was incorporated in a standard chow diet, at doses exposing mice to the acceptable daily intake (ADI) of each pesticide. Wild-type (WT) and Constitutive Androstane Receptor knock-out (CAR-/-) C57Bl6/J male and female mice were exposed for 52 weeks. We assessed metabolic parameters (body-weight, food and water consumption, glucose tolerance, urinary metabolome) throughout the experiment. At the end of the experiment, we evaluated liver metabolism (histology, transcriptomics, metabolomics) and pesticide detoxification using LC/MS.
RESULTS: In males, pesticide exposure increased body weight and adiposity and induced hepatic steatosis and glucose intolerance. Exposed females exhibited fasted hyperglycaemia, hepatic oxidative stress and perturbations of gut microbiota-related urinary metabolites. The Constitutive Androstane Receptor is involved in the sexually dimorphic response to pesticide exposure.

CONCLUSIONS: We show for the first time the sexually dimorphic obesogen and diabetogen effects of a chronic dietary exposure to a realistic mixture of pesticides, which are partially mediated through CAR. This raises questions about the relevance of ADI for individual pesticides when present in a mixture.

Untargeted urine UPLC-MS assay protocols and data are reported in the current study MTBLS596.

Untargeted urine, plasma and liver NMR assay protocols and data associated to this study are reported in MTBLS602.

OTHER RELATED OMICS DATASETS IN: GSE101405

INSTRUMENT(S): LTQ XL (Thermo Scientific)

SUBMITTER: Emilien Jamin

PROVIDER: MTBLS596 | MetaboLights | 2019-05-28

REPOSITORIES: MetaboLights

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Metabolic Effects of a Chronic Dietary Exposure to a Low-Dose Pesticide Cocktail in Mice: Sexual Dimorphism and Role of the Constitutive Androstane Receptor.

Lukowicz Céline C Ellero-Simatos Sandrine S Régnier Marion M Polizzi Arnaud A Lasserre Frédéric F Montagner Alexandra A Lippi Yannick Y Jamin Emilien L EL Martin Jean-François JF Naylies Claire C Canlet Cécile C Debrauwer Laurent L Bertrand-Michel Justine J Al Saati Talal T Théodorou Vassilia V Loiseau Nicolas N Mselli-Lakhal Laïla L Guillou Hervé H Gamet-Payrastre Laurence L

Environmental health perspectives 20180625 6

<h4>Background</h4>Epidemiological evidence suggests a link between pesticide exposure and the development of metabolic diseases. However, most experimental studies have evaluated the metabolic effects of pesticides using individual molecules, often at nonrelevant doses or in combination with other risk factors such as high-fat diets.<h4>Objectives</h4>We aimed to evaluate, in mice, the metabolic consequences of chronic dietary exposure to a pesticide mixture at nontoxic doses, relevant to consu ...[more]

PMID: 29950287

Similar Datasets

Project description:<div>BACKGROUND: Epidemiological evidence suggests a link between pesticide exposure and the development of metabolic diseases. However, most experimental studies have evaluated the metabolic effects of pesticides using individual molecules, often at non-relevant doses or in combination with other risk factors such as high fat diets.<br></div><div>OBJECTIVES: We aimed to evaluate, in mice, the metabolic consequences of chronic dietary exposure to a pesticide mixture at non-toxic doses, relevant to consumers’ risk assessment.<br></div>METHODS: A mixture of six pesticides commonly used in France i.e. boscalid, captan, chlorpyrifos, thiofanate, thiacloprid, and ziram was incorporated in a standard chow diet, at doses exposing mice to the acceptable daily intake (ADI) of each pesticide. Wild-type (WT) and Constitutive Androstane Receptor knock-out (CAR-/-) C57Bl6/J male and female mice were exposed for 52 weeks. We assessed metabolic parameters (body-weight, food and water consumption, glucose tolerance, urinary metabolome) throughout the experiment. At the end of the experiment, we evaluated liver metabolism (histology, transcriptomics, metabolomics) and pesticide detoxification using LC/MS.<br>RESULTS: In males, pesticide exposure increased body weight and adiposity and induced hepatic steatosis and glucose intolerance. Exposed females exhibited fasted hyperglycaemia, hepatic oxidative stress and perturbations of gut microbiota-related urinary metabolites. The Constitutive Androstane Receptor is involved in the sexually dimorphic response to pesticide exposure.<br><div> CONCLUSIONS: We show for the first time the sexually dimorphic obesogen and diabetogen effects of a chronic dietary exposure <br>to a realistic mixture of pesticides, which are partially mediated through CAR. This raises questions about the relevance of ADI for <br>individual pesticides when present in a mixture.</div><div><br></div><div><b>Untargeted urine, plasma and liver NMR assay</b> protocols and data are reported in the current study <b>MTBLS602</b>.<br><br><b>Untargeted urine UPLC-MS assay</b> protocols and data associated to this study are reported in <a href="https://www.ebi.ac.uk/metabolights/MTBLS596"><b>MTBLS596</b></a>.<br></div><div><br></div>

Project description:<div>BACKGROUND: Epidemiological evidence suggests a link between pesticide exposure and the development of metabolic diseases. However, most experimental studies have evaluated the metabolic effects of pesticides using individual molecules, often at non relevant doses or in combination with other risk factors such as high fat diets.<br></div><div>OBJECTIVES: We aimed to evaluate, in mice, the metabolic consequences of chronic dietary exposure to a pesticide mixture at non-toxic doses, relevant to consumers’ risk assessment.<br></div> METHODS: A mixture of six pesticides commonly used in France i.e. boscalid, captan, chlorpyrifos, thiofanate, thiacloprid, and ziram was incorporated in a standard chow diet, at doses exposing mice to the acceptable daily intake (ADI) of each pesticide. Wild-type (WT) and Constitutive Androstane Receptor knock-out (CAR-/-) C57Bl6/J male and female mice were exposed for 52 weeks. We assessed metabolic parameters (body-weight, food and water consumption, glucose tolerance, urinary metabolome) throughout the experiment. At the end of the experiment, we evaluated liver metabolism (histology, transcriptomics, metabolomics) and pesticide detoxification using LC/MS.<br>RESULTS: In males, pesticide exposure increased body weight and adiposity and induced hepatic steatosis and glucose intolerance. Exposed females exhibited fasted hyperglycaemia, hepatic oxidative stress and perturbations of gut microbiota-related urinary metabolites. The Constitutive Androstane Receptor is involved in the sexually dimorphic response to pesticide exposure.<br><div> CONCLUSIONS: We show for the first time the sexually dimorphic obesogen and diabetogen effects of a chronic dietary exposure to a realistic mixture of pesticides, which are partially mediated through CAR. This raises questions about the relevance of ADI for individual pesticides when present in a mixture.</div><div><br></div><div><b>Untargeted urine UPLC-MS assay</b> protocols and data are reported in the current study <b>MTBLS596</b>.</div><div><br><b>Untargeted urine, plasma and liver NMR assay</b> protocols and data associated to this study are reported in <a href=https://www.ebi.ac.uk/metabolights/mtbls602><b>MTBLS602</b></a>.<br></div>

			Action	DRS
	MTBLS596	Other
	FILES	Other
	a_MTBLS596_UPLC_MS2_mass_spectrometry.txt	Txt
	a_MTBLS596_UPLC_MS_mass_spectrometry.txt	Txt
	i_Investigation.txt	Txt