Description
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.
[dataset license:
CC0 1.0 Universal (CC0 1.0)]
Keywords: GNPS Metabolomics MetaboLights
Contact
Principal Investigators:
(in alphabetical order)
|
Emilien Jamin, UMR1331 INRA, 180 chemin de Tournefeuille F-31027 Toulouse
|
Submitting User: |
caceves
|
Number of Files: |
|
Total Size: |
|
Spectra: |
|
Subscribers: |
|
|
|
Owner |
Conditions:
|
|
|
Biological Replicates:
|
|
|
Technical Replicates:
|
|
|
|
Identification Results |
Proteins (Human, Remapped):
|
|
|
Proteins (Reported):
|
|
|
Peptides:
|
|
|
Variant Peptides:
|
|
|
PSMs:
|
|
|
|
Differential Proteins:
|
|
|
Quantified Proteins:
|
|
|
|
GNPS content goes here (MSV000085634 [task=2977ff3423764847b878a2afba7d0f70])
Click here to queue conversion of this dataset's submitted spectrum files
to open formats (e.g. mzML). This process may take some time.
When complete, the converted files will be available in the "ccms_peak"
subdirectory of the dataset's FTP space (accessible via the "FTP Download"
link to the right).
Number of distinct conditions across all analyses (original submission and reanalyses)
associated with this dataset.
Distinct condition labels are counted across all files submitted in the "Metadata" category
having a "Condition" column in this dataset.
"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses)
associated with this dataset.
Distinct replicate labels are counted across all files submitted in the "Metadata" category
having a "BioReplicate" or "Replicate" column in this dataset.
"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses)
associated with this dataset.
The technical replicate count is defined as the maximum number of times any one distinct
combination of condition and biological replicate was analyzed across all files submitted in the
"Metadata" category. In the case of fractionated experiments, only the first fraction is
considered.
"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically
remapped by MassIVE to proteins in the
SwissProt
human reference database.
"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and
reanalyses) associated with this dataset.
"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original
submission and reanalyses) associated with this dataset.
"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported
across all analyses (original submission and reanalyses) associated with this dataset.
"N/A" means no results of this type were submitted.
Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all
analyses (original submission and reanalyses) associated with this dataset.
"N/A" means no results of this type were submitted.
Number of distinct proteins quantified across all analyses (original submission and reanalyses)
associated with this dataset.
Distinct protein accessions are counted across all files submitted in the "Statistical Analysis
of Quantified Analytes" category having a "Protein" column in this dataset.
"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison
across all analyses (original submission and reanalyses) associated with this dataset.
A protein is differentially abundant if its change in abundance across conditions is found
to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated
with statistical tests for differential abundance.
Distinct protein accessions are counted across all files submitted in the "Statistical Analysis
of Quantified Analytes" category having a "Protein" column in this dataset.
"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE.
It has been imported to MassIVE for reanalysis purposes, so its spectra data here may
consist solely of processed peak lists suitable for reanalysis with most software.