Nonmonotonic response of type 2 diabetes by low concentration organochlorine pesticide mixture: Findings from multi-omics in zebrafish.
J Hazard Mater
; 416: 125956, 2021 08 15.
Article
in En
| MEDLINE
| ID: mdl-34492873
ABSTRACT
Exposure to a single organochlorine pesticide (OCP) at high concentration and over a short period of exposure constrain our understanding of the contribution of chemical exposure to type 2 diabetes (T2D). A total of 450 male and female zebrafish was exposed to mixtures of five OCPs at 0, 0.05, 0.25, 2.5, and 25 µg/L for 12 weeks. T2D-related hematological parameters (i.e., glucose, insulin, free fatty acid, and triglycerides) and mitochondrial complex I to IV activities were assessed. Metabolomics, proteomics, and transcriptomics were analyzed in female livers, and their data-driven integration was performed. High fasting glucose and low insulin levels were observed only at 0.05 µg/L of the OCP mixture in females, indicating a nonlinear and sexually dependent response. We found that exposure to the OCP mixture inhibited the activities of mitochondrial complexes, especially III and IV. Combining individual and integrated omics analysis, T2D-linked metabolic pathways that regulate mitochondrial function, insulin signaling, and energy homeostasis were altered by the OCP mixture, which explains the observed phenotypic hematological effects. We demonstrated the cause-and-effect relationship between exposures to OCP mixture and T2D using zebrafish model. This study gives an insight into mechanistic research of metabolic diseases caused by chemical exposure using zebrafish.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pesticides
/
Diabetes Mellitus, Type 2
/
Hydrocarbons, Chlorinated
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Hazard Mater
Journal subject:
SAUDE AMBIENTAL
Year:
2021
Document type:
Article