PUBLICATION
Nonmonotonic response of type 2 diabetes by low concentration organochlorine pesticide mixture: Findings from multi-omics in zebrafish
- Authors
- Lee, H., Gao, Y., Ko, E., Lee, J., Lee, H.K., Lee, S., Choi, M., Shin, S., Park, Y.H., Moon, H.B., Uppal, K., Kim, K.T.
- ID
- ZDB-PUB-210909-2
- Date
- 2021
- Source
- Journal of hazardous materials 416: 125956 (Journal)
- Registered Authors
- Keywords
- Multi-omics, Organochlorine pesticide mixtures, Type 2 diabetes, Zebrafish
- MeSH Terms
-
- Animals
- Diabetes Mellitus, Type 2*/chemically induced
- Diabetes Mellitus, Type 2*/genetics
- Female
- Hydrocarbons, Chlorinated*
- Insulin
- Male
- Pesticides*/analysis
- Pesticides*/toxicity
- Zebrafish
- PubMed
- 34492873 Full text @ J. Hazard. Mater.
Citation
Lee, H., Gao, Y., Ko, E., Lee, J., Lee, H.K., Lee, S., Choi, M., Shin, S., Park, Y.H., Moon, H.B., Uppal, K., Kim, K.T. (2021) Nonmonotonic response of type 2 diabetes by low concentration organochlorine pesticide mixture: Findings from multi-omics in zebrafish. Journal of hazardous materials. 416:125956.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping