Nonmonotonic response of type 2 diabetes by low concentration organochlorine pesticide mixture: Findings from multi-omics in zebrafish
- Title
- Nonmonotonic response of type 2 diabetes by low concentration organochlorine pesticide mixture: Findings from multi-omics in zebrafish
- Author
- 이현경
- Issue Date
- 2021-04
- Publisher
- Elsevier BV
- Citation
- Journal of Hazardous Materials, v. 416, Article no. 125956, 10pp
- 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.
- URI
- https://www.sciencedirect.com/science/article/pii/S0304389421009201https://repository.hanyang.ac.kr/handle/20.500.11754/166816
- ISSN
- 0304-3894
- DOI
- 10.1016/j.jhazmat.2021.125956
- Appears in Collections:
- RESEARCH INSTITUTE[E](부설연구소) > INSTITUTE OF OCENA AND ATMOSPHERIC SCIENCES(해양ㆍ대기과학연구소) > Articles
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