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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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