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J. Hazard. Mater., 2023 Mar 15;446:130659 | https://doi.org/10.1016/j.jhazmat.2022.130659 Synergetic effects of concurrent chronic exposure to a mixture of OCPs and high-fat diets on type 2 diabetes and beneficial effects of caloric restriction in female zebrafish

Hyojin Lee ^a, Yan Gao ^b,c, Jae Kwan Kim ^d, Sooim Shin ^e, Moonsung Choi ^f, Youngja Hwang ^g, Sangkyu Lee ^b,h, Dong Young Rhyu ⁱ, Ki-Tae Kim ^a

^aDepartment of Environmental Engineering, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea
^bBK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
^cDepartment of Core Analytical Service, Wuxi AppTec, Shanghai 200131, China
^dKorea Basic Science Institute, Seoul 02841, Republic of Korea
^eDepartment of Biotechnology and Bioengineering, Chonnam National University, Gwangju 61186, Republic of Korea
^fDepartment of Optometry, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea
^gMetabolomics Laboratory, College of Pharmacy, Korea University, Sejong City 30019, Republic of Korea
^hMass Spectrometry Based Convergence Research Institute, Kyungpook National University, Daegu 41566, Republic of Korea
ⁱDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 FOUR, Mokpo National University, Jeonnam 58554, Republic of Korea

Correspondence to: Ki-Tae Kim

Abstract

This study aimed to investigate the relationship among chronic exposure to a low concentration of organochlorine pesticides (OCPs), high-fat diet (HFD)-induced obesity, and caloric restriction in type 2 diabetes (T2D). Thus, female zebrafish were divided into four groups and treated for 12 weeks as follows: (i) negative control, (ii) HFD (obesity) control, (iii) obesity + a mixture of OCPs (OP), and (iv) obesity + a mixture of OCPs + caloric restriction (OPR). We then assessed T2D-related effects via hematological analysis, histopathology, mitochondrial evaluation, and multiomics analyses. The OP group showed a significant increase in glucose levels, whereas the OPR group maintained glucose at nonsignificant levels. Multiomics analyses revealed that the exacerbated metabolic effects in the OP group were associated with molecular alterations in oxidative stress, inflammation, nucleotide metabolism, and glucose/lipid homeostasis. These alterations were histologically verified by the increased numbers of hypertrophic adipocytes and inflammatory cells observed. Caloric restriction activated pathways related to antioxidant response, mitochondrial fatty acid oxidation, and energy metabolism in zebrafish, leading to preserved glucose homeostasis. In conclusion, this study identified molecular mechanisms underlying the synergistic effect of concurrent exposure to a mixture of OCPs and HFD as well as shed light on the beneficial effect of regular caloric restriction in T2D development.

논문정보

형식Research article
게재일2023년 03월 (BRIC 등록일 2023-03-21)
연구진국내(교신)+국외 연구진
분야 생명과학 > 분류/생태/환경생물학

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