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

被引:4
|
作者
Lee, Hyojin [1 ]
Gao, Yan [2 ,3 ]
Kim, Jae Kwan [4 ]
Shine, Sooim [5 ]
Choi, Moonsung [6 ]
Hwang, Youngja [7 ]
Lee, Sangkyu [2 ,8 ]
Rhyu, Dong Young [9 ]
Kim, Ki-Tae [1 ]
机构
[1] Seoul Natl Univ Sci & Technol, Dept Environm Engn, Seoul 01811, South Korea
[2] Kyungpook Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, Plus KNU Multi Based Creat Drug Res Team BK21, Daegu 41566, South Korea
[3] Wuxi AppTec, Dept Core Analyt Serv, Shanghai 200131, Peoples R China
[4] Korea Basic Sci Inst, Seoul 02841, South Korea
[5] Chonnam Natl Univ, Dept Biotechnol & Bioengn, Gwangju 61186, South Korea
[6] Seoul Natl Univ Sci & Technol, Dept Optometry, Seoul 01811, South Korea
[7] Korea Univ, Coll Pharm, Metabol Lab, Sejong City 30019, South Korea
[8] Kyungpook Natl Univ, Mass Spectrometry Based Convergence Res Inst, Daegu 41566, South Korea
[9] Mokpo Natl Univ, Dept Biomed Hlth & Life Convergence Sci, BK21 FOUR, Jeonnam 58554, South Korea
关键词
Zebrafish; Organochlorine pesticide mixtures; Type; 2; diabetes; Obesity; Caloric restriction; PERSISTENT ORGANIC POLLUTANTS; OXIDATIVE STRESS; LIPID-METABOLISM; BIOMARKERS; DIVERGENT; COMPLEX; GLUCOSE; OBESITY;
D O I
10.1016/j.jhazmat.2022.130659
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
This study aimed to investigate the relationship among chronic exposure to a low concentration of organo-chlorine 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 re-striction 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.
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页数:11
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