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Effects of PM2.5 and high-fat diet on glucose and lipid metabolisms and role of MT-COX3 methylation in male rats
[Display omitted] •PM2.5 and HFD co-exposure led to MT-COX3 hypermethylation in Wistar rats.•The methylation levels of MT-COX3-Pos.1 and MT-COX3-Pos.2 were negatively correlated with HOMA-β index.•MT-COX3-Pos.2 methylation mediated the combined effects of PM2.5 and HFD on HOMA-β index.•MT-COX3-Pos.2...
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Published in: | Environment international 2024-06, Vol.188, p.108780, Article 108780 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | [Display omitted]
•PM2.5 and HFD co-exposure led to MT-COX3 hypermethylation in Wistar rats.•The methylation levels of MT-COX3-Pos.1 and MT-COX3-Pos.2 were negatively correlated with HOMA-β index.•MT-COX3-Pos.2 methylation mediated the combined effects of PM2.5 and HFD on HOMA-β index.•MT-COX3-Pos.2 was found for the first time as a potential biomarker for abnormal glucose metabolism.
Both fine particulate matter (PM2.5) and high-fat diet (HFD) can cause changes in glucose and lipid metabolisms; however, the mechanism of their combined effects on glucose and lipid metabolisms is still unclear. This study aimed to investigate the effects of PM2.5 and HFD co-exposure on glucose and lipid metabolisms and mitochondrial DNA methylation in Wistar rats. PM2.5 and HFD co-treatment led to an increase in fasting blood glucose levels, an alteration in glucose tolerance, and a decrease in high density lipoprotein cholesterol (HDL-C) levels in Wistar rats. In the homeostasis model assessment (HOMA), HOMA-insulin resistance (HOMA-IR) increased and HOMA-insulin sensitivity (HOMA-IS) and HOMA-β cell function (HOMA-β) decreased in rats co-exposed to PM2.5 and HFD. Additionally, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were increased, and interleukin-6 (IL-6) and interleukin-10 (IL-10) mRNA expressions were upregulated in the brown adipose tissue following PM2.5 and HFD co-exposure. Bisulfite pyrosequencing was used to detect the methylation levels of mitochondrially-encoded genes (MT-COX1, MT-COX2 and MT-COX3), and MT-COX3 was hypermethylated in the PM2.5 and HFD co-exposure group. Moreover, MT-COX3-Pos.2 mediated 36.41 % (95 % CI: −27.42, −0.75) of the total effect of PM2.5 and HFD exposure on HOMA-β. Our study suggests that PM2.5 and HFD co-exposure led to changes in glucose and lipid metabolisms in rats, which may be related to oxidative stress and inflammatory responses, followed by mitochondrial stress leading to MT-COX3 hypermethylation. Moreover, MT-COX3-Pos.2 was found for the first time as a mediator in the impact of co-exposure to PM2.5 and HFD on β-cell function. It could serve as a potential biomarker, offering fresh insights into the prevention and treatment of metabolic diseases. |
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ISSN: | 0160-4120 1873-6750 1873-6750 |
DOI: | 10.1016/j.envint.2024.108780 |