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Molecular mechanisms underlying zinc oxide nanoparticle induced insulin resistance in mice

ABSTRACT: Zinc oxide nanoparticles (ZnO NPs) represent an important class of commercially applied materials. Recently, adverse effects of ZnO NPs were found in humans and animals following ingestion, although the effects on endocrine system disease remain unclear. In this study, ZnO NPs were orally administered to mice, and at doses of 25 mg/kg bw (body weight) ZnO NPs and above, plasma glucose increased significantly. The genome-wide effects of ZnO NPs were then investigated using RNA-sequencing technology. In the cluster analysis, the most significantly enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways concerned membranes and their close association with endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation. Biochemical and gene and protein expression analyses revealed that ZnO NPs activated a xenobiotic biodegradation response and increased the expression of cytochrome P450 (CYP) enzymes in mice livers, leading to ER stress. The ER stress increased ROS generation. The high levels of ROS activated the MAPK and NF-B pathways and induced an inflammation response, resulting in the phosphorylation of insulin receptor substrate 1. Thus, the insulin resistance that developed was the primary mechanism for the increase in the plasma glucose of mice treated orally with ZnO NPs.

ORGANISM(S): Mus musculus

PROVIDER: GSE136174 | GEO | 2022/08/20

REPOSITORIES: GEO

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RNA sequencing analysis shows that titanium dioxide nanoparticles induce endoplasmic reticulum stress, which has a central role in mediating plasma glucose in mice

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2019-11-14 | GSE107084 | GEO

Continuous ZnO nanoparticle exposure induces melanoma-like skin lesions in epidermal barrier dysfunction model mice through anti-apoptotic effects mediated by the oxidative stress–activated NF-κB pathway

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Differential Gene Expression in Daphnia magna Suggests Distinct Modes of Action and Bioavailability for ZnO nanoparticles and Zn ions

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Differential Gene Expression in Daphnia magna Suggests Distinct Modes of Action and Bioavailability for ZnO nanoparticles and Zn ions

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2013-07-24 | E-GEOD-49136 | biostudies-arrayexpress

Toxicity and transcriptomic analysis in Hyalella azteca suggests increased exposure and susceptibility of epibenthic organisms to Zinc Oxide Nanoparticles

2013-07-24 | GSE49136 | GEO

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