Tian Yuchai, Wu Xiaoyun, Gong Zhihua, Liang Xiaomin, Zhu Huizhen, Zhang Jiyue, Hu Yangcheng, Li Bin, Xu Pengchong, Guo Kaiyue, Yue Huifeng
Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China.
Department of Clinical Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan 030032, China.
Toxics. 2025 Jul 31;13(8):652. doi: 10.3390/toxics13080652.
(1) Background: Epidemiological studies link ozone (O) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related to impaired glucose tolerance and insulin resistance were screened through the Comparative Toxicogenomics Database (CTD), and verified using quantitative real-time PCR. In addition, liver histopathological observations and the determination of basic biochemical indicators were conducted, and targeted metabolomics analysis was performed on the liver to verify glycogen levels and gene expression. In vitro validation was conducted with HepG2 and Min6 cell lines. (3) Results: Fasting blood glucose and insulin resistance were elevated following O exposure. Given that the liver plays a critical role in glucose metabolism, we further investigated hepatocyte apoptosis and alterations in glycogen metabolism, including reduced glycogen levels and genetic dysregulation. Metabolomics analysis revealed abnormalities in fructose metabolism and glycogen synthesis in the livers of the O-exposed group. In vitro studies demonstrated that oxidative stress enhances both liver cell apoptosis and insulin resistance in pancreatic islet β cells. (4) Conclusions: O triggers prediabetes symptoms via hepatic metabolic dysfunction and hepatocyte apoptosis. The identified metabolites and genes offer potential as early biomarkers and therapeutic targets.
(1) 背景：流行病学研究将臭氧（O₃）暴露与糖尿病风险联系起来，但机制和早期生物标志物仍不清楚。(2) 方法：对暴露于0.5/1.0 ppm O₃的雌性小鼠进行葡萄糖耐量和HOMA（稳态模型评估）指数评估。通过比较毒理基因组学数据库（CTD）筛选与葡萄糖耐量受损和胰岛素抵抗相关的基因，并使用定量实时PCR进行验证。此外，进行肝脏组织病理学观察和基本生化指标测定，并对肝脏进行靶向代谢组学分析以验证糖原水平和基因表达。使用HepG2和Min6细胞系进行体外验证。(3) 结果：暴露于O₃后空腹血糖和胰岛素抵抗升高。鉴于肝脏在葡萄糖代谢中起关键作用，我们进一步研究了肝细胞凋亡和糖原代谢改变，包括糖原水平降低和基因失调。代谢组学分析显示，O₃暴露组肝脏中果糖代谢和糖原合成存在异常。体外研究表明，氧化应激增强了肝细胞凋亡和胰岛β细胞中的胰岛素抵抗。(4) 结论：O₃通过肝脏代谢功能障碍和肝细胞凋亡引发糖尿病前期症状。所鉴定的代谢物和基因具有作为早期生物标志物和治疗靶点的潜力。
