Ozone induced multigenerational glucose and lipid metabolism disorders in Drosophila

Ozone (O₃), a persistent pollutant, poses a significant health threat. However, research on its multigenerational toxicity remains limited. Leveraging the Drosophila model with its short lifespan and advanced genetic tools, we explored the effects of O₃ exposure across three generations of fruit flies. The findings revealed that O₃ disrupted motility, body weight, stress resistance, and oxidative stress in three generations of flies, with varying effects observed among them. Transcriptome analysis highlighted the disruption of glucose metabolism-related pathways, encompassing gluconeogenesis/glycolysis, galactose metabolism, and carbon metabolism. Hub genes were identified, and RT-qPCR results indicated that O₃ decreased their transcription levels. Comparative analysis of their human orthologs was conducted using Comparative Toxicogenomics Database (CTD) and DisGeNET databases. These genes are linked to various metabolic diseases, including diabetes, hypoglycemia, and obesity. The trehalose content was reduced in F0 generation flies but increased in F1-F2 generations after O₃ exposure. While the trehalase and glucose levels were decreased across F0-F2 generations. TAG synthesis-related genes were significantly upregulated in F0 generation flies but downregulated in F1-F2 generations. The expression patterns of lipolysis-related genes varied among the three generations of flies. Food intake was increased in F0 generation flies but decreased in F1-F2 generations. Moreover, TAG content was significantly elevated in F0 generation flies by O₃ exposure, while it was reduced in F2 generation flies. These differential effects of O₃ across three generations of flies suggest a metabolic reprogramming aimed at mitigating the damage caused by O₃ to flies. The study affirms the viability of employing the Drosophila model to investigate the mechanisms underlying O₃-induced glucose and lipid metabolism disorders while emphasizing the importance of studying the long-term health effects of O₃ exposure. Moreover, this research highlights the Drosophila model as a viable tool for investigating the multigenerational effects of pollutants, particularly atmospheric pollutants.