Scofield Sydney, Koshko Lisa, Stilgenbauer Lukas, Booms Alix, Berube Roxanne, Kassotis Christopher, Lin Chung-Ho, Jang Hyejeong, Kim Seongho, Stemmer Paul, Lempradl Adelheid, Sadagurski Marianna
bioRxiv. 2024 Dec 23:2024.12.22.629805. doi: 10.1101/2024.12.22.629805.
Type 2 Diabetes Mellitus (T2DM) is a significant public health burden. Emerging evidence links volatile organic compounds (VOCs), such as benzene to endocrine disruption and metabolic dysfunction. However, the effects of chronic environmentally relevant VOC exposures on metabolic health are still emerging.
Building on our previous findings that benzene exposure at smoking levels (50 ppm) induces metabolic impairments in male mice, we investigated the effects of occupationally relevant, below OSHA approved, benzene exposure on metabolic health.
Adult male C57BL/6 mice were exposed to 0.9ppm benzene 8 hours a day for 9 weeks. We assessed measures of metabolic homeostasis and conducted RNA and proteome sequencing on insulin-sensitive organs (liver, skeletal muscle, adipose tissue).
This low-dose exposure caused significant metabolic disruptions, including hyperglycemia, hyperinsulinemia, and insulin resistance. Transcriptomic analysis of liver, skeletal muscle, and adipose tissue identified key changes in metabolic and immune pathways especially in liver. Proteomic analysis of the liver revealed mitochondrial dysfunction as a shared feature, with disruptions in oxidative phosphorylation, mitophagy, and immune activation. Comparative analysis with high-dose (50 ppm) exposure showed both conserved and dose-specific transcriptomic changes in liver, particularly in metabolic and immune responses.
Our study is the first to comprehensively assess the impacts of occupational benzene exposure on metabolic health, highlighting mitochondrial dysfunction as a central mechanism and the dose-dependent molecular pathways in insulin-sensitive organs driving benzene-induced metabolic imbalance. Our data indicate that current OSHA occupational exposure limits for benzene are insufficient, as they could result in adverse metabolic health in exposed workers, particularly men, following chronic exposure.
2型糖尿病（T2DM）是一项重大的公共卫生负担。新出现的证据表明，挥发性有机化合物（VOCs），如苯，与内分泌紊乱和代谢功能障碍有关。然而，长期接触与环境相关的VOCs对代谢健康的影响仍在不断显现。
基于我们之前的研究发现，即吸烟水平（50 ppm）的苯暴露会导致雄性小鼠出现代谢损伤，我们研究了与职业相关的、低于职业安全与健康管理局（OSHA）批准水平的苯暴露对代谢健康的影响。
成年雄性C57BL/6小鼠每天暴露于0.9 ppm苯中，持续9周，每天8小时。我们评估了代谢稳态指标，并对胰岛素敏感器官（肝脏、骨骼肌、脂肪组织）进行了RNA和蛋白质组测序。
这种低剂量暴露导致了显著的代谢紊乱，包括高血糖、高胰岛素血症和胰岛素抵抗。对肝脏、骨骼肌和脂肪组织的转录组分析确定了代谢和免疫途径的关键变化，尤其是在肝脏中。肝脏的蛋白质组分析显示线粒体功能障碍是一个共同特征，氧化磷酸化、线粒体自噬和免疫激活均受到干扰。与高剂量（50 ppm）暴露的比较分析表明，肝脏中存在保守的和剂量特异性的转录组变化，特别是在代谢和免疫反应方面。
我们的研究首次全面评估了职业性苯暴露对代谢健康的影响，突出了线粒体功能障碍作为核心机制以及胰岛素敏感器官中驱动苯诱导的代谢失衡的剂量依赖性分子途径。我们的数据表明，目前OSHA对苯的职业暴露限值是不够的，因为长期暴露后，这些限值可能会导致接触工人，尤其是男性，出现不良的代谢健康状况。
