System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ppublish 7 citations

PubMed: 40068415 DOI: 10.1016/j.scitotenv.2025.179060

Integrative multi-omics analysis of metabolic dysregulation induced by occupational benzene exposure in mice.

Sci Total Environ 971:179060

Authors: Sydney Scofield, Lisa Koshko, Lukas Stilgenbauer, Alix Booms, Roxanne Berube, Christopher Kassotis, Chung-Ho Lin, Hyejeong Jang, Seongho Kim, Paul Stemmer, Adelheid Lempradl, Marianna Sadagurski

Affiliations

  • Department of Biological Sciences, Integrative Biosciences Center (IBio), Wayne State University, Detroit, MI, USA.
  • Van Andel Research Institute, Grand Rapids, MI, USA.
  • Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA; Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI, USA.
  • School of Natural Resources, University of Missouri, Columbia, MO, USA.
  • Department of Oncology, School of Medicine, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
  • Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA.
  • Department of Biological Sciences, Integrative Biosciences Center (IBio), Wayne State University, Detroit, MI, USA; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA.

Abstract

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 benzene exposure below OSHA's Occupational Exposure Limit (OEL) on metabolic health. Adult male C57BL/6 mice were exposed to 0.9 ppm benzene 8 h 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). At this dose, exposure caused significant metabolic disruptions, including hyperglycemia, hyperinsulinemia, and insulin resistance. Transcriptomic analysis of liver, 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 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 the current OSHA OEL for benzene is insufficient and needs to be lowered, as they could result in adverse metabolic health in exposed workers, particularly men, following chronic exposure.

MeSH

Diabetes Mellitus, Muscles, Insulin, Multiple Chronic Conditions, Liver, Research, Environmental Health, Tissues, Environment, Benzene, Adipose Tissue, Diabetes Mellitus, Type 2