Current studies have shown that insulin resistance, T2D have been associated with long- term exposure to air and traffic pollution. Benzene is a highly volatile liquid, which is a constituent of crude petroleum. Given its ubiquitous utilization in industry as well as consumer products, it is classified as a common airborne pollutant. We hypothesized that benzene, at levels below carcinogenic contributes to insulin resistance and inflammatory responses linking persistent organic pollutants exposure to T2D mellitus. For this purpose, C57BL/6 mice in inhalation chambers were exposed to benzene concentration of 50 ppm for 6h/day for 4 weeks. We found that under these conditions, exposure to benzene did not significantly influence mice body weight, neither had it trigger any toxic responses in these animals. Despite normal fasting glucose and insulin levels, benzene-exposed male mice displayed significantly impaired glucose tolerance. Consequently, we detected an increase in hepatic genes associated with gluconeogenesis, G6Pase and Pck1, and the expression of SREBP-1c and SREBP-2, genes associated with lipid synthesis was significantly elevated in livers from benzene exposed male mice as compared to control mice. Female mice were completely resistant to the negative metabolic consequences of chronic benzene exposure. Further sex differences were apparent in neuroinflammatory responses, with greater male vulnerability observed in the hypothalamus of benzene- exposed animals. Benzene exposure promoted hypothalamic gliosis and robust neuronal activation in the arcuate, paraventricular, ventromedial and dorsomedial hypothalamic nucleus. These findings demonstrate male vulnerability to air pollution, and provide evidence that exposure to benzene induces metabolic imbalance and severe neuroinflammatory responses in a sex-specific manner. Persistent ambient benzene exposure may be a heretofore unrecognized contributor to metabolic diseases with male bias.
L.K. Debarba: None. A. Mulka: None. A.A. Awada: None. O. Didyuk: None. U. Klueh: Research Support; Self; The Leona M. and Harry B. Helmsley Charitable Trust. Other Relationship; Self; Cell and Molecular Tissue Engineering, LLC. M. Sadagurski: None.
The Leona M. and Harry B. Helmsley Charitable Trust