SAT-179 Low Grade Benzene Exposure Induces Metabolic Dysbalance and Hypothalamic Inflammation in Mice

Type 2-diabetes mellitus (T2D) has become a global pandemic resulting in a reduced quality of life due to comorbidity and premature mortality. The World Health Organization estimates the current global prevalence at 8.4%, which represents a fourfold increase over the last four decades. In this same interval, the US prevalence has increased by 160%, such that it affects 1 in 11 Americans with a disproportionate impact on minorities. The choice of lifestyle, diet, lack of physical activity and the growing aging population is often used to explain the rise of the diabetes pandemic. However, it is now increasingly accepted that insulin resistance, T2D prevalence and mortality 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. As such, any exposure to petroleum or its products can result in significant occupational benzene exposure. While it is well accepted that excessive benzene exposure is carcinogenic in animals and humans, little is known regarding the effect of non-carcinogenic benzene level exposure and its metabolic effects. Notably, benzene exposure from motor vehicle exhaust is higher in inner city populations, which suggests a causative role in the pathogenesis of T2D. We hypothesized that benzene, at levels below carcinogenic contributes to insulin resistance and inflammatory responses linking persistent organic pollutants (POP) exposure to type 2 diabetes 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 change male mice body weight, neither had it trigger any toxic responses in these animals. However, despite normal fasting glucose and insulin levels, glucose tolerance test (GTT) of benzene exposed male mice displayed significantly impaired IP 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 mice as compared to control mice. Additionally, we detected significant neuroinflammatory response in the hypothalamus of benzene exposed mice. Benzene exposure promoted a significant increase on microglia and astrocytes numbers in the arcuate, ventromedial and dorsomedial hypothalamic nucleus. We conclude that exposure to benzene induces hyperglycemia and that hypothalamic inflammatory responses may be a sensitive indicator of inhaled benzene toxicity.