Benzene is a well-known human carcinogen that is one of the major components of air pollution. Sources of benzene in ambient air include cigarette smoke, e-cigarettes, vaping, and evaporation of benzene-containing petrol processes. Epidemiological studies demonstrated the association with type 2 diabetes (T2D) and the development of insulin resistance (IR). Because maternal environmental stressors can greatly affect offspring health, we hypothesized that exposure to low concentrations of benzene during critical windows of development may contribute to the escalating prevalence of metabolic imbalance and diabetes in offspring. Specifically, we tested the hypothesis that prenatal exposure to benzene at concentrations relevant to cigarette smoking or vaping, would prime hypothalamic gliosis, resulting in exacerbated metabolic outcomes following exposure to a high-fat diet in adulthood. Pregnant C57BL/6JB dams were exposed to benzene at 50ppm or filtered air throughout gestation, and offspring metabolic phenotype was evaluated before and after high-fat-diet (HFD) feeding for 6 months. The male offspring of benzene-exposed dams exhibited exaggerated hyperglycemia on a chow diet compared to the male offspring of control dams, whereas female offspring did not differ according to prenatal treatment. No changes in body weight, body composition, or early postnatal hypothalamic glial activation were observed between groups. Regardless, adult male offspring of benzene-exposed dams exhibited severe impairment in the parameters of energy homeostasis (Vo2, VCO2, and heat production), suggesting the effect of metabolic reprogramming in whole-body metabolic regulation in adult offspring.

In summary, prenatal benzene exposure at low dose programs offspring for increased susceptibility to diet induced metabolic changes in adulthood in a sexually dimorphic manner.

Disclosure

L. Koshko: None. L.K. Debarba: None. O. Didyuk: None. P.I. Fakhoury: None. M. Sadagurski: None. U. Klueh: Research Support; Self; Abbott. Other Relationship; Self; Cell and Molecular Tissue Engineering, LLC.

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