Abstract
Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), are ubiquitous environmental pollutants found in tobacco smoke, air pollution, and grilled foods. Reactive metabolites and reactive oxygen species generated during PAH metabolism are detoxified by reactions involving glutathione (GSH). Early life exposures to tobacco smoke and air pollution have been linked to increased risk of obesity and metabolic syndrome. We investigated the independent and interactive effects of prenatal exposure to BaP and GSH deficiency due to deletion of the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, on adiposity and hepatic steatosis in adult female F1 offspring. We mated Gclm+/− dams with Gclm+/− males and treated the pregnant dams with 0, 2, or 10mg/kg/day BaP in sesame oil by oral gavage daily from gestational day 7 through 16. We analyzed metabolic endpoints in female Gclm−/− and Gclm+/+ littermate F1 offspring. Prenatal BaP exposure significantly increased visceral adipose tissue weight, weight gain between 3 weeks and 7.5 months of age, hepatic lipid content measured by oil red O staining, and hepatic fatty acid beta-oxidation gene expression in Gclm+/+, but not in Gclm−/−, female offspring. Hepatic expression of lipid biosynthesis and antioxidant genes were decreased and increased, respectively, in Gclm−/− mice. Our results suggest that reported effects of pre- and peri-natal air pollution and tobacco smoke exposure on obesity may be mediated in part by PAHs. GSH deficiency is protective against the metabolic effects of prenatal BaP exposure.
Highlights
IntroductionMaternal smoking during pregnancy is associated with increased risk of obesity, diabetes, and hypertension in offspring (Ino, 2010; Morley et al, 1995; Oken et al, 2005; Power and Jefferis, 2002)
In recent years, it has become increasingly clear that various aspects of the intrauterine environment, such as exposure to environmental pollutants, influence the developmental origins of obesity and other risk factors for cardiovascular disease (Janesick and Blumberg, 2011a, b; La Merrill and Birnbaum, 2011).Maternal smoking during pregnancy is associated with increased risk of obesity, diabetes, and hypertension in offspring (Ino, 2010; Morley et al, 1995; Oken et al, 2005; Power and Jefferis, 2002)
The mean adipose tissue weights in the control, oil-treated Gclm+/+ female mice were increased compared to their null littermates, but Gclm-/- females exposed to BaP in utero did not have increased adipose tissue weights compared to oil-treated Gclm-/- females (Figure 1)
Summary
Maternal smoking during pregnancy is associated with increased risk of obesity, diabetes, and hypertension in offspring (Ino, 2010; Morley et al, 1995; Oken et al, 2005; Power and Jefferis, 2002). Maternal exposure to second-hand tobacco smoke during pregnancy has been associated with increased BMI in offspring at 2 and 3 years of age (Braun et al, 2011). The total carcinogenic PAH content of one cigarette has been estimated at 25-250 ng (Lodovici et al, 2004; Shopland et al, 2001). Sidestream or second-hand tobacco smoke contains 10-fold higher concentrations of PAHs than mainstream smoke, or about 2.3-3.9 μg total PAHs and 0.5-1.2 μg carcinogenic PAHs per cigarette (Lodovici et al, 2004)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
