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Reprint of "In utero exposure to benzo[a]pyrene increases adiposity and causes hepatic steatosis in female mice, and glutathione deficiency is protective".

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 10 mg/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.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Ortiz L,Nakamura B,Li X,Blumberg B,Luderer U

doi

10.1016/j.toxlet.2013.11.017

subject

Has Abstract

pub_date

2014-10-15 00:00:00

pages

314-21

issue

2

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(13)01423-9

journal_volume

230

pub_type

杂志文章

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