Article

Perinatal and childhood origins of cardiovascular disease

School of Medicine and Pharmacology, The University of Western Australia (UWA) (M570), Royal Perth Hospital, Perth, Western Australia, Australia.
International Journal of Obesity (Impact Factor: 5.39). 02/2007; 31(2):236-44. DOI: 10.1038/sj.ijo.0803394
Source: PubMed

ABSTRACT Features of the metabolic syndrome comprise a major risk for cardiovascular disease and will increase in prevalence with rising childhood obesity. We sought to identify early life influences on development of obesity, hypertension and dyslipidemia in children.
Cluster analysis was used on a subset of a longitudinal Australian birth cohort who had blood samples at age 8 (n=406). A quarter of these 8-year-olds fell into a cluster with higher body mass index, blood pressure (BP), more adverse lipid profile and a trend to higher serum glucose resembling adult metabolic syndrome. There was a U-shaped relationship between percentage of expected birth weight (PEBW) and likelihood of being in the high-risk cluster. The high-risk cluster had elevated BP and weight as early as 1 and 3 years old. Increased likelihood of the high-risk cluster group occurred with greatest weight gain from 1 to 8 years old (odds ratio (OR)=1.4, 95% confidence interval (CI)=1.3-1.5/kg) and if mothers smoked during pregnancy (OR=1.82, CI=1.05-3.2). Risk was lower if children were breast fed for >/=4 months (OR=0.6, 95% CI=0.37-0.97). Newborns in the upper two quintiles for PEBW born to mothers who smoked throughout pregnancy were at greatest risk (OR=14.0, 95% CI=3.8-51.1) compared to the nadir PEBW quintile of non-smokers.
A U-shaped relationship between birth weight and several components of the metabolic syndrome was confirmed in a contemporary, well-nourished Western population of full-term newborns, but post-natal weight gain was the dominant factor associated with the high-risk cluster. There was a prominence of higher as well as lowest birth weights in those at risk. Future health programs should focus on both pre- and post-natal factors (reducing excess childhood weight gain and smoking during pregnancy), and possibly the greatest benefits may arise from targeting the heaviest, as well as lightest newborns, especially with a history of maternal smoking during pregnancy.

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    • "Although the daily dose of PAHs in highly exposed humans (about 0.002 mg/kg/day from tobacco smoke, food, and air pollution) is about three orders of magnitude lower than the 2 mg/kg/day dose of BaP in the present study (Lodovici et al., 2004; Shopland et al., 2001; ATSDR, 1995; Menzie et al., 1992), the cumulative dose to a highly exposed woman during all of pregnancy (about 0.55 mg/kg PAHs) is only 36-fold lower than our cumulative dose during gestation of 20 mg/kg in the 2 mg/kg/day dose group. Therefore, our observations that prenatal exposure to BaP increased visceral adipose tissue weight and body weight gain in female mice (Section 3.1) suggest that BaP and other PAHs found in tobacco smoke and PM air pollution may be responsible, at least in part, for the reported associations between prenatal tobacco smoke exposure and increased BMI and obesity (Huang et al., 2007; Oken et al., 2005; Power and Jefferis, 2002) and between childhood PM exposure and increased BMI (Jerrett et al., 2010). In contrast to our findings with prenatal exposure in mice, neonatal treatment of rat pups with 2 mg/kg/day BaP by oral gavage on PND 5–11 was reported to decrease adult body weight (Chen et al., 2012), but the diet fed the rats was not specified and effects on adipose tissue and liver were not examined in that study. "
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    • "Although the daily dose of PAHs in highly exposed humans (about 0.002 mg/kg/day from tobacco smoke, food, and air pollution) is about three orders of magnitude lower than the 2 mg/kg/day dose of BaP in the present study (Lodovici et al., 2004; Shopland et al., 2001; ATSDR, 1995; Menzie et al., 1992), the cumulative dose to a highly exposed woman during all of pregnancy (about 0.55 mg/kg PAHs) is only 36-fold lower than our cumulative dose during gestation of 20 mg/kg in the 2 mg/kg/day dose group. Therefore, our observations that prenatal exposure to BaP increased visceral adipose tissue weight and body weight gain in female mice (Section 3.1) suggest that BaP and other PAHs found in tobacco smoke and PM air pollution may be responsible, at least in part, for the reported associations between prenatal tobacco smoke exposure and increased BMI and obesity (Huang et al., 2007; Oken et al., 2005; Power and Jefferis, 2002) and between childhood PM exposure and increased BMI (Jerrett et al., 2010). In contrast to our findings with prenatal exposure in mice, neonatal treatment of rat pups with 2 mg/kg/day BaP by oral gavage on PND 5–11 was reported to decrease adult body weight (Chen et al., 2012), but the diet fed the rats was not specified and effects on adipose tissue and liver were not examined in that study. "
    [Show abstract] [Hide abstract]
    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 wks 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.
    Toxicology Letters 10/2013; 223(2). DOI:10.1016/j.toxlet.2013.09.017 · 3.36 Impact Factor
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