Maternal tobacco smoke increased visceral adiposity and serum corticosterone levels in adult male rat offspring

Abstract

Background: Maternal tobacco smoke (MTS) predisposes human and rat offspring to visceral obesity in early adulthood. Glucocorticoid excess also causes visceral obesity. We hypothesized that in utero MTS would increase visceral adiposity and alter the glucocorticoid pathway in young adult rats. Methods:We developed a novel model of in utero MTS exposure in pregnant rats by exposing them to cigarette smoke from E11.5 to term. Neonatal rats were cross-fostered to control dams and weaned to standard rat chow through young adulthood (postnatal day 60). results: We demonstrated increased visceral adiposity (193%)*, increased visceral adipose 11-β hydroxysteroid dehydrogenase 1 mRNA (204%)*, increased serum corticosterone (147%)*, and no change in glucocorticoid receptor protein in adult male MTS rat offspring. Female rats exposed to MTS in utero demonstrated no change in visceral or subcutaneous adiposity, decreased serum corticosterone (60%)*, and decreased adipose glucocorticoid receptor protein (66%)*. *P < 0.05. conclusion: We conclude that in utero MTS exposure increased visceral adiposity and altered in the glucocorticoid pathway in a sex-specific manner. We speculate that in utero MTS exposure programs adipose dysfunction in adult male rat offspring via alteration in the glucocorticoid pathway.M aternal tobacco smoke (MTS) impacts more than 13% of pregnancies despite aggressive antismoking campaigns (1). In adult human studies, MTS exposure in utero predisposes to the development of metabolic syndrome, including increased visceral adiposity (2). The increased adiposity seen after gestating in an adverse intrauterine environment, such as maternal tobacco or nicotine exposure, is often adipose depot specific, with the visceral adipose tissue (VAT) increasing in excess to the subcutaneous adipose tissue (SAT) (3,4).VAT seems to have a detrimental role in the development of metabolic syndrome (5,6). Even when considering dietary and lifestyle choices, MTS exposure in utero independently increases the risk of developing visceral obesity (7,8). Children whose mothers smoked during pregnancy had decreased birth weights yet an increased obesity and BMI index as early as 9-10 y of age, independent of dietary intake and activity levels (8). Furthermore, the effect of MTS on body weight was stronger when mothers smoked during pregnancy compared with that of isolated smoke exposure in childhood (7). Taken together, these findings suggest that MTS exposure during this developmentally sensitive time period both causes intrauterine growth restriction (IUGR) and adversely programs obesity later in life.Little insight exists on how MTS programs increased visceral adiposity. Rodent studies examining the effect of in utero MTS exposure on the offspring have not examined the etiology of increased visceral adiposity. Rodent studies of tobacco smoke exposure only during lactation demonstrate increased adiposity (9). Furthermore, rodent studies of maternal nicotine, one of the many compounds found in tobacco smoke, demonstrate increa...

Neuroinflammatory and Behavioral Outcomes Measured in Adult Offspring of Mice Exposed Prenatally to E-Cigarette Aerosols

“…Subcutaneous nicotine given to pregnant rat dams beginning 14 d prior to breeding and continuing until offspring weaning (PND21) resulted in increased body weight in male offspring (females not examined) beginning at 10 weeks of age (Gao et al 2005). In our study, maternal e-cigarette exposure did not affect offspring weight at weaning (PND21), which is in contrast with the findings of Zinkhan et al (2014); however, by 12 weeks of age female offspring of +Nic dams weighed significantly more than females of FA control dams, similar to the male offspring as reported by Gao et al (2005) following perinatal maternal nicotine exposure. These discrepancies highlight the importance of also examining nonnicotine constituents when investigating the neurodevelopmental effects of gestational nicotine delivery systems and the importance of including female offspring in all analyses.…”

“…These consequences include reproductive, endocrine, metabolic, immune, and neurobiological changes, as well as an increased risk of the offspring developing obesity (Ino 2010) or having an attention deficit hyperactivity disorder diagnosis (Tiesler and Heinrich 2014) later in life. In rats, maternal exposure to tobacco cigarette smoke 5 d/week between GD11.5 and GD21.5 transiently decreased offspring body weight at PND21, a difference no longer evident at 60 d of age (Zinkhan et al 2014). Subcutaneous nicotine given to pregnant rat dams beginning 14 d prior to breeding and continuing until offspring weaning (PND21) resulted in increased body weight in male offspring (females not examined) beginning at 10 weeks of age (Gao et al 2005).…”

Placental DNA methylation of peroxisome-proliferator-activated receptor-γ co-activator-1α promoter is associated with maternal gestational glucose level

“…For instance, maternal gestational glycaemia concentrations correlate with placental DNA methylation adaptations of LEP (leptin) [16,17], ADIPOQ (adiponectin, C1Q and collagen domain-containing) [18] and ABCA1 (ATPbinding cassette transporter A1) [19] genes. Although the tenet of fetal metabolic programming has been extensively explored in animal models [20,21], only a small number of studies on epigenetic modification have been conducted in humans, especially in those with GDM.…”

The Role of Endocrine Disruptors on Metabolic Dysfunction

“…Furthermore, the extensive harms of perinatal tobacco smoke exposure, namely as regards nicotine [108,109], and its relationship with childhood overweight/obesity provides a proof-of-concept of how early-life exposure to EDCs can be a risk factor for obesity and MetS [109]. The mechanisms by which this perinatal exposure programs the AT and endocrine function are under investigation, but it is known that maternal tobacco smoke predisposes human and rat offspring to visceral obesity in early adulthood, possibly by programming AT dysfunction via alterations in the glucocorticoid pathway and development of leptin and insulin resistance [108,110]. The increasing identification of genes with smoking related methylation changes in newborns and adults reinforces epigenetic modifications such as DNA methylation as one of the main mechanism by which smoking (and other EDCs) might have long lasting effects [111].…”