Article

Fetal and neonatal exposure to nicotine in Wistar rats results in increased beta cell apoptosis at birth and postnatal endocrine and metabolic changes associated with type 2 diabetes

Department of Obstetrics and Gynaecology, McMaster University, Hamilton, Ontario, Canada
Diabetologia (Impact Factor: 6.67). 01/2006; 48(12):2661-6. DOI: 10.1007/s00125-005-0022-5
Source: PubMed

ABSTRACT

Epidemiological studies report an increased risk of obesity and type 2 diabetes in children born to women who smoked during pregnancy. This study examines the effect of fetal and neonatal exposure to nicotine, the major addictive component of cigarettes, on postnatal growth, adiposity and glucose homeostasis.
Female Wistar rats were given either saline (vehicle) or nicotine (1 mg kg(-1) day(-1)) during pregnancy and lactation. Serum and pancreas tissue were collected from the infant rats at birth. Postnatal growth was assessed weekly until the rats reached 26 weeks of age and glucose homeostasis was examined by OGTTs performed at 7 and 26 weeks of age.
Exposure to nicotine resulted in increased postnatal growth and adiposity. Nicotine exposure also resulted in dysglycaemia at 7 and 26 weeks of age. Serum insulin concentrations were decreased in the pups exposed to nicotine at birth. This was associated with increased beta cell apoptosis (pups of saline-treated mothers 8.8+/-1.21% apoptotic beta cells; pups of nicotine-treated mothers 27.8+/-3.1% apoptotic beta cells).
Fetal and neonatal exposure to nicotine results in metabolic changes in the offspring that are consistent with obesity and type 2 diabetes. We propose that these metabolic changes may be a consequence of the initial insult to the beta cell during fetal life and that this animal model has many characteristics of diabetes in humans.

Download full-text

Full-text

Available from: Katherine M Morrison
  • Source
    • "Some studies associate metabolic illness, such as obesity and their comorbidities, with an increase in oxidative stress (Bullon et al. 2000; Tariq et al. 2014). However, there are few reports showing the close association between neonatal oxidative stress and the development of diseases at adulthood (Holloway et al. 2005; Bruin et al. 2008; Niu et al. 2013). Habbout and colleagues (2012 and 2013a) showed that increased plasma and cardiac oxidative stress were associated with higher susceptibility to cardiac injury at adulthood . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neonatal overfeeding induced by litter size reduction leads to further obesity and other metabolic disorders, such as liver oxidative stress and microesteatosis at adulthood. We hypothesized that overfeeding cause an early redox unbalance at weaning, which could program the animals to future liver dysfunction. Thus, we studied lipogenesis, adipogenesis, catecholamine status and oxidative balance in weaned overfed pups. To induce early overfeeding, litters were adjusted to 3 pups at the 3(rd) day of lactation (SL group). The control group remained with 10 pups per litter until weaning (NL group). The peripheral autonomic nerve function was determined in vivo at 21 days-old. Thereafter, pups were killed for further analysis. Significant differences had P < 0.05. The SL pups presented higher visceral adipocyte area, higher content of lipogenic enzymes (ACC, FAS) with lower content of adipogenic factors (CEBP, PPARγ) in visceral adipose tissue (VAT). Although the autonomic nerve activity and adrenal catecholamines production were not significantly altered, catecholamine receptor (β3ADR) was lower in VAT. They presented higher triglyceride, PPARγ, PPARα and PGC1α contents in liver. In plasma and liver, the SL pups showed an oxidative unbalance, with higher lipid peroxidation and protein oxidation. The SL group presented higher serum ALT. The early increased lipogenesis at adipose tissue and liver in weaned overfed rats, suggest that the higher oxidative stress and lower catecholamine effect in VAT is associated with the early development of liver dysfunctions and adipocyte hypertrophy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Sep 2015 · The Journal of Physiology
  • Source
    • "In the present study, we observed an increase of body mass and visceral fat mass in adult S animals. Our data corroborate the literature, which demonstrated the association between neonatal exposure to cigarette smoke or nicotine with obesity development in adulthood (von Kries et al., 2002; Wideroe et al., 2003; Holloway et al., 2005; Goldani et al., 2007; Somm et al., 2008, 2009; Oliveira et al., 2009; Koshy et al., 2010; Durmus et al., 2011; Santos-Silva et al., 2013). Santos-Silva et al. (2013) showed glucose intolerance , characterized by higher fasting glucose with normoinsulinemia in animals programed by cigarette smoke with a higher dose of nicotine than in the present study. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Children from pregnant smokers are more susceptible to become obese adults and to become drug or food addicts. Drugs and food activate the mesolimbic reward pathway, causing a sense of pleasure that induces further consumption. Here, we studied the relationship between tobacco smoke exposure during lactation with feeding, behavior and brain dopaminergic reward system parameters at adulthood. Nursing Wistar rats and their pups were divided into two groups: tobacco smoke-exposed (S: 4 times/day, from the 3(rd) to the 21(th) day of lactation), and ambient air-exposed (C). On PN175, both offspring groups were subdivided for a food challenge: S and C that received standard chow (SC) or that chose between high-fat (HFD) and high-sucrose diets (HSD). Food intake was recorded after 30 min and 12 h. Offspring were tested in the elevated plus maze and open field on PN178-179; they were euthanized for dopaminergic analysis on PN180. SSD (self-selected diet) animals presented a higher food intake compared to SC ones. S-SSD animals ate more than C-SSD ones at 30 min and 12 h. Both groups preferred the HFD. However, S-SSD animals consumed relatively more HFD than C-SSD at 30 min. No behavioral differences were observed between groups. S animals presented lower tyrosine hydroxylase (TH) content in the ventral tegmental area, lower TH, dopaminergic receptor 2, higher dopaminergic receptor 1 contents in the nucleus accumbens and lower OBRb in hypothalamic arcuate nucleus. Tobacco-smoke exposure during lactation increases preference for fat in the adult progeny possibly due to alterations in the dopaminergic system. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jun 2015 · Neuroscience
  • Source
    • "As in these animal studies, the impact of maternal smoking on BMI in the children appeared to increase with age. Changes in the hypothalamic regulation of energy homeostatic resulting in changes in appetite control and energy expenditure might be instrumental (Bruin et al. 2010; Grove et al. 2001; Holloway et al. 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Offspring of smoking mothers during pregnancy have a lower birth weight but have a higher chance to become overweight during childhood. We followed children longitudinally to assess the age when higher BMI z-scores became evident in the children of mothers who smoked during pregnancy, and evaluate the trajectory of changes until adolescence. We pooled data from two German cohort studies that included repeated anthropometric measurements until 14 years and information on smoking during pregnancy and other risk factors for overweight. We used longitudinal quantile regression to estimate age- and sex-specific associations between maternal smoking and the 10(th), 25(th), 50(th), 75(th), and 90(th) quantiles of the BMI z-score distribution in study participants from birth through 14 years of age, adjusted for potential confounders. We used additive mixed models to estimate associations with mean BMI z-scores. Mean and median (50(th) quantile) BMI z-scores at birth were smaller in the children of mothers who smoked during pregnancy compared with children of nonsmoking mothers, but BMI z-scores were significantly associated with maternal smoking beginning at the age of 4-5 years, and differences increased over time. For example, the difference in the median BMI z-score between the daughters of smokers versus nonsmokers was 0.12 (95% CI: 0.01, 0.21) at 5 years, and 0.30 (95% CI: 0.08, 0.39) at 14 years of age. For lower BMI z-score quantiles the association with smoking was more pronounced in girls, whereas in boys the association was more pronounced for higher BMI z-score quantiles. A clear difference in BMI z-score (mean and median) between offspring of smoking and nonsmoking mothers emerged at the age of 4 to 5 years. The shape and size of age-specific effect estimates for maternal smoking during pregnancy varied by age and gender across the BMI z-score distribution.
    Full-text · Article · Apr 2014 · Environmental Health Perspectives
Show more