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


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.

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    • "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. "
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    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.
    Neuroscience 06/2015; 301. DOI:10.1016/j.neuroscience.2015.06.001 · 3.36 Impact Factor
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    • "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). "
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    Environmental Health Perspectives 04/2014; 122(7). DOI:10.1289/ehp.1307139 · 7.98 Impact Factor
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    • "Furthermore, SE offspring showed a higher total and VFM that could not be explained only by the small increment of cumulative food intake. The development of late-onset obesity is frequently associated with maternal smoking during gestation in humans (von Kries et al. 2002, Wideroe et al. 2003, Goldani et al. 2007, Koshy et al. 2010, Durmus et al. 2011) and with maternal nicotine exposure during gestation/lactation in experimental studies (Holloway et al. 2005, Somm et al. 2008, 2009, Oliveira et al. 2009). Here, the same outcome was found in rats exposed to tobacco smoke exclusively in postnatal life both by transfer through the milk and direct inhalation (sidestream smoking). "
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    Journal of Endocrinology 04/2013; 218(1). DOI:10.1530/JOE-13-0003 · 3.72 Impact Factor
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