Maternal nicotine (NIC) exposure during lactation leads to overweight, hyperleptinemia, and hypothyroidism in adult rat offspring. In this model, we analyzed adipocyte morphology, glucose homeostasis (serum insulin and adiponectin; liver and muscle glycogen), serum lipid, and the leptin signaling pathway. After birth, osmotic minipumps were implanted in lactating rats, which were divided into the groups NIC (6 mg/kg per day s.c. for 14 days) and control (C, saline). NIC and C offspring were killed at the age of 180 days. Adult NIC rats showed higher total body fat (C10%, P!0 . 05), visceral fat mass (C12%, P!0 . 05), and cross-sectional area of adipocytes (epididymal: C12% and inguinal: C43%, P!0 . 05). Serum lipid profile showed no alteration except for apolipoprotein AI, which was lower. We detected a lower adiponectin:fat mass ratio (K24%, P!0 . 05) and higher insulinemia (C56%, P!0 . 05), insulin resistance index (C43%, P!0 . 05), leptinemia (C113%, P!0 . 05), and leptin:adiponectin ratio (C98%, P!0 . 05) in the adult NIC group. These rats presented lower hypothalamic contents of the proteins of the leptin signaling pathway (leptin receptor (OB-R): K61%, janus tyrosine kinase 2: K41%, and p-signal transducer and activator of transcription 3: K56%, P!0 . 05), but higher suppressor of cytokine signaling 3 (C81%, P!0 . 05). Therefore, NIC exposure only during lactation programs rats for adipocyte hypertrophy in adult life, as well as for leptin and insulin resistance. Through the effects of NIC, perinatal maternal cigarette smoking may be responsible for the future development of some components of the metabolic syndrome in the offspring.

No abstract

BackgroundThere is strong evidence of an association between maternal smoking during pregnancy and restriction of intrauterine growth, but the effects of this exposure on postnatal linear growth are not well defined. Furthermore, few studies have investigated the role of tobacco smoke exposure also after pregnancy on linear growth until adolescence. In this study we investigated the effect of maternal smoking exposure during pregnancy and preschool age on linear growth from birth to adolescence.MethodsWe evaluated a cohort of children born between 1994 and 1999 in Cuiabá, Brazil, who attended primary health clinics for vaccination between the years 1999 and 2000 (at preschool age) and followed-up after approximately ten years. Individuals were located in public and private schools throughout the country using the national school census. Height/length was measured, and length at birth was collected at maternity departments. Stature in childhood and adolescence was assessed using the height-for-age index sex-specific expressed as z-score from curves published by the World Health Organization. Linear mixed effects models were used to estimate the association between exposure to maternal smoking, during pregnancy and preschool age, and height of children assessed at birth, preschool and school age, adjusted for age of the children.ResultsWe evaluated 2405 children in 1999–2000, length at birth was obtained from 2394 (99.5%), and 1716 at follow-up (71.4% of baseline), 50.7% of the adolescents were male. The z-score of height-for-age was lower among adolescents exposed to maternal smoking both during pregnancy and childhood (p < 0.01). Adjusting for age, sex, maternal height, maternal schooling, socioeconomic position at preschool age, and breastfeeding, children exposed to maternal smoking both during pregnancy and preschool age showed persistent lower height-for-age since birth to adolescence (coefficient: −0.32, p < 0.001) compared to non-exposed. Paternal smoking at preschool age was not associated with growth after adjustment for confounders.ConclusionExposure to maternal smoking not only during pregnancy, but also at early childhood, showed long-term negative effect on height of children until adolescence.

Exposure to tobacco smoke is related to changes in energy balance regulation and several endocrine dysfunctions. Previously, we showed that maternal nicotine (the main addictive compound of tobacco) exposure exclusively during lactation affects biochemical profiles in mothers, milk, and pups. As the possible consequences for mothers and offspring of maternal smoking during lactation are still unknown, we evaluated the effects of tobacco smoke exposure on nutritional, biochemical, and hormonal parameters in dams and pups at weaning. After 72 h from birth, lactating rats were divided into two groups: smoke-exposed (S) in a cigarette-smoking machine, 4!1 h per day throughout the lactation period without pups; control (C), rats were treated the same as the experimental group but exposed to filtered air. Dams and pups were killed at weaning (21 days of lactation). Body weight and food intake were evaluated. Milk, blood, visceral fat, adrenal, and carcass were collected. S dams showed hyperprolactinemia (C50%), hypoinsulinemia (K40%), hypoleptinemia (K46%), as well as lower triglycerides (K53%) and very low-density lipoprotein cholesterol (K50%). Milk of S dams had higher lactose (C52%) and triglycerides (C78%). S pups presented higher body protein (C17%), lower total (K24%) and subcutaneous fat contents (K25%), hypoglycemia (K11%), hyperinsulinemia (C28%), hypocorticosteronemia (K40%), lower adrenal catecholamine content (K40%), hypertriglyceridemia (C34%), higher high-density lipoprotein cholesterol (C16%), and lower low-density lipoprotein cholesterol (K45%). In conclusion, tobacco smoke exposure leads to changes in nutritional, biochemical, and hormonal parameters in dams and, passively through the milk, may promote several important metabolic disorders in the progeny.

Undernutrition during brain development causes long lasting alterations in different neurotransmitter systems that may alter responses to psychoactive drugs. Despite the recognized effects of early undernutrition on the cholinergic system, no evidence that demonstrates the influence of this insult on nicotine susceptibility has been reported. We investigated the effects of protein/calorie restriction during lactation on the susceptibility to nicotine in adolescent mice. Dams were randomly assigned to one of the following groups: Control (C, 20 litters)—free access to standard laboratory diet (23% protein); Protein Restricted (PR, 12 litters)—free access to a isoenergetic, 8% protein diet; Calorie Restricted (CR, 12 litters)—access to standard laboratory diet in restricted quantities (mean ingestion of PR: pair‐fed group). Undernutrition extended from postnatal day 2 (PN2) to weaning (PN21). At PN30, animals either received an i.p. injection of nicotine (0.5 mg/Kg) or saline and were immediately placed in open field (OF). After the OF, adrenal glands and serum were collected for the analyses of stress‐related endocrine parameters and leptin concentration. PR and CR offspring showed less body mass gain and visceral fat mass. PR offspring presented reduced serum leptin concentration. In the OF, nicotine increased locomotor activity of C and PR, but not of CR. CR and PR offspring showed decreased adrenal catecholamine content, which was not dependent on nicotine exposure. Our results indicate that early undernutrition interferes with nicotine‐elicited locomotor effects in adolescent mice and suggest that endocrine parameters alterations in malnourished animals do not influence the behavioral response to nicotine.