Postnatal nicotine exposure causes precocious primary hypothyroidism and programs for overweight, hyperleptinemia and secondary hypothyroidism in adulthood. As leptin and thyroid hormones share the ability to increase energy expenditure, we studied the effects of maternal nicotine exposure during lactation on the leptin signaling in the hypothalamus-pituitary-thyroid axis of suckling and adult offspring.
Two days after delivery, osmotic minipumps were implanted in lactating rats, and nicotine (NIC, 6 mg/kg/day s.c.) or saline (C) was administered for 14days. Offspring were killed at 15 and 180 days-old. Proteins belonging to leptin signaling were analyzed by Western blot. Significant differences had p<0.05.
In the hypothalamus, NIC offspring showed higher OB-R and pSTAT-3 content (+58%,+1.34x) at 15 days, and lower OB-R, JAK-2 and pSTAT-3 (-61%, -42%, -56%) at 180 days. In the pituitary gland, NIC offspring showed lower JAK-2 content (-52%) at 15 days, but no differences in adulthood. In the thyroid gland, the NIC group presented lower OB-R, JAK-2 and STAT-3 (-44%, -50%, -47%) and higher pSTAT-3 expression (+80%) at 15 days. At 180 days-old, NIC offspring presented higher thyroid OB-R (+1.54x) and lower pSTAT-3 content (-34%).
Neonatal primary hypothyroidism induced by maternal nicotine exposure during lactation may be partially explained by decreased leptin signaling in the thyroid, though the early stimulation of the central leptin pathway did not prevent the thyroid dysfunction. Long-term effects of postnatal nicotine exposure on leptin signaling in the hypothalamus and thyroid appear to involve central and peripheral leptin resistance in adulthood.
"This could explain, in part, the higher intake of palatable diet by the S group in the food challenge. Previously, we have reported hyperleptinemia and hypothalamic leptin resistance, characterized by lower OBRb, JAK2 and pSTA3 with higher SOCS3 in the programming model of maternal exposure to nicotine (Oliveira et al., 2009; Santos-Silva et al., 2010) and in the model of programming by direct exposure to cigarette smoke, in which we only showed hyperleptinemia and hyperphagia (Santos-Silva et al., 2013) with a higher dose of nicotine than in the present study. Since we only observed lower OBRb content in the leptin signalling pathway in the ARC, without significant changes in NPY and POMC contents in the S group, we cannot tell for sure that these animals have leptin resistance. "
"Nicotine is transferred by breast milk and promotes, in pups, higher body fat mass with metabolic alterations featured by hyperleptinemia, primary thyroid hypofunction, higher adrenal catecholamine content, and corticosterone levels (Oliveira et al. 2009, 2010). In adult Q2 life, it programs the progeny for overweight and higher adiposity associated with leptin and insulin resistance as well as secondary hypothyroidism with alterations in the leptin signaling pathway of hypothalamus–pituitary– thyroid axis (Oliveira et al. 2009, de Oliveira et al. 2010, Santos-Silva et al. 2010). "
[Show abstract][Hide abstract] ABSTRACT: Children from pregnant smokers show more susceptibility to develop obesity in adult life. Previously, we failed to demonstrate in rats offspring a programming for obesity when only the mothers were tobacco smoke-exposed during lactation. Here, we studied the short- and long-term effects of smoke exposure to both dams and their pups during lactation upon endocrine and metabolic parameters. For this, we designed an experimental model where nursing rats and their pups were divided into: SE group, smoke-exposed in a cigarette smoking machine (4 times/day, from the 3rd to the 21th day of lactation) and C group, exposed to filtered air. Pups were killed at 21 and 180 days old. At weaning, SE pups showed lower body weight (7%), length (5%), retroperitoneal fat mass (59%), visceral adipocyte area (60%) and higher subcutaneous adipocyte area (95%) with hypoinsulinemia (-29%), hyperthyroxinemia (59%), hypercorticosteronemia (60%) and higher adrenal catecholamine content (+58%). In adulthood, SE offspring showed higher food intake (+10%), body total fat mass (+50%), visceral fat mass (retroperitoneal: 55%; mesenteric: 67%; epididymal: 55%), and lower subcutaneous adipocyte area (24%) with higher serum glucose (11%), leptin (85%), adiponectin (1.4 fold-increase), TT3 (71%), FT4 (57%), TSH (36%), triglycerides (65%), VLDL-c (+66%), HDL-c (91%) levels, lower corticosteronemia (41%) and adrenal cathecolamine content (57%). Our present findings suggest that tobacco smoke exposure to both dams and their pups during lactation causes a malnutrition in early life that programs for obesity and hormonal and metabolic disturbances in adulthood, only if the pups are submitted to the same smoke environment than the mother.
Journal of Endocrinology 04/2013; 218(1). DOI:10.1530/JOE-13-0003 · 3.72 Impact Factor
"The likely mechanism of the pups’ primary hypothyroidism is decreased leptin signaling in the thyroid. However, long-term thyroid hypofunction is related to central and peripheral leptin resistance in adulthood (Santos-Silva et al., 2010). "
[Show abstract][Hide abstract] ABSTRACT: Obesity is a global epidemic, and maternal smoking has been shown to be associated with the development of childhood obesity. Overall, approximately 40% of children worldwide are exposed to tobacco smoke at home. It is well known that environmental changes within a critical window of development, such as gestation or lactation, can initiate permanent alterations in metabolism that lead to diseases in adulthood, a phenomenon called programming. It is known that programming is based on epigenetic alterations (changes in DNA methylation, histone acetylation, or small interfering RNA expression) that change the expression pattern of several genes. However, little is known concerning the mechanisms by which smoke exposure in neonatal life programs the adipose tissue and endocrine function. Here, we review several epidemiological and experimental studies that confirm the association between maternal nicotine or tobacco exposure during gestation or lactation and the development of obesity and endocrine dysfunction. For example, a positive correlation was demonstrated in rodents between increased serum leptin in the neonatal period and exposure of the mothers to nicotine during lactation, and the further development of leptin and insulin resistance, and thyroid and adrenal dysfunction, in adulthood in the same offspring. Thus, a smoke-free environment during the lactation period is essential to improving health outcomes in adulthood and reducing the risk for future diseases. An understanding of the pathophysiological mechanisms underlying the effects of smoking on programming can provide new insights into therapeutic strategies for obesity.
Frontiers in Physiology 11/2012; 3:437. DOI:10.3389/fphys.2012.00437 · 3.53 Impact Factor
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