Neonatal nicotine exposure causes insulin and leptin resistance and inhibits hypothalamic leptin signaling in adult rat offspring

Oliveira, Elaine de; Moura, Egberto Gaspar de; Santos-Silva, Ana Paula; Pinheiro, C. R.; Lima, Natália S.; Nogueira-Neto, José Firmino; Nunes‐Freitas, André L.; Abreu‐Villaça, Yael; Passos, M. C. F.; Lisboa, Patrícia Cristina

doi:10.1677/joe-10-0104

Cited by 59 publications

(60 citation statements)

References 43 publications

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“…The pumps were prepared with nicotinefree base diluted in a saline solution (NaCl 0.9%) and set to deliver an initial dose of 6 mg/kg of nicotine per day for 14 days of lactation. Cotinine milk and serum concentrations had already been determined in this experimental model (de Oliveira et al 2010. The chosen dose in our study produces plasma nicotine levels of approximately 25 ng/ml, which are similar to those observed in typical smokers (Lichtensteiger et al 1988).…”

Section: Model Of Postnatal Nicotine Exposuresupporting

confidence: 77%

“…In adulthood, they were programed for overweight, secondary hypothyroidism (lower TSH, T 4 , and T 3 levels), and hyperleptinemia ). We also showed leptin and insulin resistance (de Oliveira et al 2010), increased medullary adrenal function and serum glucocorticoid levels with higher levels of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in adult offspring whose mothers were nicotine-exposed .…”

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confidence: 89%

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Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny

Lisboa¹,

Oliveira²,

Manhães³

et al. 2015

Journal of Endocrinology

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Postnatal nicotine exposure leads to obesity and hypothyroidism in adulthood. We studied the effects of maternal nicotine exposure during lactation on thyroid hormone (TH) metabolism and function in adult offspring. Lactating rats received implants of osmotic minipumps releasing nicotine (NIC, 6 mg/kg per day s.c.) or saline (control) from postnatal days 2 to 16. Offspring were killed at 180 days. We measured types 1 and 2 deiodinase activity and mRNA, mitochondrial a-glycerol-3-phosphate dehydrogenase (mGPD) activity, TH receptor (TR), uncoupling protein 1 (UCP1), hypothalamic TRH, pituitary TSH, and in vitro TRH-stimulated TSH secretion. Expression of deiodinase mRNAs followed the same profile as that of the enzymatic activity. NIC exposure caused lower 5 0 -D1 and mGPD activities; lower TRb1 content in liver as well as lower 5 0 -D1 activity in muscle; and higher 5 0 -D2 activity in brown adipose tissue (BAT), heart, and testis, which are in accordance with hypothyroidism. Although deiodinase activities were not changed in the hypothalamus, pituitary, and thyroid of NIC offspring, UCP1 expression was lower in BAT. Levels of both TRH and TSH were lower in offspring exposed to NIC, which presented higher basal in vitro TSH secretion, which was not increased in response to TRH. Thus, the hypothyroidism in NIC offspring at adulthood was caused, in part, by in vivo TRH-TSH suppression and lower sensitivity to TRH. Despite the hypothyroid status of peripheral tissues, these animals seem to develop an adaptive mechanism to preserve thyroxine to triiodothyronine conversion in central tissues.

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Section: Model Of Postnatal Nicotine Exposuresupporting

confidence: 77%

mentioning

confidence: 89%

Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny

Lisboa¹,

Oliveira²,

Manhães³

et al. 2015

Journal of Endocrinology

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“…Surprisingly, when adults, these offspring were programmed only for adrenal dysfunction, characterized by decreased total adrenal catecholamine content and tyrosine hydroxylase protein expression (Santos-Silva et al 2012). These findings were different from those obtained from the maternal nicotine model (Oliveira et al 2009, de Oliveira et al 2010, suggesting that the combination of nicotine and other cigarette components programs for different outcomes than the maternal nicotine model. Actually, children from smoking mothers are exposed to cigarette components not only through breast milk but also through the household environment.…”

Section: Introductionmentioning

confidence: 82%

“…Nicotine is transferred by breast milk and promotes, in pups, higher body fat mass with metabolic alterations featured by hyperleptinemia, primary thyroid hypofunction, and higher adrenal catecholamine content and corticosterone levels (Oliveira et al 2009. In adult 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.…”

Section: Introductionmentioning

confidence: 99%

Endocrine effects of tobacco smoke exposure during lactation in weaned and adult male offspring

Santos-Silva

Oliveira

Pinheiro

et al. 2013

Journal of Endocrinology

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Children from pregnant smokers show more susceptibility to develop obesity in adult life. Previously, we failed to demonstrate a program for obesity in rat offspring only when the mothers were exposed to tobacco smoke during lactation. Here, we studied the short-and long-term effects of smoke exposure (SE) to both dams and their pups during lactation on endocrine and metabolic parameters. For this, we designed an experimental model where nursing rats and their pups were divided into two groups: SE group, exposed to smoke in a cigarette smoking machine (four times/day, from the third to the 21st day of lactation), and group, exposed to filtered air. Pups were killed at 21 and 180 days. 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 (K29%), hyperthyroxinemia (59%), hypercorticosteronemia (60%), and higher adrenal catecholamine content (C58%). In adulthood, SE offspring showed higher food intake (C10%), body total fat mass (C50%), visceral fat mass (retroperitoneal: 55%; mesenteric: 67%; and epididymal: 55%), and lower subcutaneous adipocyte area (24%) with higher serum glucose (11%), leptin (85%), adiponectin (1.4-fold increase), total triiodothyronine (71%), free thyroxine (57%), TSH (36%), triglycerides (65%), VLDL cholesterol (C66%), and HDL cholesterol (91%) levels and lower corticosteronemia (41%) and adrenal catecholamine content (57%). Our present findings suggest that tobacco SE to both dams and their pups during lactation causes 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 as the mother.

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“…Maternal nicotine exposure restricted to the lactating period also leads to early and late metabolic defects. Higher levels of HDL-C, leptin, corticosterone and adrenal catecholamine content are observed at PND15, ) and overweight (with increased fat mass and hypertrophy of adipocyte), hyperleptinemia (with impaired hypothalamic leptin signaling), hyperinsulinemia and hypothyroidism are reported in adult rat offspring exposed to nicotine through maternal milk (de Oliveira et al 2010). Different mechanisms could explain the enhanced adipose storage due to early nicotine exposure during the early stage of development such as (1) increased release and transport of fatty acids from maternal adipose tissue to the fetal circulation (Williams and Kanagasabai 1984), (2) a nicotine-mediated stimulatory effect on PPAR-c gene expression in the adipocyte (Somm et al 2008), as previously observed in monocytes (Amoruso Table 2).…”

Section: Early Deleterious Programming Actionmentioning

confidence: 99%

Nicotinic Cholinergic Signaling in Adipose Tissue and Pancreatic Islets Biology: Revisited Function and Therapeutic Perspectives

Somm

2013

Arch. Immunol. Ther. Exp.

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Nicotinic acetylcholine receptors (nAChRs) are membrane ligand-gated cation channels whose activation is triggered by the binding of the endogenous neurotransmitter acetylcholine or other biologic compounds including nicotine. Their roles in synaptic transmission in the central and peripheral nervous system as well as in the neuromuscular junction have been extensively studied. Recent implications of nAChRs in intracellular signaling and their detection in peripheral nonneural cells (including epithelial cells and immune cells) have renewed the interest for this class of ionotropic receptors. In the present review, we focus our attention on the potential use of nicotinic cholinergic signaling in the treatment of metabolic diseases (such as obesity and diabetes) in browsing functions of nAChRs in adipose tissue and pancreatic islet biology. In fact, different nAChR subunits can be detected in these metabolic tissues, as well as in immune cells interacting with them. Various rodent models of obesity and diabetes benefit from stimulation of the nicotinic cholinergic pathway, whereas mice deficient for some nAChRs, in particular the a7 nAChR subunit, harbor a worsened metabolic phenotype. In contrast to potential therapeutic applications in metabolic diseases, an overstimulation of this signaling pathway during the early stage of development (typically through nicotine exposure during fetal life) presents deleterious consequences on ontogeny and functionality of adipose tissue and the endocrine pancreas which persist throughout life.

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Neonatal nicotine exposure causes insulin and leptin resistance and inhibits hypothalamic leptin signaling in adult rat offspring

Cited by 59 publications

References 43 publications

Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny

Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny

Endocrine effects of tobacco smoke exposure during lactation in weaned and adult male offspring

Nicotinic Cholinergic Signaling in Adipose Tissue and Pancreatic Islets Biology: Revisited Function and Therapeutic Perspectives

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