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Neonatal nicotine exposure changes insulin status in fat depots: sex-related differences
Vanessa da Silva Tavares Rodrigues1, Rosiane A Miranda1, Patricia Novaes Soares1
1Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Insights
Maternal nicotine exposure during breastfeeding causes obesity and hormone changes in male offspring, but not females. This highlights sex-specific effects of neonatal nicotine on adult metabolism and fat storage.
Area of Science:
- Endocrinology
- Developmental Biology
- Toxicology
Background:
- Nicotine, a primary component of cigarette smoke, is transferred to infants via breast milk.
- Maternal nicotine exposure in rats during lactation has been shown to cause obesity and hormonal imbalances in adult male offspring.
- Glucocorticoids (GC), insulin, and vitamin D play crucial roles in regulating adipogenesis and lipogenesis.
Purpose of the Study:
- To investigate the sex-specific effects of neonatal nicotine exposure during breastfeeding on metabolic parameters and hormone action in adult rats.
- To assess alterations in visceral and subcutaneous adipose tissues (VAT and SAT) related to glucocorticoid, insulin, and vitamin D signaling pathways.
Main Methods:
- Rat dams were exposed to nicotine (6 mg/kg) or saline via osmotic minipumps from postnatal day 2.
- At postnatal day 180, parameters including fat mass, hormone levels, and protein expression of key metabolic biomarkers were evaluated in male and female offspring.
- Assessed biomarkers included those for GC (11beta-HSD1, GRα), insulin signaling (IRβ, pIRS1, IRS1, pAKT, AKT, GLUT4), and vitamin D (1α-hydroxylase, VDR).
Main Results:
- Nicotine-exposed males exhibited increased fat mass, hypercorticosteronemia, hyperinsulinemia, and elevated 25-hydroxyvitamin D compared to controls.
- Nicotine-exposed females did not show these systemic hormonal alterations but presented hyperglycemia and altered insulin signaling markers (higher pAKT in VAT; lower IRβ, IRS1, GLUT4 in SAT).
- Specific alterations in IRS1 were noted in VAT of males, while GC and vitamin D metabolism/action parameters remained largely unchanged in both sexes.
Conclusions:
- Neonatal nicotine exposure during breastfeeding induces significant sex-dependent metabolic and hormonal disturbances in adult rats.
- Male offspring are more susceptible to nicotine-induced obesogenesis and hormonal dysregulation.
- These findings underscore the critical impact of early-life environmental exposures on long-term health outcomes in a sex-specific manner.
Abstract:
Nicotine is the main psychoactive substance present in cigarette smoke that is transferred to the baby by breast milk. In rats, maternal nicotine exposure during breastfeeding induces obesogenesis and hormone dysfunctions in adult male offspring. As glucocorticoid (GC), insulin, and vitamin D change both adipogenesis and lipogenesis processes, we assessed parameters related to metabolism and action of these hormones in visceral and subcutaneous adipose tissues (VAT and SAT) of adult male and female rats in a model of neonatal nicotine exposure. At postnatal (PN) day 2, dams were kept with six pups (three per sex) and divided into nicotine and control groups for implantation of osmotic minipumps that released 6 mg/kg nicotine or saline, respectively. At PN180, fat mass, hormone levels, and protein contents of biomarkers of the GC activation and receptor (11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor alpha), insulin signaling pathway [insulin receptor beta (IRβ), phosphorylated insulin receptor substrate 1, insulin receptor substrate 1 (IRS1), phosphorylated serine/threonine kinase (pAKT), serine/threonine kinase, glucose transporter type 4 (GLUT4)], and vitamin D activation and receptor (1α-hydroxylase and vitamin D receptor) were evaluated. While nicotine-exposed males showed increased fat mass, hypercorticosteronemia, hyperinsulinemia, and higher 25-hydroxyvitamin D, these alterations were not observed in nicotine-exposed females. Nicotine-exposed males only showed lower IRS1 in VAT, while the females had hyperglycemia, higher pAKT in VAT, while lower IRβ, IRS1, and GLUT4 in SAT. Parameters related to metabolism and action of GC and vitamin D were unaltered in both sexes. We evidence that exposure exclusively to nicotine during breastfeeding affects the hormone status and fat depots of the adult progeny in a sex-dependent manner.
