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We had previously shown that neonatal leptin treatment programs thyroid function in adulthood. As both thyroid hormones (TH) and leptin increased thermogenesis, it was interesting to evaluate the effect of cold exposure on the thyroid function of neonate rats treated with leptin. Pups were divided into two groups: Lep, injected with leptin (8 μg/100 g/BW, s.c.) for the first 10 days of lactation and control (C), injected with saline. When they were 30 days old, the groups were subdivided into two subgroups: LepC and CC, which were exposed to 8 °C for 12 h and compared with C and Lep groups, maintained at 25 ± 1 °C. Serum leptin, TH, and TSH were measured by RIA. Type I liver deiodinase (D1) and mitochondrial α-glycerol-3-phosphate dehydrogenase (mGPD) activities were assayed by the release of 125I from 125I-reverse and colorimetric method respectively. Leptin receptor (OB-Rb) was evaluated by western blot. Lep group had hyperleptinemia (+22%) and lower free tri-iodothyronine (FT3; −33%). Cold exposure increased TH both in LepC and CC groups compared with respective controls free thyroxine (FT4:+63 and +39%; FT3:+75 and +40%). Liver D1 activity was lower in Lep (−22%) and increased with cold exposure (LepC +51% and CC +22%). The mGPD activity was lower in Lep (−34%) and increased (fourfold) when this group is cold exposed. Hypothalamic and thyroidal OB-Rb receptors were lower in Lep group (−47 and −36% respectively) and they were restored to normal levels after cold exposure. Leptin-programmed rats had higher TH response after cold exposure. OB-Rb had a fast response to cold exposure normalizing the lower levels observed in the leptin-programmed animals and may contribute to the higher TH cold responses.
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Department of Physiological Sciences, Laboratory of Lipids, Department of Physiology and Biophysics, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute
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Department of Physiological Sciences, Laboratory of Lipids, Department of Physiology and Biophysics, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute
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We have shown that maternal nicotine exposure during lactation has long-lasting effects on body adiposity and hormonal status of rat offspring. Here, we studied the nutritional and hormonal profiles in this experimental model. Two days after birth, osmotic minipumps were implanted in lactating rats divided into two groups: NIC – continuous s.c. infusions of nicotine (6 mg/kg per day) for 14 days and C – saline. Dams and pups were killed at 15 and 21 days of lactation. Body weight and food intake were evaluated. Milk, blood, visceral fat, carcass, and adrenal gland were collected. All the significant data were P<0.05. At the end of nicotine exposure (15 days), dams presented higher milk production, hyperprolactinemia, and higher serum high-density lipoprotein cholesterol (HDL-C). Milk from NIC dams had higher lactose concentration and energy content. After nicotine withdrawal (21 days), dams showed lower food intake and hyperleptinemia. The 15-day-old NIC pups presented higher total body fat, higher HDL-C, serum leptin, serum corticosterone, and adrenal catecholamine content, but lower tyrosine hydroxylase protein levels. The 21-day-old NIC pups had higher body protein content and serum globulin. Thus, maternal nicotine exposure during lactation results in important changes in nutritional, biochemical, and hormonal parameters in dams and offspring. The pattern of these effects is clearly distinct when comparing the nicotine-exposed group to the withdrawal group, which could be important for the programming effects observed previously.
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Department of Physiological Sciences, Laboratory of Lipids, Department of Applied Nutrition, Roberto Alcantara Gomes Biology Institute
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Epidemiological studies show a higher prevalence of obesity in children from smoking mothers and smoking may affect human thyroid function. To evaluate the mechanism of smoking as an imprinting factor for these dysfunctions, we evaluated the programing effects of maternal nicotine (NIC) exposure during lactation. Two days after birth, osmotic minipumps were implanted in lactating rats, divided into: NIC (6 mg/kg per day s.c.) for 14 days; Control – saline. All the significant data were P<0.05 or less. Body weight was increased from 165 days old onwards in NIC offspring. Both during exposure (at 15 days old) and in adulthood (180 days old), NIC group showed higher total fat (27 and 33%). In addition, NIC offspring presented increased visceral fat and total body protein. Lipid profile was not changed in adulthood. Leptinemia was higher at 15 and 180 days old (36 and 113%), with no changes in food intake. Concerning the thyroid status, the 15-days-old NIC offspring showed lower serum-free tri-iodothyronine (FT3) and thyroxine (FT4) with higher TSH. The 180-days-old NIC offspring exhibited lower TSH, FT3, and FT4). In both periods, liver type 1 deiodinase was lower (26 and 55%). We evidenced that NIC imprints a neonatal thyroid dysfunction and programs for a higher adiposity, hyperleptinemia, and secondary hypothyroidism in adulthood. Our study identifies lactation as a critical period to NIC programing for obesity, with hypothyroidism being a possible contributing factor.