Nicotine exposure during breastfeeding reduces sympathetic activity in brown adipose tissue and increases in white adipose tissue in adult rats: Sex-related differences.

Nicotine transfer via breast milk induces obesity in the adult offspring. We hypothesize that sympathetic nervous system (SNS) activity, brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) lipogenesis/adipogenesis are altered in adult rats that were exposed to nicotine exclusively during the breastfeeding period. Lactating Wistar rats were separated into two groups: nicotine (NIC), dams implanted with osmotic minipumps containing 6 mg/kg of nicotine at postnatal day (PN) 2; control, dams were implanted with saline-containing minipumps. Euthanasia occurred at PN120 or PN180. NIC offspring had lower BAT SNS activity and higher BAT lipid content. NIC males showed lower UCP1, ß3-AR and CPT1a, while NIC females showed lower UCP1, TRα1, CPT1a, suggesting lower thermogenesis. NIC males showed higher WAT SNS activity, WAT ß3-AR, adrenal catecholamine, FAS, PPARγ and adipocytes area, while NIC females showed higher ACC, FAS, CEBPß and PPARγ. These findings indicate increased lipogenesis/adipogenesis in both sexes, with a possible compensatory sympathetic activated-lipolysis in males. NIC males had higher hypothalamic pAMPK/AMPK, explaining the lower BAT sympathetic activity. Neonatal nicotine exposure reduces BAT SNS activity and thermogenesis, and, only in males, increases WAT adipogenesis/lipogenesis, despite higher WAT SNS activity. These alterations can be associated with obesogenesis in this programming model.

Early weaning alters the thermogenic capacity of brown adipose tissue in adult male and female rats.

PURPOSE: Early weaning (EW) is a risk factor for obesity development. Brown adipose tissue (BAT) hypofunction is related to obesity onset. Here, we evaluated whether sympathetic nervous system (SNS) activity in BAT and the thermogenic function of BAT are decreased in adulthood in obese rats from two EW models. METHODS: At the time of birth, lactating Wistar rats and their pups (three males and three females) were separated into three groups: the control group, in which pups consumed milk throughout lactation; the non-pharmacological EW (NPEW) group, in which suckling was interrupted with a bandage during the last 3 days of lactation; and the pharmacological EW (PEW) group, in which dams were treated with bromocriptine (0.5 mg/twice a day) 3 days before weaning. The offspring were sacrificed on PN180. RESULTS: Adult male rats from both EW models exhibited lower BAT SNS activity. Female rats from the PEW group showed a decrease in BAT SNS activity. The protein levels of UCP1 were lower in the NPEW males, while PGC1α levels were lower in both PEW and NPEW males. Both groups of EW females showed reductions in the levels of ß3-AR, TRß1, and PGC1α. The UCP1 protein level was reduced only in the NPEW females. The EW groups of both sexes had lower AMPK protein levels in BAT. In the hypothalamus, only the PEW females showed an increase in AMPK protein levels. In both groups of EW males, adrenal catecholamine was increased and tyrosine hydroxylase was decreased, while in EW females, adrenal catecholamine was decreased. CONCLUSIONS: Early weaning alters the thermogenic capacity of BAT, which partially contributes to obesity in adulthood, and there are sex-related differences in these alterations.

Effects of maternal bisphenol A on behavior, sex steroid and thyroid hormones levels in the adult rat offspring.

AIMS: Bisphenol A (BPA), an endocrine disruptor used in industrial applications, has been detected in both placenta and milk. We studied the effects of BPA exposure during pregnancy and lactation on body composition, palatable food intake, biochemical, hormonal and behavioral profiles of young and adult Wistar rat offspring. MAIN METHODS: Female rats were divided into: control, BPA10 (10 µg/kg/day) and BPA50 (50 µg/kg/day). BPA was administered by gavage to dams from gestation until the end of lactation. Euthanasia occurred at weaning [postnatal day (PN) 21] or adulthood (PN180). KEY FINDINGS: At weaning, BPA10 female pups had higher plasma cholesterol and triacylglycerol. BPA10 male pups showed lower plasma T3. BPA10 pups of both sexes had higher plasma progesterone, testosterone and estradiol. At adulthood, females of both BPA groups had lower food intake and higher insulinemia, whereas males had lower visceral fat, lower progesterone and testosterone concentrations. BPA10 females and males had lower T4 levels, while only males showed lower estradiol. BPA50 females showed lower fat mass, higher lean mass and lower corticosteronemia, while males had lower food intake. In the feeding study, BPA10 males ate more fat at 30 min, while BPA10 females and males ingested less fat after 12 h. BPA10 females showed hyperactivity while both groups showed less exploration. SIGNIFICANCE: Maternal exposure to BPA during gestation and lactation, even at low doses, induces life-long changes in the regulation of metabolic homeostasis of the progeny, affects sex steroids and thyroid hormones levels, compromises behavior, but does not lead to obesity or dyslipidemia.