Evidences of Metabolic Disruptor Hypothesis: Perinatal Exposure to BPA Impairs Neuroendocrine Mechanisms Regulating Food Intake in Adult Male Rats

STOKER C, ANDREOLI MF, ROSSETTI MF, KASS L, BOSQUIAZZO VL, RAMOS JG.

Congreso; SETAC LatinAmerica 11th Biennal Meeting; 2015

Obesity and metabolic syndrome are endocrine diseases and thus sensitive toenvironmental agents that can interfere with hormone and neuroendocrine action.Bisphenol A (BPA) is a compound used in the polymerization of polycarbonateplastics and is an endocrine disrupter (ED). Kisspeptin (kiss1), a hypothalamicneuropeptide that drives fertility by stimulating GnRH secretion, has beenproposed to be the link between energy balance and reproductive function. Wepreviously demonstrate that BPA impairs glucose homeostasis and induces anincrease in body weight as a consequence of a higher energy intake. Here, weevaluate the influence of perinatal exposure to a dose considered safe of BPA onhypothalamic signals that regulate food intake, both in adult males fed withcontrol diet (CD) or a high fat diet (HFD). Male rats were exposed to 50mg/kg/day of BPA or vehicle (0.002 % ethanol) from day 9 of gestation toweaning in the drinking water. Since weaning, males were fed with CD or HFDfor 20 weeks. We evaluated hypothalamic mRNA expression of theneuropeptides: Kiss1, POMC, CART, AGRP, NPY; the receptors: ERb, ERa andthe relative activity of its promoters (OS, O, OT, and E1). In BPA exposedanimals fed with CD, the higher energy intake was mediated by a down regulationof the neuropeptides CART, NPY, and the receptors ERb, ERa and its promoters(p< 0.05). Animals fed with HFD shown the same alterations plus the fall inPOMC expression (p< 0.05). Kiss1 expression was increased in BPA exposedanimals (p< 0.05). Perinatal exposure to BPA impairs glucose homeostasis,induces obesity and increases food intake in adult life of male rats alteringhypothalamic signals. These effects could be mediated by the down regulation ofERa through a reduction of its promoters activity. BPA partially mimics themechanisms of obesity produced by HFD. The combination of exposure to BPAand HFD resulted in an exacerbation of the individual effects. The proposed roleof kiss1 in regulating energy balance is to decrease food intake and increaseenergy expenditure. Since it has been demonstrated that early life exposure toEDs could modify kiss1 expression, the increase in Kiss1 produced by BPA couldbe an organizational effect that try to counteract the orexigenic signals. Themetabolic disruptor hypothesis proposes that EDs can act during developmentpredisposing to obesity or metabolic syndrome later in life. Evidences showed inthis work support this hypothesis