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

C STOKER; MF ANDREOLI; MF ROSSETTI; L KASS; VL BOSQUIAZZO; JG RAMOS

Buenos Aires

Congreso; SETAC Latin America 11th Biennial Meeting; 2015

Society of Environmental Toxicology and Chemistry Latin America

Obesity and metabolicsyndrome are endocrine diseases and thus sensitive to environmental agents thatcan interfere with hormone and neuroendocrine action. Bisphenol A (BPA) is acompound used in the polymerization of polycarbonate plastics and is an endocrinedisrupter (ED). Kisspeptin (kiss1), a hypothalamic neuropeptide that drivesfertility by stimulating GnRH secretion, has been proposed to be the linkbetween energy balance and reproductive function. We previously demonstratethat BPA impairs glucose homeostasis and induces an increase in body weight asa consequence of a higher energy intake. Here, we evaluate the influence ofperinatal exposure to a dose considered safe of BPA on hypothalamic signalsthat regulate food intake, both in adult males fed with control diet (CD) or ahigh fat diet (HFD). Male rats were exposed to 50 mg/kg/day of BPA or vehicle(0.002 % ethanol) from day 9 of gestation to weaning in the drinking water.Since weaning, males were fed with CD or HFD for 20 weeks. We evaluated hypothalamicmRNA expression of the neuropeptides: Kiss1, POMC, CART, AGRP, NPY; thereceptors: ERb, ERa and the relative activity of its promoters (OS, O, OT, andE1). In BPA exposed animals fed with CD, the higher energy intake was mediatedby a down regulation of the neuropeptides CART, NPY, and the receptors ERb, ERaand its promoters (p< 0.05). Animals fed with HFD shown the same alterationsplus the fall in POMC expression (p< 0.05). Kiss1 expression was increasedin BPA exposed animals (p< 0.05). Perinatal exposure to BPA impairs glucosehomeostasis, induces obesity and increases food intake in adult life of malerats altering hypothalamic signals. These effects could be mediated by the downregulation of ERa through a reduction of its promoters activity. BPA partiallymimics the mechanisms of obesity produced by HFD. The combination of exposureto BPA and HFD resulted in an exacerbation of the individual effects. Theproposed role of kiss1 in regulating energy balance is to decrease food intakeand increase energy expenditure. Since it has been demonstrated that early lifeexposure to EDs could modify kiss1 expression, the increase in Kiss1 producedby BPA could be an organizational effect that try to counteract the orexigenicsignals. The metabolic disruptor hypothesis proposes that EDs can act duringdevelopment predisposing to obesity or metabolic syndrome later in life. Evidencesshowed in this work support this hypothesis.