Perinatal exposure to bisphenol a (BPA) alters kiss1 expression and impairs neuroendocrine mechanisms regulating food intake in adult male rats.

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

Mendoza

Workshop; International Workshop in Neuroendocrinology; 2015

2015 International Workshop in Neuroendocrinology

Kisspeptin (kiss1) is a hypothalamic neuropeptide that drives fertilityby stimulating GnRH secretion. Evidences show that kiss1 could be the linkbetween energy balance and reproductive function. Bisphenol A (BPA) is a compound used in the polymerization ofpolycarbonate plastics and has activity as endocrine disruptor. Our objective was to determine the influence of perinatal exposure to adose considered safe of BPA on body weight, metabolic parameters andhypothalamic signals that regulate food intake, both in adult males fed withregular diet or a high fat diet.Male rats were exposed to 50 ug/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 control diet(CD) or high fat diet (HFD) for 20 weeks. We evaluated: energy intake, body andfat pad weights, glucose tolerance test (GTT) and hypothalamic mRNA expressionof the neuropeptides: Kiss1, POMC, CART, AGRP, NPY; the receptors: InsR, ob-Rb,ERb, ERa and the relative activity of its promoters (OS, O, OT, and E1). Serum insulin,testosterone and estradiol were also assessed.BPA exposure induces an increase in body and fat pad weights as aconsequence of a higher energy intake (p<0.05). Glucose homeostasis wasimpaired (p<0.05). The same effects were observed in males fed with HFD. Thecombination of exposure to BPA and HFD resulted in an exacerbation of theindividual effects (p<0.05). In BPA exposed animals fed with CD, the higherenergy intake was mediated by a down regulation of the neuropeptides CART, NPY,and the receptors InsR, ERb,  ERa and its promoters (p<0.05). Animals fed with HFDshown the same alterations plus the fall in POMC expression and in serumtestosterone level (p<0.05). Kiss1 expression was increased in BPA exposed animals(p<0.05). No modifications were seen in the other parameters studied.Conclusions: Perinatal exposure to BPA impairs glucose homeostasis, inducesobesity 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 BPA andHFD resulted in an exacerbation of the individual effects. The proposed role of kiss1 in regulating energy balance is to decreasedfood intake and increase energy expenditure. BPA increase hypothalamic Kiss1 expression.If this is an organizational or activational effect still needs to beelucidated. Early life exposure to estrogens has been demonstrated to modifythis system but it also could be a response to counteract the orexigenic signals.Financial Support: Universidad Nacional del Litoral and ArgentineNational Agency for the Promotion of Science and Technology.