Early postnatal genistein administration affects neural circuits controlling food intake in cd1 mice.

Genistein (GEN), a phytoestrogen contained in soy and other legumes [1], can act as 'obesogen' and increase the risk of developing metabolic disorders such as diabetes or obesity [2]. Recent studies demonstrated that some of them might induce permanent morphological alterations of estrogen sensitive circuits in adults as the systems that influence food intake [3]. The neuroendocrine control of food intake and energy expenditure is based on many circuits including both orexinergic (Orexin, NPY) and anorexinergic [pro-opiomelanocortin (POMC)] elements that are targets for a series of chemical signals coming from the periphery (as leptin, ghrelin). From the arcuate nucleus (ARC) and the lateral hypothalamic area (LHA) these systems project to many other hypothalamic nuclei. Due to the frequent use of soy milk in the neonatal diet, we aimed to study the effects of early GEN exposure on neural circuits controlling metabolism and food intake. We analyzed the effects on adult CD1 mice of both sexes of an early postnatal treatment (from PND1 to PND8) with GEN (50 mg/kg body weight dissolved in sesame oil) or with the vehicle (control, CON). In particular, we examined the expression of the POMC neuronal system within different hypothalamic nuclei [ARC, Paraventricular Nucleus (PVN) and Dorsomedial Nucleus (DM)] and the orexin system in LHA. Early postnatal exposure to GEN, in a dose comparable to the exposure level in babies fed with soy-based formulas, induced sexually dimorphic effects. In fact, only in adult females GEN treatment significantly increased the body weight. POMC immunoreactivity was significantly reduced in adult GEN females compared to CON females only in PVN, while we have not observed any significant difference in DM and ARC, and in males. In addition, we observed an increase of the positive cell number in the inner part of ARC only in GEN-treated females. The orexin system in the LHA is sexually dimorphic in CON mice (having males more cells than females), and this dimorphism was totally reverted in GEN mice: the cell number increased in GEN female and decreased in GEN male. In conclusion, the early postnatal exposure of CD1 mice to GEN determines long-term sex specific organizational effects on neural circuits controlling food intake and energy metabolism. The increase of body weight as well as the morphological alterations of the two circuits expressing orexin and POMC suggest that the obesogenic effect of GEN is sexually dimorphic and is due, at least partly, to alteration of metabolic regulation. [ABSTRACT FROM AUTHOR]