Abstract

In the arcuate nucleus, neuropeptide Y (NPY) neurons, increase food intake and decrease energy expenditure, and control the activity of pro-opiomelanocortin (POMC) neurons, that decrease food intake and increase energy expenditure. Both systems project to other hypothalamic nuclei such as the paraventricular and dorsomedial hypothalamic nuclei. Endocrine disrupting chemicals (EDCs) are environmental contaminants that alter the endocrine system causing adverse health effects in an intact organism or its progeny. We investigated the effects of long-term exposure to some EDCs on the hypothalamic NPY and POMC systems of adult male mice that had been previously demonstrated to be a target of some of these EDCs after short-term exposure. Animals were chronically fed for four months with a phytoestrogen-free diet containing two different concentrations of bisphenol A, diethylstilbestrol, tributyltin, or E2. At the end, brains were processed for NPY and POMC immunohistochemistry and quantitatively analyzed. In the arcuate and dorsomedial nuclei, both NPY and POMC immunoreactivity showed a statistically significant decrease. In the paraventricular nucleus, only the NPY system was affected, while the POMC system was not affected. Finally, in the VMH the NPY system was affected whereas no POMC immunoreactive material was observed. These results indicate that adult exposure to different EDCs may alter the hypothalamic circuits that control food intake and energy metabolism.

Highlights

  • Two neurochemically distinct sets of hypothalamic neurons controlling food intake are located in the arcuate nucleus (ARC)

  • The control of energy metabolism and food intake is in part dependent on central neuroendocrine circuits that have been detailed in the introduction

  • The neuropeptide Y (NPY) and the POMC systems exert orexigenic (NPY) and anorexigenic (POMC) effects

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Summary

Introduction

Two neurochemically distinct sets of hypothalamic neurons controlling food intake are located in the arcuate nucleus (ARC). The other group expresses cocaine- and amphetamine-regulated transcript (CART) and pro-opiomelanocortin POMC, which is processed to melanocortin peptides, such as α-melanocyte-stimulating hormone (α-MSH) The activation of these neurons decreases food intake and increases energy expenditure [1] with an opposite effect of the NPY/AgRP system. Studies on the action of EDC on hypothalamic neurons related to eating behavior and energy control used a variety of experimental conditions (exposure to isoflavones, in vitro experiments, and short-term exposure) For this reason, in the present study, we exposed, for a longer time period (4 months), adult male mice to phytoestrogen-free food containing different putative MDCs to understand if the central neuroendocrine, orexinergic, and anorexinergic circuits are differentially affected by these compounds. Due to the alleged xenoestrogenic activity of some of them we included, as a positive control, a group of animals treated with E2

Body Weight
POMC System
Discussion
Animals and Treatment
Tissue Sampling and Histological Examination
Quantitative Analysis
Statistical Analysis
Full Text
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