Leptin Signaling Modulates Expression of Polycomb and Trithorax Complexes in the Brain of Fat Tissue Implanted Polycystic Ovarian Sindrome Mice

Eduardo Henrique Da Silva Freitas,Silvana Aparecida Alves Correa-Noronha,Carlos Fernandes Baptista,Ismael Dale Cotrim Guerreiro Da Silva,Samuel Marcos Ribeiro De Noronha,Maria Nazareth Gamboa Ritto ,Ivaldo Silva

doi:10.4236/ajmb.2014.44020

Eduardo Henrique Da Silva Freitas, Silvana Aparecida Alves Correa-Noronha + Show 5 more

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https://doi.org/10.4236/ajmb.2014.44020

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Abstract

The Polycystic Ovary Syndrome (PCOS) is the most common androgenic disorder in women during reproductive life. PCOS may also be accompanied by metabolic syndrome and recent studies point to leptin as playing a role in disrupting infertility and in changing the energy balance in obese mice through its action on the hypothalamus. The aim is to assess the expression of the Polycomb & Trithorax Complexes genes in brain of mice transplanted with fat tissue from normal mice, in order to better understand the neuronal mechanisms underlying the reversion of PCOS. Three B6 V-Lepob/J mouse groups: Normal weight, obese and seven-day-treatment obese had their brain RNA extracted and submitted to an 84 Polycomb & Trithorax Complexes genes PCR Array plate and MetacoreTM pathways localization. Genomic profiles obtained were compared to the ones of the normal-weight-mice group. Differentially expressed genes were 13% and 26% respectively to control and treatment. Major changes were in genes: Snai1/31; Smarca1/?17; Dnmt3b/4.7; Ezh1/ 15. Altered genes were associated to canonical pathways and provided 3 networks related to epigenetics. Underlying neuronal changes caused by leptin in obese mice brain, there is an important role being played by the histone code. Here there is evidence that leptin drives the chromatin packing to a more condensed pattern. Upregulation of methyltransferase genes, like Ezh1, favors this thought. In summary the Polycomb & Trithorax complexes might answer for the silencing of some downregulated genes in the obese mice brain when exposed to leptin.

Highlights

The Polycystic Ovary Syndrome (PCOS) is the most common androgenic disorder in women during reproductive life [1]
The objective of this study is to assess the expression of the Polycomb & Trithorax Complexes genes in the brain of mice transplanted with fat tissue from normal mice, in order to better understand the neuronal mechanisms underlying the reversion of PCOS
The results presented in this subsection is relate to the treatment for seven days with implantation of gonadal fat in obese ob/ob mice

Summary

Introduction

The Polycystic Ovary Syndrome (PCOS) is the most common androgenic disorder in women during reproductive life [1]. PCOS may be accompanied by metabolic syndrome and recent studies point to leptin as playing a role in disrupting infertility and in changing the energy balance in obese mice through its action on the hypothalamus [2] [3]. DNA methylation is involved in the regulation of many genes expressed in a tissue, playing a crucial role in determining cells fate [5] and it is closely related to chromatin structure [6] [7]. Cellular differentiation involves various genome-wide histone (H) modifications that have been directly linked to active and inactive structures of the chromatin [8] [9]. It is known that nonhistone methylation may function as a fingerprint that establishes repressive and active chromatin configuration at target loci causing heritable changes in gene expression [11]. The histone code tightly controls DNA packaging and chromatin remodeling, which leads to repression or activation of gene transcription [12]

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