The increase in body weight induced by lack of methyl CpG binding protein-2 is associated with altered leptin signalling in the hypothalamus.

Abstract:

:Methyl CpG binding protein-2 (MECP2) is a chromatin-remodelling factor with a dual role in gene expression. Evidence from patients carrying MECP2 mutations and from transgenic mouse models demonstrates that this protein is involved in the control of body weight. However, the mechanism for this has not been fully elucidated. To address this, we used a previously characterized Mecp2-null mouse model and found that the increase in body weight is associated with an increased amount of adipose tissue and high leptin levels. Appropriate body weight control requires the proper expression of pro-opiomelanocortin (Pomc) and agouti-related peptide (Agrp), two neuropeptides essential for satiety and appetite signals, respectively. Our results show that in the absence of Mecp2, Pomc and Agrp mRNA expression are altered, and the mice are leptin resistant. To determine the mechanism underlying the defective leptin sensing, we evaluated the expression of genes and the post-translational modifications associated with leptin signalling, which are fundamental to Pomc and Agrp transcriptional control and proper leptin response. We found a decrease in the phosphorylation level of Akt and its target protein Foxo1, which indicate an alteration in leptin-induced signal transduction. Our results demonstrate that the absence of Mecp2 disrupted body weight balance by altering post-translational modifications in leptin-signalling components that regulate Pomc and Agrp expression.

journal_name

Exp Physiol

journal_title

Experimental physiology

authors

Torres-Andrade R,Moldenhauer R,Gutierrez-Bertín N,Soto-Covasich J,Mancilla-Medina C,Ehrenfeld C,Kerr B

doi

10.1113/expphysiol.2014.079798

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

1229-40

issue

9

eissn

0958-0670

issn

1469-445X

pii

expphysiol.2014.079798

journal_volume

99

pub_type

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