Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/76818
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Type: Journal article
Title: Obesity alone or with type 2 diabetes is associated with tissue specific alterations in DNA methylation and gene expression of PPARGC1A and IGF2
Author: Chen, M.
Macpherson, A.
Owens, J.
Wittert, G.
Heilbronn, L.
Citation: Journal of Diabetic Research & Clinical Metabolism, 2012; 2012(1):1-8
Publisher: Herbert Publications Ltd
Issue Date: 2012
ISSN: 2050-0866
2050-0866
Organisation: Robinson Institute
Statement of
Responsibility: 
Miaoxin Chen, Anne Macpherson, Julie Owens, Gary Wittert and Leonie K. Heilbronn
Abstract: BACKGROUND: Epigenetic modifications of key genes have been linked to the development of aging related diseases, such as type 2 diabetes, with increased DNA methylation of the transcriptional co-activator, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) in islets and skeletal muscle of patients with type 2 diabetes. Here, we examined DNA methylation and gene expression of PPARGC1A and insulin like growth factor-2 (IGF2) in adipose tissue and skeletal muscle of lean and morbidly obese individuals with or without type 2 diabetes. METHODS: Adipose tissue and skeletal muscle biopsies were collected from 24 lean, obese, and obese patients with type 2 diabetes (n=8/group). DNA methylation and gene expression of PPARGC1A and IGF2 were measured using pyrosequencing and quantitative real-time PCR respectively. RESULTS: DNA methylation and expression of both genes varied in a tissue specific manner (P<0.05). The highest levels of PPARGC1A methylation were observed in subcutaneous adipose tissue and lowest in muscle (P≤0.001), whereas IGF2 methylation was lowest in subcutaneous adipose tissue as compared with visceral adipose tissue and muscle (P≤0.04). Expression of PPARGC1A and IGF2 was highest in muscle and lowest in subcutaneous adipose tissue (P≤0.001) and PPARGC1A expression was conversely correlated with DNA methylation in skeletal muscle (r=-0.54, P=0.008). Obese patients with type 2 diabetes had higher PPARGC1A methylation in subcutaneous adipose tissue (P=0.01) and lower IGF2 DNA methylation in muscle (P=0.01) as compared with lean individuals. Obese patients with and without type 2 diabetes had reduced expression of both genes in subcutaneous adipose tissue (P≤0.04) as compared to lean individuals. CONCLUSIONS: This study showed tissue specific DNA methylation and gene expression of PPARGC1A and IGF2, which may also be associated with obesity and type 2 diabetes. Further study of the effects of tissue specific DNA methylation on risk of obesity and type 2 diabetes in a larger cohort is now warranted.
Keywords: DNA methylation; gene expression; PPARGC1A; IGF2; type 2 diabetes; obesity
Rights: © 2012 Heilbronn et al; licensee Herbert Publications Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
RMID: 0020126061
DOI: 10.7243/2050-0866-1-16
Appears in Collections:Obstetrics and Gynaecology publications

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