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https://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 diabetes 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. |
DOI: | 10.7243/2050-0866-1-16 |
Published version: | http://dx.doi.org/10.7243/2050-0866-1-16 |
Appears in Collections: | Aurora harvest 4 Obstetrics and Gynaecology publications |
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hdl_76818.pdf | Published version | 628.56 kB | Adobe PDF | View/Open |
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