Journal of Diabetes Research & Clinical Metabolism

Journal of Diabetes Research & Clinical
Metabolism

ISSN 2050-0866
Case report

Obesity alone or with type 2 diabetes is associated with tissue specific alterations in DNA methylation and gene expression of PPARGC1A and IGF2

Miaoxin Chen1,2,3, Anne Macpherson2, Julie Owens2, Gary Wittert1, Leonie K. Heilbronn1,2*

*Corresponding author: Leonie K. Heilbronn leonie.heilbronn@adelaide.edu.au

1. Discipline of Medicine, The University of Adelaide, SA.


Author Affiliations

2. Robinson Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, SA.

3. Department of Obstetrics and Gynaecology, The Affiliated Hospital of Guiyang Medical College, Guiyang, China.

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

ISSN 2050-0866
Volume 1
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