Altered DNA methylation in liver and adipose tissues derived from individuals with obesity and type 2 diabetes

Francisco Barajas-Olmos,Iván Imaz-Rosshandler,Angélica Martínez-Hernández,Francisco Campos,Federico Centeno-Cruz,Faustino Gálvez,Diana Gabriela Maldonado-Pintado,Armando Castillo,Hernán Maydón,Claudia Rangel-Escareño,Lorena Orozco,Carlos Zerrweck,Emilio J Cordova

doi:10.1186/s12881-018-0542-8

Francisco Barajas-Olmos, Iván Imaz-Rosshandler + Show 11 more

Open Access

https://doi.org/10.1186/s12881-018-0542-8

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Abstract

BackgroundObesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose tissues, liver, and blood from individuals with obesity.MethodsThe study included individuals with obesity, with and without T2D. From these patients, we obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose tissues (n = 30), and peripheral blood (n = 38). We analyzed DNA methylation using Illumina Infinium Human Methylation arrays, and gene expression profiles using HumanHT-12 Expression BeadChip Arrays.ResultsAnalysis of DNA methylation profiles revealed several loci with differential methylation between individuals with and without T2D, in all tissues. Aberrant DNA methylation was mainly found in the liver and visceral adipose tissue. Gene ontology analysis of genes with altered DNA methylation revealed enriched terms related to glucose metabolism, lipid metabolism, cell cycle regulation, and response to wounding. An inverse correlation between altered methylation and gene expression in the four tissues was found in a subset of genes, which were related to insulin resistance, adipogenesis, fat storage, and inflammation.ConclusionsOur present findings provide additional evidence that aberrant DNA methylation may be a relevant mechanism involved in T2D pathogenesis among individuals with obesity.

Highlights

Obesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), the precise mechanisms underlying the relationship remain unknown
To determine whether the DNA methylation differences between Diabetic individuals with obesity (DO) and non-diabetic individuals with obesity (NDO) led to functional effects in transcription, we investigated the correlation of DNA methylation with gene expression data, using a previously reported strategy [15]
In summary, here we provide a catalog of genes affected by altered methylation in liver, visceral and adipose tissues, and peripheral blood samples from patients with obesity and T2D

Summary

Introduction

Obesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), the precise mechanisms underlying the relationship remain unknown. Recent decades have seen an accelerated increase of the worldwide prevalence of overweight and obesity [1] At this time, the leading causes of adult mortality are co-morbid conditions associated with obesity, such as cardiovascular diseases, T2D, and cancer [2]. Barajas-Olmos et al BMC Medical Genetics (2018) 19:28 varies considerably among individuals with obesity, many of them do not progress to the diabetic state [6]. Both obesity and T2D are associated with many polymorphisms, but they share only a few susceptibility loci [7]. We still lack sufficient understanding of the precise molecular mechanisms underlying T2D pathophysiology, regarding mechanisms involving metabolic pathways in insulin target tissues [8]

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