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BMC Med Genet. 2018 Feb 21;19(1):28. doi: 10.1186/s12881-018-0542-8.

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

Author information

1
Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS México City, Mexico.
2
Clínica Integral de Cirugía para la Obesidad y Enfermedades Metabólicas, Hospital General Tláhuac, Secretaría de Salud de la CDMX, México City, Mexico.
3
Computational Genomics Consortium, Instituto Nacional de Medicina Genómica, SS México City, Mexico.
4
Hospital Ángeles Pedregal, México City, Mexico.
5
Clínica Integral de Cirugía para la Obesidad y Enfermedades Metabólicas, Hospital General Dr. Rubén Leñero, Secretaría de Salud de la CDMX, México City, Mexico.
6
Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS México City, Mexico. lorozco@inmegen.gob.mx.

Abstract

BACKGROUND:

Obesity 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.

METHODS:

The 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.

RESULTS:

Analysis 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.

CONCLUSIONS:

Our present findings provide additional evidence that aberrant DNA methylation may be a relevant mechanism involved in T2D pathogenesis among individuals with obesity.

KEYWORDS:

Adipose tissue; DNA methylation; Gene expression; Type 2 diabetes; and liver tissue

PMID:
29466957
PMCID:
PMC5822594
DOI:
10.1186/s12881-018-0542-8
[Indexed for MEDLINE]
Free PMC Article

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