Dysfunctional Gene Regulation of Obesity studied in Subcutaneous Adipose Tissue

[ File # csp5751103, License # 1467423 ] Licensed through http://www.canstockphoto.com in accordance with the End User License Agreement (http://www.canstockphoto.com/legal.php) (c) Can Stock Photo Inc. / pixelbrat

DNA methylation is a process wherein methyl groups are added to DNA and when this process occurs specifically occurs in the nucleotide cytosine present in the CpG site (cytosine separated by a phosphate) it is methylated to form 5-methylcytosine. This methylation within the gene and alters its expression, mostly suppressing it. Studies related to alterations in DNA are termed epigenetics and one of its very many aims is to comprehend how obesity and its related comorbidites occur due to DNA methylation.

A collaborative study between the Department of Epigenetics, German Institute of Human Nutrition Potsdam-Rehbrueke (DIfE), Nuthetal; AOK Research Insititute (AOK), Berlin; University of Saarland, Saarbrüken and University of Rostock, Rostock was published in the journal of Nutrition & Diabetes this month, where they focussed on studying the regional distribution of body fat in relation to DNA methylation within promoters of 3 genes involved in the regulation of fat metabolism in the subcutaneous adipose tissue (SAT). Under strict regulations of the Ethics committee, the study began in 2009 and SAT samples were collected from humans.

DNA methylation i.e. the CpG islands of 3 genes were studied namely, Lipoprotein lipase (LPL); adiponectin encoding gene ADIPOQ and peroxisome proliferator-activated receptor γ (PPARγ). LPL regulates the uptake of triglycerides and fatty acids into the AT so that fat can be metabolised, adiponectin regulates insulin sensitivity and PPARγ regulates metabolism plus insulin levels. It is known that there are defects in the expression of these genes in obesity, mainly being too less.

This investigation found increased DNA methylation only in the CpG sites of LPL in AT, directly correlating to the fact that the expression is drastically reduced in obese subjects but failed to prove the same in the CpG sites of ADIPOQ and PPARγ. Dr. Drogan and his team speculate that this lack of reproducibility of results in ADIPOQ and PPARγ sites could be due to different cell types of people, non-homogenous cell samples, obesity-induced macrophage infiltration. They strongly believe that there is a possibility to disprove this data with more samples and more methylation sites in the future.

However, the key message of the study was regional fat distribution (SAT) is associated with differential DNA methylation in genes that encode key proteins involved in the regulation of AT metabolism. This directly links the degree of obesity with the susceptibility to develop a metabolic dysfunction.

The original publication can be accessed here.