321-LB: The Link between Obesity and Changes in Epigenetic Marks in Adipose Tissue—In Vivo Study

Obesity is a leading problem in modern civilization. It is also the main risk factor of metabolic disorders like insulin resistance or type 2 diabetes. Numerous studies indicate in obesity the aberrant profile of various genes expressions like insulin signaling, adipokines, and cytokines genes as well as transcription factors regulating adipocytes development and metabolism. One of the reasons that might lead to dysregulation in genes expression is epigenetic changes in chromatin. In our study, we compared the global and site-specific DNA methylation and histones modifications (activate expression: H3K4me3 and H3K9ac, responsible for chromatin repression: H3K9me3) between subcutaneous (SAT) and visceral (VAT) adipose tissue from patients in a wide range of BMI with equal distribution of sex and in similar age. We have displayed a slight difference between epigenetic marks between SAT and VAT of enrolled patients, however, when classified into two groups according to BMI (lean group <25 kg/m² and obese group ≥25 kg/m²) the difference in analyzed epigenetic markers were major. We found that global DNA methylation was increased in the obese group compared to lean, both in SAT and VAT. What is more, a similar correlation occurs in the case of site-specific methylation. The increased methylation of CpG islands was observed within promotor of the two important genes - PPARγ and CEBPα, transcription factors that regulate numerous genes in adipocytes metabolism, including insulin pathway. The observed epigenetic modifications in obesity may suggest a role of epigenetic regulation in the development of obesity. In addition, in the obese group, apart from increased methylation within DNA, we also observed disorders in the level of expression of genes which are important for the metabolic pathway, including the insulin pathway. These results may suggest a potential mechanism with an epigenetic regulation basis, which is responsible for the coexistence of metabolic disorders with obesity.