Abstract

A higher level of IL10 expression in obesity and insulin resistance was observed in both human and mouse WAT. In our research, we analyzed the influence of insulin resistance on epigenetic modification within the promoter region IL10 gene and the potential influence of these modifications on its expression. Studies were performed using two cell models for the analysis: human, preadipocytes derived from adipose (visceral and subcutaneous) tissues and murine 3T3-L1 fibroblasts. We demonstrated a significant increase in the IL10 expression level, IL10 promoter region methylation, and histone 3 epigenetic modifications: H3K4me and H3K9/14ac, in insulin resistance cells (IR) from SAT cell culture. In IR cells from VAT cell culture, we observed decreased IL10 expression with a simultaneous increase of IL10 promoter region methylation. In IR cells from 3T3L1 cell culture, we observed the increased expression of IL10 as well as the decreased levels of methylation in the IL10 promoter region and histone methylation (H3K4me) and acetylation (H3K9/14ac). The presented analyses suggest a potential impact of epigenetic modifications on gene expression and a potential mutual influence of epigenetic modifications on each other or the activation of specific epigenetic regulation at a different stage of the development of insulin resistance in cells.

Highlights

  • We analyzed the influence of insulin resistance on epigenetic modification within the promoter region of the gene encoding

  • The use of adipocytes in the study is essential in the analysis of potential relationships between obesity and insulin resistance

  • Insulin resistance and obesity belong to serious epidemiological problems in the world

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Summary

Introduction

The excessive accumulation of adipose tissue is associated with environmental, metabolic, psychological, endocrine and genetic factors. The process of excessive adipogenesis causes changes in metabolism and endocrine function, which can lead to an increased release of hormones, fatty acids and proinflammatory factors that contribute to metabolic disorders. One of the pathomechanisms that could explain the relationship between obesity and insulin resistance is chronic inflammation. Obesity is characterized by altered levels of circulating cytokines, adipose tissue macrophage accumulation, and inflammation state [3,4]. Studies conducted on both murine and human tissues indicate an increased accumulation of proinflammatory factors and cells in white adipose tissue (WAT) [5,6,7]

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