Genome Profiling of H3k4me3 Histone Modification in Human Adipose Tissue during Obesity and Insulin Resistance

Abstract

Background: Adipose tissue (AT) dysfunction is involved in obesity-related comorbidities. Epigenetic alterations have been recently associated with AT deterioration in obesity conditions. In this work, we profiled the H3K4me3 histone mark in human AT, with special emphasis on the changes in the pattern of histone modification in obesity and insulin resistance (IR). Visceral AT (VAT) was collected and subjected to chromatin immunoprecipitation (ChIP) using anti-H3K4me3 antibody and then sequenced to obtain the H3K4me3 genome profile. Results: We found that most of the H3K4me3 enriched regions were located in gene promoters of pathways related to AT biology and function. H3K4me3 enrichment at gene promoters was strongly related to higher mRNA levels. Differentially expressed genes in AT of patients classified as non-obese, obese with low IR, and obese with high IR could be regulated by differentially enriched H3K4me3; these genes encoded for pathways that could in part explain AT functioning during obesity and insulin resistance (e.g., extracellular matrix organization, PPARG signaling or inflammation). Conclusions: In conclusion, we emphasize the importance of the epigenetic mark H3K4me3 in VAT dysfunction in obesity and IR. The understanding of such mechanisms could give rise to the development of new epigenetic-based pharmacological strategies to ameliorate obesity-related comorbidities.

Visceral Adipose Tissue Molecular Networks and Regulatory microRNA in Pediatric Obesity: An In Silico Approach

“…Kochmanski et al [ 32 ] studied DNA methylation patterns in neonatal blood spots and found both LEP and SREBF1 to be associated with growth and adiposity. Notably, epigenetic-based pharmacological strategies are being explored in VAT to ameliorate obesity-related comorbidities [ 34 ]. TIMP1 is a negative regulator of adipogenesis.…”

Exploring the Intricate Interplay of Epigenetic Mechanisms in the Pathophysiology of Obesity: an Overview

“…Insulin is a hormone that helps cells to absorb glucose from the blood. People with obesity have higher levels of histone H3K4me3 in adipocytes (18). This condition suggests that histone H3K4me3 may play a role in the development of insulin resistance.…”

“…A study has detected differentially expressed genes in adipose tissue of non-obese, obese with low insulin resistance, and obese with high insulin resistance, which could be controlled by the differentially enhanced H3K4me3 (18). H3K4me3 is a histone modification that is associated with gene activation.…”

“…In contrast, histone H3K4me3 reduces gene expression in fat burning. People with obesity have higher levels of histone H3K4me3 in adipocytes (18); hence, suggesting that histone H3K4me3 may play a role in the development of obesity. Moreover, H3K4me3 is also involved in insulin resistance, a condition in which cells do not respond normally to insulin.…”

Nutritional programming of white adipose tissue and mitochondrial function : Fat quality matters

“…Further insight in the role of epigenetic analyses can be obtained by analyses of histone modifications (acetylation and methylation). Specific histone modifications are seen with obesity and insulin resistance in WAT of human subjects (H3K4me3 and H3K9/14c) and with mitochondrial dysfunction (H3K9me2 and H3K27me2/3) and may be a good starting point to assess the effect of the Concept on histone modifications (110)(111)(112).…”