Epigenetic Regulation of Depot-Specific Gene Expression in Adipose Tissue

Abstract

In humans, adipose tissue is distributed in subcutaneous abdominal and subcutaneous gluteal depots that comprise a variety of functional differences. Whereas energy storage in gluteal adipose tissue has been shown to mediate a protective effect, an increase of abdominal adipose tissue is associated with metabolic disorders. However, the molecular basis of depot-specific characteristics is not completely understood yet. Using array-based analyses of transcription profiles, we identified a specific set of genes that was differentially expressed between subcutaneous abdominal and gluteal adipose tissue. To investigate the role of epigenetic regulation in depot-specific gene expression, we additionally analyzed genome-wide DNA methylation patterns in abdominal and gluteal depots. By combining both data sets, we identified a highly significant set of depot-specifically expressed genes that appear to be epigenetically regulated. Interestingly, the majority of these genes form part of the homeobox gene family. Moreover, genes involved in fatty acid metabolism were also differentially expressed. Therefore we suppose that changes in gene expression profiles might account for depot-specific differences in lipid composition. Indeed, triglycerides and fatty acids of abdominal adipose tissue were more saturated compared to triglycerides and fatty acids in gluteal adipose tissue. Taken together, our results uncover clear differences between abdominal and gluteal adipose tissue on the gene expression and DNA methylation level as well as in fatty acid composition. Therefore, a detailed molecular characterization of adipose tissue depots will be essential to develop new treatment strategies for metabolic syndrome associated complications.

Differentiation and characterization of human facial subcutaneous adipocytes

“…15 A significant change of almost 9 fold up regulation in the facial adipocytes is also registered for the DIO2 gene (deiodinase, iodothryonine, type II), which is a marker of brown adipocytes.…”

“…suggested epigenetic regulation, in particular, DNA methylation of HOX genes as a mechanism that explains how this transcriptional factors exhibit such a distinct depot specific expression pattern. 15 A strong correlation between HOX gene expression and body fat mass has been observed. 16,26 Dankel et.…”

“…16 Among the genes that posses a metabolic involvement, phospholipase A2, group 2A (PLA2G2A), fibroblast growth factor 10 (FGF10) and insulin -like growth factor binding protein 5 (IGFBP5) were found to be regulated depot specifically between abdominal compared to gluteal fat. 15 Differential fatty acid composition was also reported, showing abdominal fat tissue has more saturated fatty acids than gluteal region. 15 In this study, we undertook for the first time the isolation, culture, characterization, and induced differentiation in vitro of facial preadipocytes obtained from face lift surgery.…”

“…15 Differential fatty acid composition was also reported, showing abdominal fat tissue has more saturated fatty acids than gluteal region. 15 In this study, we undertook for the first time the isolation, culture, characterization, and induced differentiation in vitro of facial preadipocytes obtained from face lift surgery. The focus was to identify possible differences of the facial preadipocytes in differentiation pattern and metabolic properties in relation to abdominal preadipocytes isolated from the adjacent to the dermis subcutaneous layer.…”

“…15,16 For example, Gesta et.al have shown the difference in gene expression pattern between visceral and subcutaneous fat cells (mature adipocytes as well as preadipocytes) from mice and human by microarray analysis, and found that developmental genes such as homeobox (HOX) genes are one of the most profoundly changed, suggesting a new function of these genes in body fat distribution. 16 Among the genes that posses a metabolic involvement, phospholipase A2, group 2A (PLA2G2A), fibroblast growth factor 10 (FGF10) and insulin -like growth factor binding protein 5 (IGFBP5) were found to be regulated depot specifically between abdominal compared to gluteal fat.…”