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.

Highlights

  • In humans, different adipose tissue depots are associated with different metabolic effects. 80-90% of total body fat is stored in subcutaneous adipose tissue depots, mainly in the abdominal, subscapular and gluteal areas [1]

  • We observed genes that are involved in lipid metabolism such as fibroblast growth factor 10 (FGF 10) and phospholipase A2 (PLA2G2A), as well as genes which seem to be implicated in metabolic processes such as insulin-like growth factor binding protein 5 (IGFBP5)

  • These findings demonstrate that abdominal and gluteal adipose tissues show distinct gene expression profiles that might account for functional differences

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Summary

Introduction

Different adipose tissue depots are associated with different metabolic effects. 80-90% of total body fat is stored in subcutaneous adipose tissue depots, mainly in the abdominal, subscapular and gluteal areas [1]. Different adipose tissue depots are associated with different metabolic effects. 80-90% of total body fat is stored in subcutaneous adipose tissue depots, mainly in the abdominal, subscapular and gluteal areas [1]. It has been consistently shown that visceral fat mass is more strongly associated with metabolic syndrome than subcutaneous fat [2,3,4]. Excessive subcutaneous abdominal fat mass is strongly associated with insulin resistance and has been positively correlated with metabolic complications such as obesity [5]. Adipose tissue expands by increasing the volume of preexisting adipocytes (hypertrophy) or by generating new adipocytes through adipogenesis (hyperplasia) with a positive correlation between fat mass and fat cell volume, which is strongly linked to metabolic complications of obesity [7]. A detailed characterization of molecular differences between adipose tissue depots would provide an important basis to understand its heterogeneous characteristics and infer consequences for health and disease

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