Abstract

Identification of adipose-specific genes has contributed to an understanding of mechanisms underlying adipocyte development and obesity. Herein, our analyses of the recent Genotype-Tissue Expression (GTEx) database revealed 38 adipose-specific/enhanced protein coding genes, among which 3 genes were novel adipose-specific, and 414 highly differentially expressed genes (DEGs) between subcutaneous and omental adipose depots. By integrative analyses of genome-wide association studies (GWASs), 14 adipose-specific/enhanced genes and 60 DEGs were found to be associated with obesity-related traits and diseases, consolidating evidence for contribution of these genes to the regional fat distribution and obesity phenotypes. In addition, expression of HOXC cluster was up-regulated in subcutaneous adipose tissue, and the majority of the HOXB cluster was expressed highly in omental adipose tissue, indicating differential expression patterns of HOX clusters in adipose depots. Our findings on the distinct gene expression profiles in adipose tissue and their relation to obesity provide an important foundation for future functional biological studies and therapeutic targets in obesity and associated diseases.

Highlights

  • Functional studies about adipose-specific genes have increased our understanding of adipocyte biology and their etiological significance for the obesity and related diseases

  • Prior to initiating our workflow (Fig. 1), the Genotype-Tissue Expression (GTEx) dataset was downloaded from the GTEx portal, and adipose-specific genes under the category of adipose-enhanced genes were explored

  • Distribution of medians in the GTEx dataset was first examined by plotting the number of genes against their relative median values, defined as a median expression value of subcutaneous or omental adipose tissue divided by an average of other medians (Fig. 2a)

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Summary

Introduction

Functional studies about adipose-specific genes have increased our understanding of adipocyte biology and their etiological significance for the obesity and related diseases. A large number of candidate genes for obesity have been documented by genome-wide association studies (GWAS) to determine genetic factors associated with obesity[25,26,27,28,29]. Despite findings from these studies, evidence linking adipose-specific genes and obesity in humans is still unclear. Our analysis of diverse databases have identified novel adipose-specific genes and consolidated evidence for their genetic relationship with obesity, providing a basis for further elucidation of therapeutic targets for obesity and related diseases

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