Chords represent a detailed relationship between the expression levels of up-regulated DEGs (left semicircle perimeter) and their enriched KEGG pathways (right semicircle perimeter). of the cluster was expressed highly in omental adipose tissue, indicating differential expression patterns of 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. Introduction Obesity is one of the major global health issues because of its relation to various metabolic complications including type 2 diabetes, coronary heart disease, hypertension, dyslipidemia and a number of cancers1C4. Previous studies regarding obesity identified a significant contribution of genetic factors to obesity traits5,6. Among genetic factors, genes prominently expressed in adipose tissue are involved in various metabolic and endocrine functions of adipose tissue such as adipocyte development, lipid metabolism, glucose homeostasis and immune/inflammatory responses7C9. Altered expression of these adipose-specific genes leads to an increased release of fatty acids, hormones, and pro-inflammatory cytokines that contribute to obesity-related metabolic diseases10. Functional studies about adipose-specific genes have increased our understanding of adipocyte biology and their etiological significance for the obesity and related diseases. These adipose-specific genes include genes encoding LEP/leptin (adipokine)11,12, ADIPOQ/adiponectin (adipokine)13,14, peroxisome proliferator-activated receptor gamma (PPAR; adipose-specific transcription factor)15C17, and fatty acid binding protein 4 (FABP4; adipocyte fatty acid binding protein)18,19. In the early 2000s, high throughput screening methods including gene filter and gene chip arrays became available. Several groups, including ours, identified adipose-specific genes including and genes in subcutaneous and visceral (omental) adipose tissues was examined to comprehensively evaluate developmental gene expression patterns for regional fat distribution. Herein, 3 novel common adipose-specific genes and 414 differentially expressed genes (DEGs) between subcutaneous and omental adipose depots were identified. By integrating data of GWAS, evidence of interrelationships between those genes and major obesity-related traits or diseases including adiposity, type 2 diabetes, blood lipids, inflammation, and waist-to-hip ratio, were solidified. Furthermore, differential expression patterns of genes in different adipose tissue depots were identified. Overall, 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. Results Identification of adipose-specific genes Prior to initiating our workflow (Fig.?1), the GTEx dataset was downloaded from the GTEx portal (www.gtexportal.org), and then 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 AEZS-108 or omental adipose tissue divided by an average of other medians (Fig.?2a). Most of the data were centered around the value 1 (indicating no difference), and fewer values on the right side of the value 1 represent adipose-enhanced expression (for example, expression of 64 subcutaneous AEZS-108 adipose genes hToll and 85 omental adipose genes were more than 10-fold). After the AEZS-108 above initial evaluation of the dataset, adipose-specific genes were investigated under rigorous criteria of more than median-5-fold in all pairwise comparisons and an FDR-corrected value? ?0.01. As a result, 14 subcutaneous adipose- and 11 omental adipose-specific protein coding genes were identified (Fig.?2b; Supplementary Table?1). There were 9 genes that were overlapped between subcutaneous and omental tissues, and has not been reported in terms of its function in adipose tissue (Fig.?2c; Supplementary Table?1). Regarding subcutaneous exclusive expression, the functions of the gene and (also named AEZS-108 as (expression map; and, (3) both adipose-enhanced genes and depot DEGs were located to mapped obesity-related loci published in GWAS. Open in a.
Chords represent a detailed relationship between the expression levels of up-regulated DEGs (left semicircle perimeter) and their enriched KEGG pathways (right semicircle perimeter)
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