Dataset Information

Integrative Analysis Revealing Human Adipose-Specific Genes and Consolidating Obesity Loci.

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.

SUBMITTER: Ahn J

PROVIDER: S-EPMC6395763 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Integrative Analysis Revealing Human Adipose-Specific Genes and Consolidating Obesity Loci.

Ahn Jinsoo J Wu Huiguang H Lee Kichoon K

Scientific reports 20190228 1

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 adi ...[more]

PMID: 30816281

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Project description:Transforming growth factor beta (Tgfb) is a well-studied pro-fibrotic cytokine, which upregulates cellular communication network factor 2 (Ccn2), collagen, and actin alpha 2, smooth muscle (Acta2) expression. Obesity induces adipose tissue fibrosis, which contributes to metabolic diseases. This work aimed to analyze the expression of Tgfb, Ccn2, collagen1a1 (Col1a1), Acta2 and BMP and activin membrane-bound inhibitor (Bambi), which is a negative regulator of Tgfb signaling, in different adipose tissue depots of mice fed a standard chow, mice fed a high fat diet (HFD) and ob/ob mice. Principally, these genes were low expressed in brown adipose tissues and this difference was less evident for the ob/ob mice. Ccn2 and Bambi protein as well as mRNA expression, and collagen1a1 mRNA were not induced in the adipose tissues upon HFD feeding whereas Tgfb and Acta2 mRNA increased in the white fat depots. Immunoblot analysis showed that Acta2 protein was higher in subcutaneous and perirenal fat of these mice. In the ob/ob mice, Ccn2 mRNA and Ccn2 protein were upregulated in the fat depots. Here, Tgfb, Acta2 and Col1a1 mRNA levels and serum Tgfb protein were increased. Acta2 protein was, however, not higher in subcutaneous and perirenal fat of these mice. Col6a1 mRNA was shown before to be higher in obese fat tissues. Current analysis proved the Col6a1 protein was induced in subcutaneous fat of HFD fed mice. Notably, Col6a1 was reduced in perirenal fat of ob/ob mice in comparison to the respective controls. 3T3-L1 cells express Ccn2 and Bambi protein, whose levels were not changed by fatty acids, leptin, lipopolysaccharide, tumor necrosis factor and interleukin-6. All of these factors led to higher Tgfb in 3T3-L1 adipocyte media but did not increase its mRNA levels. Free fatty acids induced necrosis whereas apoptosis did not occur in any of the in vitro incubations excluding cell death as a main reason for higher Tgfb in cell media. In summary, Tgfb mRNA is consistently induced in white fat tissues in obesity but this is not paralleled by a clear increase of its target genes. Moreover, discrepancies between mRNA and protein expression of Acta2 were observed. Adipocytes seemingly do not contribute to higher Tgfb mRNA levels in obesity. These cells release more Tgfb protein when challenged with obesity-related metabolites connecting metabolic dysfunction and fibrosis.

Dataset Information

Integrative Analysis Revealing Human Adipose-Specific Genes and Consolidating Obesity Loci.

Publications

Integrative Analysis Revealing Human Adipose-Specific Genes and Consolidating Obesity Loci.

Similar Datasets

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