Stearoyl-CoA desaturase regulates inflammatory gene expression by changing DNA methylation level in 3T3 adipocytes.

Abstract

Adipocytes are one of the primary sources of inflammatory cytokines that drive the low-grade inflammation associated with obesity and obesity-related diseases. Stearoyl-CoA desaturase, a key adipogenic enzyme in rodents and humans, plays significant role in the regulation of adipocyte inflammation via a mechanism that involves the regulation of inflammatory gene expression. In the present study, we tested the hypothesis that the stearoyl-CoA desaturase 1-related regulation of gene expression might be driven by changes in DNA methylation. We showed that stearoyl-CoA desaturase 1 overexpression causes the global hypomethylation of DNA, even as early as 12h after the induction of differentiation, with the greatest difference seen in mature adipocytes. In contrast, both the silencing of stearoyl-CoA desaturase 1 gene expression by siRNA and inhibition of stearoyl-CoA desaturase 1 activity resulted in DNA hypermethylation in 3T3-L1 adipocytes. The analysis of the promoter methylation of 22 genes that are related to the inflammatory response showed that the level of methylation of CpG sites in interleukin-10 receptor a, interleukin-4 receptor a, interleukin-6 signal transducer, and transforming growth factor β 1 promoters was strongly related to stearoyl-CoA desaturase 1 expression or activity. The changes in methylation at CpG promoter sites correlated with differential expression of the aforementioned genes. The results show that stearoyl-CoA desaturase 1 regulates the level of DNA methylation in adipocytes and suggest that the mechanism by which stearoyl-CoA desaturase 1 affects adipocyte inflammation may involve changes in the methylation of inflammatory genes.

• Authors: Malgorzata Malodobra-Mazur, Anna Dziewulska, Kamil Kozinski, Pawel Dobrzyn, Katarzyna Kolczynska, Justyna Janikiewicz, Agnieszka Dobrzyn
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 55 Pg. 40-50 (Oct 2014) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 25130896 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Il6st protein, mouse
• Inflammation Mediators
• Interleukin-10 Receptor alpha Subunit
• Interleukin-4 Receptor alpha Subunit
• Transforming Growth Factor beta1
• Cytokine Receptor gp130
• Scd1 protein, mouse
• Stearoyl-CoA Desaturase

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, metabolism)
• Animals
• Blotting, Western
• Cell Differentiation (genetics)
• CpG Islands (genetics)
• Cytokine Receptor gp130 (genetics, metabolism)
• DNA Methylation
• Gene Expression Regulation
• Inflammation Mediators (metabolism)
• Interleukin-10 Receptor alpha Subunit (genetics, metabolism)
• Interleukin-4 Receptor alpha Subunit (genetics, metabolism)
• Mice
• Promoter Regions, Genetic (genetics)
• RNA Interference
• Reverse Transcriptase Polymerase Chain Reaction
• Sequence Analysis, DNA
• Stearoyl-CoA Desaturase (genetics, metabolism)
• Transforming Growth Factor beta1 (genetics, metabolism)