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

• Published in: The international journal of biochemistry & cell biology Vol. 55; pp. 40 - 50
• Main Authors: Malodobra-Mazur, Malgorzata, Dziewulska, Anna, Kozinski, Kamil, Dobrzyn, Pawel, Kolczynska, Katarzyna, Janikiewicz, Justyna, Dobrzyn, Agnieszka
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.2014
• Subjects: 3T3-L1 Cells; Adipocytes - cytology; Adipocytes - metabolism; Adipocytokines; Animals; Blotting, Western; Cell Differentiation - genetics; CpG Islands - genetics; Cytokine Receptor gp130 - genetics; Cytokine Receptor gp130 - metabolism; Deoxyribonucleic acid; DNA Methylation; Enzymes; Gene expression; Gene Expression Regulation; Genes; Inflammation; Inflammation Mediators - metabolism; Interleukin; Interleukin-10 Receptor alpha Subunit - genetics; Interleukin-10 Receptor alpha Subunit - metabolism; Interleukin-4 Receptor alpha Subunit - genetics; Interleukin-4 Receptor alpha Subunit - metabolism; Methylation; Mice; Promoter methylation; Promoter Regions, Genetic - genetics; Receptors; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; SCD1; Sequence Analysis, DNA; Stearoyl-CoA Desaturase - genetics; Stearoyl-CoA Desaturase - metabolism; Transducers; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Atf2; Cxcl12; TNFα; Il6st; Il; MUFA; WAT; Il10ra; LPS; SFA; Tbck; Tgfb1; MCP1; FAs; SCD1; Inha; Cx3cl1; Tyk2; Promoter methylation; Inflammation; Mif; Gene expression; Adipocytokines; IL6; TG; Fadd; Gata3; Ltb; SAM
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2014.08.005

•Global DNA methylation level in adipocytes depends on SCD1 expression/activity.•SCD1 regulates the methylation of CpG promoter sites of inflammatory genes (Il10ra, Il4ra, Il6st, and Tgfb1).•SCD1 affects adipocyte inflammation by changes in methylation of the inflammatory genes. 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.