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

Małodobra-Mazur, Małgorzata; Dziewulska, Anna; Koziński, Kamil; Dobrzyń, Paweł; Kolczyńska, Katarzyna; Janikiewicz, Justyna; Dobrzyń, Agnieszka

doi:10.1016/j.biocel.2014.08.005

Cited by 34 publications

(31 citation statements)

References 52 publications

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“…Significant methylation differences were detected in the promoter regions of 7 genes; moreover, DNA methylation levels were altered to different degrees after infection with different strains (Mukherjee et al, 2013). Malodobra-Mazur et al (2014) studied the regulatory activity of stearoyl-CoA desaturase in 22 genes involved in the inflammatory response in 3T3-L1 adipocytes, and reported that the overexpression or silencing of stearoyl-CoA desaturase 1 led to changes in the methylation of inflammatory genes, in turn causing changes in the related genes. In this study, the DNA methylation levels were altered in various immune organs following H5N1 infection, indicating that DNA methylation is involved in the regulation of gene expression in avian influenza.…”

Section: Discussionmentioning

confidence: 99%

Changes in methylation of genomic DNA from chicken immune organs in response to H5N1 influenza virus infection

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Changes in methylation of genomic DNA from chicken immune organs in response to H5N1 influenza virus infection

et al. 2016

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“…Moreover, they also observed a reduction in total TAG and the SCD-18 desaturation ratio in SCD1-inhibited adipocytes [162]. Additional studies that have used inhibitors or other techniques to reduce SCD1 activity in adipocyte models include work by Yee et al [112].…”

Section: Malodobra-mazur Et Al Used the Same Scd1 Inhibitor As Hyun mentioning

confidence: 96%

“…SCD1 influences inflammation through altered DNA methylation [162]. Moreover, they also observed a reduction in total TAG and the SCD-18 desaturation ratio in SCD1-inhibited adipocytes [162].…”

Section: Malodobra-mazur Et Al Used the Same Scd1 Inhibitor As Hyun mentioning

confidence: 98%

“…SCD1 has been previously associated 100 with alterations in cellular inflammation and stress, where primary adipocytes isolated from whole-body SCD1-deficient mice were shown to have reduced inflammation compared to wildtype adipocytes [120,193]. Additionally, Malodobra-Mazur et al have recently shown that SCD1 can mediate inflammation in 3T3-L1 adipocytes by regulating DNA methylation [162].…”

Section: Introductionmentioning

confidence: 98%

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Elucidating the roles of stearoyl-CoA desaturase 1 in adipocyte fatty acid metabolism and cellular function

Ralston

2015

Appl. Physiol. Nutr. Metab.

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Worldwide obesity rates have risen to epidemic proportions, with over 600 million obese individuals across the globe. These individuals are prone to obesity-related health complications including type 2 diabetes, hypertension, cancer and cardiovascular disease. Obesity also coincides with the expansion of adipose tissue (AT), which has an important role storing excess calories in the form of triacylglycerol (TAG) within adipocyte lipid droplets. The predominant fatty acids (FAs) comprising adipocyte TAGs are monounsaturated FAs (MUFAs), which are produced by stearoyl-CoA desaturase 1 (SCD1). Specifically, SCD1 converts saturated FAs palmitate (PA) and stearate (SA) into palmitoleate (PMA) and oleate (OA), respectively.Interestingly, whole-body SCD1-deficiency is associated with reduced lipogenesis and adiposity.This places SCD1 as a potential target for obesity therapies; however, our understanding of the mechanisms linking SCD1 with changes in adipocyte function remains unclear. This thesis provides important new insights into how SCD1 impacts adipocyte FA metabolism and cellular function. Using a specific SCD1 inhibitor, changes in lipid metabolism, global gene expression, inflammation, cellular stress and basal insulin signaling were assessed in 3T3-L1 adipocytes.Results demonstrated that SCD1 inhibition caused a reduction in TAGs and phospholipids, which coincided with the down-regulation of genes associated with the biosynthesis of these lipid fractions. Cellular diacylglyerols were increased with SCD1 inhibition and insulin signaling was partially impaired. In contrast, markers of cellular stress were unaltered. Furthermore, the FA composition of each lipid fraction was dramatically modified, with SCD1-inhibited adipocytes specifically up-regulating the elongation of PA to SA. Stable isotope tracer experiments revealed that this elongation was occurring via elongase 6. Additionally, reduced SCD1 activity in adipocytes exacerbated the effects of exogenous SA on markers or inflammation. Taken together, SCD1 activity has many indirect influences on adipocyte metabolism in addition to its role in FA desaturation. Importantly, SCD1 facilitates the storage of FAs in TAGs and the ability of adipocytes to handle exogenous FAs. SCD1 also prevents saturated FA and DAG accumulation, and preserves insulin signaling in adipocytes. Ultimately this thesis highlights the importance of SCD1 in the maintenance of adipocyte cellular function, and emphasizes the wide-ranging impact of SCD1 on adipocyte FA metabolism.iv

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“…Recently published results of the study performed by Malodobra-Mazur et al on differentiated 3T3-L1 adipocytes suggested that the level of proinflammatory cytokine expression might be regulated by stearoyl-CoA desaturase 1 (SCD1) through DNA methylation [32]. SCD1, an enzyme highly expressed in differentiated adipocytes, is responsible for the biosynthesis of monounsaturated fatty acids from saturated fatty acids.…”

Section: Epigenetic Modifications In Adipose Tissuementioning

confidence: 99%

Epigenetic modifications in adipose tissue – relation to obesity and diabetes

Kasińska

Drzewoski

Śliwińska

2016

aoms

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The growing number of people suffering from obesity and type 2 diabetes mellitus (T2DM) is a global health problem that results in increased mortality from their complications, mainly cardiovascular diseases. Although the relationship between obesity and T2DM is well established, the common molecular pathomechanisms are still under investigation. Recently, it has been suggested that epigenetic modifications may be involved in both obesity and T2DM development. Epigenetics plays a pivotal role in the regulation of gene expression by the reversible modifications of chromatin structure without any changes in DNA sequence. Epigenetic modifications include DNA methylation, posttranslational histone modifications and miRNA interference. Therefore, the aim of this article is to discuss the current knowledge on epigenetic modifications in adipose tissue and their association with obesity and T2DM.

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

Cited by 34 publications

References 52 publications

Changes in methylation of genomic DNA from chicken immune organs in response to H5N1 influenza virus infection

Changes in methylation of genomic DNA from chicken immune organs in response to H5N1 influenza virus infection

Elucidating the roles of stearoyl-CoA desaturase 1 in adipocyte fatty acid metabolism and cellular function

Epigenetic modifications in adipose tissue – relation to obesity and diabetes

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