DNA methylation of the Klf14 gene region in whole blood cells provides prediction for the chronic inflammation in the adipose tissue

Iwaya, Chihiro; Kitajima, Hidetoshi; Yamamoto, Ken; Maeda, Yasutaka; Sonoda, Noriyuki; Shibata, Hiroki; Inoguchi, Toyoshi

doi:10.1016/j.bbrc.2017.12.104

Cited by 25 publications

(20 citation statements)

References 29 publications

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“…In addition to the possible reduction of these compounds, spermine suppresses LFA-1 expression via regulation of gene methylation. Because inflammation is also closely associated with gene methylation [ 44 , 368 , 369 , 370 , 371 ], suppression of immune cell activation may counteract the progression of aging-associated pathologies.…”

Section: Future Perspectivesmentioning

confidence: 99%

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Soda

2018

IJMS

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Recent investigations have revealed that changes in DNA methylation status play an important role in aging-associated pathologies and lifespan. The methylation of DNA is regulated by DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) in the presence of S-adenosylmethionine (SAM), which serves as a methyl group donor. Increased availability of SAM enhances DNMT activity, while its metabolites, S-adenosyl-l-homocysteine (SAH) and decarboxylated S-adenosylmethionine (dcSAM), act to inhibit DNMT activity. SAH, which is converted from SAM by adding a methyl group to cytosine residues in DNA, is an intermediate precursor of homocysteine. dcSAM, converted from SAM by the enzymatic activity of adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize the polyamines spermine and spermidine. Increased homocysteine levels are a significant risk factor for the development of a wide range of conditions, including cardiovascular diseases. However, successful homocysteine-lowering treatment by vitamins (B6, B12, and folate) failed to improve these conditions. Long-term increased polyamine intake elevated blood spermine levels and inhibited aging-associated pathologies in mice and humans. Spermine reversed changes (increased dcSAM, decreased DNMT activity, aberrant DNA methylation, and proinflammatory status) induced by the inhibition of ornithine decarboxylase. The relation between polyamine metabolism, one-carbon metabolism, DNA methylation, and the biological mechanism of spermine-induced lifespan extension is discussed.

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Section: Future Perspectivesmentioning

confidence: 99%

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Soda

2018

IJMS

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“…The downregulated expression of KLF14 in endothelial cells in both acute and chronic inflammatory conditions suggests an insufficient effect of KLF14 in inflammatory response. Iwaya et al also reported that methylation level of KLF14 is increased in the adipose tissue after HFD challenge and this epigenetic change is significantly associated with inflammatory levels 29 . Restoration of KLF14 in human endothelial cells by adenovirus-mediated overexpression inhibits the upregulation of adhesion molecules induced by pro-inflammatory factors.…”

Section: Discussionmentioning

confidence: 95%

Krüppel-like factor 14, a coronary artery disease associated transcription factor, inhibits endothelial inflammation via NF-κB signaling pathway

Zhang

et al. 2018

Atherosclerosis

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“…Their study showed that, the expression of Klf14 was reduced in adipose tissue of aged wild type mice and HFD-fed mice and consistent with this change in expression, Klf14 promoter region was hypermethylated in adipose tissue in response to aging and HFD. Consistent with reduced Klf14 expression, downstream target genes, many of which were associated with metabolic traits (88,89), were also downregulated (87). In a study by Bacos et al KLF14 hypermethylation was also associated with aging, insulin secretion and T2D (90).…”

Section: The Role Of Klf14 In Adipose Tissuementioning

confidence: 86%

“…In a recent study, Iwaya et al analyzed the DNA methylation status of the Klf14 promoter in adipose tissue to investigate if there was a correlation between aging and state of obesity, both of which are risk factors of T2D (87). Their study showed that, the expression of Klf14 was reduced in adipose tissue of aged wild type mice and HFD-fed mice and consistent with this change in expression, Klf14 promoter region was hypermethylated in adipose tissue in response to aging and HFD.…”

Section: The Role Of Klf14 In Adipose Tissuementioning

confidence: 99%

Transcription Factor KLF14 and Metabolic Syndrome

Yang

Civelek

2020

Front. Cardiovasc. Med.

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Metabolic syndrome (MetSyn) is a combination of metabolic abnormalities that lead to the development of cardiovascular disease (CVD) and Type 2 Diabetes (T2D). Although various criteria for defining MetSyn exist, common abnormalities include abdominal obesity, elevated serum triglyceride, insulin resistance, and blood glucose, decreased high-density lipoprotein cholesterol (HDL-C), and hypertension. MetSyn prevalence has been increasing with the rise of obesity worldwide, with significantly higher prevalence in women compared with men and in Hispanics compared with Whites. Affected individuals are at a higher risk of developing T2D (5-fold) and CVD (2-fold). Heritability estimates for individual components of MetSyn vary between 40 and 70%, suggesting a strong contribution of an individual's genetic makeup to disease pathology. The advent of nextgeneration sequencing technologies has enabled large-scale genome-wide association studies (GWAS) into the genetics underlying MetSyn pathogenesis. Several such studies have implicated the transcription factor KLF14, a member of the Krüpple-like factor family (KLF), in the development of metabolic diseases, including obesity, insulin resistance, and T2D. How KLF14 regulates these metabolic traits and increases the risk of developing T2D, atherosclerosis, and liver dysfunction is still unknown. There have been some debate and controversial results with regards to its expression profile and functionality in various tissues, and a systematic review of current knowledge on KLF14 is lacking. Here, we summarize the research progress made in understanding the function of KLF14 and describe common attributes of its biochemical, physiological, and pathophysiological roles. We also discuss the current challenges in understanding the role of KLF14 in metabolism and provide suggestions for future directions.

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DNA methylation of the Klf14 gene region in whole blood cells provides prediction for the chronic inflammation in the adipose tissue

Cited by 25 publications

References 29 publications

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Krüppel-like factor 14, a coronary artery disease associated transcription factor, inhibits endothelial inflammation via NF-κB signaling pathway

Transcription Factor KLF14 and Metabolic Syndrome

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