S-adenosylmethionine mediates inhibition of inflammatory response and changes in DNA methylation in human macrophages

Pfalzer, Anna C; Choi, Sang‐Woon; Tammen, Stephanie A.; Park, Lara K.; Bottiglieri, Teodoro; Parnell, Laurence D.; Lamon‐Fava, Stefania

doi:10.1152/physiolgenomics.00056.2014

Cited by 72 publications

(47 citation statements)

References 46 publications

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“…For 60% mouse high-fat diet studies, plasma and liver metabolites were analyzed by LC-MS (19). Liver betaine, S-adenosylmethionine, S-adenosylhomocysteine, methionine, and choline were quantified using stable-isotope dilution liquid chromatography–electrospray ionization tandem mass spectrometry (Baylor Research Institute, Dallas, TX) (20). Hepatic lipid was quantified in chloroform-methanol extracts (50 mg) using a Triglyceride Assay kit (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice

et al. 2016

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Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21−/− mice, demonstrating that Fgf21 is necessary for betaine’s beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans.

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Section: Methodsmentioning

confidence: 99%

Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice

et al. 2016

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“…SAM is a methyl donor in DNA methylation, and has been shown to lower lipopolysaccharide-induced expression of the proinflammatory cytokine TNF-α and increase the expression of the anti-inflammatory cytokine IL-10 in macrophages. SAM was found to modulate the expression of inflammatory genes in association with changes in specific gene promoter DNA methylation [55]. Treatment with folic acid (FA)/B12 was found to be associated with more rapid progression of coronary artery disease (CAD).…”

Section: Discussionmentioning

confidence: 99%

An Epigenome-Wide Association Study of Inflammatory Response to Fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network

et al. 2017

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Aim: Fenofibrate, a PPAR-α inhibitor used for treating dyslipidemia, has well-documented anti-inflammatory effects that vary between individuals. While DNA sequence variation explains some of the observed variability in response, epigenetic patterns present another promising avenue of inquiry due to the biological links between the PPAR-α pathway, homocysteine and S-adenosylmethionine – a source of methyl groups for the DNA methylation reaction. Hypothesis: DNA methylation variation at baseline is associated with the inflammatory response to a short-term fenofibrate treatment. Methods: We have conducted the first epigenome-wide study of inflammatory response to daily treatment with 160 mg of micronized fenofibrate over a 3-week period in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n = 750). Epigenome-wide DNA methylation was quantified on CD4+ T cells using the Illumina Infinium HumanMethylation450 array. Results: We identified multiple CpG sites significantly associated with the changes in plasma concentrations of inflammatory cytokines such as high sensitivity CRP (hsCRP, 7 CpG sites), IL-2 soluble receptor (IL-2sR, one CpG site), and IL-6 (4 CpG sites). Top CpG sites mapped to KIAA1324L (p = 2.63E-10), SMPD3 (p = 2.14E-08), SYNPO2 (p = 5.00E-08), ILF3 (p = 1.04E-07), PRR3, GNL1 (p = 6.80E-09), FAM50B (p = 3.19E-08), RPTOR (p = 9.79e-07) and several intergenic regions (p < 1.03E-07). We also derived two inflammatory patterns using principal component analysis and uncovered additional epigenetic hits for each pattern before and after fenofibrate treatment. Conclusion: Our study provides preliminary evidence of a relationship between DNA methylation and inflammatory response to fenofibrate treatment.

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“…The latter is mandatory for DNA and protein methylation, and a lack of this molecule may lead to DNA hypermethylation and inflammation [15,16]. …”

Section: Causes Of Increased Inflammation In Esrdmentioning

confidence: 99%

Targeting Immunity in End-Stage Renal Disease

2017

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Background: Despite the stable incidence of end-stage renal disease (ESRD), it continues to be associated with an unacceptably high cardiovascular risk. Summary: ESRD is characterized by enhanced oxidative stress and severe inflammation, which boost cardiovascular risk, thus increasing cardiovascular-associated mortality rate. While substantial effort has been made in the technological innovation of dialytic techniques, few significant advances have been made to reduce inflammation in patients with ESRD. Indeed, this contrasts with the extensive scientific breakthroughs made in the basic field of science in targeting inflammation. There is thus a pressing need for clinical trials to test the effect of reducing inflammation in patients with ESRD. Here, we will revisit the negative effect of ESRD on inflammation and explore the impact of enhanced inflammation on cardiovascular outcomes and survival in patients with ESRD. Finally, we will discuss the need for clinical trials that target inflammation in ESRD, as well as weigh potential disadvantages and offer novel innovative approaches. Key Message: We will try to understand why the issue of inflammation has not been successfully addressed thus far in patients with ESRD, while at the same time weighing the potential disadvantages and offering novel innovative approaches for targeting inflammation in patients with ESRD.

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S-adenosylmethionine mediates inhibition of inflammatory response and changes in DNA methylation in human macrophages

Cited by 72 publications

References 46 publications

Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice

Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice

An Epigenome-Wide Association Study of Inflammatory Response to Fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network

Targeting Immunity in End-Stage Renal Disease

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