Dataset Information

Eicosapentaenoic acid induces an anti-inflammatory transcriptomic landscape in T cells implicating a pathway independent of triglyceride lowering in cardiovascular risk reduction [RNA-seq]

ABSTRACT: A twice-daily dose of highly purified eicosapentaenoic acid (EPA) reduces the risk of atherosclerotic cardiovascular disease among patients with high triglycerides and either known cardiovascular disease or those at high risk for developing it. However, the process by which EPA exerts its beneficial effects remains ill understood. Here, we show that EPA can induce an anti-inflammatory transcriptional profile in non-activated CD4+ T cells. We find that EPA exposed CD4+ T cells downregulate immune response related genes, such as HLA-DRA, CD69, and IL2RA, while upregulating genes involved in oxidative stress prevention, such as NQO1. Furthermore, transcription footprint analysis reveals downregulation of GATA3 and PU.1, key transcription factors in TH2 and TH9 differentiation, and upregulation of REV-ERB, an antagonist of TH17 differentiation. Additionally, we examine T cell responses to two other fatty acids of varying degrees of saturation, namely oleic and palmitic acid, and find EPA has a distinct effect on CD4+ T cells transcriptomic landscape as compared to control. Thus, our study shows that EPA can already induce beneficial transcriptomic profiles in CD4+ T cells prior to activation, a process that may contribute to the unexpectedly strong beneficial effects of EPA on atherosclerotic cardiovascular disease observed in clinical trials.

ORGANISM(S): Homo sapiens

PROVIDER: GSE254695 | GEO | 2025/04/30

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background & Aims: Non-alcoholic fatty liver disease accompanies obesity and is independently associated with cardiovascular disease. Omega-3 fatty acids, such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid, reduce the risk of cardiovascular disease due to their anti-inflammatory and hypolipidemic effects. Recent data suggested that metabolic effects of EPA/DHA as marine phospholipids could be stronger than triglycerides (fish oil). We characterised the mechanisms underlying beneficial effects of EPA/DHA phospholipids alone or in combination with antidiabetic drugs on hepatosteatosis in dietary obese mice. Methods: Male C57BL/6N mice were fed for 7 weeks a corn oil-based high-fat diet (cHF) or subjected to cHF-based interventions: (i) cHF with DHA/EPA as phosphatidylcholine-rich concentrate replacing ~10 % of dietary lipids (PC); ii) cHF with a low-dose of thiazolidinedione rosiglitazone (10 mg/kg diet), which retains some of the beneficial effects but also potentiates hepatic lipid accumulation (R); and iii) PC+R. Metabolic profiling together with hepatic gene expression and lipidomic analyses were performed. Results: PC and PC+R prevented weight gain and glucose intolerance induced by cHF, while all interventions reduced abdominal fat and plasma triglycerides. In contrast to R, PC and PC+R lowered hepatic and plasma cholesterol and eliminated hepatosteatosis. Hepatic microarray analysis primarily revealed a complex downregulation of lipogenic and cholesterol biosynthesis pathways by PC. Lipidomic analysis identified arachidonic acid, DHA and EPA in hepatic phosphatidylcholine and phosphatidylethanolamine fractions as the most important variables. Importantly, down-regulation of genes within these pathways was enlarged by phospholipid versus triglyceride forms of EPA/DHA in an independent experiment. Conclusions: Obesity-associated hepatosteatosis and hypercholesterolemia were ameliorated by marine phospholipids in association with a complex inhibition of biosynthetic pathways in liver. Stronger effects of phospholipids versus triglyceride form of EPA/DHA suggest their preferential use in the prevention and possible treatment of obesity-associated metabolic hepatic dysfunctions.

Dataset Information

Eicosapentaenoic acid induces an anti-inflammatory transcriptomic landscape in T cells implicating a pathway independent of triglyceride lowering in cardiovascular risk reduction [RNA-seq]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets