Palmitic acid alters enhancers/super-enhancers near inflammatory and efferocytosis-associated genes in human monocytes

Journal of Lipid Research, Journal Year: 2025, Volume and Issue: unknown, P. 100774 - 100774

Published: March 1, 2025

Free fatty acids like palmitic acid (PA) are elevated in obesity and diabetes dysregulate monocyte macrophage functions, contributing to enhanced inflammation these cardiometabolic diseases. Epigenetic mechanisms regulating enhancer functions play key roles inflammatory gene expression, but their role PA-induced monocyte/macrophage dysfunction is unknown. We found that PA treatment altered the epigenetic landscape of enhancers super-enhancers (SEs) human monocytes. Integration with RNA-seq data revealed enhancers/SEs correlated PA-increased expression immune response genes, while PA-inhibited downregulation phagocytosis efferocytosis genes. These genes were similarly regulated macrophages from mouse models accelerated atherosclerosis, by infectious agents. PA-regulated harbored SNPs associated diabetes, obesity, body mass index indicating disease relevance. verified increased chromatin interactions between promoters, reduced at was inhibitors BRD4, NF-κB. inhibited macrophages. Together, our findings demonstrate dynamics regulate responses. Targeting changes could provide novel therapeutic opportunities for disorders.

Language: Английский

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SIRT3-IDH2 axis is a target of dietary fructose: implication of IDH2 as a key player in dietary carcinogen toxicity in mice colon

Published: April 22, 2025

Introduction The potential roles of fructose in colon cancer are growing concerns. Fructose consumption has been linked to oxidative stress and mitochondrial dysfunction, yet its specific molecular mechanisms carcinogenesis remain underexplored. Objectives This study aimed investigate the by which dietary contributes carcinogenesis, focusing on role NADP⁺-dependent isocitrate dehydrogenase (IDH2). Methods Using an unbiased multi-omics approach (transcriptomics proteomics), liver tissues from fructose-fed wild-type (WT) mice were analyzed identify key genes involved cancer-related pathways. Human transcriptomic data (GSE256398) was confirm alterations aryl hydrocarbon receptor (AhR) signaling SIRT3-IDH2 axis. IDH2 knockout (KO) exposed a carcinogen, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), validate IDH2's development. In vitro, fructose’s effects SIRT3 expression activity assessed. Results Fructose-fed WT exhibited suppressed AhR signaling, increased stress, dysfunction via human datasets, AhR-associated reduced MASLD cirrhosis. KO showed heightened DNA damage, colonic tumorigenesis, GSH-mediated detoxification disruptions following PhIP exposure. activity, further supporting promoting carcinogenesis. Conclusion promotes disrupting function impairing damage response mechanisms, particularly through axis suppression. These findings highlight critical fructose-induced suggest as therapeutic target.

Language: Английский

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The multifaceted modulation of mitochondrial metabolism in tumorigenesis

Mitochondrion, Journal Year: 2024, Volume and Issue: 80, P. 101977 - 101977

Published: Nov. 4, 2024

Language: Английский

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Cutaneous Manifestations in D-2-Hydroxyglutaric Aciduria Type 2 and Response to Enasidenib Therapy

JAAD Case Reports, Journal Year: 2024, Volume and Issue: 56, P. 11 - 13

Published: Nov. 8, 2024

Language: Английский

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