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The Activation of the NF-κB Pathway in Human Adipose-Derived Stem Cells Alters the Deposition of Epigenetic Marks on H3K27 and Is Modulated by Fish Oil

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Author(s):
Simao, Jussara de Jesus ; Bispo, Andressa Franca de Sousa ; Plata, Victor Tadeu Goncalves ; Abel, Ana Beatriz Marques ; Saran, Raphael Justa ; Barcella, Julia Fernandes ; Alonso, Joao Carlos Cardoso ; Santana, Andre Valente ; Armelin-Correa, Lucia Maria ; Alonso-Vale, Maria Isabel Cardoso
Total Authors: 10
Document type: Journal article
Source: LIFE-BASEL; v. 14, n. 12, p. 17-pg., 2024-12-01.
Abstract

Background: Chronic low-grade inflammation in obesity is linked to white adipose tissue (WAT) dysfunction. Plasma lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4), triggering NF-kappa B and worsening these disturbances. Previously, we showed that histone H3 lysine 27 (H3K27) epigenetic modifications affect WAT gene expression in high-fat-diet mice, identifying key pathways in adipose-derived stem cells (ASCs). This study explores whether NF-kappa B influences H3K27 modifiers in human ASCs and evaluates fish oil (FO) as a modulator. Methods: Human visceral WAT ASCs were stimulated with LPS and treated with FO enriched with eicosapentaenoic acid (EPA). Flow cytometry, PCR array, RT-PCR, and Western blot assays were used. Results: LPS increased NF-kappa B activity, elevating KDM6B demethylase levels and H3K27 acetylation. These epigenetic modifications in LPS-stimulated ASCs were associated with persistent changes in the expression of genes involved in adipogenesis, metabolic regulation, and inflammation, even after LPS removal and cell differentiation. FO mitigated these effects, reducing H3K27 acetylation and promoting methylation. Conclusions: FO demonstrates potential in modulating inflammation-induced epigenetic changes and preserving adipocyte function. (AU)

FAPESP's process: 23/12836-8 - EFFECTS OF CADMIUM ON HUMAN PRE-ADIPOCYTES
Grantee:Raphael Justa Saran
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 19/13618-9 - Modulation of Ezh2 expression, and other H3K27 modifiers, by NF-kB transcription factors in adipose cells
Grantee:Maria Isabel Cardoso Alonso-Vale
Support Opportunities: Regular Research Grants
FAPESP's process: 22/15127-5 - Modulation of NF-kB signaling pathway and repercussions on epigenetic marks in adipose cells: role of Oncotherad®
Grantee:Andressa Franca de Sousa Bispo
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 19/26240-4 - Signaling pathways affected by fish oil in Adipose tissue-Derived Stem Cells (AdSCs) and adipocytes: correlation with metabolic, endocrine and adipogenic changes that impact its anti-Hypertrophic Obesity properties
Grantee:Jussara de Jesus Simão
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 23/12708-0 - EFFECTS OF THE HEAVY METAL CADMIUM ON THE ENDOCRINE FUNCTION OF ADIPOCYTES
Grantee:Julia Fernandes Barcella
Support Opportunities: Scholarships in Brazil - Scientific Initiation