Preprint Article Version 1 This version is not peer-reviewed

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

Jussara de Jesus Simao
,
Andressa França Sousa Bispo
ORCID logo ,
Victor Tadeu Gonçalves Plata
,
Ana Beatriz Marques Abel
ORCID logo ,
Lucia Armelin-Correa
ORCID logo ,
Júlia Fernandes Barcella
,
João Carlos Cardoso Alonso
,
André Valente Santana
,
Lucia Maria Armelin-Correa
,
Maria Isabel Cardoso Alonso
*
Version 1 : Received: 24 October 2024 / Approved: 24 October 2024 / Online: 24 October 2024 (18:08:11 CEST)

How to cite: Simao, J. D. J.; Bispo, A. F. S.; Plata, V. T. G.; Abel, A. B. M.; Armelin-Correa, L.; Barcella, J. F.; Alonso, J. C. C.; Santana, A. V.; Armelin-Correa, L. M.; Alonso, M. I. C. 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. Preprints 2024, 2024101970. https://doi.org/10.20944/preprints202410.1970.v1 Simao, J. D. J.; Bispo, A. F. S.; Plata, V. T. G.; Abel, A. B. M.; Armelin-Correa, L.; Barcella, J. F.; Alonso, J. C. C.; Santana, A. V.; Armelin-Correa, L. M.; Alonso, M. I. C. 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. Preprints 2024, 2024101970. https://doi.org/10.20944/preprints202410.1970.v1

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-κB and worsening these disturbances. Previously, we showed that 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-κB 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-κB 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.

Keywords

adipose tissue; mesenchymal stem/stromal cells; lipopolysaccharide; inflammation; H3K27ac; H3K27me3; KDM6B; n-3 PUFA

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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