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 de Sousa Bispo,
Victor Tadeu Gonçalves Plata,
Ana Beatriz Marques Abel,
Raphael Justa Saran,
Júlia Fernandes Barcella,
João Carlos Cardoso Alonso,
André Valente Santana,
Lucia Maria Armelin-Correa,
Maria Isabel Cardoso Alonso-Vale
Affiliations
Jussara de Jesus Simao
Post-Graduate Program in Chemical Biology, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, Brazil
Andressa França de Sousa Bispo
Post-Graduate Program in Chemical Biology, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, Brazil
Victor Tadeu Gonçalves Plata
Post-Graduate Program in Chemical Biology, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, Brazil
Ana Beatriz Marques Abel
Post-Graduate Program in Nutrition, Paulista School of Medicine, Federal University of São Paulo—UNIFESP, Sao Paulo 04023-062, Brazil
Raphael Justa Saran
Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, Brazil
Júlia Fernandes Barcella
Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, Brazil
João Carlos Cardoso Alonso
Paulínia Municipal Hospital, Paulínia 13140-000, Brazil
André Valente Santana
Post-Graduate Program in Interdisciplinary Surgical Science, Paulista School of Medicine, Federal University of São Paulo—UNIFESP, Sao Paulo 04023-062, Brazil
Lucia Maria Armelin-Correa
Post-Graduate Program in Chemical Biology, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, Brazil
Maria Isabel Cardoso Alonso-Vale
Post-Graduate Program in Chemical Biology, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, Brazil
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 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-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.
