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
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 modi...
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2024-12-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Jussara de Jesus Simao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d7c3036e51b94ca49234666af7df17be |
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| issn | 2075-1729 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Life |
| spelling | doaj-art-d7c3036e51b94ca49234666af7df17be2025-08-20T02:00:29ZengMDPI AGLife2075-17292024-12-011412165310.3390/life14121653The 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 OilJussara de Jesus Simao0Andressa França de Sousa Bispo1Victor Tadeu Gonçalves Plata2Ana Beatriz Marques Abel3Raphael Justa Saran4Júlia Fernandes Barcella5João Carlos Cardoso Alonso6André Valente Santana7Lucia Maria Armelin-Correa8Maria Isabel Cardoso Alonso-Vale9Post-Graduate Program in Chemical Biology, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, BrazilPost-Graduate Program in Chemical Biology, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, BrazilPost-Graduate Program in Chemical Biology, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, BrazilPost-Graduate Program in Nutrition, Paulista School of Medicine, Federal University of São Paulo—UNIFESP, Sao Paulo 04023-062, BrazilDepartment of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, BrazilDepartment of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, BrazilPaulínia Municipal Hospital, Paulínia 13140-000, BrazilPost-Graduate Program in Interdisciplinary Surgical Science, Paulista School of Medicine, Federal University of São Paulo—UNIFESP, Sao Paulo 04023-062, BrazilPost-Graduate Program in Chemical Biology, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, BrazilPost-Graduate Program in Chemical Biology, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo—UNIFESP, Diadema 09913-030, BrazilBackground: 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.https://www.mdpi.com/2075-1729/14/12/1653adipose tissuemesenchymal stem cellslipopolysaccharideinflammationH3K27acH3K27me3 |
| spellingShingle | 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 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 Life adipose tissue mesenchymal stem cells lipopolysaccharide inflammation H3K27ac H3K27me3 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | adipose tissue mesenchymal stem cells lipopolysaccharide inflammation H3K27ac H3K27me3 |
| url | https://www.mdpi.com/2075-1729/14/12/1653 |
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