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A High-Fat Diet Increases IL-1, IL-6, and TNF-α Production by Increasing NF-κB and Attenuating PPAR-γ Expression in Bone Marrow Mesenchymal Stem Cells

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Abstract

It is well established that a high-fat diet (HFD) can lead to overweight and ultimately to obesity, as well as promoting low-grade chronic inflammation associated with increased levels of such mediators as TNF-α, IL-1, and IL-6. Bone marrow mesenchymal stem cells (MSCs), which are involved in hematopoietic niches and microenvironments, can be affected by these cytokines, resulting in induction of NF-κB and inhibition of PPAR-γ. Because this phenomenon could ultimately lead to suppression of bone marrow adipogenesis, we set out to investigate the effect of an HFD on the expression of PPAR-γ and NF-κB, as well as the production of IL-1, IL-6, and TNF-α in MSCs. Two-month-old male Wistar rats were fed a HFD diet and evaluated by means of leukograms and myelograms along with blood total cholesterol, triglyceride, and C-reactive protein levels. MSCs were isolated, and PPAR-γ and NF-κB were quantified, as well as IL-1, IL-6, and TNF-α production. Animals that were fed a HFD showed higher levels of blood total cholesterol, triglycerides, and C-reactive protein with leukocytosis and bone marrow hyperplasia. MSCs from HFD animals showed increased production of IL-1, IL-6, and TNF-α and increased NF-κB and reduced PPAR-γ expression. Therefore, ingestion of an HFD induces alterations in MSCs that may influence modulation of hematopoiesis.

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Acknowledgments

This investigation was supported by grants from the Fundação de Amparo a Pesquisa do Estado de São Paulo.

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Authors and Affiliations

  1. Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900, São Paulo, São Paulo, Brazil

    Mayara Cortez, Luciana Simão Carmo, Primavera Borelli & Ricardo Ambrósio Fock

  2. Department of Nutrition, School of Public Health, São Paulo University, 01246-904, São Paulo, São Paulo, Brazil

    Marcelo Macedo Rogero

  3. Experimental Hematology Laboratory, Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Lineu Prestes, 580 Bloco 17., São Paulo, São Paulo, Brazil, 05508-900

    Ricardo Ambrósio Fock

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  1. Mayara Cortez
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Correspondence to Ricardo Ambrósio Fock.

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Cortez, M., Carmo, L.S., Rogero, M.M. et al. A High-Fat Diet Increases IL-1, IL-6, and TNF-α Production by Increasing NF-κB and Attenuating PPAR-γ Expression in Bone Marrow Mesenchymal Stem Cells. Inflammation 36, 379–386 (2013). https://doi.org/10.1007/s10753-012-9557-z

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