4.5 Article

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

Journal

INFLAMMATION
Volume 36, Issue 2, Pages 379-386

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-012-9557-z

Keywords

high-fat diet; mesenchymal stem cells; PPAR-gamma; NF-kappa B; IL-1; IL-6; TNF-alpha

Funding

  1. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo

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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-alpha, 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-kappa B and inhibition of PPAR-gamma. 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-gamma and NF-kappa B, as well as the production of IL-1, IL-6, and TNF-alpha 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-gamma and NF-kappa B were quantified, as well as IL-1, IL-6, and TNF-alpha 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-alpha and increased NF-kappa B and reduced PPAR-gamma expression. Therefore, ingestion of an HFD induces alterations in MSCs that may influence modulation of hematopoiesis.

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