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
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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DOI：
10.1007/s10753-012-9557-z
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发表时间：
2013-04-01
期刊：
影响因子：
5.1
通讯作者：
Fock, Ricardo Ambrosio
中科院分区：
文献类型：
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作者：
Cortez, Mayara;Carmo, Luciana Simao;Fock, Ricardo Ambrosio
众所周知，高脂饮食（HFD）可导致超重并最终导致肥胖，以及促进与TNF-α、IL-1和IL-6等介质水平升高相关的低度慢性炎症。骨髓间充质干细胞（MSCs）参与造血微环境和微环境，可受到这些细胞因子的影响，导致NF-κ B的诱导和PPAR-gamma的抑制。由于这种现象最终可能导致骨髓脂肪生成的抑制，我们着手研究HFD对间充质干细胞中PPAR-γ和NF-κ B表达以及IL-1、IL-6和TNF-α产生的影响。两个月大的雄性Wistar大鼠喂食HFD饮食，并通过白细胞和骨髓象沿着血液总胆固醇、甘油三酯和C-反应蛋白水平进行评价。分离MSC，定量PPAR-gamma和NF-κ B B，以及IL-1、IL-6和TNF-α的产生。喂食HFD的动物显示血液总胆固醇、甘油三酯和C反应蛋白水平较高，伴有白细胞增多和骨髓增生。来自HFD动物的MSC显示IL-1、IL-6和TNF-α的产生增加，NF-κ B增加，而PPAR-gamma表达减少。因此，摄取HFD诱导MSC的改变，这可能影响造血的调节。
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.