Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900, São Paulo, São Paulo, Brazil.
Inflammation. 2013 Apr;36(2):379-86. doi: 10.1007/s10753-012-9557-z.
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.
高脂肪饮食(HFD)可导致超重,最终导致肥胖,并促进与 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)参与造血龛和微环境,可受这些细胞因子影响,导致 NF-κB 诱导和 PPAR-γ 抑制。由于这种现象最终可能导致骨髓脂肪生成抑制,我们着手研究 HFD 对 MSCs 中 PPAR-γ 和 NF-κB 的表达以及 IL-1、IL-6 和 TNF-α 的产生的影响。将 2 月龄雄性 Wistar 大鼠用 HFD 喂养,并通过白细胞计数和骨髓涂片以及血液总胆固醇、甘油三酯和 C 反应蛋白水平进行评估。分离 MSCs,并定量 PPAR-γ 和 NF-κB 以及 IL-1、IL-6 和 TNF-α 的产生。用 HFD 喂养的动物表现出血液总胆固醇、甘油三酯和 C 反应蛋白水平升高,白细胞增多和骨髓增生。HFD 动物的 MSCs 表现出增加的 IL-1、IL-6 和 TNF-α 产生以及增加的 NF-κB 和减少的 PPAR-γ 表达。因此,HFD 的摄入可引起 MSCs 的改变,可能影响造血的调节。