Dietary fatty acids differentially regulate production of TNF-α and IL-10 by murine 3T3-L1 adipocytes
Dietary fatty acids differentially regulate production of TNF-α and IL-10 by murine 3T3-L1 adipocytes
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DOI：
10.1038/oby.2008.39
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发表时间：
2008-05-01
期刊：
影响因子：
6.9
通讯作者：
Maratos-Flier, Eleftheria
中科院分区：
文献类型：
--
作者：
Bradley, Richard L.;Fisher, FFolliott M.;Maratos-Flier, Eleftheria
目的：肥胖与脂肪细胞源性细胞因子的产生增加有关，这可能导致肥胖个体出现慢性亚临床炎症。本研究评估了特定脂肪酸在小鼠3T3-L1脂肪细胞中调节促炎细胞因子、肿瘤坏死因子- α (tnf - α)和抗炎细胞因子、白细胞介素-10 （IL-10）产生的能力。对核因子- κ B (nf - κ B)（炎症级联的关键转录激活因子）和细胞因子信号传导3的抑制因子（SOCS-3）（细胞因子信号传导的负调节因子）的影响也进行了测定。方法和步骤：将脂肪细胞分别与50或500 μ mol/l棕榈酸、油酸或二十二碳六烯酸（DHA）孵育24和48小时。采用实时荧光定量PCR和小鼠多重荧光定量检测试剂盒检测对tnf - α和IL-10基因表达和蛋白分泌的影响。用northern印迹法检测SOCS-3的表达，用市售的方法评估NF-kappa B的结合活性。结果：与未处理的细胞相比，棕榈酸处理24小时的脂肪细胞tnf - α的产生增加了70%，IL-10的产生减少了75%。相反，DHA处理对tnf - α没有影响，但使IL-10的产生增加了两倍。油酸对tnf - α或IL-10的产生没有影响。在48小时的孵育过程中也得到了类似的结果。此外，NF-kappa B dna结合活性对棕榈酸的反应增加了4倍，对DHA的反应降低了60%。在dha处理的细胞中，SOCS-3的表达增加了两倍。讨论：总的来说，这些结果表明，膳食脂肪酸直接作用于脂肪细胞，调节细胞因子的产生。由于肥胖个体的循环脂肪酸水平长期升高，这种影响可能部分解释了肥胖相关的炎症。
Objective: Obesity correlates with increased production of adipocyte-derived cytokines, which may contribute to a chronic subclinical inflammation seen in obese individuals. This study evaluated the ability of specific fatty acids to modulate production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokine, interleukin-10 (IL-10), in murine 3T3-L1 adipocytes. Effects on nuclear factor-kappa B (NF-kappa B), a key transcriptional activator of the inflammatory cascade, and suppressor of cytokine signaling 3 (SOCS-3), a negative regulator of cytokine signaling, were also determined.Methods and Procedures: Adipocytes were incubated for 24 and 48 h with and without 50 or 500 mu mol/l of palmitic acid, oleic acid, or docosahexaenoic acid, (DHA). Effects on gene expression and protein secretion of TNF-alpha and IL-10 were determined using real-time PCR and a murine multipex RIA kit. SOCS-3 expression was determined by northern blotting and NF-kappa B binding activity was assessed using a commercially available assay.Results: Adipocytes treated for 24 h with palmitic acid exhibited a 70% increase in TNF-alpha production and up to a 75% decrease in IL-10 production, relative to untreated cells. In contrast, DHA treatment had no effect on TNF-alpha, but increased IL-10 production twofold. No effect of oleic acid was seen on either TNF-alpha or IL-10 production. Similar results were obtained during a 48-h incubation. Furthermore, NF-kappa B DNA-binding activity increased fourfold in response to palmitic acid and decreased 60% in response to DHA. Expression of SOCS-3 increased twofold in DHA-treated cells.Discussion: In aggregate, these results suggest that dietary fatty acids act directly on adipocytes to modulate cytokine production. As circulating fatty acids levels are chronically elevated in obese individuals, this effect may account in part for obesity-associated inflammation.