Palmitate activates the NF-κB transcription factor and induces IL-6 and TNFα expression in 3T3-L1 adipocytes
Palmitate activates the NF-κB transcription factor and induces IL-6 and TNFα expression in 3T3-L1 adipocytes
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DOI：
10.1093/jn/135.8.1841
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发表时间：
2005-08-01
影响因子：
4.2
通讯作者：
Spurlock, ME
中科院分区：
文献类型：
--
作者：
Ajuwon, KM;Spurlock, ME
脂肪酸及其代谢物调节基因表达和免疫途径。此外，肥胖个体经常具有增加的循环脂肪酸浓度，并且脂肪组织中的局部炎症可能促进与肥胖的胰岛素抵抗相关的全身炎症。尽管棕榈酸酯会诱发肌管炎症（即激活促炎途径），但脂肪酸对脂肪细胞炎症过程的影响尚未确定。因此，我们研究了棕榈酸酯、月桂酸酯和二十二碳六烯酸 (DHA) 调节 3T3-L1 脂肪细胞炎症的潜力。棕榈酸酯（而非 DHA 或月桂酸酯）诱导核因子 kappa B (NF-kappa B) 驱动的荧光素酶活性和白细胞介素 6 (IL-6) 表达 (P < 0.05)。用 Triacsin C 抑制脂肪酰辅酶 A 合酶 (FACS) 可抑制棕榈酸酯诱导的 NF-κ B 激活 (P < 0.05)，但会导致棕榈酸酯诱导的 IL-6 表达增加 (P < 0.05)。分别用 U0126 和 Bisindolylmaleimide (Bis) 破坏丝裂原激活蛋白激酶/Erk 激酶 (MEK) 和蛋白激酶 C (PKC) 活性，抑制棕榈酸诱导的 IL-6 表达 (P < 0·05)，但对 NF-kappa B 报告基因活性没有影响 (P > 0.05)。然而，磷酸肌醇 3 激酶 (PI3K) 抑制剂渥曼青霉素单独使用或与棕榈酸酯联合使用，可激活 NF-κ B 报告基因并诱导 IL-6 表达 (P < 0.05)。棕榈酸酯还诱导肿瘤坏死因子α（TNF α）的mRNA表达（P < 0.05），但mRNA丰度的增加并未反映在培养基中较高的蛋白质浓度（P > 0.05）。这些数据表明棕榈酸酯会诱发脂肪细胞炎症，并且这并不是所有 SFA 的普遍效应。此外，PI3K 可能发挥组成型抑制炎症的作用。因此，抑制这种酶可能会促进和加剧与肥胖和胰岛素抵抗相关的脂肪组织炎症。
Fatty acids and their metabolites regulate gene expression and immunological pathways. Furthermore, obese individuals frequently have increased circulating fatty acid concentrations, and localized inflammation in adipose tissue may facilitate the systemic inflammation associated with the insulin resistance of obesity. Although palmitate induces inflammation (i.e., activates proinflammatory pathways) in myotubes, the effects of fatty acids on inflammatory processes in adipocytes have not been established. Therefore, we examined the potential for palmitate, laurate, and docosahexaenoic acid (DHA) to modulate inflammation in 3T3-L1 adipocytes. Palmitate, but not DHA or laurate, induced nuclear factor kappa B (NF-kappa B)-driven luciferase activity and interleukin-6 (IL-6) expression (P < 0.05). Inhibition of fatty acyl Co-A synthase (FACS) with triacsin C suppressed palmitate-induced NF-kappa B activation (P < 0.05), but caused an additive increase in palm itate-induced IL-6 expression (P < 0.05). Disrupting mitogen-activated protein kinase/Erk kinase (MEK) and protein kinase C (PKC) activity with U0126 and Bisindolylmaleimide (Bis), respectively, suppressed palmitate-induced IL-6 expression (P < 0 05), but had no effect on NF-kappa B reporter gene activity (P > 0.05). However, the phosphoinositide-3 kinase (PI3K) inhibitor, wortmannin, alone and additively with palmitate, activated the NF-kappa B reporter gene and induced IL-6 expression (P < 0.05). Palmitate also induced the mRNA expression of tumor necrosis factor alpha (TNF alpha) (P < 0.05), but the increase in mRNA abundance was not reflected in a greater protein concentration in the media (P > 0.05). These data indicate that palmitate induces inflammation in adipocytes, and that this is not a generalized effect of all SFA. Furthermore, PI3K may act constitutively to suppress inflammation. Consequently, inhibition of this enzyme may promote and exacerbate the inflammation in adipose tissue that is associated with obesity and insulin resistance.