| 促酰化蛋白对3T3-L1脂肪细胞炎性反应的影响 |
| 投稿时间：2015-01-24 修订日期：2015-01-27 点此下载全文 |
| 引用本文：杨姗姗,胡秀芬,温宇.促酰化蛋白对3T3-L1脂肪细胞炎性反应的影响[J].医学研究杂志,2015,44(9):39-42,46 |
| DOI：
10.11969/j.issn.1673-548X.2015.09.011 |
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| 基金项目:国家自然科学基金青年科学基金资助项目(30800385);教育部新教师基金资助项目(200804871059) |
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| 中文摘要:目的 观察3T3-L1成熟脂肪细胞胰岛素抵抗状态下促酰化蛋白(acylation stimulating protein,ASP)对炎性因子(IL-6、MCP-1、MIP-1α和TNF-α)分泌水平以及炎性信号因子(JNK1、IKKβ)蛋白表达的影响。 方法 3T3-L1成熟脂肪细胞分别给予不同浓度(0、0.125、0.5、1.0mmol/L)油酸(C18∶ 1)或棕榈酸(C16∶ 0)温育过夜,诱导胰岛素抵抗,在此基础上给予ASP刺激,用ELISA测定IL-6、MCP-1、 MIP-1α和TNF-α 4种细胞炎性因子的分泌水平,采用Western blot法检测JNK1和KKβ蛋白表达。 结果 油酸诱导的胰岛素抵抗下,ASP刺激的脂肪细胞IL-6和MCP-1的分泌水平轻度下调,但差异无统计学意义;而ASP刺激的脂肪细胞MIP-1α和TNF-α的分泌水平显著下降,MIP-1α和TNF-α的分泌分别下调57%(P<0.05)和48%(P<0.05)(1.0mmol/L油酸组)。棕榈酸诱导的胰岛素抵抗下,ASP刺激的脂肪细胞IL-6分泌水平呈下降趋势,最大下调50% IL-6(P<0.05);22% MCP-1(P>0.05),35% MIP-1α(P>0.05)和38%TNF-α(P>0.05)的分泌。高浓度(1.0mmol/L) 油酸和棕榈酸诱导的脂肪细胞胰岛素抵抗状态下,ASP刺激的炎性信号蛋白JNK1蛋白表达显著下调,分别为34%(P<0.05)和54%(P<0.01)。但IKKβ蛋白表达差异无统计学意义。 结论 在脂肪酸诱导的脂肪细胞胰岛素抵抗状态下,ASP在一定程度上调节炎性因子分泌,参与调节JNK、IKK/NF-κB信号通路中重要信号分子的功能,ASP参与了脂肪细胞脂毒性-炎性反应的调控。 |
| 中文关键词:脂肪细胞 胰岛素抵抗 促酰化蛋白 脂毒性 炎性反应 |
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| Acylation Stimulating Protein Regulates the Inflammation in 3T3-L1 Adipocytes |
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| Abstract:Objective To study the changes of ASP on the inflammatory factors expression in 3T3-L1 adipocytes under the conditions which produce insulin resistance by free fatty acids. Methods 3T3-L1 preadipocytes were induced differentiated by cocktail hormones containing 10μg/ml insulin, 1μmol/L dexamethasone and 0.5mmol/L isobutylmethylxanthine. Then 0mmol/L (FFA-freeDMEM/F12), 0.125mmol/L, 0.5mmol/L and 1.0mmol/L oleate or palmitate was added to cultured 3T3-L1 adipocytes overnight. Both non-FFA treated and FFA treated 3T3-L1 cells were cultured with 1.0μmol/L ASP for 2 hours.Then the cultured media and cell proteins were extracted. Interlukin (IL)-6, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor (TNF)-α concentrations were measured using mouse ELISA kits according to the manufacturer's instructions. The c-Jun nterminal kinase (JNK)1 and inhibitor of nuclear factor kappa-B kinase(IKK)β protein expression was measured by western blot. Results Oleate did not change ASP-stimulated IL-6 and MCP-1 secretion significantly in 3T3-L1 adipocytes, but high dose of oleate effectively reduced the ASP-stimulated MIP-1α and TNF-α secretions by 57%(P<0.05)and 48%(P<0.05)at 1mmol/L oleate in adipocytes. On palmitate groups, ASP-stimulated IL-6 secretion was decreased by dose-response and reached a maximal suppression by 50% (P<0.05,1.0mmol/L). However, ASP-stimulated MCP-1, MIP-1α, and TNF-α secresions had no significant change. In 3T3-L1 adipocytes, high dose of oleate or palmitate effectively reduced the ASP-induced JNK1 protein expression with a significant reduction by 34%(P<0.05 for oleate)and 54%(P<0.01 for palmitate) at 1.0mmol/L FFA. However, overnight exposure of 3T3-L1 adipocytes to FFA leaded to little inhibition(P>0.05) of ASP-induced IKKβ protein expression. Conclusion ASP showed a function not only on inflammatory factors secretion, but also on some signal molecules changes in JNK signal pathway under the condition of insulin resistance induced by FFA in a cellular model. The study provides direct evidence of ASP involves in moderating the lipotocity-inflammation in adipocytes. |
| keywords:Acylation stimulating protein Insulin resistance Adipocytes Lipotoxicity Inflammation |
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