Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol
Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol
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DOI：
10.1194/jlr.m800258-jlr200
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发表时间：
2009-02-01
影响因子：
6.5
通讯作者：
McIntosh, Michael
中科院分区：
文献类型：
--
作者：
Kennedy, Arion;Overman, Angel;McIntosh, Michael
炎症在脂肪细胞中反式-10，顺式-12（10,12）共轭亚油酸（CLA）介导的脱脂和胰岛素抵抗中起作用。鉴于白藜芦醇（RSV）的抗炎作用，我们假设RSV可以减轻10,12 CLA在人脂肪细胞中引起的炎症和胰岛素抵抗。RSV通过在12小时内阻止细胞外信号相关激酶的激活和炎症基因表达（即IL-6、IL-8、IL-1b）的诱导，阻断了10,12 CLA对炎症反应的诱导。同样，RSV抑制了10,12 CLA介导的炎性前列腺素途径的激活，包括磷脂酶A(2)、环氧化酶-2和PGF（2 α）。此外，RSV在12小时内减弱了与细胞应激相关的10、12 CLA细胞内钙和活性氧的增加，以及应激相关蛋白（即激活转录因子3，JNK）的激活。RSV减弱了10、12 CLA介导的胰岛素抵抗以及脂肪酸摄取和甘油三酯含量的抑制。最后，10,12 cla介导的过氧化物酶体增殖物激活受体γ (PPAR γ)蛋白水平的降低和过氧化物酶体增殖物反应元件（PPRE）报告因子的激活被RSV阻止。RSV增加了PPRE的基础活性，表明RSV增加了PPARg的活性。总的来说，这些数据首次证明RSV通过减轻炎症和细胞应激以及增加PPARg活性来阻止10,12 cla介导的人脂肪细胞的胰岛素抵抗和脱脂。-肯尼迪，A.奥弗曼，K. lappoint， R.霍普金斯，T.韦斯特，c . c .庄，K.马丁内斯，D.贝尔和M.麦金托什。白藜芦醇可减轻共轭亚油酸介导的炎症和人脂肪细胞的胰岛素抵抗。[j] .油脂杂志。2009。[50]: 225 -232。
Inflammation plays a role in trans-10, cis-12 ( 10,12)-conjugated linoleic acid (CLA)-mediated delipidation and insulin resistance in adipocytes. Given the anti-inflammatory role of resveratrol (RSV), we hypothesized that RSV would attenuate inflammation and insulin resistance caused by 10,12 CLA in human adipocytes. RSV blocked 10,12 CLA induction of the inflammatory response by preventing activation of extracellular signal-related kinase and induction of inflammatory gene expression (i.e., IL-6, IL-8, IL-1b) within 12 h. Similarly, RSV suppressed 10,12 CLA-mediated activation of the inflammatory prostaglandin pathway involving phospholipase A(2), cyclooxygenase-2, and PGF(2 alpha). In addition, RSV attenuated 10,12 CLA increase of intracellular calcium and reactive oxygen species associated with cellular stress, and activation of stress-related proteins (i.e., activating transcription factor 3, JNK) within 12 h. 10,12 CLA-mediated insulin resistance and suppression of fatty acid uptake and triglyceride content were attenuated by RSV. Finally, 10,12 CLA-mediated decrease of peroxisome proliferator-activated receptor gamma (PPAR gamma) protein levels and activation of a peroxisome proliferator response element (PPRE) reporter were prevented by RSV. RSV increased the basal activity of PPRE, suggesting that RSV increases PPARg activity. Collectively, these data demonstrate for the first time that RSV prevents 10,12 CLA-mediated insulin resistance and delipidation in human adipocytes by attenuating inflammation and cellular stress and increasing PPARg activity. - Kennedy, A., A. Overman, K. LaPoint, R. Hopkins, T. West, C-C. Chuang, K. Martinez, D. Bell, and M. McIntosh. Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol. J. Lipid Res. 2009. 50: 225 -232.