Kim Kyeongjin, Kim Hye Young, Son Eun Jeong, Heo Jeong, Cheong Jaehun
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
Cell Signal. 2009 Aug;21(8):1269-76. doi: 10.1016/j.cellsig.2009.03.019. Epub 2009 Mar 27.
Elevated free fatty acids (FFAs) are known to induce the impairment of insulin signaling. However, the insulin signaling components that are deregulated by FFAs in the liver remain unknown. Here, we examined the mechanisms of disruption of oleic acid on insulin signaling in hepatic cell lines. Oleic acid decreased the expression of insulin receptor substrate (IRS) 1 and augmented the expression of suppressor of cytokine signaling (SOCS) 3, which can induce the proteasome-mediated degradation of IRS. Moreover, oleic acid enhanced the phosphorylation of signal transducer and activator of transcription (STAT) 3 and induced the expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha). The interaction between STAT3 and C/EBPalpha was increased by oleic acid; these proteins subsequently enhanced the promoter activity of SOCS3 in the presence of oleic acid. Finally, oleic acid impaired the insulin signaling cascades through inhibition of the alpha-associated signaling pathway.
已知游离脂肪酸（FFA）水平升高会导致胰岛素信号传导受损。然而，肝脏中被FFA失调的胰岛素信号传导成分仍不清楚。在此，我们研究了油酸对肝细胞系中胰岛素信号传导的破坏机制。油酸降低了胰岛素受体底物（IRS）1的表达，并增加了细胞因子信号传导抑制因子（SOCS）3的表达，后者可诱导蛋白酶体介导的IRS降解。此外，油酸增强了信号转导和转录激活因子（STAT）3的磷酸化，并诱导了CCAAT/增强子结合蛋白α（C/EBPα）的表达。油酸增加了STAT3与C/EBPα之间的相互作用；随后，这些蛋白在油酸存在的情况下增强了SOCS3的启动子活性。最后，油酸通过抑制α相关信号通路损害胰岛素信号级联反应。
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