Silveira Leonardo R, Fiamoncini Jarlei, Hirabara Sandro M, Procópio Joaquim, Cambiaghi Tavane D, Pinheiro Carlos Hermano J, Lopes Lúcia R, Curi Rui
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
J Cell Physiol. 2008 Oct;217(1):1-12. doi: 10.1002/jcp.21514.
In this review we updated the fatty acid (FA) effects on skeletal muscle metabolism. Abnormal FA availability induces insulin resistance and accounts for several of its symptoms and complications. Efforts to understand the pathogenesis of insulin resistance are focused on disordered lipid metabolism and consequently its effect on insulin signaling pathway. We reviewed herein the FA effects on metabolism, signaling, regulation of gene expression and oxidative stress in insulin resistance. The elevated IMTG content has been associated with increased intracellular content of diacylglycerol (DAG), ceramides and long-chain acyl-coenzyme A (LCA-CoA). This condition has been shown to promote insulin resistance by interfering with phosphorylation of proteins of the insulin pathway including insulin receptor substrate-1/2 (IRS), phosphatidylinositol-3-kinase, (PI3-kinase) and protein kinase C. Although the molecular mechanism is not completely understood, elevated reactive oxygen (ROS) and nitrogen species (RNS) are involved in this process. Elevated ROS/RNS activates nuclear factor-kappaB (NFkB), which promotes the transcription of proinflammatory tumoral necrosis factor alpha (TNFalpha), decreasing the insulin response. Therefore, oxidative stress induced by elevated FA availability may constitute one of the major causes of insulin resistance in skeletal muscle.
在本综述中，我们更新了脂肪酸（FA）对骨骼肌代谢的影响。脂肪酸可用性异常会诱发胰岛素抵抗，并导致其多种症状和并发症。对胰岛素抵抗发病机制的研究重点在于脂质代谢紊乱及其对胰岛素信号通路的影响。我们在此回顾了脂肪酸对胰岛素抵抗中代谢、信号传导、基因表达调控及氧化应激的影响。细胞内甘油三酯（IMTG）含量升高与二酰基甘油（DAG）、神经酰胺和长链酰基辅酶A（LCA-CoA）的细胞内含量增加有关。这种情况已被证明可通过干扰胰岛素途径蛋白的磷酸化来促进胰岛素抵抗，这些蛋白包括胰岛素受体底物-1/2（IRS）、磷脂酰肌醇-3-激酶（PI3-激酶）和蛋白激酶C。尽管分子机制尚未完全明确，但活性氧（ROS）和活性氮（RNS）水平升高参与了这一过程。ROS/RNS水平升高会激活核因子-κB（NFkB），后者促进促炎肿瘤坏死因子α（TNFα）的转录，从而降低胰岛素反应。因此，脂肪酸可用性升高所诱导的氧化应激可能是骨骼肌胰岛素抵抗的主要原因之一。
