Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity
Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity
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DOI：
10.1016/j.metabol.2008.03.010
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发表时间：
2008-08-01
影响因子：
9.8
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
--
作者：
Matsuzawa-Nagata, Naoto;Takamura, Toshinari;Kaneko, Shuichi
胰岛素抵抗是代谢综合征的重要病理生理特征。然而，引发胰岛素抵抗的最初事件及其与葡萄糖和脂肪酸代谢失调的因果关系仍不清楚。我们研究了有可能诱导高脂饮食(HFD)小鼠胰岛素抵抗的生物途径。我们证明，在胰岛素抵抗开始之前，给予HFD的小鼠肝脏和脂肪组织中的ROS产生和氧化应激的途径被协同上调，这是通过离散的机制。在肝脏中，hfd上调的基因涉及与固醇调节元件结合蛋白1c相关的脂肪酸合成和与过氧化体增殖物激活的受体a相关的脂肪酸氧化。然而，在脂肪组织中，HFD下调了参与脂肪酸合成的基因，上调了烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶复合体的表达。此外，在血浆和肝脏中肿瘤坏死因子-a和游离脂肪酸的升高之前，ROS的产生增加。ROS可能是引发HFD诱导的胰岛素抵抗的初始关键事件。(C)2008 Elsevier Inc.保留所有权利。
insulin resistance is a key pathophysiological feature of metabolic syndrome. However, the initial events triggering the development of insulin resistance and its causal relations with dysregulation of glucose and fatty acids metabolism remain unclear. We investigated biological pathways that have the potential to induce insulin resistance in mice fed a high-fat diet (HFD). We demonstrate that the pathways for reactive oxygen species (ROS) production and oxidative stress are coordinately up-regulated in both the liver and adipose tissue of mice fed an HFD before the onset of insulin resistance through discrete mechanism. In the liver, an HFD up-regulated genes involved in sterol regulatory element binding protein 1c-related fatty acid synthesis and peroxisome proliferator-activated receptor a-related fatty acid oxidation. In the adipose tissue, however, the HFD down-regulated genes involved in fatty acid synthesis and up-regulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Furthermore, increased ROS production preceded the elevation of tumor necrosis factor-a and free fatty acids in the plasma and liver. The ROS may be an initial key event triggering HFD-induced insulin resistance. (C) 2008 Elsevier Inc. All rights reserved.