Adipocyte-Specific Deficiency of NADPH Oxidase 4 Delays the Onset of Insulin Resistance and Attenuates Adipose Tissue Inflammation in Obesity.
Adipocyte-Specific Deficiency of NADPH Oxidase 4 Delays the Onset of Insulin Resistance and Attenuates Adipose Tissue Inflammation in Obesity.
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DOI：
10.1161/atvbaha.116.308749
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Han CY
中科院分区：
文献类型：
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作者：
Den Hartigh LJ;Omer M;Goodspeed L;Wang S;Wietecha T;O'Brien KD;Han CY
肥胖与胰岛素抵抗和脂肪组织炎症有关。在肥胖的发展过程中，脂肪组织中的活性氧（ROS）增加。我们以前表明，在响应过量的营养物质，如葡萄糖和棕榈酸，脂肪细胞产生ROS通过NADPH氧化酶（NOX）4，主要的脂肪细胞亚型，而不是使用线粒体氧化。然而，NOX 4衍生的ROS在肥胖症发展过程中全身胰岛素抵抗、脂肪细胞炎症和巨噬细胞向脂肪组织募集的发展中的作用尚不清楚。在这项研究中，对照C57 BL/6小鼠和脂肪细胞中特异性缺失NOX 4的小鼠被喂食高脂肪，高蔗糖（HFHS）饮食。在对照小鼠肥胖的发展过程中，脂肪细胞NOX 4和PPP活性短暂增加。原代脂肪细胞分化的小鼠与脂肪细胞缺乏的NOX 4表现出抵抗高葡萄糖或棕榈酸诱导的脂肪细胞炎症。具有NOX 4缺陷的脂肪细胞的小鼠在肥胖症的发展过程中表现出胰岛素抵抗的延迟发作，脂肪组织炎症的初始减少随着延长的HFHS喂养而正常化。这些发现表明，NOX 4衍生的ROS可能在胰岛素抵抗和脂肪组织炎症的发病中起作用。因此，靶向NOX 4介导的ROS产生的治疗剂可以有效预防肥胖相关疾病，如胰岛素抵抗。
Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown. In this study, control C57BL/6 mice and mice in which NOX4 has been deleted specifically in adipocytes were fed a high fat, high sucrose (HFHS) diet. During the development of obesity in control mice, adipocyte NOX4 and PPP activity were transiently increased. Primary adipocytes differentiated form mice with adipocytes deficient in NOX4 showed resistance against high glucose or palmitate-induced adipocyte inflammation. Mice with adipocytes deficient in NOX4 showed a delayed onset of insulin resistance during the development of obesity, with an initial reduction in adipose tissue inflammation that normalized with prolonged HFHS feeding. These findings imply that NOX4-derived ROS may play a role in the onset of insulin resistance and adipose tissue inflammation. As such, therapeutics targeting NOX4-mediated ROS production could be effective in preventing obesity-associated conditions such as insulin resistance.