Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.
Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.
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DOI：
10.1172/jci19451
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发表时间：
2003-12
期刊：
影响因子：
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通讯作者：
Haiyan Xu;Glenn Barnes;Qing Yang;G. Tan;Daseng Yang;C. Chou;Jason Sole;A. Nichols;J. Ross-
中科院分区：
文献类型：
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作者：
Haiyan Xu;Glenn Barnes;Qing Yang;G. Tan;Daseng Yang;C. Chou;Jason Sole;A. Nichols;J. Ross-
胰岛素抵抗是由于胰岛素不能正常调节外周组织的营养代谢而引起的。来自人群研究和动物研究的越来越多的证据表明，慢性炎症和胰岛素抵抗之间既有相关关系，也有因果关系。然而，潜在的分子途径在很大程度上是未知的。在本报告中，我们发现遗传性和高脂肪饮食引起的肥胖（DIO）小鼠模型中，许多炎症和巨噬细胞特异性基因在白色脂肪组织（WAT）中显著上调。这种上调在DIO小鼠的WAT中逐渐增加，并先于循环胰岛素水平的急剧增加。在用罗格列酮（一种胰岛素增敏药物）治疗后，这些巨噬细胞起源的基因被下调。组织学上，肥胖小鼠WAT有巨噬细胞浸润，但中性粒细胞和淋巴细胞未见浸润，并有脂肪细胞脂解和多核巨细胞形成的迹象。这些数据表明，WAT中的巨噬细胞在病态肥胖中发挥积极作用，巨噬细胞相关的炎症活动可能有助于肥胖诱导的胰岛素抵抗的发病机制。我们认为，肥胖相关的胰岛素抵抗至少部分是由脂肪组织引发的慢性炎症性疾病。
Insulin resistance arises from the inability of insulin to act normally in regulating nutrient metabolism in peripheral tissues. Increasing evidence from human population studies and animal research has established correlative as well as causative links between chronic inflammation and insulin resistance. However, the underlying molecular pathways are largely unknown. In this report, we show that many inflammation and macrophage-specific genes are dramatically upregulated in white adipose tissue (WAT) in mouse models of genetic and high-fat diet-induced obesity (DIO). The upregulation is progressively increased in WAT of mice with DIO and precedes a dramatic increase in circulating-insulin level. Upon treatment with rosiglitazone, an insulin-sensitizing drug, these macrophage-originated genes are downregulated. Histologically, there is evidence of significant infiltration of macrophages, but not neutrophils and lymphocytes, into WAT of obese mice, with signs of adipocyte lipolysis and formation of multinucleate giant cells. These data suggest that macrophages in WAT play an active role in morbid obesity and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance. We propose that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue.