Adipose tissue is a major source of interleukin-1 receptor antagonist - Upregulation in obesity and inflammation
Adipose tissue is a major source of interleukin-1 receptor antagonist - Upregulation in obesity and inflammation
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DOI：
10.2337/diabetes.52.5.1104
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发表时间：
2003-05-01
期刊：
影响因子：
7.7
通讯作者：
Meier, CA
中科院分区：
文献类型：
--
作者：
Juge-Aubry, CE;Somm, E;Meier, CA
白细胞介素-1受体拮抗剂（IL-1 Ra）的分泌形式是干预炎症过程的反调节的急性期蛋白。我们先前发现，这种细胞因子拮抗剂在肥胖患者血清中上调，与BMI和胰岛素抵抗相关。在这项研究中，我们检查了IL-1 Ra的表达模式，并表明它不仅在肝脏和脾脏中高度表达，而且在白色脂肪组织（WAT）中也高度表达，在肥胖症中上调。在肥胖者的WAT中，IL-1 Ra也显著增加。此外，人WAT外植体分泌IL-1 Ra到介质中，一个过程，可以刺激五倍的干扰素-P。最后，脂多糖管理诱导IL-1 Ra在小鼠WAT的持久表达，表明脂肪组织是一个重要的来源IL-1 Ra米肥胖和炎症。总之，我们证明了WAT是IL-1 Ra定量的最重要来源之一，这表明该组织可能代表抗炎治疗的新靶点。此外，可以推测，IL-1 Ra的产生在肥胖个体的WAT中显著增加，由于其分别对下丘脑和脂肪细胞的内分泌和旁分泌作用，其进一步有助于体重增加。
The secreted form of the interleukin-1 receptor antagonist (IL-1Ra) is an acute-phase protein intervening in the counterregulation of inflammatory processes. We previously showed that this cytokine antagonist is upregulated in the serum of obese patients, correlating with BMI and insulin resistance. In this study, we examined the expression pattern of IL-1Ra and showed that it is highly expressed not only in liver and spleen, but also in white adipose tissue (WAT), where it is upregulated in obesity. In WAT of obese humans, IL-1Ra was also markedly increased. Moreover, human WAT explants secreted IL-1Ra into the medium, a process that could be stimulated fivefold by interferon-P. Finally, lipopolysaccharide administration induced a longlasting expression of IL-1Ra in mouse WAT, suggesting that adipose tissue is an important source of IL-1Ra mi both obesity and inflammation. In summary, we demonstrated that WAT is one of the most important sources of IL-1Ra quantitatively, suggesting that this tissue could represent a novel target for anti-inflammatory treatment. Moreover, it can be speculated that IL-1Ra, whose production is markedly increased in WAT in obese individuals, contributes further to weight gain because of its endocrine and paracrine effects on the hypothalamus and adipocytes, respectively.