The role of GM-CSF in adipose tissue inflammation
The role of GM-CSF in adipose tissue inflammation
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DOI：
10.1152/ajpendo.00061.2008
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发表时间：
2008-11-01
影响因子：
5.1
通讯作者：
Seeley, Randy J.
中科院分区：
文献类型：
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作者：
Kim, Dong-Hoon;Sandoval, Darleen;Seeley, Randy J.
Kim DH，桑多瓦尔D，Reed JA，Matter EK，Tolod EG，Woods SC，塞利RJ. GM-CSF在脂肪组织炎症中的作用Am J Physiol Endocrinol Metab 295：E1038-E1046，2008.首次发表于2008年9月2日; doi：10.1152/ajpendo.00061.2008。粒细胞-巨噬细胞集落刺激因子（GM-CSF）是一种促炎细胞因子，具有减少食物摄入和体重的中枢作用。与此相一致，GM-CSF敲除小鼠比野生型小鼠更肥胖和贪食。然而，在肺部，GM-CSF是巨噬细胞浸润的重要决定因素。因此，我们试图确定GM-CSF是否可能有助于脂肪组织巨噬细胞积累、胰岛素抵抗和当动物在高脂饮食（HFD）上体重增加时发生的低度炎症。因此，我们确定了GM-CSF的靶向遗传破坏如何影响脂肪组织巨噬细胞和细胞因子基因表达以及通过进行高胰岛素-正常血糖钳夹的葡萄糖稳态。与野生型小鼠相比，GM-CSF敲除小鼠脂肪组织中巨噬细胞的数量和CCR 2基因表达减少，并且与野生型小鼠相比，HFD的GM-CSF敲除小鼠肠系膜脂肪的脂肪细胞大小增加。促炎细胞因子白细胞介素-1 β、肿瘤坏死因子-α和巨噬细胞炎性蛋白-1 α的mRNA水平在HFD的GM-CSF敲除小鼠的肠系膜脂肪中显著低于野生型小鼠。使用高胰岛素-正葡萄糖钳夹技术，GM-CSF敲除小鼠具有更高的总体胰岛素敏感性。这种增加是由于外周摄取和利用葡萄糖的增强，而不是肝脏胰岛素敏感性增加。总的来说，数据表明，尽管肥胖增加，但GM-CSF敲除突变通过减少HFD引起的脂肪组织炎症来改善外周胰岛素抵抗。
Kim DH, Sandoval D, Reed JA, Matter EK, Tolod EG, Woods SC, Seeley RJ. The role of GM-CSF in adipose tissue inflammation. Am J Physiol Endocrinol Metab 295: E1038-E1046, 2008. First published September 2, 2008; doi:10.1152/ajpendo.00061.2008. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine that has a central action to reduce food intake and body weight. Consistent with this, GM-CSF knockout mice are more obese and hyperphagic than wild-type mice. However, in lung, GM-CSF is an important determinant of macrophage infiltration. Consequently, we sought to determine if GM-CSF might contribute to adipose tissue macrophage accumulation, insulin resistance, and lowgrade inflammation that occurs when animals gain weight on a high-fat diet (HFD). We therefore determined how targeted genetic disruption of GM-CSF can affect adipose tissue macrophage and cytokine gene expression as well as glucose homeostasis by performing hyperinsulinemic-euglycemic clamps. The number of macrophages and CCR2 gene expression in adipose tissue of GM-CSF knockout mice was decreased relative to those in wild-type mice, and the adipocyte size of mesenteric fat was increased in GM-CSF knockout mice on a HFD compared with wild-type mice. The level of mRNA of the proinflammatory cytokines interleukin-1 beta, tumor necrosis factor-alpha, and macrophage inflammatory protein-1 alpha was significantly lower in mesenteric fat of GM-CSF knockout mice on the HFD than in wild-type mice. Using the hyperinsulinemic-euglycemic clamp technique, GM-CSF knockout mice had greater overall insulin sensitivity. This increase was due to enhanced peripheral uptake and utilization of glucose rather than to increased hepatic insulin sensitivity. Collectively, the data suggest that the GM-CSF knockout mutation ameliorates peripheral insulin resistance in spite of increased adiposity by reducing inflammation in adipose tissue in response to a HFD.