Inflammation, adipose tissue, and T cells: what is the "straight skinny" on lean versus fat mice?
Inflammation, adipose tissue, and T cells: what is the "straight skinny" on lean versus fat mice?
复制标题
炎症、脂肪组织和 T 细胞：瘦小鼠与胖小鼠的“瘦”是什么？
DOI：
10.1161/circresaha.109.201244
复制
发表时间：
2009
影响因子：
20.1
通讯作者：
Ballantyne,ChristieM
中科院分区：
文献类型：
--
作者：
Wu,Huaizhu;Ballantyne,ChristieM
肥胖症与脂肪组织（AT）中的慢性炎症相关，如通过细胞因子/趋化因子的水平增加以及巨噬细胞和T细胞的积累和活化所证明的，1-3其被认为是肥胖症中胰岛素抵抗的重要贡献者。最近，苏丹等人使用Apoe/CD 4dnTGFbR小鼠报道了T细胞介导的炎症不会引起瘦小鼠的胰岛素抵抗。4与对照组（Apoe/小鼠）相比，瘦型Apoe/CD 4dnTGFbR小鼠在AT中（但不特异于AT）表现出炎症增加，如T细胞和巨噬细胞含量增加，肿瘤坏死因子、干扰素和单核细胞趋化蛋白-1水平升高，但白细胞介素（IL）-6水平相当。4然而，与Apoe/小鼠相比，瘦型Apoe/CD 4dnTGFbR小鼠没有显示出恶化的胰岛素抵抗。4因此，作者得出结论，AT中T细胞介导的炎症不会导致高脂血症小鼠的胰岛素抵抗。4我们感谢苏丹等人关于T细胞介导的炎症在胰岛素抵抗中的作用的研究报告。4然而，由于本研究的以下局限性，我们认为现在就T细胞介导的AT炎症在代谢功能障碍中的潜在作用做出任何明确的结论还为时过早，特别是饮食诱导的肥胖，这通常伴有血脂异常。首先，Apoe/CD 4dnTGFbR小鼠在AT中显示出独特的炎症模式，与Apoe/对照相比IL-6水平不变，但IL-6水平低于B6小鼠。4然而，与瘦小鼠相比，肥胖小鼠显示出增加的IL-6水平。因此，该小鼠模型不代表在肥胖症中观察到的AT炎症模式，因此可能与肥胖症中T细胞介导的AT炎症几乎没有任何相关性。与胰岛素抵抗和肥胖相关的脂质紊乱的病理生理学，特别是与脂肪酸代谢相关的脂质紊乱的病理生理学，与Apoe/模型显著不同。其次，作者使用的是瘦老鼠。[4]当我们和其他人研究慢性AT炎症在胰岛素抵抗中的作用时，我们主要是指肥胖状况，并检查肥胖相关炎症对代谢功能障碍的贡献。在一项关于炎症本身在胰岛素抵抗中的作用的研究中，在瘦小鼠中获得的结果可能与肥胖状况几乎没有直接关系。4.以前大多数与肥胖相关的炎症研究使用的是雄性小鼠。1，5，6正如我们之前所展示的，2只雌性小鼠比肥胖的雄性小鼠更不容易发生胰岛素抵抗，即使它们在相同的时间内保持相同类型的高脂肪饮食。因此，尚不清楚本研究中是否存在性别效应。4
Obesity is associated with chronic inflammation in adipose tissue (AT), as evidenced by increased levels of cytokines/chemokines and accumulation and activation of macrophages and T cells, 1–3 which are acknowledged as important contributors to insulin resistance in obesity. Recently, using Apoe/ CD4dnTGFbR mice, Sultan et al reported that T cell–mediated inflammation does not cause insulin resistance in lean mice. 4 Compared to controls (Apoe/mice), lean Apoe/ CD4dnTGFbR mice showed increased inflammation in AT (but not specifically in AT), as indicated by increased content of T cells and macrophages, higher levels of tumor necrosis factor-, interferon-, and monocyte chemoattractant protein-1, but a comparable level of interleukin (IL)-6. 4 However, lean Apoe/ CD4dnTGFbR mice did not show worsened insulin resistance compared to Apoe/mice. 4 Therefore, the authors concluded that T cell–mediated inflammation in AT does not cause insulin resistance in hyperlipidemic mice. 4 We acknowledge Sultan et al for their report on the study of the role of T cell–mediated inflammation in insulin resistance. 4 However, because of the following limitations of this study, we feel that it is too early to make any firm conclusions on the potential role of T cell–mediated AT inflammation in metabolic dysfunctions, particularly with diet-induced obesity, which is commonly accompanied by dyslipidemia. First, Apoe/ CD4dnTGFbR mice displayed a unique inflammation pattern in AT, with unchanged IL-6 level compared to Apoe/controls but lower IL-6 level than B6 mice. 4 However, obese mice show increased IL-6 level compared to leans. Thus, this mouse model does not represent the AT inflammation pattern observed in obesity and therefore may have little if any relevance to the T cell–mediated AT inflammation in obesity. The pathophysiology of the lipid disorders associated with insulin resistance and obesity, particularly as related to fatty acid metabolism, is markedly different than the Apoe/model. Second, the authors used lean mice. 4 When we and others study the role of chronic AT inflammation in insulin resistance, we mostly refer to obese conditions and examine the contribution of obesity-related inflammation to metabolic dysfunctions. Results obtained in lean mice in a study of the role of inflammation per se in insulin resistance may have little direct relevance to obese conditions.Third, this study used female mice. 4 Most previous studies of obesity-related inflammation used male mice. 1, 5, 6 As we showed previously, 2 female mice were less predisposed to develop insulin resistance than male mice with obesity, even though they were maintained on the same type of high-fat diet for the same period of time. Therefore, it is unclear whether a sex effect existed in this study. 4