Absence of CC chemokine ligand 2 does not limit obesity-associated infiltration of macrophages into adipose tissue
Absence of CC chemokine ligand 2 does not limit obesity-associated infiltration of macrophages into adipose tissue
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DOI：
10.2337/db07-0425
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发表时间：
2007-09-01
期刊：
影响因子：
7.7
通讯作者：
Flier, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Inouye, Karen E.;Shi, Hang;Flier, Jeffrey S.
在肥胖症中，巨噬细胞向脂肪组织的募集导致脂肪组织炎症活动增强，因此可能是肥胖相关代谢功能障碍的基础。肥胖的脂肪组织中CC趋化因子配体2（CCL2，即单核细胞趋化蛋白 - 1）增加，它是一种重要的巨噬细胞募集因子。因此我们假设，升高的CCL2可能有助于肥胖相关的脂肪组织巨噬细胞募集。将6周龄的雄性CCL2基因敲除（-/-）小鼠和野生型小鼠（每组n = 11 - 14）分别喂食标准饮食和高脂肪饮食直至34周龄。在12 - 16周龄和25 - 29周龄时，采集血液用于测量血浆葡萄糖和激素，并进行葡萄糖耐量和胰岛素耐量测试。在34周龄时采集脂肪组织用于分析巨噬细胞浸润情况。令人惊讶的是，高脂肪饮食的CCL2基因敲除小鼠的脂肪组织巨噬细胞并未减少。与野生型小鼠相比，标准饮食和高脂肪饮食的CCL2基因敲除小鼠也存在葡萄糖不耐受，血浆葡萄糖轻度升高，血清脂联素水平降低。在高脂肪饮食下，与野生型小鼠相比，CCL2基因敲除小鼠体重增加略多，且存在高胰岛素血症。由于CCL2基因敲除小鼠的巨噬细胞水平未改变，这种表型似乎是由CCL2本身的缺乏引起的。尽管脂肪组织巨噬细胞水平没有变化，但CCL2基因敲除小鼠的代谢功能发生了改变，这表明CCL2对代谢的影响与其巨噬细胞募集能力无关。重要的是，我们得出结论，CCL2对于脂肪组织巨噬细胞募集并非至关重要。因此，在肥胖期间脂肪组织中募集巨噬细胞的主要因素仍有待确定。
Macrophage recruitment to adipose tissue in obesity contributes to enhanced adipose tissue inflammatory activity and thus may underlie obesity-associated metabolic dysfunction. Obese adipose tissue exhibits increases in CC chemokine ligand 2 (CCL2, or monocyte chemoattractant protein-1), an important macrophage-recruiting factor. We therefore hypothesized that elevated CCL2 may contribute to obesity-associated adipose tissue macrophage recruitment. Male 6-week-old CCL2(-/-) and wild-type mice (n = 11-14 per group) were fed standard and high-fat diets until 34 weeks of age. At 12-16 and 25-29 weeks of age, blood was collected for plasma glucose and hormone measurements, and glucose tolerance and insulin tolerance tests were performed. Adipose tissue was collected at 34 weeks for analysis of macrophage infiltration. Surprisingly, CCL2(-/-) mice on high-fat diet showed no reductions in adipose tissue macrophages. CCL2(-/-) mice on standard and high-fat diet were also glucose intolerant and had mildly increased plasma glucose and decreased serum adiponectin levels compared with wild-type mice. On high-fat diet, CCL2(-/-) mice also gained slightly more weight and were hyperinsulinemic compared with wild-type mice. Because macrophage levels were unchanged in CCL2(-/-) mice, the phenotype appears to be caused by lack of CCL2 itself. The fact that metabolic function was altered in CCL2(-/-) mice, despite no changes in adipose tissue macrophage levels, suggests that CCL2 has effects on metabolism that are independent of its macrophage-recruiting capabilities. Importantly, we conclude that CCL2 is not critical for adipose tissue macrophage recruitment. The dominant factor for recruiting macrophages in adipose tissue during obesity therefore remains to be identified.