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促炎型 CD11c+CD206+脂肪组织巨噬细胞与人类肥胖的胰岛素抵抗有关。

Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity.

机构信息

Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.

出版信息

Diabetes. 2010 Jul;59(7):1648-56. doi: 10.2337/db09-0287. Epub 2010 Mar 31.

DOI:10.2337/db09-0287
PMID:20357360
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2889764/
Abstract

OBJECTIVE

Insulin resistance and other features of the metabolic syndrome have been causally linked to adipose tissue macrophages (ATMs) in mice with diet-induced obesity. We aimed to characterize macrophage phenotype and function in human subcutaneous and omental adipose tissue in relation to insulin resistance in obesity.

RESEARCH DESIGN AND METHODS

Adipose tissue was obtained from lean and obese women undergoing bariatric surgery. Metabolic markers were measured in fasting serum and ATMs characterized by immunohistology, flow cytometry, and tissue culture studies. RESULTS ATMs comprised CD11c(+)CD206(+) cells in "crown" aggregates and solitary CD11c(-)CD206(+) cells at adipocyte junctions. In obese women, CD11c(+) ATM density was greater in subcutaneous than omental adipose tissue and correlated with markers of insulin resistance. CD11c(+) ATMs were distinguished by high expression of integrins and antigen presentation molecules; interleukin (IL)-1beta, -6, -8, and -10; tumor necrosis factor-alpha; and CC chemokine ligand-3, indicative of an activated, proinflammatory state. In addition, CD11c(+) ATMs were enriched for mitochondria and for RNA transcripts encoding mitochondrial, proteasomal, and lysosomal proteins, fatty acid metabolism enzymes, and T-cell chemoattractants, whereas CD11c(-) ATMs were enriched for transcripts involved in tissue maintenance and repair. Tissue culture medium conditioned by CD11c(+) ATMs, but not CD11c(-) ATMs or other stromovascular cells, impaired insulin-stimulated glucose uptake by human adipocytes.

CONCLUSIONS

These findings identify proinflammatory CD11c(+) ATMs as markers of insulin resistance in human obesity. In addition, the machinery of CD11c(+) ATMs indicates they metabolize lipid and may initiate adaptive immune responses.

摘要

目的

在饮食诱导肥胖的小鼠中，胰岛素抵抗和代谢综合征的其他特征与脂肪组织巨噬细胞（ATMs）有关。我们旨在描述肥胖患者中与胰岛素抵抗有关的人类皮下和内脏脂肪组织中巨噬细胞的表型和功能。

研究设计和方法

从接受减肥手术的瘦人和肥胖女性中获取脂肪组织。通过免疫组织化学、流式细胞术和组织培养研究来描述 ATMs，并测量空腹血清中的代谢标志物。

结果

ATMs 由“冠”状聚集的 CD11c(+)CD206(+)细胞和在脂肪细胞连接处的单个 CD11c(-)CD206(+)细胞组成。在肥胖女性中，CD11c(+)ATM 密度在皮下脂肪组织中比内脏脂肪组织中更高，并且与胰岛素抵抗的标志物相关。CD11c(+)ATMs 具有高表达整合素和抗原呈递分子的特点；白细胞介素（IL）-1β、-6、-8 和 -10；肿瘤坏死因子-α；和 CC 趋化因子配体-3，表明处于激活的促炎状态。此外，CD11c(+)ATMs 富含线粒体，并且富含编码线粒体、蛋白酶体和溶酶体蛋白、脂肪酸代谢酶和 T 细胞趋化因子的 RNA 转录本，而 CD11c(-)ATMs 则富含参与组织维持和修复的转录本。由 CD11c(+)ATMs 而不是 CD11c(-)ATMs 或其他基质血管细胞分泌的组织培养培养基可损害人脂肪细胞对胰岛素刺激的葡萄糖摄取。

结论

这些发现确定了促炎 CD11c(+)ATMs 是人类肥胖症胰岛素抵抗的标志物。此外，CD11c(+)ATMs 的机制表明它们可以代谢脂质并可能引发适应性免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/5da179cc862e/zdb0071061650007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/23a079f756f3/zdb0071061650001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/d1f4487dcebc/zdb0071061650002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/d8514f511033/zdb0071061650004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/ba8162d798cc/zdb0071061650005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/21ca4bfacd8c/zdb0071061650006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/5da179cc862e/zdb0071061650007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/23a079f756f3/zdb0071061650001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/d1f4487dcebc/zdb0071061650002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/0bf5e420eb2c/zdb0071061650003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/d8514f511033/zdb0071061650004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/ba8162d798cc/zdb0071061650005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/21ca4bfacd8c/zdb0071061650006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1c8/2889764/5da179cc862e/zdb0071061650007.jpg

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