Angiopoietin Like Protein 2 (ANGPTL2) Promotes Adipose Tissue Macrophage and T lymphocyte Accumulation and Leads to Insulin Resistance.
Angiopoietin Like Protein 2 (ANGPTL2) Promotes Adipose Tissue Macrophage and T lymphocyte Accumulation and Leads to Insulin Resistance.
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DOI：
10.1371/journal.pone.0131176
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Aikawa M
中科院分区：
文献类型：
--
作者：
Sasaki Y;Ohta M;Desai D;Figueiredo JL;Whelan MC;Sugano T;Yamabi M;Yano W;Faits T;Yabusaki K;Zhang H;Mlynarchik AK;Inoue K;Mizuno K;Aikawa M
血管生成素样蛋白2（ANGPTL 2）是一种新近发现的促炎细胞因子，主要由脂肪组织分泌。本研究旨在探讨ANGPTL 2在糖尿病小鼠模型脂肪组织炎症和巨噬细胞活化中的作用。腺病毒介导的lacZ（Ad-LacZ）或人ANGPTL 2（Ad-ANGPTL 2）通过尾静脉递送到糖尿病db/db小鼠中。与Ad-LacZ治疗相比，Ad-ANGPTL 2治疗2周损害葡萄糖耐量和胰岛素敏感性。Ad-ANGPTL 2治疗显著诱导白色脂肪组织中的促炎基因表达。我们还从附睾脂肪垫中分离出间质血管成分，并通过流式细胞术分析脂肪组织巨噬细胞和T淋巴细胞群。Ad-ANGPTL 2处理的小鼠具有更多的脂肪组织巨噬细胞（F4/80+ CD 11b+）和更大的M1巨噬细胞亚群（F4/80+ CD 11b + CD 11 c+）。此外，Ad-ANGPTL 2处理增加了脂肪组织中的CD 8阳性T细胞群，这先于增加的巨噬细胞积累。与我们的体内结果一致，重组人ANGPTL 2蛋白处理增加了人巨噬细胞样细胞系THP-1中促炎基因产物的mRNA水平和TNF-α蛋白的产生。此外，Ad-ANGPTL 2可诱导小鼠肝脏脂质蓄积，增加脂肪酸合成和脂质代谢相关基因的表达。ANGPTL 2处理促进巨噬细胞积累和活化。这些结果提示了胰岛素抵抗的潜在机制。
Angiopoietin-like protein 2 (ANGPTL2), a recently identified pro-inflammatory cytokine, is mainly secreted from the adipose tissue. This study aimed to explore the role of ANGPTL2 in adipose tissue inflammation and macrophage activation in a mouse model of diabetes. Adenovirus mediated lacZ (Ad-LacZ) or human ANGPTL2 (Ad-ANGPTL2) was delivered via tail vein in diabetic db/db mice. Ad-ANGPTL2 treatment for 2 weeks impaired both glucose tolerance and insulin sensitivity as compared to Ad-LacZ treatment. Ad-ANGPTL2 treatment significantly induced pro-inflammatory gene expression in white adipose tissue. We also isolated stromal vascular fraction from epididymal fat pad and analyzed adipose tissue macrophage and T lymphocyte populations by flow cytometry. Ad-ANGPTL2 treated mice had more adipose tissue macrophages (F4/80+CD11b+) and a larger M1 macrophage subpopulation (F4/80+CD11b+CD11c+). Moreover, Ad-ANGPTL2 treatment increased a CD8-positive T cell population in adipose tissue, which preceded increased macrophage accumulation. Consistent with our in vivo results, recombinant human ANGPTL2 protein treatment increased mRNA levels of pro-inflammatory gene products and production of TNF-α protein in the human macrophage-like cell line THP-1. Furthermore, Ad-ANGPTL2 treatment induced lipid accumulation and increased fatty acid synthesis, lipid metabolism related gene expression in mouse liver. ANGPTL2 treatment promotes macrophage accumulation and activation. These results suggest potential mechanisms for insulin resistance.
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炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1126/science.1230721
发表时间：
2013-01-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Odegaard JI;Chawla A
通讯作者：
Chawla A
影响因子：
30.8
作者：
Koishi, R;Ando, Y;Furukawa, H
通讯作者：
Furukawa, H
影响因子：
6
作者：
Okada, Tatsuya;Tsukano, Hiroto;Oike, Yuichi
通讯作者：
Oike, Yuichi
影响因子：
5.3
作者：
Suzuki, H;Aoki, T;Saito, Y
通讯作者：
Saito, Y