Angiopoietin Like Protein 2 (ANGPTL2) Promotes Adipose Tissue Macrophage and T lymphocyte Accumulation and Leads to Insulin Resistance
| Autor: | Mary C. Whelan, Ken Mizuno, Tomohiro Sugano, Hengmin Zhang, Masaki Yamabi, Wataru Yano, Dhruv Desai, Andrew K. Mlynarchik, Jose-Luiz Figueiredo, Masayuki Ohta, Yusuke Sasaki, Tyler Faits, Katsumi Yabusaki, Masanori Aikawa, Keisuke Inoue |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty FGF21 Adipose Tissue White T-Lymphocytes medicine.medical_treatment Adipose tissue macrophages Genetic Vectors lcsh:Medicine Adipose tissue Inflammation Biology Adenoviridae Diabetes Mellitus Experimental Mice Insulin resistance Cell Movement Internal medicine medicine Animals Humans Macrophage Obesity lcsh:Science Angiopoietin-Like Protein 2 CD11b Antigen Multidisciplinary Tumor Necrosis Factor-alpha Macrophages Insulin lcsh:R Glucose Tolerance Test Lipid Metabolism medicine.disease Antigens Differentiation CD11c Antigen Cell biology Mice Inbred C57BL Angiopoietin-like Proteins Endocrinology Cytokine Liver lcsh:Q Insulin Resistance medicine.symptom Angiopoietins Signal Transduction Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 7, p e0131176 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Objectives 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. Methodology/Principal Findings 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. Conclusion ANGPTL2 treatment promotes macrophage accumulation and activation. These results suggest potential mechanisms for insulin resistance. |
| Databáze: | OpenAIRE |
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