Open AccessOverexpressing STAMP2 Improves Insulin Resistance in Diabetic ApoE−/−/LDLR−/− Mice via Macrophage Polarization Shift in Adipose Tissues
Author(s) -
Lu Han,
Mengxiong Tang,
Yun Ti,
Zhi-Hao Wang,
Jia Wang,
Wenyuan Ding,
Hua Wang,
Yun Zhang,
Wei Zhang,
Ming Zhong
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0078903
Subject(s) - adipose tissue , macrophage polarization , insulin resistance , adipose tissue macrophages , endocrinology , medicine , inflammation , proinflammatory cytokine , infiltration (hvac) , m2 macrophage , streptozotocin , apolipoprotein e , white adipose tissue , chemistry , insulin , biology , macrophage , diabetes mellitus , materials science , biochemistry , disease , in vitro , composite material
STAMP2 is a counterregulator of inflammation and insulin resistance. The aim of this study is to investigate whether activation of STAMP2 improves insulin resistance by regulating macrophage polarization in adipose tissues. The diabetic ApoE −/− /LDLR −/− mouse model was induced by high-fat diet and low-dose streptozotocin. Samples were obtained from epididymal, subcutaneous and brown adipose tissues. Infiltration of M1/M2 macrophages and inflammatory cytokines were investigated by immunohistochemistry. We then used gene overexpression to investigate the effect of STAMP2 on macrophages infiltration and polarization and inflammatory cytokines expression. Our results showed that infiltration of macrophages, the ratio of M1/M2 macrophages and the expression of pro-inflammatory cytokines were enhanced and STAMP2 was downregulated in adipose tissues of diabetic ApoE −/− /LDLR −/− mice compared with control mice. STAMP2 gene overexpression could significantly reduce macrophages infiltration, the ratio of M1/M2 macrophages and the expression of pro-inflammatory cytokines in epididymal and brown adipose tissues, improving insulin resistance. Our results suggested that STAMP2 gene overexpression may improve insulin resistance via regulating macrophage polarization in visceral and brown adipose tissues.