Overexpressing STAMP2 improves insulin resistance in diabetic ApoE⁻/⁻/LDLR⁻/⁻ mice via macrophage polarization shift in adipose tissues.
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.
Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Ji'nan, People's Republic of China ; Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, People's Republic of China.
Lu
L
Han
Meng-Xiong
MX
Tang
Yun
Y
Ti
Zhi-Hao
ZH
Wang
Jia
J
Wang
Wen-Yuan
WY
Ding
Hua
H
Wang
Yun
Y
Zhang
Wei
W
Zhang
Ming
M
Zhong
D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D016764:Cell Polarity; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D014617:Vacuoles / Q000378:metabolism
D001057:Apolipoproteins E; D008565:Membrane Proteins; D011973:Receptors, LDL; C436323:Tiarp protein, mouse