Overexpressing STAMP 2 attenuates adipose tissue angiogenesis and insulin resistance in diabetic ApoE −/− / LDLR −/− mouse via a PPAR γ/ CD 36 pathway

The aim of this study was to investigate whether overexpression of STAMP 2 improves insulin resistance by regulating angiogenesis in adipose tissues. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. Samples were obtained from epididymal, subcutaneous and brown adipose tissues. Histological and morphological analysis demonstrated that STAMP 2 gene overexpression reduced adipocyte size, angiogenesis in epididymal and brown adipose tissues. On aortic ring assay, microvessels sprouting from aortas were significantly inhibited after STAMP 2 gene overexpression. The cellular effect of STAMP 2 on angiogenesis was explored in human umbilical vein endothelial cells ( HUVEC s) model. Correlation of STAMP 2 and angiogenesis was validated by Ad‐ STAMP 2 transfection and STAMP 2 si RNA inhibition. In vitro , overexpression of STAMP 2 significantly inhibited endothelial cell migration, tube formation. The effects of Ad‐ STAMP 2 transfection on HUVEC s were abolished by treatment with PPAR γ antagonist GW 9662 (2.5 μM), and the roles of STAMP 2 si RNA on HUVEC s were also reversed by treatment with PPAR γ agonist rosiglitazone ( RSG ) (0.1 mM). RT ‐ PCR indicated that STAMP 2 could regulate levels of adhesion molecules, vascular endothelial growth factor A and CD 36. The expression of PPAR γ and CD 36 was decreased when STAMP 2 was inhibited by si RNA , while PPAR γ and CD 36 were highly expressed after overexpression of STAMP 2. Our results suggested that STAMP 2 gene overexpression may improve insulin resistance via attenuating angiogenesis in epididymal and brown adipose tissues through the PPAR γ/ CD 36 signalling pathway.