Abstract
Adipose tissue is considered to be an endocrine organ, and adipocyte size correlates with insulin resistance and metabolic parameters in obesity. There is little data on the effects of angiopoietin-1 in adipose tissue and kidney in streptozotocin (STZ)-induced diabetes. In this study, we investigated the protective effect of COMP-angiopoietin-1 (COMP-Ang1), a potent variant of angiopoietin-1, on vascular endothelial cells in epididymal adipose tissue and its regulatory effect on other metabolic parameters, such as lipid droplet diameter, macrophage infiltration, and renal inflammation in STZ-treated mice. Our data showed that COMP-Ang1 increased the density of platelet endothelial cell adhesion molecule-1 (PECAM-1)-1-positive vascular endothelial cells in adipose tissue, which were significantly decreased by treatment with STZ. COMP-Ang1 ameliorated the STZ–induced decrease in lipid droplet diameter and increase in macrophage infiltration in adipose tissue. Serum free fatty acid and triglyceride levels were decreased after administration of COMP-Ang1. There was a beneficial effect on serum insulin levels after treatment with COMP-Ang1 in STZ-induced diabetic mice. Fasting blood glucose levels in COMP-Ang1-treated mice were significantly lower than those of LacZ-treated mice. Cotreatment with COMP-Ang1 and STZ also had similar effects on the above parameters. Administration of soluble Tie2, an inhibitor of angiopoietin-1, reversed the effects of COMP-Ang1. COMP-Ang1 was found to ameliorate the up-regulation of proinflammatory molecules and F4/80-positive macrophage infiltration in the kidneys of STZ-treated mice. COMP-Ang1 increased the phosphorylation of Akt in epididymal adipose tissue and kidneys of STZ-induced diabetic mice. These data indicate that COMP-Ang1 regulates lipogenic effects in adipose tissue and renal inflammation in STZ-induced diabetic mice.
Highlights
Adipose tissue is regarded as an endocrine organ that produces cytokines and adipokines [1]
We investigated the protective effect of cartilage oligomeric matrix protein (COMP)-angiopoietin-1 (COMP-Ang1), a potent variant of angiopoietin-1, on vascular endothelial cells in epididymal adipose tissue and its regulatory effect on other metabolic parameters, such as lipid droplet diameter, macrophage infiltration, and renal inflammation in STZ-treated mice
We report the effects of exogenous COMP-Ang1 on vascular endothelial cells in adipose tissue, and its effects on adipocyte lipid diameter, macrophage infiltration, and serum free fatty acid (FFA), serum triglycerides, serum insulin, glucose levels, ICAM1, vascular cell adhesion molecule (VCAM)-1 expression and macrophage recruitment in the kidney with a mouse model of diabetes induced by STZ
Summary
Adipose tissue is regarded as an endocrine organ that produces cytokines and adipokines [1]. Dysfunction and inflammation of endothelial cells in the kidney are critical factors related to diabetic nephropathy [13]. We demonstrated that COMP-Ang ameliorated perturbations of the diameter of epididymal adipocyte fat droplets and of metabolic parameters in a type 2 diabetes model [21]. There is little data on the effects of Ang on lipid droplet sizes, adipocyte macrophage infiltration, metabolic parameters or renal inflammation in a STZ-induced diabetes model. We report the effects of exogenous COMP-Ang on vascular endothelial cells in adipose tissue, and its effects on adipocyte lipid diameter, macrophage infiltration, and serum free fatty acid (FFA), serum triglycerides, serum insulin, glucose levels, ICAM1, VCAM-1 expression and macrophage recruitment in the kidney with a mouse model of diabetes induced by STZ
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