COMP-angiopoietin-1 mitigates changes in lipid droplet size, macrophage infiltration of adipose tissue and renal inflammation in streptozotocin-induced diabetic mice

// Yu Jin Jung 1 , Woong Park 1 , Tung Nguyen-Thanh 1 , Kyung Pyo Kang 1, 3 , Heung Young Jin 2, 3 , Suhn Hee Kim 4 , Wonhee Suh 5 and Won Kim 1, 3 1 Department of Internal Medicine, Division of Nephrology, Chonbuk National University Medical School, Jeonju, Republic of Korea 2 Department of Internal Medicine, Division of Endocrinology, Chonbuk National University Medical School, Jeonju, Republic of Korea 3 Research Institute of Clinical Medicine of Chonbuk National University-Chonbuk National University Hospital, Jeonju, Republic of Korea 4 Department of Physiology, Chonbuk National University Medical School, Jeonju, Republic of Korea 5 College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea Correspondence to: Won Kim, email: kwon@jbnu.ac.kr Keywords: angiopoietin-1; adipose tissue; fat droplet; kidney; inflammation Received: July 17, 2017      Accepted: August 17, 2017      Published: October 23, 2017 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.