Adiponectin accumulation in the retinal vascular endothelium and its possible role in preventing early diabetic microvascular damage

• Published in: Scientific reports Vol. 12; no. 1; p. 4159
• Main Authors: Sakaue, Taka-aki, Fujishima, Yuya, Fukushima, Yoko, Tsugawa-Shimizu, Yuri, Fukuda, Shiro, Kita, Shunbun, Nishizawa, Hitoshi, Ranscht, Barbara, Nishida, Kohji, Maeda, Norikazu, Shimomura, Iichiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337; 692/163; 692/163/2743; 692/163/2743/137; 692/163/2743/137/138; 692/163/2743/2037; Adipocytes; Adiponectin; Arterioles; Cadherins; Cardiovascular diseases; Diabetes; Diabetes mellitus; Diabetic retinopathy; Endothelium; Glucose transporter; Humanities and Social Sciences; Hyperglycemia; Immunofluorescence; Localization; Microvasculature; multidisciplinary; Permeability; Retina; Retinopathy; Science; Science (multidisciplinary); Streptozocin; T-cadherin; Vascular cell adhesion molecule 1
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-08041-2

Adiponectin (APN), a protein abundantly secreted from adipocytes, has been reported to possess beneficial effects on cardiovascular diseases in association with its accumulation on target organs and cells by binding to T-cadherin. However, little is known about the role of APN in the development of diabetic microvascular complications, such as diabetic retinopathy (DR). Here we investigated the impact of APN on the progression of early retinal vascular damage using a streptozotocin (STZ)-induced diabetic mouse model. Our immunofluorescence results clearly showed T-cadherin-dependent localization of APN in the vascular endothelium of retinal arterioles, which was progressively decreased during the course of diabetes. Such reduction of retinal APN accompanied the early features of DR, represented by increased vascular permeability, and was prevented by glucose-lowering therapy with dapagliflozin, a selective sodium-glucose co-transporter 2 inhibitor. In addition, APN deficiency resulted in severe vascular permeability under relatively short-term hyperglycemia, together with a significant increase in vascular cellular adhesion molecule-1 (VCAM-1) and a reduction in claudin-5 in the retinal endothelium. The present study demonstrated a possible protective role of APN against the development of DR.