Omentin: A novel therapeutic approach for the treatment of endothelial dysfunction in type 2 diabetes

Abstract

Background: Perivascular adipose tissue (PVAT) locally influences the functioning of blood vessels and promotes vascular complications associated with diabetes and obesity. The aim of this work was to study the impact of omentin-1 on endothelial function and PVAT in a non-obese type 2 diabetes mellitus animal model, Goto-Kakizaki (GK) rats with or without high fat diet.

Material and methods: Diabetic GK rats were divided into four groups: 1) control group; 2) group treated with omentin-1; 3) group of GK rats fed a high fat diet (GKHFD) and 4) group of GKHFD treated with omentin-1. Several in vivo parameters such as adiposity and Lee indexes, lipid profile, fasting glucose levels, glucose and insulin tolerance tests were determined. At the vascular level, endothelial dependent and independent relaxation and contraction studies were performed in aortic rings in the absence (PVAT-) or in the presence (PVAT+) of thoracic PVAT. We also evaluated vascular oxidative stress and determined the pro-inflammatory status of PVAT.

Results: Endothelium-dependent relaxation to acetylcholine, assessed by wire myography, was impaired in GK and GKHFD rats and improved by the omentin-1 treatment. In addition, vascular superoxide production was increased in the vascular wall of diabetic rats, accompanied by reduced nitric oxide bioavailability and significantly improved by omentin treatment. PVAT anti-contractile action found under physiological conditions was lost in type 2 diabetes, and partially recovered with omentin-1 administration. In addition, omentin-1 treatment significantly improved proinflammatory and pro-oxidant PVAT phenotype (decreasing C-reactive protein and nitrotyrosine levels). Furthermore, it was observed an improvement in various systemic and metabolic biochemical parameters of diabetic animals treated for one month with omentin.

Conclusions: Omentin-1 ameliorates endothelial dysfunction in type 2 diabetes and presents therapeutic potential for the treatment of vascular complications associated with type 2 diabetes.

Keywords: Endothelial dysfunction; Inflammation; Omentin-1; Oxidative stress; Type 2 diabetes.