Abstract 8309: Adiponectin Deficiency Exacerbates Endothelial Dysfunction By Increasing Inflammation In High-fat Diet Induced Obese Mice

Abstract

Adiponectin (APN) is a 30-kDa protein exclusively secreted by adipose tissue. Clinical data show obese and type 2 diabetic patients have decreased APN levels in the circulation. Previously, we showed that APN is deficient in the serum and in aorta protein expression in type 2 diabetic mice ( db/db , Lepr db ), which suggests APN may play an important role in vascular dysfunction and the development of type 2 diabetes. Accordingly, we hypothesized that APN deficiency will impair endothelial function in aortas in high fat diet (HF) induced obese mice. To test this hypothesis, we fed HF diet (60% calories from fat) in wild type (WT) and APN knock-out (APNKO) mice for 18 weeks and studied vascular function of aorta ex vivo. Endothelium-dependent vasodilator acetylcholine (Ach)-induced vasodilation was blunted in APNKO+HF compare to WT+HF, but sodium nitroprusside (SNP)-induced endothelium-independent vasodilation was identical. Previously, we showed that adenoviral delivery of APN (Ad-APN) improved endothelial function in diabetic mice compare to control virus treatment (Ad-βgal). Real-time PCR results showed that mRNA gene expression of TNFα, IL-6 and intercellular adhesion molecule-1(ICAM-1) was higher in db/db aortas compared to control mice, suggesting that inflammation and recruitment of immune cells may contribute to endothelial dysfunction. However, Ad-APN treatment decreased TNFα, IL-6 and ICAM-1 suggesting APN may suppress inflammation and adhesion molecules. This suggests that APN may contribute to an increase in nitric oxide bioavailability by decreasing inflammation and recruitment of immune cells in the aorta. APN appears to play an important role in the prevention of vascular dysfunction in the aortas by preventing inflammation and immune response the animal and infers a similar role may occur is in obese/diabetic patients.