Abstract 14793: Obesity-induced Inflammation of the Visceral Adipose Tissue is Mediated by Upregulation of Arginase 1 in Vascular Endothelial Cells

Obesity-induced cardiovascular dysfunction involves pathological expansion of visceral adipose tissue (VAT). Our previous studies have shown that arginase 1 (A1) expression in vascular endothelial cells (EC) is critically involved in obesity-induced vascular dysfunction. Elevated arginase activity can reduce availability of L-Arginine to NO synthase, resulting in decreased NO production, oxidative stress, leukocyte attachment and vascular infiltration. Here we tested the hypothesis that EC A1 activity also drives obesity-related pathological VAT remodeling. Our study utilized 70 wild type (WT) and EC-A1 knockout (EC-A1-KO) mice made obese by high fat/high sucrose (HFHS) diet (6 mos). In WT mice, HFHS diet increased body weight (0.4X), fasting blood glucose (0.8X), and postprandial plasma insulin (3X). The metabolic dysfunction was accompanied by significant increases in VAT mRNA expression of A1, A2 and iNOS (p In conclusion, VAT inflammation induced by HFHS diet is mediated by EC A1 expression. Furthermore, activation/inflammation of ECs by high glucose and palmitate also involves A1 activity. Limiting arginase activity appears to be a therapeutic means to control obesity-induced inflammation pathology.