Abstract P241: Uric Acid-Induced Adipocyte Dysfunction is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity
Increased uric acid levels have been implicated in the pathogenesis of metabolic syndrome. To examine the mechanisms by which this occurs we hypothesized that an increase in Heme Oxygenase-1, a potent anti-oxidant gene will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase levels. We examined the effect of uric acid, on adipogenesis in human mesenchymal stem cells (MSCs) in the presence and absence of cobalt protoporphyrin (CoPP), HO-1 inducer and tin mesoporphyrin (SnMP), HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBPα, PPARγ, Mest while decreasing small lipid droplets and the expression of Wnt10b. Importantly, we treated MSCs with fructose, a fuel source that increase uric acid levels. Our results showed that fructose increased XO expression as compared to the control and concomitant treatment with CoPP significantly decreased XO expression and also decreased uric acid levels. These beneficial effects of CoPP were reversed by SnMP; supporting a role for HO activity in mediating these effects. These novel findings demonstrate that increased levels of HO-1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in down regulating XO and NADPH oxidase levels. Furthermore, this study offers new insight into potential therapies by which targeting the production and/or downstream signaling of uric acid can curtail adipogenesis.
Author Disclosures: N. Puri: None. K. Sodhi: None. M. Getty: None. Z. Khitan: None.
- © 2015 by American Heart Association, Inc.