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 antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS...

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Main Authors: Komal Sodhi, Jordan Hilgefort, George Banks, Chelsea Gilliam, Sarah Stevens, Hayden A. Ansinelli, Morghan Getty, Nader G. Abraham, Joseph I. Shapiro, Zeid Khitan
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/8197325
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author Komal Sodhi
Jordan Hilgefort
George Banks
Chelsea Gilliam
Sarah Stevens
Hayden A. Ansinelli
Morghan Getty
Nader G. Abraham
Joseph I. Shapiro
Zeid Khitan
author_facet Komal Sodhi
Jordan Hilgefort
George Banks
Chelsea Gilliam
Sarah Stevens
Hayden A. Ansinelli
Morghan Getty
Nader G. Abraham
Joseph I. Shapiro
Zeid Khitan
author_sort Komal Sodhi
collection DOAJ
description 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 antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO) 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), an HO-1 inducer, and tin mesoporphyrin (SnMP), an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBPα, PPARγ, and Mest, while decreasing small lipid droplets and Wnt10b levels. We treated MSCs with fructose, a fuel source that increases 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 uric acid levels. These beneficial effects of CoPP were reversed by SnMP, supporting a role for HO activity in mediating these effects. These findings demonstrate that increased levels of HO-1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in downregulating XO and NADPH oxidase levels.
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spelling doaj-art-56484b218b9147f2984fe4d009f05ae22025-02-03T01:03:15ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/81973258197325Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target ObesityKomal Sodhi0Jordan Hilgefort1George Banks2Chelsea Gilliam3Sarah Stevens4Hayden A. Ansinelli5Morghan Getty6Nader G. Abraham7Joseph I. Shapiro8Zeid Khitan9Departments of Internal Medicine and Surgery, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USADepartments of Internal Medicine and Surgery, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USADepartments of Internal Medicine and Surgery, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USADepartments of Internal Medicine and Surgery, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USADepartments of Internal Medicine and Surgery, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USADepartments of Internal Medicine and Surgery, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USADepartments of Internal Medicine and Surgery, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USADepartments of Pharmacology and Medicine, New York Medical College, Valhalla, NY 10595, USADepartments of Internal Medicine and Surgery, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USADepartments of Internal Medicine and Surgery, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USAIncreased 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 antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO) 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), an HO-1 inducer, and tin mesoporphyrin (SnMP), an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBPα, PPARγ, and Mest, while decreasing small lipid droplets and Wnt10b levels. We treated MSCs with fructose, a fuel source that increases 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 uric acid levels. These beneficial effects of CoPP were reversed by SnMP, supporting a role for HO activity in mediating these effects. These findings demonstrate that increased levels of HO-1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in downregulating XO and NADPH oxidase levels.http://dx.doi.org/10.1155/2016/8197325
spellingShingle Komal Sodhi
Jordan Hilgefort
George Banks
Chelsea Gilliam
Sarah Stevens
Hayden A. Ansinelli
Morghan Getty
Nader G. Abraham
Joseph I. Shapiro
Zeid Khitan
Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity
Stem Cells International
title Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity
title_full Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity
title_fullStr Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity
title_full_unstemmed Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity
title_short Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity
title_sort uric acid induced adipocyte dysfunction is attenuated by ho 1 upregulation potential role of antioxidant therapy to target obesity
url http://dx.doi.org/10.1155/2016/8197325
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