Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity.
Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity.
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DOI：
10.1155/2016/8197325
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发表时间：
2016
影响因子：
4.3
通讯作者：
Khitan Z
中科院分区：
文献类型：
--
作者：
Sodhi K;Hilgefort J;Banks G;Gilliam C;Stevens S;Ansinelli HA;Getty M;Abraham NG;Shapiro JI;Khitan Z
尿酸水平升高与代谢综合征的发病机制有关。为了研究这种情况发生的机制，我们假设，一种有效的抗氧化剂基因--血红素加氧酶1的增加，将通过抑制ROS和黄嘌呤氧化酶(XO)水平来降低尿酸水平和脂肪细胞功能障碍。我们研究了尿酸对人骨髓间充质干细胞(MSCs)在有无HO-1诱导剂钴原卟啉(CoPP)和HO活性抑制剂锡中卟啉(SNMP)存在和不存在的情况下，对人骨髓间充质干细胞(MSCs)脂肪形成的影响。尿酸通过增加NADPH氧化酶在成脂标记物C/EBPα、PPARγ和Mest中的表达和升高，同时减少小脂滴和WNT10b水平来促进成脂。我们用果糖处理间充质干细胞，果糖是一种增加尿酸水平的燃料来源。我们的结果表明，与对照组相比，果糖增加了XO的表达，同时CoPP显著降低了XO的表达和尿酸水平。COPP的这些有益作用被SNMP逆转，支持HO活性在调节这些作用中的作用。这些发现表明，HO-1水平的增加似乎在调节暴露于尿酸的脂肪细胞的表型和下调XO和NADPH氧化酶水平方面至关重要。
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.