Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity
Authors: George Banks
Nader G Abraham
Komal Sodhi
Jordan Hilgefort
Chelsea Gilliam
Sarah Stevens
Morghan Getty
Joseph I Shapiro
Zeid Khitan
Hayden A Ansinelli
Journal: Stem Cells International (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: uric acid levels; metabolic syndrome; heme oxygenase 1; antioxidant gene; adipocyte dysfunction
Affiliations: Departments of Internal Medicine and Surgery, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USA., Departments of Pharmacology and Medicine, New York Medical College, Valhalla, NY 10595, USA.

Abstract:  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/EBPŒ±, PPARŒ≥, 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. 

Retracted: No

PubPeer comments:
 FIG. 3.  The effects of incompatibility of VN and RPA on the histology of the uterus and vagina in immature and OVX mice. Representative photomicrographs taken at... 400xu00b7 magnification of vaginal sections. ... (B, D) are the histology of the vagina in immature mice and OVX mice. VN significantly reduced the estrogenic efficacy of RPA in promoting the growth and development of the uterus in immature mice and restoring the atrophy of the uterus in OVX mice. The treatment groups in immature mice are shown as follows: (i) control group; (ii) treated with E2; (iii) treated with E2 and ICI; (iv) treated with E2 and VN; (v) treated with RPA at 2 g kg and ICI182780, (vi) treated with RPA at 2 g kg and ICI182780; (vii) treated with RPA at 2 g kg and VN; (vii) treated with RPA at 4 g kg; (ix) treated with RPA at 4 g kg and ICI182780; and (x) treated with RPA at 4 g kg and VN. The resolution is not great but enough to inspire concerns. I have not attempted to mark all of the repeating motifs, and have left two panels as an exercise for the reader.  , 
 Fig 3D. I have not tried to mark all or even most of the repeating motifs.  , 
 Fig 4D.  The effects of incompatibility of VN and RPA on the expressions of ER a and b in the uterus and vagina. ER expressions were assessed by immunohistochemistry. Representative photomicrographs taken at ... 400-x magnification of vaginal sections. ... (C, D) show the expression of ERs in the OVX mice. Treatment groups are shown as follows: (i) sham-operated mice; (ii) untreated OVX mice; (iii) treated with E2; (iv) treated with E2 and ICI182780, (v) treated with E2 and VN; (vi) treated with RPA at 2 g kg; (vii) treated with RPA at 2 g kg and ICI182780, (vii) treated with RPA at 2 g kg and VN; (ix) treated with RPA at 4 g kg; (x) treated with RPA at 4 g kg and ICI182780; and (xi) treated with RPA at 4 g kg and VN.  The lamentable resolution becomes more of a problem for these smaller images. Even so, I cannot avoid the feeling that many of the images arose through crystallisation more than from any biological process.   , 
 Fig 4B.  Perhaps there was an accident with the scanner.     ,