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      Serum Uric Acid Levels are Associated with Cardiometabolic Risk Factors in Healthy Young and Middle-Aged Adults

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          Abstract

          Background

          Observational studies have highlighted an association between serum uric acid (SUA) levels and cardiovascular risk factors. Despite the growing body of evidences, several studies were conducted in older individuals or in carriers of diseases susceptible to affect SUA levels and cardiometabolic risk markers.

          Objective

          To evaluate the relationship of SUA with body adiposity, metabolic profile, oxidative stress, inflammatory biomarkers, blood pressure and endothelial function in healthy young and middle-aged adults.

          Methods

          149 Brazilian adults aged 20-55 years, both sexes, underwent evaluation of body adiposity, SUA, fasting glucose and insulin, lipid profile, malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), adiponectin, blood pressure and endothelial function. Endothelial function was assessed by the reactive hyperemia index (RHI) derived from peripheral arterial tonometry method. Participants were allocated in two groups according to SUA levels: control group (CG; n = 130; men ≤ 7 mg/dL, women ≤ 6 mg/dL) and hyperuricemia group (HG; n = 19; men > 7 mg/dL, women > 6 mg/dL). A P-value < 0.05 was considered statistically significant.

          Results

          After adjustment for confounders, participants in HG compared with those in CG displayed higher body mass index (BMI): 34.15(33.36-37.19) vs.31.80 (26.26-34.42) kg/m 2,p = 0.008, higher MDA: 4.67(4.03-5.30) vs. 3.53(3.10-4.07) ng/mL, p < 0.0001 and lower RHI: 1.68 ± 0.30 vs. 2.05 ± 0.46, p = 0.03). In correlation analysis adjusted for confounders, SUA was positively associated (p < 0.05) with BMI, waist circumference, LDL-cholesterol, triglycerides and MDA, and negatively associated (p < 0.05) with HDL-cholesterol, adiponectin and RHI.

          Conclusions

          This study suggests that in healthy young and middle-aged adults higher SUA levels are associated with higher body adiposity, unfavorable lipid and inflammatory phenotype, higher oxidative stress and impaired endothelial function.

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          Most cited references28

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          Sugar, Uric Acid, and the Etiology of Diabetes and Obesity

          The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that “a calorie is just a calorie” and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.
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            Gout.

            Gout is a common arthritis caused by deposition of monosodium urate crystals within joints after chronic hyperuricaemia. It affects 1-2% of adults in developed countries, where it is the most common inflammatory arthritis in men. Epidemiological data are consistent with a rise in prevalence of gout. Diet and genetic polymorphisms of renal transporters of urate seem to be the main causal factors of primary gout. Gout and hyperuricaemia are associated with hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular diseases. Non-steroidal anti-inflammatory drugs and colchicine remain the most widely recommended drugs to treat acute attacks. Oral corticosteroids could be an alternative to these drugs. Interleukin 1beta is a pivotal mediator of acute gout and could become a therapeutic target. When serum uric acid concentrations are lowered below monosodium urate saturation point, the crystals dissolve and gout can be cured. Patient education, appropriate lifestyle advice, and treatment of comorbidities are an important part of management of patients with gout. Copyright 2010 Elsevier Ltd. All rights reserved.
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              Hydrogen peroxide is the major oxidant product of xanthine oxidase.

              Xanthine oxidase (XO) is a critical source of reactive oxygen species (ROS) in inflammatory disease. Focus, however, has centered almost exclusively on XO-derived superoxide (O(2)(*-)), whereas direct H(2)O(2) production from XO has been less well investigated. Therefore, we examined the relative quantities of O(2)(*-) and H(2)O(2) produced by XO under a range (1-21%) of O(2) tensions. At O(2) concentrations between 10 and 21%, H(2)O(2) accounted for approximately 75% of ROS production. As O(2) concentrations were lowered, there was a concentration-dependent increase in H(2)O(2) formation, accounting for 90% of ROS production at 1% O(2). Alterations in pH between 5.5 and 7.4 did not affect the relative proportions of H(2)O(2) and O(2)(*-) formation. Immobilization of XO, by binding to heparin-Sepharose, further enhanced relative H(2)O(2) production by approximately 30%, under both normoxic and hypoxic conditions. Furthermore, XO bound to glycosaminoglycans on the apical surface of bovine aortic endothelial cells demonstrated a similar ROS production profile. These data establish H(2)O(2) as the dominant (70-95%) reactive product produced by XO under clinically relevant conditions and emphasize the importance of H(2)O(2) as a critical factor when examining the contributory roles of XO-catalyzed ROS in inflammatory processes as well as cellular signaling. Published by Elsevier Inc.
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                Author and article information

                Journal
                Arq Bras Cardiol
                Arq. Bras. Cardiol
                abc
                Arquivos Brasileiros de Cardiologia
                Sociedade Brasileira de Cardiologia - SBC
                0066-782X
                1678-4170
                December 2018
                December 2018
                : 111
                : 6
                : 833-840
                Affiliations
                [1 ] Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Rio de Janeiro, RJ - Brazil
                [2 ] Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ - Brazil
                Author notes
                Mailing Address: Thaís da Silva Ferreira, Avenida Pasteur, 296 Prédio da Escola de Nutrição, Departamento de Nutrição Aplicada. Postal Code 22290-240, Urca, Rio de Janeiro, RJ - Brazil. E-mail: thaissferreira@ 123456gmail.com , thais.ferreira@ 123456unirio.br
                Article
                10.5935/abc.20180197
                6263461
                30328946
                272a57b4-dc6f-4f1c-a302-c0c82a85c58f

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 May 2018
                : 19 June 2018
                : 02 July 2018
                Categories
                Original Article

                uric acid/metabolism,oxidative stress,inflammation,endothelium/ dysfunction,adults

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