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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uric acid is involved in nitrogenous waste in animals, together with ammonia and urea. Uric acid has also antioxidant properties and is a surrogate marker of metabolic syndrome. We observed that the elevated plasma uric acid of high-fat fed mice was normalized by benzylamine treatment. Indeed, benzylamine is the reference substrate of semicarbazide-sensitive amine oxidase (SSAO), an enzyme highly expressed in fat depots and vessels, which generates ammonia when catalysing oxidative deamination. Ammonia interferes with uric acid metabolism/solubility. Our aim was therefore to investigate whether the lowering action of benzylamine on uric acid was related to an improvement of diabetic complications, or was connected with SSAO-dependent ammonia production. First, we observed that benzylamine administration lowered plasma uric acid in diabetic db/db mice while it did not modify uric acid levels in normoglycemic and lean mice. In parallel, benzylamine improved the glycemic control in diabetic but not in normoglycemic mice, while plasma urea remained unaltered. Then, uric acid plasma levels were measured in mice invalidated for AOC3 gene, encoding for SSAO. These mice were unable to oxidize benzylamine but were not diabetic and exhibited unaltered plasma uric levels. Therefore, activated or abolished ammonia production by SSAO was without influence on uric acid in the context of normoglycemia. Our observations confirm that plasma uric acid increases with diabetes and can be normalized when glucose tolerance is improved. They also show that uric acid, a multifunctional metabolite at the crossroads of nitrogen waste and of antioxidant defences, can be influenced by SSAO, in a manner apparently related to changes in glucose homeostasis.
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PMID:Long-term activation of semicarbazide-sensitive amine oxidase lowers circulating levels of uric acid in diabetic conditions. 2248 Apr 18

Hyperuricemia is known to be associated with obesity and metabolic syndrome. The aims of this study were to evaluate the prevalence of hyperuricemia in the Indian obese population and to determine if a correlation exists between hyperuricemia, body mass index, waist circumference and components of metabolic syndrome. This was a retrospective observational study. Four hundred nine obese patients were included. Anthropometric parameters were recorded. Prevalence of type 2 diabetes mellitus (T2DM), hypertension and dyslipidemia were recorded. Uric acid levels were measured in all patients. Hyperuricemia was defined as serum uric acid levels greater than 6 mg/dl. The population studied had a median body mass index (BMI) of 44.14 kg/m(2) (range 28.1-88.2 kg/m(2)) and a median age of 41 years (range 18 to 75 years). Overall prevalence of hyperuricemia was 44.6 %. Thirty-four percent in the BMI range of 28-35 kg/m(2) and 47 % of patients with a BMI of >35 kg/m(2) had hyperuricemia. The incidence of hyperuricemia in males was 50 vs 21.7 % in females. Of patients in the hyperuricemia group, 47.3 % had hypertension as compared to 37 % in the normouricemic group. Dyslipidemia was seen in 7.3 % of hyperuricemic patients as compared to 5.8 % of the normouricemic subjects. The prevalence of T2DM was comparable in both the groups. The Indian obese population has a significant high prevalence of hyperuricemia; the incidence of hyperuricemia in male patients was greater than in female patients. Central obesity had no direct link to hyperuricemia. There was no significant correlation between the occurrence of T2DM and dyslipidemia and hyperuricemia. Hypertension was the only comorbidity seen to occur in conjunction with hyperuricemia.
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PMID:Hyperuricemia: a reality in the Indian obese. 2252 98

Higher prevalence rates of metabolic syndrome (MetS) in patients with schizophrenia are getting more and more attention. Uric acid (UA) has been frequently reported to be associated with MetS in the general population. Sex difference in this relationship is inconsistent. As a selective antioxidant, UA has also been found to be reduced in patients with schizophrenia, and this effect may be prominent in men. With the inconsistent presentations, higher rate of MetS but possible lower UA concentrations, the aim of this study was to investigate the relationship by sexes between serum UA concentrations and prevalence of MetS in patients with schizophrenia or schizoaffective disorder. A total of 637 patients, 342 male and 295 female, were enrolled from 36 psychiatric rehabilitation institutions. Cross-sectional anthropometrical data, biochemical analysis, and serum UA were measured. Serum UA concentrations were divided into quartiles by sexes. Modified National Cholesterol Education Program Adult Treatment Panel III criteria for Asians were used as diagnosis of MetS. After adjustment, higher UA concentrations are associated with hypertriglyceridemia, low high-density lipoprotein cholesterol level, and high blood pressure in men and with hypertriglyceridemia in women. Significantly higher odds ratios for MetS in the UA third (4.02; 95% confidence interval, 1.33-12.1) and fourth quartiles (9.28; 95% confidence interval, 2.90-29.8) compared with the lowest quartile were found in men but not in women after adjustment. These results suggest that lower UA concentrations in male patients with schizophrenia or schizoaffective disorder are associated with lower risk of MetS.
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PMID:The relationship between serum uric acid concentration and metabolic syndrome in patients with schizophrenia or schizoaffective disorder. 2292 90

Hyperuricaemia is common in subjects with cardiovascular disease, but is not commonly considered a true risk factor. Recent studies suggest that uric acid is biologically active and can stimulate oxidative stress, endothelial dysfunction, inflammation and vasoconstriction. Epidemiological studies have found that uric acid can independently predict the development of hypertension, as well as stroke and heart failure. Experimentally raising uric acid in animals increases blood pressure, and pilot studies suggest that lowering uric acid in humans can reduce blood pressure in hypertensive individuals. Uric acid may also have emerging roles in the pathogenesis of kidney disease, metabolic syndrome and diabetes. More studies need to be performed on the pathophysiology and clinical consequences of hyperuricaemia in cardiovascular disease.
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PMID:The role of uric acid in the pathogenesis of human cardiovascular disease. 2334 89

Diabetes mellitus and the metabolic syndrome are becoming leading causes of death in the world. Identifying the etiology of diabetes is key to prevention. Despite the similarity in their structures, fructose and glucose are metabolized in different ways. Uric acid, a byproduct of uncontrolled fructose metabolism is known risk factor for hypertension. In the liver, fructose bypasses the two highly regulated steps in glycolysis, glucokinase and phosphofructokinase, both of which are inhibited by increasing concentrations of their byproducts. Fructose is metabolized by fructokinase (KHK). KHK has no negative feedback system, and ATP is used for phosphorylation. This results in intracellular phosphate depletion and the rapid generation of uric acid due to activation of AMP deaminase. Uric acid, a byproduct of this reaction, has been linked to endothelial dysfunction, insulin resistance, and hypertension. We present possible mechanisms by which fructose causes insulin resistance and suggest actions based on this association that have therapeutic implications.
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PMID:Fructose: a key factor in the development of metabolic syndrome and hypertension. 2376 44

Uric acid is the end product of purine metabolism in humans. High levels are causative in gout and urolithiasis. Hyperuricaemia has also been implicated in the pathophysiology of hypertension, chronic kidney disease (CKD), congestive heart failure (CHF), the metabolic syndrome, type 2 diabetes mellitus (T2DM), and atherosclerosis, with or without cardiovascular events. This article briefly reviews uric acid metabolism and summarizes the current literature on hyperuricaemia in cardiovascular disease and related co-morbidities, and emerging treatment options.
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PMID:The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. 2389 42

Plasma levels of uric acid, the final product of purine degradation in humans, are elevated in metabolic syndrome and are strongly associated with insulin resistance and nonalcoholic fatty liver disease (NAFLD). Hepatic and blood levels of purine metabolites (inosine, hypoxanthine, and xanthine) are also altered in pathophysiological states. We optimized a rat hepatocyte model to test the hypothesis that the production of uric acid by hepatocytes is a potential marker of compromised homeostasis of hepatocellular inorganic phosphate (Pi) and/or ATP. The basal rate of uric acid production from endogenous substrates in rat hepatocytes was comparable to that in human liver and was <10% of the maximum rate with saturating concentrations of purine substrates. It was marginally (~20%) decreased by insulin and increased by glucagon but was stimulated more than twofold by substrates (fructose and glycerol) that lower both cell ATP and Pi, and by inhibitors of mitochondrial respiration (complexes I, III, and V) that lower ATP but raise cell Pi. Clearance of inosine and its degradation to uric acid were also inhibited by cell Pi depletion. Analysis of gene expression in NAFLD biopsies showed an association between mRNA expression of GCKR, the glucokinase regulatory protein that is functionally linked to uric acid production, and mRNA expression of the phosphate transporters encoded by SLC17A1/3. Uric acid production by hepatocytes is a very sensitive index of ATP depletion irrespective of whether cell Pi is lowered or raised. This suggests that raised plasma uric acid may be a marker of compromised hepatic ATP homeostasis.
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PMID:The rate of production of uric acid by hepatocytes is a sensitive index of compromised cell ATP homeostasis. 2404 66

Kidney stones and metabolic syndrome (MetS) are common conditions in industrialized countries. There is growing evidence of associations between kidney stone disease and MetS or some of its components. The link between uric acid stones and MetS is well understood, but the link with calcium oxalate (CaOx) stones, the most common kidney stone composition, is more complex, and MetS is frequently overlooked as a risk factor for calcium nephrolithiasis. The physiopathological mechanisms of kidney stone disease in MetS are reviewed in this article. Uric acid stones are a consequence of the excessively acidic urine that results from insulin resistance. The pathophysiology of CaOx stones may include: increased excretion of lithogenesis promoters and decreased excretion of inhibitors; increased risk of Randall's plaque development; and inflammatory damage to renal epithelia by oxidative stress, as a consequence of the insulin-resistant milieu that characterizes MetS. The last mechanism contributes to the adhesion of CaOx crystals to subepithelial calcium deposits working as anchor sites where stones can grow. The predominant MetS features could determine the chemical composition of the stones in each patient. Kidney stones may be a renal manifestation of MetS and features of this syndrome should be looked for in patients with idiopathic nephrolithiasis.
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PMID:Metabolic syndrome: a multifaceted risk factor for kidney stones. 2470 98

Uric acid affects endothelial and adipose cell function and has been linked to diseases such as hypertension, metabolic syndrome, and cardiovascular disease. Interestingly uric acid has been shown to increase endothelial progenitor cell (EPC) mobilization, a potential mechanism to repair endothelial injury. Since EPC mobilization is dependent on activity of the enzyme CD26/dipeptidyl peptidase (DPP)IV, we examined the effect uric acid will have on CD26/DPPIV activity. Uric acid inhibited the CD26/DPPIV associated with human umbilical vein endothelial cells but not human recombinant (hr) CD26/DPPIV. However, triuret, a product of uric acid and peroxynitrite, could inhibit cell associated and hrCD26/DPPIV. Increasing or decreasing intracellular peroxynitrite levels enhanced or decreased the ability of uric acid to inhibit cell associated CD26/DPPIV, respectively. Finally, protein modeling demonstrates how triuret can act as a small molecule inhibitor of CD26/DPPIV activity. This is the first time that uric acid or a uric acid reaction product has been shown to affect enzymatic activity and suggests a novel avenue of research in the role of uric acid in the development of clinically important diseases.
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PMID:Uric acid inhibition of dipeptidyl peptidase IV in vitro is dependent on the intracellular formation of triuret. 2492 78

Uric acid nephrolithiasis is characteristically a manifestation of a systemic metabolic disorder. It has a prevalence of about 10% among all stone formers, the third most common type of kidney stone in the industrialized world. Uric acid stones form primarily due to an unduly acid urine; less deciding factors are hyperuricosuria and a low urine volume. The vast majority of uric acid stone formers have the metabolic syndrome, and not infrequently, clinical gout is present as well. A universal finding is a low baseline urine pH plus insufficient production of urinary ammonium buffer. Persons with gastrointestinal disorders, in particular chronic diarrhea or ostomies, and patients with malignancies with a large tumor mass and high cell turnover comprise a less common but nevertheless important subset. Pure uric acid stones are radiolucent but well visualized on renal ultrasound. A 24 h urine collection for stone risk analysis provides essential insight into the pathophysiology of stone formation and may guide therapy. Management includes a liberal fluid intake and dietary modification. Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is essential, as undissociated uric acid deprotonates into its much more soluble urate form.
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PMID:Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder. 2504 26


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