Leptin Might be a Regulator of Serum Uric Acid Concentrations in Humans

Abstract

SUMMARYIncreased serum urate concentration is a frequent finding in patients with hypertension. Since hyperuricemia is associated with obesity, renal disease, hyperlipidemia, and atherosclerosis, whether or not serum urate is a cardiovascular risk factor per se has remained elusive.The subjects were 210 Turkish male and 210 female adults over 20 years of age. None had diabetes mellitus, endocrine diseases, or renal or hepatic disease, and those receiving antihypertensive drugs, systemic corticosteroids, or lipid-lowering drugs were excluded. Height, weight, blood pressure, serum glucose, lipid profiles, serum insulin, DHEA-SO 4 , and leptin were measured in the morning after an overnight fast.Women had significantly higher mean leptin (20.3 ± 0.88 ng/mL vs 5.78 ± 0.39 ng/ mL, P < 0.001) and lower mean uric acid (248.03 ± 4.76 µmol/L vs 311.6 ± 5.35 µmol/ L, P < 0.001), triglyceride (1.42 ± 0.06 mmol/L vs 1.61 ± 0.06 mmol/L, P < 0.001), and DHEA-SO 4 (3.02 ± 0.17 µmol/L vs 4.43 ± 0.19 µmol/L, P < 0.001) concentrations than men, even when adjusted for BMI. On univariate correlation analysis, leptin showed the strongest association with BMI in both sexes and also correlated significantly with BMI, insulin, uric acid, glucose, total cholesterol, and triglycerides in males and BMI, insulin, uric acid, total cholesterol, apo B, and creatinine in females after adjustment for age and BMI. A statistical model containing creatinine, leptin, insulin, and triglycerides accounted for 34% of the variance in serum uric acid levels in men, whereas another consisting of creatinine, triglycerides, leptin, SBP, and insulin explained 42% of the variance in serum uric acid in women. The present study suggests that leptin could be one of the possible candidates for the missing link between obesity and hyperuricemia. Our study may also suggest that hyperuricemia is not only a metabolic end product but also a marker of a major pressor or pathogenic mechanism underlying the hypertension in obesity. (Jpn Heart J 2003; 44: 527-536)

Prevalence of the metabolic syndrome in patients with gout: The Third National Health and Nutrition Examination Survey

“…Insulin may enhance renal urate reabsorption via stimulation of urate-anion exchanger URAT1 (22) and/or the Na ϩ -dependent anion cotransporter in brush border membranes of the renal proximal tubule (8). Additionally, because serum levels of leptin and urate tend to increase together (23,24), some investigators have suggested that leptin may affect renal reabsorption (8). Finally, in insulin resistance syndrome, impaired oxidative phosphorylation may increase systemic adenosine concentrations by increasing the intracellular levels of coenzyme A esters of long-chain fatty acids (8).…”

Factors Associated with Early Platelet Activation in Obese Children

“…32 The role of UA as an additional risk factor for developing endothelial dysfunction and smooth muscle cell proliferation is caused by an excessive activity of xanthine oxidase enzyme by degraded purine metabolism and formation of reactive oxygen and nitrogen species that lead to oxidative stress and later to development of endothelial dysfunction. 33 Bedir et al 11 showed that serum leptin level was independently associated with UA only in overweight and obese adults. Our results about the correlation between leptin and UA in obese children are consistent with the theory by Bedir that leptin appears to be a good candidate for the missing link between obesity and hyperuricemia.…”

Uric acid levels in metabolically healthy and unhealthy obese patients

“…Serum ÜA ile obezite, dislipidemi, hipertansiyon, bozulmuş glukoz metabolizması gibi KVH risk parametrelerinin ilişkisini açıklamak için birçok sebep ileri sürülmüştür. Artmış insülin seviyeleri ve insülin direnci, artmış leptin seviyeleri, obeziteye de yol açan artmış fruktoz tüketiminin ÜA'in renal klerensini azalttığı ya da renal tübüler reabsorbsiyonunu arttır-dığı ileri sürülen faktörlerdendir [15][16][17][18][19][20][21][22]. Ek olarak; hipertrigliserideminin kendisinin de ÜA'in renal atı-lımını azalttığını, TG seviyelerinde azalmanın idrar ÜA seviyelerini arttırdığını ortaya koyan çalışmalar da vardır [23][24][25].…”