Effect of Plasma Uric Acid on Antioxidant Capacity, Oxidative Stress, and Insulin Sensitivity in Obese Subjects

  1. Samuel Klein1
  1. 1Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO
  2. 2Agricultural Research Council-Research Centre on Food and Nutrition, Rome, Italy
  3. 3Center for Cardiovascular Diagnostics and Prevention, Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
  1. Corresponding author: Samuel Klein, sklein{at}


Oxidative stress is purported to be involved in the pathogenesis of obesity-associated insulin resistance. We evaluated whether alterations in levels of circulating uric acid (UA), a systemic antioxidant, affects the following: 1) systemic (plasma and saliva) nonenzymatic antioxidant capacity (NEAC); 2) markers of systemic (urinary 8-iso-prostaglandin-F) and muscle (carbonylated protein content) oxidative stress; and 3) whole-body insulin sensitivity (percentage increase in glucose uptake during a hyperinsulinemic-euglycemic clamp procedure). Thirty-one obese subjects (BMI 37.1 ± 0.7 kg/m2) with either high serum UA (HUA; 7.1 ± 0.4 mg/dL; n = 15) or normal serum UA (NUA; 4.5 ± 0.2 mg/dL; n = 16) levels were studied; 13 subjects with HUA levels were studied again after reduction of serum UA levels to 0 by infusing a recombinant urate oxidase. HUA subjects had 20–90% greater NEAC, but lower insulin sensitivity (40%) and levels of markers of oxidative stress (30%) than subjects in the NUA group (all P < 0.05). Acute UA reduction caused a 45–95% decrease in NEAC and a 25–40% increase in levels of systemic and muscle markers of oxidative stress (all P < 0.05), but did not affect insulin sensitivity (from 168 ± 25% to 156 ± 17%, P = NS). These results demonstrate that circulating UA is a major antioxidant and might help protect against free-radical oxidative damage. However, oxidative stress is not a major determinant of insulin action in vivo.

  • Received September 9, 2013.
  • Accepted December 5, 2013.

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  1. Diabetes vol. 63 no. 3 976-981
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