title: Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects.
abstract: 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-F2α) 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/m(2)) 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.
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fabbrini
authors.forename: Mauro
authors.initials: M
authors.lastname: Serafini
authors.forename: Irena
authors.initials: I
authors.lastname: Colic Baric
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D018384:Oxidative Stress; D014527:Uric Acid / Q000097:blood*
chemical_list: D000975:Antioxidants; D014527:Uric Acid