Xanthine oxidase and cardiovascular risk in obese children

Abstract

Background: Pathological mechanisms of how childhood obesity leads to increased risk of cardiovascular disease (CVD) are not fully characterized. Oxidative-stress-related enzymes, such as xanthine oxidase (XO), have been linked to obesity, endothelial dysfunction, and CVD in adults, but little is known about this pathway in children. The aim of this study was to determine whether differential XO activity is associated with endothelial dysfunction, CVD risk factors, or cytokine levels.

Methods: Fasting plasma samples were obtained from obese (BMI ≥ 95th percentile; n = 20) and age- and gender-matched healthy weight (BMI > 5th and < 85th percentile; n = 22) children and adolescents (mean age, 12 ± 3 years) to quantify XO activity. In addition, fasting cholesterol, insulin, glucose, blood pressure, endothelial function, and cytokine levels were assessed.

Results: We observed a 3.8-fold increase in plasma XO activity in obese, compared to healthy weight, children (118 ± 21 vs. 31 ± 9 nU/mg of protein; p < 0.001). Plasma XO activity was correlated with BMI z-score (r = 0.41), waist circumference (r = 0.41), high-density lipoprotein cholesterol (r = -0.32), oxidized low-density lipoprotein (r = 0.57), adiponectin (r = -0.53), and monocyte chemotactic protein-1 (r = -0.59).

Conclusion: XO activity is highly elevated in obese children and correlates with CVD risk factors, suggesting that XO may play a role in increasing cardiovascular risk early in life in the context of obesity.

Figure 1.

Plasma xanthine oxidase (XO) activity in healthy weight and obese children. Isoxantholumazine production from healthy weight (n=22) and obese (n=20) plasma samples standardized to purified XO standards of known activity. One unit of XO activity is defined as the production of one micromole of uric acid per minute at 25°C. Data are mean±standard error of the mean. *p<0.001, compared to the healthy weight group.