Prolonged reactive oxygen species generation and nuclear factor-κB activation after a high-fat, high-carbohydrate meal in the obese

Background: Because obesity is associated with chronic oxidative and inflammatory stress, and high- fat, high- carbohydrate meals induce significant oxidative and inflammatory stress in normal subjects, we have now hypothesized that the intake of a high- fat, high-carbohydrate meal would result in a greater and more prolonged oxidative and inflammatory stress in the obese than in normal subjects. Methods: Ten normal- weight and eight obese subjects were given a high- fat, high- carbohydrate meal after an overnight fast. Blood samples were collected at baseline and hourly following the meal for 3 h. Results: Reactive oxygen species generation by mononuclear cells increased significantly by 2 h in both groups but continued to increase significantly at 3 h in the obese subjects, whereas in normal subjects it returned to baseline. Levels of p47(phox) increased significantly ( by 81 +/- 26%) at 3 h in obese individuals ( P < 0.05), whereas there was no significant change in p47(phox) in normal subjects. Nuclear factor- kappa B DNA binding in mononuclear cells increased significantly ( by 48 +/- 58%, P < 0.036) at 2 h but not at 3 h in normal subjects, whereas in the obese, nuclear factor- kappa B increased significantly at both 2 and 3 h ( by 36 +/- 57 and 42 +/- 63%, respectively, P < 0.004). Matrix metal-loproteinase-9 concentrations were significantly higher in the obese at baseline ( 580 +/- 103.9 vs. 373 +/- 30.03 ng/ ml, P < 0.05) and increased to significantly greater concentrations after the meal than in the lean subjects. Conclusions: High- fat, high- carbohydrate meals induced a significantly more prolonged and greater oxidative and inflammatory stress in the obese. This may contribute to the increased atherogenic risk in obesity.