Prolonged reactive oxygen species generation and nuclear factor-kappaB 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-kappaB 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-kappaB increased significantly at both 2 and 3 h (by 36 +/- 57 and 42 +/- 63%, respectively, P < 0.004). Matrix metalloproteinase-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.
Patel
Chinmay
C
Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209, USA.
Ghanim
Husam
H
Ravishankar
Shreyas
S
Sia
Chang Ling
CL
Viswanathan
Prabhakar
P
Mohanty
Priya
P
Dandona
Paresh
P
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005502:Food; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood