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Increase in intranuclear nuclear factor kappaB and decrease in inhibitor kappaB in mononuclear cells after a mixed
Ahmad Aljada1, Priya Mohanty, Husam Ghanim
1Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, NY, USA.
Background:
In view of the stimulatory effect of glucose on reactive oxygen species (ROS) generation, we investigated the possibility that a mixed meal stimulates ROS generation and possibly induces concomitant proinflammatory changes.
Objective:
The objective was to determine whether the intake of a 900-kcal mixed meal induces an increase in ROS generation by leukocytes and an inflammatory response at the cellular level.
Design:
Nine normal-weight subjects were given a 900-kcal mixed meal, and 8 normal-weight subjects were given 300 mL water after an overnight fast. Blood samples were collected at 0, 1, 2, and 3 h. ROS generation by mononuclear cells and polymorphonuclear leukocytes and the expression of p47(phox) subunit were measured. Intranuclear nuclear factor kappaB (NF-kappaB) binding and the expression of inhibitor kappaBalpha (IkappaBalpha), IkappaB kinase alpha (IKKalpha), and IkappaB kinase beta (IKKbeta) were measured. Plasma concentrations of C-reactive protein (CRP) and soluble intercellular adhesion molecule were also measured.
Results:
ROS generation by mononuclear cells and polymorphonuclear leukocytes and p47(phox) expression increased significantly. The expression of IKKalpha and IKKbeta and DNA-binding activity of NF-kappaB increased significantly, whereas IkappaBalpha expression decreased. Plasma CRP concentrations increased. The intake of 300 mL water did not induce a change in any of the above indexes.
Conclusions:
These data show that the intake of a mixed meal results in significant inflammatory changes characterized by a decrease in IkappaBalpha and an increase in NF-kappaB binding, plasma CRP, and the expression of IKKalpha, IKKbeta, and p47(phox) subunit. These proinflammatory changes are probably relevant to the state of chronic hypertension and obesity and to its association with atherosclerosis.
Insights
A mixed meal significantly increases reactive oxygen species (ROS) generation and inflammatory markers in leukocytes. These findings suggest a link between meal intake and chronic inflammatory conditions like obesity and atherosclerosis.
Area of Science:
- Biochemistry
- Immunology
- Nutrition Science
Background:
- Glucose intake stimulates reactive oxygen species (ROS) generation.
- Investigating the link between mixed meals, ROS production, and inflammation is crucial.
Purpose of the Study:
- To determine if a 900-kcal mixed meal increases ROS generation by leukocytes.
- To assess if a mixed meal induces cellular-level inflammatory responses.
Main Methods:
- Nine subjects consumed a 900-kcal mixed meal; eight consumed water.
- Blood samples analyzed for ROS generation, p47(phox) expression, NF-kappaB activity, IkappaBalpha, IKKalpha, IKKbeta, CRP, and soluble intercellular adhesion molecule.
- Measurements taken at 0, 1, 2, and 3 hours post-ingestion.
Main Results:
- Mixed meal intake significantly increased ROS generation and p47(phox) expression in leukocytes.
- NF-kappaB binding activity and IKKalpha/IKKbeta expression increased, while IkappaBalpha decreased.
- Plasma C-reactive protein (CRP) levels rose significantly post-meal; water intake had no effect.
Conclusions:
- Mixed meal consumption triggers significant inflammatory changes, including decreased IkappaBalpha and increased NF-kappaB binding, CRP, IKKalpha, IKKbeta, and p47(phox) expression.
- These meal-induced inflammatory changes may contribute to chronic conditions like hypertension, obesity, and atherosclerosis.
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