Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance.
OBJECTIVE
To compare the effect of a high-fat, high-carbohydrate meal (HFHC) with that of a high-fiber and fruit meal on the concentrations of endotoxin (lipopolysaccharide [LPS]), LPS-binding protein (LBP), the expression of toll-like receptors (TLRs), and the suppressor of cytokine signaling-3 (SOCS-3) in mononuclear cells.


METHODS
Healthy lean subjects were given 910 calories of either an HFHC meal (n = 10) or an American Heart Association (AHA)-recommended meal rich in fiber and fruit (n = 10) after an overnight fast. Blood was collected before and at 1, 2, and 3 h after the meal. Cellular indexes of oxidative and inflammatory stress; the expression of SOCS-3, TLR2, and TLR4 in mononuclear cells; and plasma concentrations of LPS and LBP were measured.


RESULTS
HFHC meal intake induced an increase in plasma LPS concentration and the expression of SOCS-3, TLR2, and TLR4 protein, reactive oxygen species generation, and nuclear factor-kappaB binding activity (P < 0.05 for all). These increases were totally absent after the AHA meal rich in fiber and fruit.


CONCLUSIONS
The novel changes described after the HFHC meal elucidate further the mechanisms underlying postprandial inflammation and also provide the first evidence explaining the pathogenesis of insulin and leptin resistance mediated by SOCS-3 after such meals. In contrast, an AHA meal does not induce these effects.
Ghanim
Husam
H
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, NY, USA.
Abuaysheh
Sanaa
S
Sia
Ching Ling
CL
Korzeniewski
Kelly
K
Chaudhuri
Ajay
A
Fernandez-Real
Jose Manuel
JM
Dandona
Paresh
P
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology*; D004043:Dietary Fiber; D004731:Endotoxins / Q000097:blood* / Q000494:pharmacology; D005260:Female; D005638:Fruit; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D012016:Reference Values; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000097:blood* / Q000235:genetics; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000097:blood* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000097:blood* / Q000235:genetics; D055815:Young Adult
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004043:Dietary Fiber; D004731:Endotoxins; D007328:Insulin; D008070:Lipopolysaccharides; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D017392:Thiobarbituric Acid Reactive Substances; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4