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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. RESEARCH DESIGN AND 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-κB 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. [ABSTRACT FROM AUTHOR]