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

TLDR

The study compared the effects of a high‑fat, high‑carbohydrate meal versus a high‑fiber, fruit‑rich meal on plasma endotoxin, LBP, TLR, and SOCS‑3 expression in mononuclear cells. Healthy lean subjects received 910‑calorie HFHC or AHA‑recommended fiber‑fruit meals after fasting; blood was drawn at baseline and 1, 2, 3 h post‑meal, and plasma LPS, LBP, oxidative/inflammatory markers, SOCS‑3, TLR2/4 expression, and NF‑κB activity were measured. HFHC intake raised plasma LPS, SOCS‑3, TLR2/4, ROS, and NF‑κB activity, whereas the AHA meal produced no such changes, indicating that post‑prandial inflammation and insulin/leptin resistance may be mediated by SOCS‑3.

Abstract

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.