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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-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. [ABSTRACT FROM AUTHOR]

AIMS: We have studied the relationships between soluble fractions of tumour necrosis factor receptors (sTNFR1 and sTNFR2) in Type 2 diabetes (DM2) and its chronic microvascular complications. Likewise, we have analysed the genetic susceptibility of 196T > G exon6/CA-repeat intron 4 mutations in the TNFR2 gene in this population. METHODS: A case-control study was conducted to examine the role of sTNFRs in 345 DM2 patients and 173 healthy subjects. The mutations were studied in all healthy subjects and in a subset of 232 patients. RESULTS: sTNFRs levels were similar in healthy and DM2 patients. A positive correlation between age and both sTNFRs was observed in healthy subjects. In DM2 patients, sTNFR1 showed a positive correlation with age, systolic blood pressure and leptin levels (r = 0.53, P < 0.0001; r = 0.28, P = 0.005; r = 0.46, P < 0.0001, respectively) and sTNFR2 was positively correlated with age, triglycerides and leptin levels (r = 0.34, P < 0.0001; r = 0.21, P < 0.0001; r = 0.28, P = 0.002, respectively). Patients with micro- or macroalbuminuria showed higher plasma levels of sTNFR1 and sTNFR2 than normoalbuminuric patients, after adjusting for confounding variables (B = 0.85, P = 0.022, 95% CI: 0.12-1.58 for sTNFR1 and B = 1.50, P < 0.001, 95% CI: 0.67-2.33 for sTNFR2). In DM2 patients, TT-exon 6 homozygous showed lower levels of sTNFR1 [2,4 (1.1) vs. 3.4 (1.2) ng/ml], and the CA273-allele tracked with elevated plasma HDL-cholesterol [1.8 (0.7), 1.4 (0.3) and 1.3 (0.3) mm, for CA273/273, CA273/- and CA-/-, respectively]. No association was seen with other analysed variables. CONCLUSIONS: Our findings suggest that chronic TNF activation may have some pathogenic role in diabetic nephropathy in DM2 patients. Genetic variations in exon 6/intron 4 of the TNFR2 gene do not predispose to a major risk for DM2 or its microvascular complications. [ABSTRACT FROM AUTHOR]