Toll-like receptors (TLR) mediate infection-induced inflammation and sterile inflammation by endogenous molecules. Among the TLR family, TLR4 is the best understood. However, while its downstream signaling pathways have been well defined, not all ligands of TLR4 are currently known. Current evidence suggests that saturated fatty acids (SFA) act as non-microbial TLR4 agonists, and trigger its inflammatory response. Thus, our present review provides a new perspective on the potential mechanism by which SFAs could modulate TLR4-induced inflammatory responses: (1) SFAs can be recognized by CD14-TLR4-MD2 complex and trigger inflammatory pathways, similar to lipopolysaccharide (LPS). (2) SFAs lead to modification of gut microbiota with an overproduction of LPS after a high-fat intake, enhancing this natural TLR4 ligand. (3) In addition, this metabolic endotoxemia leads to an oxidative stress thereby producing atherogenic lipids - oxLDL and oxidized phospholipids - which trigger CD36-TLR4-TLR6 inflammatory response. (4) Also, the high SFA consumption increases the lipemia and the mmLDL and oxLDL formation through oxidative modifications of LDL. The mmLDL, unlike oxLDL, is involved in activation of the CD14-TLR4-MD2 inflammatory pathway. Those molecules can induce TLR4 inflammatory response by MyD88-dependent and/or MyD88-independent pathways that, in turn, promotes the expression of proinflammatory transcript factors such as factor nuclear kappa B (NF-κB), which plays a crucial role in the induction of inflammatory mediators (cytokines, chemokines, or costimulatory molecules) implicated in the development and progression of many chronic diseases.

The consumption of legumes (4 servings/week) within a hypocaloric diet resulted in a specific reduction in proinflammatory markers, such as CRP and C3 and a clinically significant improvement of some metabolic features (lipid profile and BP) in overweight/ obese subjects, which were in some cases independent from weight loss.

BackgroundDietary total antioxidant capacity (TAC) has been assumed as a useful tool to assess the relationship between the cumulative antioxidant food capacity and several chronic disorders. The aim of this cross-sectional study was to investigate the potential relationships of dietary TAC with adiposity, metabolic and oxidative stress markers in healthy young adults.MethodsThis study enrolled 266 healthy subjects (105 men/ 161 women; 22 ± 3 years-old; 22.0 ± 2.7 kg/m2). Dietary intake, anthropometry, blood pressure, lifestyle features, and biochemical data were assessed with validated procedures.ResultsIn linear regression analyses, dietary TAC values were inversely associated with glycemia, total cholesterol:HDL-c ratio, triglycerides and oxidized-LDL concentrations, and positively associated with HDL-c concentrations, independently of gender, age, smoking status, physical activity, vitamin use supplement, waist circumference, energy intake, fatty acid intake. In addition, plasma TAC was negatively correlated with ox-LDL concentrations (r= -0.20, P = 0.003), independently of the assessed confounding variables. Finally, dietary TAC values were inversely related to waist circumference values (r= -0.17, P = 0.005) as well as to lower mild central obesity occurrence (waist circumference ≥ 80/ 94 cm for women/ men, respectively).ConclusionDietary TAC values are inversely associated with glucose and lipid biomarkers as well as with central adiposity measurements in healthy young adults, indicating dietary TAC as a useful tool to assess the health benefits of cumulative antioxidant capacity from food intake. In addition, the independent and inverse relationships of ox-LDL concentrations with dietary and plasma TAC respectively suggest a putative role of antioxidant rich-diet in the link between redox state and atherogenesis at early stage.

Background The triglyceride-glucose index (TyG index) is a tool for insulin resistance evaluation, however, little is known about its association with coronary artery disease (CAD), which is the major cardiovascular death cause, and what factors may be associated with TyG index. Objective To evaluate the association between the TyG index and the prevalence of CAD phases, as well as cardiovascular risk factors. Methods The baseline data of patients in secondary care in cardiology from Brazilian Cardioprotective Nutritional Program Trial (BALANCE Program Trial) were analyzed. Anthropometric, clinical, socio-demographic and food consumption data were collected by trained professionals. The TyG index was calculated by the formula: Ln (fasting triglycerides (mg/dl) × fasting blood glucose (mg/dl)/2) and regression models were used to evaluate the associations. Results We evaluated 2330 patients, which the majority was male (58.1%) and elderly (62.1%). The prevalence of symptomatic CAD was 1.16 times higher in patients classified in the last tertile of the TyG index (9.9 ± 0.5) compared to those in the first tertile (8.3 ± 0.3). Cardiometabolic risk factors were associated with TyG index, with the highlight for higher carbohydrate and lower lipid consumption in relation to recommendations that reduced the chance of being in the last TyG index tertile. Conclusion The TyG index was positively associated with a higher prevalence of symptomatic CAD, with metabolic and behavioral risk factors, and could be used as a marker for atherosclerosis. Trial registration ClinicalTrials.gov identifier: NCT01620398. Registered 15 June, 2012 Electronic supplementary material The online version of this article (10.1186/s12933-019-0893-2) contains supplementary material, which is available to authorized users.

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BackgroundFruits and vegetables are important sources of fiber and nutrients with a recognized antioxidant capacity, which could have beneficial effects on the proinflammatory status as well as some metabolic syndrome and cardiovascular disease features. The current study assessed the potential relationships of fruit and vegetable consumption with the plasma concentrations and mRNA expression values of some proinflammatory markers in young adults.MethodsOne-hundred and twenty healthy subjects (50 men/70 women; 20.8 ± 2.6 y; 22.3 ± 2.8 kg/m2) were enrolled. Experimental determinations included anthropometry, blood pressure and lifestyle features as well as blood biochemical and inflammatory measurements. The mRNA was isolated from peripheral blood mononuclear cells (PBMC) and the gene expression concerning selected inflammatory markers was assessed by quantitative real-time PCR. Nutritional intakes were estimated by a validated semi-quantitative food-frequency questionnaire.ResultsThe highest tertile of energy-adjusted fruit and vegetable consumption (>660 g/d) was associated with lower plasma concentrations of C-reactive protein (CRP) and homocysteine and with lower ICAM1, IL1R1, IL6, TNFα and NFκB1 gene expression in PBMC (P for trend < 0.05), independently of gender, age, energy intake, physical activity, smoking, body mass index, systolic blood pressure and circulating non-esterified fatty acids. In addition, plasma CRP, homocysteine and TNFα concentrations and ICAM1, TNFα and NFκB1 gene expression in PBMC showed a descending trend as increased fiber intake (>19.5 g/d) from fruits and vegetables (P for trend < 0.05). Furthermore, the participants within the higher tertile (>11.8 mmol/d) of dietary total antioxidant capacity showed lower plasma CRP and mRNA values of ICAM1, IL1R1, IL6, TNFα and NFκB1 genes (P for trend < 0.05). The inverse association between fruit and vegetable consumption and study proinflammatory markers followed the same trend and remained statistically significant, after the inclusion of other foods/nutrients in the linear regression models.ConclusionA higher fruit and vegetable consumption was independently associated not only with reduced CRP and homocysteine concentrations but also with a lower mRNA expression in PBMC of some relevant proinflammatory markers in healthy young adults.

This study assessed the potential association of some proinflammatory markers with adiposity (total vs. central) and metabolic features in young adults. Measurements included body composition, lifestyle features, blood biochemical, and selected inflammatory indicators on 154 healthy subjects (53 M/101 F; 21.5 ± 3 years; 22.1 ± 2.6 kg/m(2)). Those subjects with higher waist circumference (WC) and waist-hip ratio (WHR) showed higher (P < 0.05) C-reactive protein (CRP), complement C3, interleukin-6 (IL6), and retinol binding protein-4 (RBP4) concentrations, while only IL6 was positively associated with total body fat (%). Furthermore, CRP and RBP4 were higher in former/current smokers, as compared to never smokers (P < 0.05). Some indicators of glucose (homeostasis model assessment-insulin resistance) and lipid metabolism (total cholesterol/high density lipoprotein-cholesterol and triglycerides) were positively associated with the assayed inflammatory markers (P < 0.05). The findings of this cross-sectional study indicate that central adiposity-related indicators (WC/WHR) correlated better than those assessing total adiposity with plasma proinflammatory markers, which additionally were associated with lifestyle and metabolic features in healthy young adults.

The adipose tissue is a dynamic organ that secrets several factors, denominated adipokines. They are associated, directly or indirectly, in a process that contributes to atherosclerosis, hypertension, insulinic resistance and diabetes type 2, dyslipidemias, presenting the link between adiposity, metabolic syndrome and cardiovascular diseases. In the obesity, body fat depots are increased, presenting eventual elevation in the adipokines expression and secretion. The different fat depots, visceral, abdominal subcutaneous, gluteal-femoral subcutaneous and intramuscular adipose tissue, have different metabolic and endocrine degrees, interfering, therefore, with specific form in the process associated with body adiposity in obese and diabetics subjects. The present study seeks to discuss the endocrine and metabolic role of each adipose tissue compartment, by way to assess their contribution to the complications linked to obesity.