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Scope: Branched Chain Amino Acids (BCAA) plasma levels may be differentially associated with type 2 diabetes mellitus (T2DM) remission through the consumption of the Mediterranean diet (Med) and a low-fat (LF) diet., Methods: One hundred eighty-three newly diagnosed T2DM patients within the CORDIOPREV study are randomized to consume the Med or a LF diet. BCAA plasma levels (isoleucine, leucine, and valine) are measured at fasting and after 120 min of an oral glucose tolerance test (OGTT) at the baseline of the study and after 5 years of the dietary intervention., Results: Isoleucine, leucine, and valine plasma levels after 120 min of an OGTT in the Med diet (N = 80) are associated by COX analysis with T2DM remission: HR per SD (95% CI): 0.53 (0.37-0.77), 0.75 (0.52-1.08), and 0.61 (0.45-0.82), respectively; no association is found in patients who consumed a LF diet (N = 103). BCAA plasma levels combined in a score show a HR of 3.33 (1.55-7.19) of T2DM remission for patients with a high score values in the Med diet, while in those with a LF diet, no association is found., Conclusion: The study suggests that BCAA measurements potentially be used as a tool to select the most suitable diet to induce T2DM remission by nutritional strategies., (© 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Scope: It is hypothesized that decreased advanced glycation end products (AGEs) levels could affect type 2 diabetes mellitus (T2DM) remission in newly diagnosed patients through the consumption of two healthy diets., Methods and Results: Patients from CORDIOPREV study, all with previous cardiovascular events, with T2DM at the beginning of the study are included. Patients are randomized to a Mediterranean or a low-fat diet for five years. No different diabetes remission rates are found among diets. Serum methylglioxal (MG) and carboximethyllysine (CML), levels dietary AGE, as well as gene expression of AGER1 and RAGE are measured. Serum MG decreases only after the consumption of the Mediterranean diet. Moreover, a COX regression analysis shows that each SD decrease in the MG, occurring after the Mediterranean diet, increases the probability of T2DM remission with HR:2.56(1.02-6.25) and p = 0.046 and each SD increase in disposition index at baseline increases the probability of remission with HR:1.94(1.32-2.87) and p = 0.001., Conclusions: It is demonstrated that the reduction of serum AGEs levels and the modulation of its metabolism, occurring after the consumption of a Mediterranean diet, might be involved in the molecular mechanism underlying the T2DM remission of newly diagnosed patients with coronary heart disease., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: The differences between the baseline gut microbiota of patients who developed type 2 diabetes (T2D) consuming a low-fat (LF) or a Mediterranean (Med) diet are explored and risk scores are developed to predict the individual risk of developing T2D associated with the consumption of LF or Med diet., Methods and Results: All the patients from the CORDIOPREV study without T2D at baseline (n = 462) whose fecal sample are available, are included. Gut microbiota is analyzed by 16S sequencing and the risk of T2D after a median follow-up of 60 months assessed by Cox analysis. Linear discriminant analysis effect size (LEfSe) analysis shows a different baseline gut microbiota in patients who developed T2D consuming LF and Med diets. A higher abundance of Paraprevotella, and lower Gammaproteobacteria and B. uniformis are associated with T2D risk when an LF diet is consumed. In contrast, higher abundances of Saccharibacteria, Betaproteobacteria, and Prevotella are associated with T2D risk when a Med diet is consumed., Conclusion: The results suggest that different interactions between the microbiome and dietary patterns may partially determine the risk of T2D development, which may be used for selecting personalized dietary models to prevent T2D., (© 2020 Wiley-VCH GmbH.)

Scope: Dysbiosis of gut microbiota is involved in metabolic syndrome (MetS) development, which has a different incidence between men (M) and women (W). The differences in gut microbiota in MetS patients are explored according to gender, and whether consuming two healthy diets, Mediterranean (MED) and low-fat (LF), may, over time, differentially shape the gut microbiota dysbiosis according to gender is evaluated., Materials and Methods: All the women from the CORDIOPREV study whose feces samples were available and a similar number of men, matched by the main metabolic variables (N = 246, 123 women and 123 men), and categorized according to the presence or not of MetS are included. Gut microbiota is analyzed at baseline and after 3 years of dietary intervention., Results: Higher abundance of Collinsella, Alistipes, Anaerotruncus, and Phascolarctobacterium genera is observed in MetS-W than in MetS-M, whereas the abundance of Faecalibacterium and Prevotella genera is higher in MetS-M than in MetS-W. Moreover, higher levels of Desulfovibrio, Roseburia, and Holdemania are observed in men than in women after the consumption of the LF diet., Conclusion: The results suggest the potential involvement of differences in gut microbiota in the unequal incidence of metabolic diseases between genders, and a sex-dependent effect on shaping the gut microbiota according to diet., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Insulin resistance (IR) and chronic low-grade inflammation are hallmarks of type 2 diabetes mellitus (T2DM). The "NOD-like receptor pyrin domain containing-3" (NLRP3) inflammasome component of innate immunity is a metabolic stress sensor modulated by dietary and genetics factors. The aim of this study was to evaluate the effects of the consumption of two diets for 3 years, Mediterranean (Med) and low fat, on glucose homeostasis in the 1002 coronary heart disease patients of the CORDIOPREV study, according to a genetic variant of NLRP3 inflammasome., Methods and Results: The study was conducted in the framework of the CORDIOPREV study, a randomized dietary intervention with Med and low-fat diets. Single nucleotide polymorphisms (SNPs) located at inflammasome NLRP3 gene were genotyped by OpenArray platform. Nondiabetic CT+TT carriers of the rs4612666 SNP and AG+AA carriers of the rs10733113 SNP increased insulin sensitivity index (ISI) after 3 years of dietary intervention, whereas no effect was observed in diabetic patients. Further analysis by diet showed that the improvement of the ISI in nondiabetic rs10733113 AG+AA carriers was specific to the consumption of the Med diet., Conclusion: Our results show that the benefits associated with a Med diet regarding glucose homeostasis in non-T2DM patients depend on genetic variation in the inflammasome., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Single nucleotide polymorphisms (SNPs) of the circadian locomotor output cycles kaput (CLOCK) gene have been associated with cardiometabolic conditions such as obesity and dyslipidemia. Our aim was to examine whether the chronic consumption of two healthy diets interacts with SNPs of the CLOCK gene in order to improve lipid metabolism and inflammation status in patients with coronary heart disease (CHD)., Methods and Results: The diets were low-fat (LF) diet and Mediterranean diet (MedDiet). CLOCK SNPs (rs1801260, rs3749474, rs4580704) and the study procedures were performed in 897 patients from the CORDIOPREV clinical trial. After 12 months of intervention, we found significant gene-diet interactions between rs4580704 SNP and the LF diet. Specifically, major allele carriers C/C displayed a greater decrease in high sensitivity C-reactive protein (p < 0.001) and a significant increase in HDL/apolipoprotein A1 ratio (p = 0.029) than minor G allele carriers (G/G + C/G). No other gene-diet interactions were observed in this research., Conclusion: These results suggest that rs4580704 SNP interacts with the LF diet improving inflammation status and dyslipidemia related with CHD. The shift toward "personalized nutrition" based on gene-nutrient interactions may be suitable for promoting cardiovascular health in patients with CHD., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: To examine whether the consumption of a Mediterranean diet (MedDiet), compared with a low-fat diet, interacts with two single nucleotide polymorphisms at the tumor necrosis factor alpha gene (rs1800629, rs1799964) in order to improve triglycerides (TG), glycemic control, and inflammation markers., Methods and Results: Genotyping, biochemical measurements, dietary intervention, and oral fat load test meal were determined in 507 metabolic syndrome (MetS) patients selected from all the subjects included in CORDIOPREV clinical trial (n = 1002). At baseline, G/G subjects (n = 408) at the rs1800629 polymorphism, showed higher fasting and postprandial TG (p = 0.003 and p = 0.025, respectively), and high sensitivity C-reactive protein (hsCRP) (p = 0.003) plasma concentrations than carriers of the minor A-allele (G/A + A/A) (n = 99). After 12 months of MedDiet, baseline differences between genotypes disappeared. The decrease in TG and hsCRP was statistically significant in G/G subjects (n = 203) compared with carriers of the minor A-allele (p = 0.005 and p = 0.034, respectively) (n = 48). No other gene-diet interactions were observed in either diet., Conclusion: These results suggest that the rs1800629 at the tumor necrosis factor alpha gene interacts with MedDiet to influence TG metabolism and inflammation status in MetS subjects. Understanding the role of gene-diet interactions may be the best strategy for personalized treatment of MetS., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The most common mode of bacterial resistance to aminoglycoside antibiotics is the enzyme-catalysed chemical modification of the drug. Over the last two decades, significant efforts in medicinal chemistry have been focused on the design of non- inactivable antibiotics. Unfortunately, this strategy has met with limited success on account of the remarkably wide substrate specificity of aminoglycoside-modifying enzymes. To understand the mechanisms behind substrate promiscuity, we have performed a comprehensive experimental and theoretical analysis of the molecular-recognition processes that lead to antibiotic inactivation by Staphylococcus aureus nucleotidyltransferase 4'(ANT(4')), a clinically relevant protein. According to our results, the ability of this enzyme to inactivate structurally diverse polycationic molecules relies on three specific features of the catalytic region. First, the dominant role of electrostatics in aminoglycoside recognition, in combination with the significant extension of the enzyme anionic regions, confers to the protein/antibiotic complex a highly dynamic character. The motion deduced for the bound antibiotic seem to be essential for the enzyme action and probably provide a mechanism to explore alternative drug inactivation modes. Second, the nucleotide recognition is exclusively mediated by the inorganic fragment. In fact, even inorganic triphosphate can be employed as a substrate. Third, ANT(4') seems to be equipped with a duplicated basic catalyst that is able to promote drug inactivation through different reactive geometries. This particular combination of features explains the enzyme versatility and renders the design of non-inactivable derivatives a challenging task., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Heating during the process of cooking alters the chemical properties of foods and may affect subsequent postprandial inflammation. We tested the effects of four meals rich in different oils subjected to heating on the postprandial inflammatory metabolism of peripheral blood mononuclear cells (PBMCs)., Methods and Results: Twenty obese participants received four breakfasts following a randomized crossover design, consisting of milk and muffins made with different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixture of seeds oil (SFO/canola oil) with added either dimethylpolysiloxane (SOD), or natural antioxidants from olive mill wastewater alperujo (phenols; SOP)), previously subjected to 20 heating cycles. Postprandial inflammatory status in PBMCs was assessed by the activation of nuclear NF-κB, the concentration in cytoplasm of the NF-κB inhibitor (IκB-α), the mRNA levels of NF-κB subunits and activators (p65, IKKβ, and IKKα) and other inflammatory molecules (TNF-α, IL-1β, IL-6, MIF, and JNK), and lipopolysaccharide (LPS) levels. VOO and SOP breakfasts reduced NF-κB activation, increased IκB-α, and decreased LPS plasma concentration. SFO increased IKKα, IKKβ, p65, IL-1b, IL-6, MIF, and JNK mRNA levels, and plasma LPS., Conclusion: Oils rich in phenols, whether natural (VOO) or artificially added (SOP), reduce postprandial inflammation, compared with seed oil (sunflower)., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)