Percepción del sabor, dieta mediterránea y nutrigenética: efecto sobre los componentes del síndrome metabólico

Una misma dieta no tiene el mismo efecto sobre el fenotipo cardiovascular de personas distintas. La hipótesis dieta-lípidos-corazón planteada en los años cincuenta sugiere que el consumo de un patrón de dieta mediterránea confiere efectos cardioprotectores al reducir la prevalencia de obesidad abdominal y síndrome metabólico en diferentes poblaciones. Actualmente se admite que la relación entre dieta y enfermedad cardiovascular es más compleja, que se extiende a todos los componentes alimenticios, y que depende en alto grado, de la susceptibilidad genética individual. Los individuos que se adhieren a los principios de una dieta tradicional mediterránea tienen una mayor calidad de vida y una esperanza de vida mayor, reduce la probabilidad de morir de enfermedad cardiovascular, cáncer, o cualquier otra causa. Este efecto se ha relacionado con el aceite de oliva, las legumbres, vegetales, la fruta, el vino tinto, ya que contienen varios componentes con potentes efectos antioxidantes (flavonoides, proantocianidinas, antocianidinas, isoflavonas) así como fibra y moléculas polifenólicas. OBJETIVO Examinar las variaciones en la percepción de los distintos sabores ayudará a establecer la asociación entre ciertos comportamientos de consumo de alimentos y el riesgo de síndrome metabólico. Las diferencias en la variación genética en los receptores del gusto y de los otros genes relevantes, pueden contribuir a las diferencias en los patrones de ingesta alimentaria. La comprensión de estas diferencias en la variación genética podría ayudar a explicar las diferencias en el riesgo de enfermedades crónicas y conducir al desarrollo de las medidas preventivas de salud. METODOLOGÍA Una parte del estudio será de tipo transversal, Integrado al proyecto OBENUTIC. Se aplicará un cuestionario con datos sobre historia médica, hábito tabáquico, actividad física y adherencia a dieta mediterránea: Cuestionario de frecuencia de consumo que evalúa el consumo habitual de alimentos y bebidas alcohólicas, recordatorio de 24 hrs de un día habitual, con el fin de determinar su consumo calórico y de macronutrimentos aproximado. La información obtenida se procesará con la plataforma informático de Obenutic y el cuestionario de evaluación simplificada de adherencia a dieta mediterránea (14 puntos). Se realizó antropometría, medición de la tensión arterial y medición de la composición corporal por impedancia bioeléctrica. Se aplicó una prueba de percepción de sabores amargo, dulce, umami, ácido y salado. Una enfermera diplomada realizó venopunción ayuno de 10 hrs, se extrajeron 10-15 ml de sangre periférica para el análisis de parámetros bioquímicos. Se extrajo ADN genómico de todas las muestras por el método del fenol, se genotiparon genes relacionados a los componentes del síndrome metabólico (obesidad, dislipidemia, hipertensión). Se elaboró la base de datos en el programa SPSS y se introdujeron todos los datos obtenidos. Para comparar los hallazgos sobre percepción de sabores y preferencias alimentarias se estudió una submuestra de pacientes de alto riesgo cardiovascular de la cohorte PREDIMED (PREvención con DIeta MEDiterránea y es un estudio de intervención aleatorizado, multicéntrico, de grupos paralelos); incluye hombres de entre 55 y 80 años y mujeres de entre 60 y 80 años, sin ECV documentada, ya sea con DT2 o bien que cumplían con 3 o más factores de riesgo cardiovascular. Se aplicaron las pruebas de sabores, así como los cuestionarios sobre preferencias alimentarias, ya que la edad es uno de los principales factores que influyen en la percepción y elección de los alimentos. Los genes analizados fueron FTO, TCF7L2, TAS2R38, PON1 y TAS1E2.The same diet has not the same effect on the cardiovascular phenotype of different people. The hypothesis lipid-diet heart raised in the fifties suggests that consumption of a Mediterranean dietary pattern confers cardio-protective effects by reducing the prevalence of abdominal obesity and metabolic syndrome in different populations. It is now recognized that the relationship between diet and cardiovascular disease is more complex, which extends to all food components, and depends to a high degree of individual genetic susceptibility. Individuals who adhere to the principles of a traditional Mediterranean diet have a higher quality of life and a longer life expectancy, reduces the chance of dying from cardiovascular disease, cancer, or any other cause. This effect has been related to olive oil, legumes, vegetables, fruit, red wine, as they contain several potent antioxidant components (flavonoids, proanthocyanidins, anthocyanosides, isoflavones) molecules as well as fiber and examine polifenólicas. OBJECTIVE: Variations in the perception of different flavors help establish the association between certain food consumption behaviors and risk of metabolic syndrome. Differences in genetic variation in taste receptors and other relevant genes, may contribute to differences in food intake patterns. Understanding these differences in genetic variation may help explain the differences in the risk of chronic diseases and lead to the development of preventive health. METHODOLOGY: A part of the study is cross-section, integrated in OBENUTIC project. There will be a questionnaire with data on medical history, smoking habits, physical activity and adherence to Mediterranean diet: food frequency questionnaire to assess habitual consumption of food and beverages, 24-hour reminder of a typical day, in order to determine your caloric intake and macronutrient approximate. The information obtained will be processed with the computer platform and questionnaire Obenutic simplified assessment of adherence to Mediterranean diet (14 points). Anthropometry was performed, blood pressure measurement and the measurement of body composition by bioelectrical impedance. We applied a perception test flavors bitter, sweet, umami, sour and salty. A nurse performed 10 hours fasting venipuncture, extracted 10-15 ml of peripheral blood for biochemical analysis. Genomic DNA was extracted from all samples by the phenol method, related genes were genotyped components of metabolic syndrome (obesity, dyslipidaemia, hypertension). A database in SPSS and introduction of all data was developed. To compare findings on perception of flavor and food preferences studied a subgroup of patients at high cardiovascular risk cohort PREDIMED (Mediterranean diet and prevention is an intervention study randomized, multicenter, parallel group) included men aged 55 and 80 and women between 60 and 80 years, without CVD documented with either T2D or who met three or more cardiovascular risk factors. We applied taste tests and questionnaires on food preferences, since age is one of the main factors that influence the perception and food choice. The genes analyzed were FTO, TCF7L2, TAS2R38, PON1 and TAS1E2

Total and high molecular weight adiponectin have similar utility for the identification of insulin resistance

<p>Abstract</p> <p>Background</p> <p>Insulin resistance (IR) and related metabolic disturbances are characterized by low levels of adiponectin. High molecular weight adiponectin (HMWA) is considered the active form of adiponectin and a better marker of IR than total adiponectin. The objective of this study is to compare the utility of total adiponectin, HMWA and the HMWA/total adiponectin index (S_Aindex) for the identification of IR and related metabolic conditions.</p> <p>Methods</p> <p>A cross-sectional analysis was performed in a group of ambulatory subjects, aged 20 to 70 years, in Mexico City. Areas under the receiver operator characteristic (ROC) curve for total, HMWA and the S_Aindex were plotted for the identification of metabolic disturbances. Sensitivity and specificity, positive and negative predictive values, and accuracy for the identification of IR were calculated.</p> <p>Results</p> <p>The study included 101 men and 168 women. The areas under the ROC curve for total and HMWA for the identification of IR (0.664 <it>vs</it>. 0.669, <it>P </it>= 0.74), obesity (0.592 <it>vs</it>. 0.610, <it>P </it>= 0.32), hypertriglyceridemia (0.661 <it>vs</it>. 0.671, <it>P </it>= 0.50) and hypoalphalipoproteinemia (0.624 <it>vs</it>. 0.633, <it>P </it>= 0.58) were similar. A total adiponectin level of 8.03 μg/ml was associated with a sensitivity of 57.6%, a specificity of 65.9%, a positive predictive value of 50.0%, a negative predictive value of 72.4%, and an accuracy of 62.7% for the diagnosis of IR. The corresponding figures for a HMWA value of 4.25 μg/dl were 59.6%, 67.1%, 51.8%, 73.7% and 64.2%.</p> <p>The area under the ROC curve of the S_Aindex for the identification of IR was 0.622 [95% CI 0.554-0.691], obesity 0.613 [95% CI 0.536-0.689], hypertriglyceridemia 0.616 [95% CI 0.549-0.683], and hypoalphalipoproteinemia 0.606 [95% CI 0.535-0.677].</p> <p>Conclusions</p> <p>Total adiponectin, HMWA and the S_Aindex had similar utility for the identification of IR and metabolic disturbances.</p

Molecular Characterization of the Lipid Genome-Wide Association Study Signal on Chromosome 18q11.2 Implicates HNF4A-Mediated Regulation of the TMEM241 GeneHighlights

We recently identified a locus on chromosome 18q11.2 for high serum triglycerides (TGs) in Mexicans. We hypothesize that the lead GWAS single nucleotide polymorphism (SNP) rs9949617, or its linkage disequilibrium (LD) proxies, regulate one of the 5 genes in the TG-associated region

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

Contribution of Known Genetic Risk Variants to Dyslipidemias and Type 2 Diabetes in Mexico: A Population-Based Nationwide Study

Dyslipidemias are common risk factors for the development of chronic disorders including type 2 diabetes (T2D). Over 100 associated loci have been identified but few reports have evaluated the population attributable fraction captured by them in population-based nationwide surveys. Therefore, we determined the population contribution of a set of known genetic risk variants to the development of dyslipidemias and T2D in Mexico. This study included 1665 participants from a Mexican National Health Survey carried out in the year 2000. It is a probabilistic complex sample survey of households, which comprises representative data at a national level. 103 previously reported SNPs associated with different dyslipidemias or T2D were genotyped and used to compute polygenic risk scores. We found that the previously known variants associated with dyslipidemias explain at most 7% of the total risk variance of lipid levels. In contrast, the known genetic risk component for T2D explained a negligible amount of variance (0.1%). Notably, variants derived from the Native-American ancestry have the strongest effect and contribute with a high proportion of the variance. These results support the need for additional studies aimed to identify specific genetic risk variants for Mexican population

Molecular Characterization of the Lipid Genome-Wide Association Study Signal on Chromosome 18q11.2 Implicates HNF4A-Mediated Regulation of the TMEM241 Gene

ObjectiveWe recently identified a locus on chromosome 18q11.2 for high serum triglycerides in Mexicans. We hypothesize that the lead genome-wide association study single-nucleotide polymorphism rs9949617, or its linkage disequilibrium proxies, regulates 1 of the 5 genes in the triglyceride-associated region.Approach and resultsWe performed a linkage disequilibrium analysis and found 9 additional variants in linkage disequilibrium (r(2)&gt;0.7) with the lead single-nucleotide polymorphism. To select the variants for functional analyses, we annotated the 10 variants using DNase I hypersensitive sites, transcription factor and chromatin states and identified rs17259126 as the lead candidate variant for functional in vitro validation. Using luciferase transcriptional reporter assay in liver HepG2 cells, we found that the G allele exhibits a significantly lower effect on transcription (P&lt;0.05). The electrophoretic mobility shift and ChIPqPCR (chromatin immunoprecipitation coupled with quantitative polymerase chain reaction) assays confirmed that the minor G allele of rs17259126 disrupts an hepatocyte nuclear factor 4 α-binding site. To find the regional candidate gene, we performed a local expression quantitative trait locus analysis and found that rs17259126 and its linkage disequilibrium proxies alter expression of the regional transmembrane protein 241 (TMEM241) gene in 795 adipose RNAs from the Metabolic Syndrome In Men (METSIM) cohort (P=6.11×10(-07)-5.80×10(-04)). These results were replicated in expression profiles of TMEM241 from the Multiple Tissue Human Expression Resource (MuTHER; n=856).ConclusionsThe Mexican genome-wide association study signal for high serum triglycerides on chromosome 18q11.2 harbors a regulatory single-nucleotide polymorphism, rs17259126, which disrupts normal hepatocyte nuclear factor 4 α binding and decreases the expression of the regional TMEM241 gene. Our data suggest that decreased transcript levels of TMEM241 contribute to increased triglyceride levels in Mexicans

Development and validation of a predictive model for incident type 2 diabetes in middle-aged Mexican adults: the metabolic syndrome cohort

Abstract Background Type 2 diabetes mellitus (T2D) is a leading cause of morbidity and mortality in Mexico. Here, we aimed to report incidence rates (IR) of type 2 diabetes in middle-aged apparently-healthy Mexican adults, identify risk factors associated to ID and develop a predictive model for ID in a high-risk population. Methods Prospective 3-year observational cohort, comprised of apparently-healthy adults from urban settings of central Mexico in whom demographic, anthropometric and biochemical data was collected. We evaluated risk factors for ID using Cox proportional hazard regression and developed predictive models for ID. Results We included 7636 participants of whom 6144 completed follow-up. We observed 331 ID cases (IR: 21.9 per 1000 person-years, 95%CI 21.37–22.47). Risk factors for ID included family history of diabetes, age, abdominal obesity, waist-height ratio, impaired fasting glucose (IFG), HOMA2-IR and metabolic syndrome. Early-onset ID was also high (IR 14.77 per 1000 person-years, 95%CI 14.21–15.35), and risk factors included HOMA-IR and IFG. Our ID predictive model included age, hypertriglyceridemia, IFG, hypertension and abdominal obesity as predictors (Dxy = 0.487, c-statistic = 0.741) and had higher predictive accuracy compared to FINDRISC and Cambridge risk scores. Conclusions ID in apparently healthy middle-aged Mexican adults is currently at an alarming rate. The constructed models can be implemented to predict diabetes risk and represent the largest prospective effort for the study metabolic diseases in Latin-American population