Submitted by MARIA PAULA FERREIRA DE FIGUEIREDO null (figueiredo.mariapaula@gmail.com) on 2016-05-21T14:46:56Z No. of bitstreams: 1 Dissertação Final Mestrado_Maria Paula Ferreira de Figueiredo.pdf: 1769339 bytes, checksum: 5089a8d0cbcf655e101e7db60a5e0e20 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-05-24T13:57:36Z (GMT) No. of bitstreams: 1 figueiredo_mpf_me_prud.pdf: 1769339 bytes, checksum: 5089a8d0cbcf655e101e7db60a5e0e20 (MD5) / Made available in DSpace on 2016-05-24T13:57:36Z (GMT). No. of bitstreams: 1 figueiredo_mpf_me_prud.pdf: 1769339 bytes, checksum: 5089a8d0cbcf655e101e7db60a5e0e20 (MD5) Previous issue date: 2016-04-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução: Pesquisas retratam a importância do exercício físico para a população como prevenção e tratamento da Síndrome Metabólica (SMet). Dentre os tipos de treinamento, destaca-se o aeróbio intervalado (TAI) como benéfico na melhora dos indicadores da SMet, entretanto, novas abordagens no tocante às dinâmicas de cargas e nos métodos aplicados para esta população, merecem atenção. Objetivo: Analisar os efeitos do TAI periodizado sobre os parâmetros antropométricos, bioquímicos e clínicos em participantes sedentários portadores de síndrome metabólica. Métodos: O estudo consistiu de 31 participantes de ambos os sexos com idade entre 35 e 60 anos, sedentários, com diagnostico de SMet, os quais foram randomizados em dois grupos, um exposto ao TAI periodizado (n=18) e outro controle (n=12) sem intervenção. O grupo TAI periodizado foi submetido à periodização por 16 semanas, três vezes por semana, com intervalos de recuperação entre 24 e 72h totalizando 39 sessões de treino e nove sessões recuperativas. A dinâmica de carga foi dividida em etapas de acordo com três níveis de intensidade: leve, moderada e alta. Antes e após o treinamento foram realizadas avaliações para análise da estatura, impedância bioelétrica corporal, circunferências corporais por fita métrica, perfil lipídico e glicemia em jejum de 12 horas, pressão arterial e frequência cardíaca (FC) em repouso. Análise estatística: Para análise estatística foi utilizado 5% de significância. Foi realizada análise de variância com ajuste por sexo e idade (Ancova) e correlação de Sperman das variáveis antropométricas com bioquímicas e clínicas. Resultados: Embora sem efeitos sobre o diagnóstico de SMet, os resultados mostram que houve elevada relevância clínica do TAI periodizado na redução de massa corpórea, IMC e circunferências corporais, com efeito moderado sobre a pressão arterial diastólica (PAD). No grupo controle houve aumento moderado da glicemia e massa gorda, e elevado da FC. As demais variáveis não tiveram significância estatística. Conclusão: O TAI não foi suficiente para mudar o diagnóstico de SMet nos participantes, porém obteve elevado efeito na redução de massa corpórea, IMC e circunferências corporais, moderado na PAD e caráter de manutenção sobre a massa gorda, glicemia, colesterol total, LDL, VLDL e FC. / Introduction: Research shows the importance of exercise for the population as prevention and treatment of metabolic syndrome (MetS). Among the types of training, there is aerobic interval (AIT) as beneficial in improving the MetS indicators, however, new approaches with regard to dynamic loads and methods applied to this population, deserve attention. Objective: To analyze the effects of periodized TAI on anthropometric, biochemical and clinical parameters in sedentary individuals with metabolic syndrome. Methods: The study consisted of 31 participants of both sexes aged between 35 and 60 years, sedentary, with diagnosis of MetS, which were randomized into two groups, one exposed to TAI periodized (n = 18) and a control (n = 12) without intervention. The periodized TAI group underwent periodization for 16 weeks, three times a week, with recovery intervals between 24 and 72 hours totaling 39 training sessions and nine recuperative sessions. The load dynamics was divided into stages according to three levels of intensity: mild, moderate and high. Before and after training evaluations were performed for analysis of height, body bioelectrical impedance, body circumferences by tape measure, lipid profile and fasting glucose 12 hours, blood pressure and heart rate (HR) at rest. Statistical analysis: Statistical analysis was performed using a 5% significance. We performed analysis of variance with adjustment for sex and age (ANCOVA) and Spearman correlation of anthropometric variables with clinical and biochemical. Results: Although no effect on the diagnosis of MetS, the results show that there was a high clinical relevance of TAI periodized in reducing body mass, BMI and body circumferences, with moderate effect on diastolic blood pressure (DBP). In the control group there was a moderate increase in blood glucose and fat mass, and high HR. The other variables were not statistically significant. Conclusion: TAI periodized was not enough to change the diagnosis of MetS in participating, but got high effect in reducing body mass, BMI and body, moderate in DBP and maintaining character on fat mass, glucose, total cholesterol, LDL, VLDL and FC.

Resumo: Tem sido evidenciado que o consumo do suco de laranja amarela melhora a sensibilidade insulínica, o perfil lipídico, a pressão arterial, o estresse oxidativo e a inflamação, condições fisiopatológicas relacionadas às doenças crônicas como cardiovasculares, síndrome metabólica, diabetes tipo II, obesidade e câncer. Tais efeitos se devem à presença de nutrientes (vitamina C e potássio) e compostos bioativos (flavonóides cítricos e carotenóides), que atuam de forma sinérgica protegendo o organismo. O suco de laranja de polpa vermelha apresenta além destes componentes, o licopeno que atua como um potente antioxidante celular. O objetivo desta pesquisa foi avaliar o efeito do consumo regular do suco de laranja vermelha sobre os fatores de risco da síndrome metabólica, incluindo circunferência da cintura aumentada, hipertrigliceridemia, baixo HDL-C, hipertensão arterial e intolerância à glicose. Os resultados obtidos foram analisados em dois diferentes estudos os quais foram escritos na forma de artigo científico, sendo que no primeiro foi dado ênfase nos parâmetros antropométricos e no segundo os parâmetros bioquímicos e hemodinâmicos. Homens e mulheres saudáveis consumiram diariamente 750mL de suco de laranja vermelha durante oito semanas consecutivas. No início e no final do tratamento foram realizadas avaliações antropométrica (peso corporal, estatura, dobras cutâneas e circunferências) bioquímica (glicose, insulina, hemoglobina glicada, colesterol total, LDL-C, HDL-C, Apo A e B, proteína C reativa, atividade antioxidante por DPPH, resistência insulínica pelo índice HOMA), hemodinâmica (pressão arterial sistólica e diastólica). O tratamento com o suco de laranja vermelha não alterou a circunferência da cintura, diminuiu o colesterol total, LDL-C, proteína C reativa e pressão arterial, além de aumentar a atividade antioxidante no soro... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: It has been shown that the consumption of blond orange juice improves insulin sensitivity, lipid profile, blood pressure, oxidative stress and inflammation, pathophysiological conditions related to chronic diseases such as cardiovascular, metabolic syndrome, diabetes type II, obesity and cancer. These effects are due to the presence of nutrients (vitamin C and potassium) and bioactive compounds (citrus flavonoids and carotenoids), which act synergistically protects the body. Besides these components the red orange juice has lycopene that acts as a potent antioxidant. The aim of this study was to evaluate the effect of regular consumption of red orange juice on the risk factors of metabolic syndrome, including increased waist circumference, hypertriglyceridemia, low HDL-C, hypertension and glucose intolerance. The results were analyzed in two different studies which were written in the form of a scientific paper, the first one emphasizes the anthropometric parameters and in the second one biochemical and hemodynamics parameters. Healthy men and women consumed daily 750mL of red orange juice for eight consecutive weeks. At the beginning and end of treatment were evaluated anthropometric (body weight, height, skinfolds and circumferences) biochemical (glucose, insulin, glycated hemoglobin, total cholesterol, LDL-C, HDL-C, Apo A and B, C-reactive protein antioxidant activity by DPPH, insulin resistance by HOMA index), hemodynamic (systolic and diastolic). Treatment with red orange juice did not alter the waist circumference, decreased total cholesterol, LDL-C, C-reactive protein and blood pressure, besides increasing the antioxidant activity in serum of volunteers. We suggest that the orange juice does not influence the increase in body weight and other measures and has properties like hypolipidemic, anti-inflammatory and antioxidant... (Complete abstract click electronic access below) / Orientador: Thaís Borges César / Coorientador: João Bosco Faria / Banca: Maria Rita Marques de Oliveira / Banca: Ellen Cristini Freitas Araújo / Mestre

Orientador: Rosangela Gonçalves Peccinini / Banca: Marina Galdino da Rocha Pitta / Banca: Anderson Rodrigo Moaraes de Oliveira / Banca: Marcelo Tadeu Marin / Banca: Marlus Chorilli / Resumo: As tiazolidinodionas (TZDs) são fármacos utilizados no tratamento de Diabetes Mellitus tipo 2 (DM2), seu mecanismo de ação é a ativação dos receptores PPAR-γ do núcleo celular. Além de sua atividade sobre o metabolismo glicídico e lipídico, há um particular interesse em sua atividade sobre a aterosclerose decorrente da síndrome metabólica que acomete estes pacientes. Tendo em vista a ampla aplicação das TZDs e a presença de apenas uma alternativa terapêutica relativamente segura no mercado, a pioglitazona, pesquisadores do Laboratório de Planejamento e Síntese de Fármacos da Universidade Federal de Pernambuco sintetizaram e selecionaram TZDs promissoras em relação à atividade anti-aterosclerose. Dentre elas destacaram-se as GQ-2, GQ-11, GQ-19 e GQ-177. Tendo em vista a maior aceitação da administração oral de medicamentos, prever a absorção destas novas moléculas para esta via empregando métodos de screening farmacocinético pode acelerar o desenvolvimento do produto farmacêutico. Neste estudo utilizou-se o método de screening farmacocinético Cassette Accelerated Rapid Rat Screen (CARRS), o screening físico-químico, principalmente através da avaliação do Log P, e screeningin vitro, utilizando modelo de monocamadas de células Caco-2, para obter informações preditivas acerca da biodisponibilidade de moléculas. Estas técnicas foram utilizadas para selecionar dentre as TZDs - GQ-2, GQ-11, GQ-19 e GQ-177 - o(s) candidato(s) com características mais apropriadas para a continuidade d... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Thiazolidinediones (TZDs) are drugs used to treat type 2 diabetes mellitus (DM2); its mechanism of action is the activation of the cell nucleus receptor PPAR-γ. In addition to its activity on glucose and lipid metabolism, there is a particular interest in its activities on atherosclerosis that is caused by the metabolic syndrome that affects these patients. Given the wide application of TZDs and the presence of a single therapeutic alternative in the market, the pioglitazone, the researchers from the Laboratório de Planejamento e Síntese de Fármacos from Universidade Federal de Pernambuco synthesized and selected promising TZDs in relation to antiatherosclerosis activity. Among them stood out the GQ-2, GQ-11, GQ-19 and GQ177. Taking into account the greater acceptance oral administered drugs, to predict the absorption of these new molecules for this route using pharmacokinetic screening methods can accelerate the development of a pharmaceutical product. In this study we used the screening method CARRS (PK), the physico-chemical screening, particularly by evaluating the Log P, and in vitro screening using Caco-2 cell monolayer model to obtain predictive information regarding the bioavailability of molecules. These techniques were used to select among the TZDs - GQ-2, GQ-11, GQ-19 and GQ-177 - the candidate(s) with the most appropriate characteristics for the continuation of pre-clinical studies. The physic-chemical screening showed that the GQ-19 and GQ-177 as favorable oral absorption, but in the in vitro screening, only the GQ-19 showed permeation in Caco-2 cell model. In in vivo screening, GQ-19 appeared unstable in animal plasma, degraded completely in less than 20 minutes. For other molecules, during the in vivo screening, the expectations arisen from the behavior observed in in vitro... (Complete abstract click electronic access below) / Doutor

Orientador: Roberto Carlos Burini / Resumo: A prevalência mundial de Síndrome Metabólica (SM) está aumentando drasticamente nos últimos anos. Esta desordem consiste de um conjunto de condições metabólicas, contemplando hiperadiposidade abdominal, resistência insulínica (RI), dislipidemia e hipertensão, e é fator de risco para o desenvolvimento de Diabetes Mellitus tipo 2 (DM2) e doenças cardiovasculares (DCVs). Muitos estudos indicam a participação do estresse oxidativo (EO) junto com o estado estresse inflamatório (EI) como parte do desenvolvimento e agravamento da SM e surgimento das doenças crônicas não-transmissíveis (DCNTs). O EO é caracterizado como estado de desequilíbrio entre os sistemas oxidativo e antioxidante, resultando no excesso de espécies reativas de oxigênio (EROs), menor capacidade antioxidante e efeitos deletérios a tecidos e células. A regulação das reações de oxidação e redução são importantes para o controle de funções fisiológicas e combate ao estresse. Diante disso, os aminotióis ou compostos tio-redox (homocisteína, cisteína e glutationa) exercem importante papel no equilíbrio do estado redox celular. Neste artigo de revisão, analisamos os aspectos fisiopatológicos de compostos tio-redox no curso da SM. / Abstract: The worldwide prevalence of Metabolic Syndrome (MetS) has been increasing dramatically in recent years. MetS is a set of metabolic conditions, including abdominal hyperadiposity, insulin resistance, dyslipidemia and hypertension, and is a risk factor for the development of type 2 diabetes mellitus and cardiovascular diseases. Many studies indicate the participation of oxidative stress along with the pro-inflammatory state as part of the development and aggravation of MetS and emergence of chronic noncommunicable diseases. Oxidative stress is characterized as a state of imbalance between oxidative and antioxidant systems, resulting in excess of reactive oxygen species, lower antioxidant capacity and deleterious effects on tissues and cells. The regulation of the oxidation and reduction reactions are important for the control of physiological functions and the fight against stress. In view of this, the aminothiols or thiol-redox compounds (homocysteine, cysteine and glutathione) play an important role in the equilibrium of the cellular redox state. In this review article, we analyze the pathophysiological aspects of thiol-redox compounds in the course of MetS. / Mestre

Resumo não disponível.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / This systematic review and meta-analysis tries to determine whether there is an association between the use of protease inhibitors (PIs) and the incidence of diabetes mellitus (DM) and/or metabolic syndrome (MS) in HIV-infected patients. A systematic literature search was performed using MEDLINE/PubMed, CENTRAL, LILACS, and EMBASE. Included articles were observational studies published on or prior to November 2015 that met specific inclusion criteria. Pooled relative risks (RRs) and hazard ratios (HRs) were calculated. Nine articles met the inclusion criteria, describing 13,742 HIV patients. Use of PIs was associated with the development of MS (RR: 2.11; 95% CI 1.28–3.48; p-value 0.003). No association between the use of PIs and development of DM was found: the HR for the incidence of DM among patients using PIs was 1.23 (95% CI 0.66–2.30; p-value: 0.51) and the RR was 1.25 (95% CI 0.99–1.58; p-value 0.06). Use of PIs in HIV-infected patients is associated with an increased risk of MS. No evidence of an increased risk of DM was found. However, because MS is a precursor to DM, it is possible that studies with a longer follow-up duration are needed in order to detect an association between PI use and onset of DM. / First, we would like to thank our families for all their support. Second, we would like to thank the Universidad Peruana de Ciencias Aplicadas, the Health Sciences Department, and the School of Medicine for their support and for all the tools they have provided throughout this process. Finally, we want to thanks to Dr Gwenyth O. Lee and Dr Daniela E. Kirwan for their comments. / Revisión por pares

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Background & aims: Several studies have examined the effect of vegetarian diets (VD) on metabolic syndrome (MetS) or its components, but findings have been inconsistent. The aim of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies to assess the association between VD and MetS or its components (systolic blood pressure [SBP], diastolic blood pressure [DBP], fasting glucose triglycerides, waist circumference [WC], HDL-cholesterol (HDL-C)) in adults. Methods: The Cochrane Library, EMBASE, PubMed, Web of Science, and Scopus were searched. RCTs, cohort studies and cross-sectional studies evaluating the effects of VD on MetS or its components in adults, with omnivore diet as control group, were included. Random effects meta-analyses stratified by study design were employed to calculate pooled estimates. Results: A total of 71 studies (n = 103 008) met the inclusion criteria (6 RCTs, 2 cohorts, 63 cross-sectional). VD were not associated with MetS in comparison to omnivorous diet (OR 0.96, 95% CI 0.50–1.85, p = 0.9) according to meta-analysis of five cross-sectional studies. Likewise, meta-analysis of RCTs and cohort studies indicated that consumption of VD were not associated with MetS components. Meta-analysis of cross-sectional studies demonstrated that VD were significantly associated with lower levels of SBP (mean difference [MD] −4.18 mmHg, 95%CI −5.57 to −2.80, p < 0.00001), DBP (MD −3.03 mmHg, 95% CI −4.93 to −1.13, p = 0.002), fasting glucose (MD −0.26 mmol/L, 95% CI −0.35to −0.17, p < 0.00001), WC (MD −1.63 cm, 95% CI −3.13 to −0.13, p = 0.03), and HDL-C (MD −0.05 mmol/L, 95% CI −0.07 to −0.03, p < 0.0001) in comparison to omnivorous diet. Heterogeneity of effects among cross-sectional studies was high. About, one-half of the included studies had high risk of bias. Conclusions: VD in comparison with omnivorous diet is not associated with a lower risk of MetS based on results of meta-analysis of cross-sectional studies. The association between VD and lower levels of SBP, DBP, HDL-C, and fasting glucose is uncertain due to high heterogeneity across the cross-sectional studies. Larger and controlled studies are needed to evaluate the association between VD and MetS and its components. / Revisión por pares

La mûre tropicale de montagne (Rubus adenotrichos Schltdl.) est largement cultivée et consommée au Costa Rica. Cependant, il existe peu de recherches scientifiques sur ce fruit. Par conséquent, nos travaux ont pour but de valoriser la mûre au travers de l’étude de ses activités biologiques sur le syndrome métabolique. Le jus microfiltré de mûre a démontré être riche en polyphénols (377,5 équivalents d’AG/100g), spécialement en ellagitanins (90,39-141,89 équivalents d’AE/100g) et anthocyanes (56,93-73,31 équivalents de cyanidine-3-glucoside/100g). Le pouvoir antioxydant du jus de mûre a été déterminé par les méthodes ORAC (4253,53 µmol ET/100g), FRAP (4703,84 µmol ET/100g), ABTS (1,075 μmol ET/100g) et LPO (15,88 µM de hydroperoxyde) et par des mesures de la capacité antioxydante des enzymes superoxyde dismutase (767,33 U/ml) et catalaseCAT (70,33 nmol/min/ml). Le jus de mûre a inhibé la production du NO induite par LPS+IFNγ lorsqu'il a été utilisé comme prétraitement sur les cellules J774A.1. L’inhibition a été de 51,95% pour le jus de mûre à 1000 g/ml, sans affecter ni la viabilité cellulaire ni la concentration de protéines dans les cellules. Cette activité antiinflammatoire a été confirmée par la diminution du taux de la synthase inductible de l'oxyde nitrique dans ces mêmes cellules par une analyse Western Blot. Cette étude a utilisé un modèle in vivo pour évaluer l'effet de la consommation du jus de mûre chez des rats insulino-résistants. L'apport en mûre a provoqué une diminution des triglycérides sériques (-50,2%), du cholestérol total (-15,6%), du cholestérol LDL (-48,2%) et de la pression artérielle systolique des rats par rapport aux témoins, sans influencer les concentrations de cholestérol HDL ni la glycémie. L’effet hypotenseur du jus a été confirmé par une réduction de la pression artérielle diastolique de 54,2% lors de la mesure de la pression artérielle après l’injection du jus de mûre chez le rat anesthésié. L’effet du jus de mûre chez homme a été évalué lors d’un essai clinique avec des patients dislypidémiques, après lequel on a observé une réduction significative du tour de taille, du glucose, de la pression artérielle diastolique et des triglycérides (-20,3%) chez les patients qui ont consommé du jus de mûre à 40% v/v durant 6 semaines. En outre, lors de la fermentation du jus de mûre costaricienne avec des levures du type Saccharomyces cerevisiae, la teneur en sucres (glucose, fructose et saccharose) a été réduite presque totalement au bout de 10 jours et le séchage par atomisation d’un jus fermenté avec 10% de maltodextrine 6DE et 1% de Aerosil, à un débit de pulvérisation de 3 ml/min et avec un débit d’air chaud (150°C) de 650 L/h garantit l’obtention d’une poudre avec un rendement élevé de séchage. Enfin, cette étude suggère que la mûre Rubus adenotrichos présente un bénéfice potentiel sur la santé, spécialement contre toutes les pathologies liées au syndrome métabolique. Mots clés: Rubus adenotrichos, mûre, jus microfiltré, syndrome métabolique, dyslipidémie, antioxydante, antiinflammatoire, hypotension / Tropical highland blackberry (Rubus adenotrichos Schltdl.) is widely cultivated and consumed in Costa Rica. However, there is little scientific research on this fruit. Therefore, our work aims to enhance blackberry importance through the study of its biological activity on the metabolic syndrome.Blackberry microfiltered juice has been shown to be rich in polyphenols (377.5 GA equivalents /100g), especially ellagitannins (from 90.39 to 141.89 EA equivalents/100g) and anthocyanins (from 56.93 to 73, 31 equivalents of cyanidin-3-glucoside/100g). The antioxidant power of blackberry juice was determined by the ORAC (4253.53 µmol TE/100g), FRAP (4703.84 µmol TE/ 100g), ABTS (1.075 µmol TE/100g) and LPO (15.88 µmol of hydroperoxide) methods and by measuring the antioxidant capacity of superoxide dismutase (767.33 U/ml) and catalase (70.33 nmol/min/ml) enzymes.Blackberry juice inhibited NO production induced by LPS+IFN gamma when used as a pretreatment on J774A.1 cells. Inhibition was 51.95% for the blackberry juice at 1000 µg/ml, without affecting neither cell viability nor the concentration of proteins in J774A.1 cells. The anti-inflammatory activity has been confirmed by the decrease in the rate of inducible nitric oxide synthase in these cells by Western blot analysis.This study used an in vivo model to assess the effect of blackberry juice consumption in insulin-resistant rats. The intake of blackberry caused a decrease in serum triglycerides (-50.2%), total cholesterol (-15.6%), LDL cholesterol (-48.2%) and in the systolic blood pressure of rats compared to controls, without affecting HDL cholesterol or blood sugar levels. The hypotensive effect of the juice has been confirmed by a reduction of 54.2% of the diastolic blood pressure in the measurement of blood pressure after injection of the blackberry juice in the anesthetized rat.The effect of blackberry juice on humans was evaluated in a clinical trial with patients suffering dyslipidemia, after which a significant reduction in waist circumference, glucose, diastolic blood pressure and triglycerides (-20,3%) was observed in patients who consumed 40% v/v blackberry juice for 6 weeks.Also, during fermentation of blackberry juice with yeasts of the Saccharomyces cerevisiae type, the sugar content (glucose, fructose and sucrose) was reduced almost totally after 10 days and the spray drying of the fermented juice with 10% maltodextrin 6DE and 1% Aerosil, at a spraying rate of 3 ml/min and with a flow of hot air (150°C) of 650 L/h ensures to obtain a powder and a high efficiency in drying.Finally, this study suggests that the blackberry specie Rubus adenotrichos presents a potential health benefit, especially against all diseases related to metabolic syndrome.Keywords: Rubus adenotrichos, blackberry, microfiltered juice, metabolic syndrome, dyslipidemia, antioxidant, anti-inflammatory, hypotension

La résistance à l’insuline (RI) est un processus biologique fondamental impliqué dans la plupart des maladies complexes avec un important impact dans la mortalité des populations humaines et qui reconnaît une composante génétique en interaction avec les facteurs nutritionnels. Les aminoacides ramifiés (BCAA) sont des composantes essentielles de notre diète et ont été reconnus comme de nouveaux acteurs dans la pathogénie de l’obésité et du diabète sucré soit comme des bio-marqueurs soit comme des régulateurs au niveau périphérique ou dans le système nerveux central. Ce travail a été proposé dans le cadre du projet Européen MEDIGENE (FP7-279171) visant le syndrome métabolique dans les populations Méditerranéennes. Dans ce contexte, nous avons utilisé une approche génétique combinant les SNP (single nucleotide polymorphism) et la cartographie dense des haplotypes. Nous avons mis en évidence de nouveaux gènes dans les phases tardives du catabolisme des BCAA, bien que le signal d’association ait été en relation complexe avec les taux plasmatiques de BCAA et la mesure in vivo de la RI. Dans une approche similaire, nous avons identifié sur le chromosome 4p14 un nouveau locus en relation avec la RI et le système de récompense cérébral impliquant le fibroblast growth factor (FGF) 21. Ces données ont soulevé l’intérêt pour une estimation rapide et efficace de l’apport en BCAA dans la diète nous emmenant à développer une nouvelle base de données du contenu des aliments en BCAA. Cette base est intégrée dans un nouveau logiciel pour le recueil des enquêtes alimentaires (rappels de 24h) et qui pourra être utilisée par des praticiens d’une manière sécurisée dans les pays de la Méditerranée, ouvrant ainsi de nouvelles perspectives en nutrigénomique. / Insulin resistance (IR) is a fundamental biological process involved in majority of complex disorders with high impact on mortality of human populations and with a strong genetic component in interaction with nutritional factors. Branched chain amino acids (BCAA) are essential components of human diet and recognized as new actors in pathogenesis of obesity and diabetes mellitus either as biomarkers or regulators at the peripheral systemic and nervous system. This work was proposed in the frame of the European project MEDIGENE (FP7-279171) studying the metabolic syndrome in several Mediterranean populations. In this context, we have used a genetic approach combining SNP (single nucleotide polymorphism) and fine scale haplotype mapping. We identified new genes in the later steps of BCAA catabolism responsible for IR, albeit displaying a complex signal in relation with BCAA plasma levels and in vivo IR measured by minimal model. With a similar approach, we identified equally a new locus of Chromosome 4p14 for IR in cooperation with the cerebral rewarding system involving fibroblast growth factor (FGF) 21 regulation. These data roused particular interest in estimating BCAA intake leading to the development of a novel database of BCAA content in food. This database is embedded in a new computer program for collecting dietary records (24HDR) and can be used securely by practitioners around Mediterranean countries and opening new perspectives in the nutrigenomic field.

BACKGROUND & AIMS - Metabolic syndrome (MetS), characterized by abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and insulin resistance is a major public health concern in the United States. The effect of Apolipoprotein E (Apo E) polymorphism has been relatively well studied in relation to cardiovascular disease; however, its effects on MetS are not well established. METHODS - We conducted a cross-sectional study consisting of 1,551 participants from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study to assess the relation of Apo E polymorphism with the prevalence of MetS. Information on the different Apo E genotypes was extracted from the database and we defined MetS according to the AHA-NHLBI-IDF-WHO Harmonized Criteria. We used generalized estimating equations to estimate adjusted odds ratios for prevalent MetS and the Bonferroni correction to account for multiple testing in the secondary analysis. RESULTS – Our study population had a mean age (SD) of 56.5 (11.0) years and 49.7% had MetS. There was no association between the Apo E genotypes and MetS. The multivariable adjusted ORs (95% CI) were 1.00 (reference), 1.26 (0.31-5.21), 0.89 (0.62- 1.29), 1.13 (0.61-2.10), 1.13 (0.88-1.47) and 1.87 (0.91-3.85) for the *e3/e3, *e2/e2, *e2/e3, *e2/e4, *e3/e4 and *e4/e4 genotype respectively. In a secondary analysis, the *e2/e3 genotype was associated with lower HDL levels, with the multivariable adjusted ORs (95% CI) of 0.59 (0.36-0.95) when compared to the reference *e3/e3 genotype. CONCLUSIONS - Our findings do not support an association between Apo E polymorphism and MetS in a multi-center population based study of predominantly white US men and women. The *e2/e3 genotype was associated with lower HDL levels as compared to the *e3/e3 genotype. KEY WORDS: Apolipoprotein E (Apo E) polymorphism, metabolic syndrome, blood pressure, glucose, waist circumference, triglycerides, high-density lipoprotein cholesterol