Background: Tech-enabled personalised nutrition is an emerging area that has promise to improve health outcomes, widen access to nutrition expertise and reduce healthcare expenditure, yet uptake by registered dietitians remains low. This research programme aimed to identify levers and barriers that contribute to adoption of personalised nutrition in order to guide practice and policy for registered dietitians, educators and consumers. Methods: A mixed methods study with a sequential exploratory design was adopted to determine what the barriers to adoption of technologies are, and secondly, what needs to be in place to make tech-enabled personalised nutrition a reality. The research programme was conducted online using qualitative (focus groups and interviews) and quantitative measures (survey and secondary analysis). Thematic analysis, statistical and secondary analyses of data were performed respectively. Results: Using diffusion of innovation and entrepreneurial theories, findings indicate that barriers to integration of personalised nutrition technologies include intrinsic and extrinsic factors which relate to a low self-efficacy, high perception of risk, low perceived importance and usefulness of technologies to dietetic practice as well as a lack of an entrepreneurial mindset and regulatory environment. Conclusion: Uptake of tech-enabled personalised nutrition by registered dietitians will require a multi-stakeholder approach. Educational, professional, regulatory and health policies will need to be in place and strategies that open discussion between Registered Dietitians (RD’s) at all levels are needed.

Introdução: Variações genéticas podem influenciar a relação entre ácidos graxos (AG) do plasma e concentração plasmática de biomarcadores inflamatórios. Objetivo: Verificar a associação entre polimorfismos de nucleotídeo único (SNP) presentes nos genes da proteína C reativa (PCR), fator de necrose tumoral (TNF) e interleucina (IL)-10 e AG do plasma e seus efeitos sobre a concentração plasmática de biomarcadores inflamatórios em um estudo de base populacional ISACapital. Métodos: Foram coletadas informações sociodemográficas, de estilo de vida, de atividade física (IPAQ longo), hábito de fumar e beber, bem como amostras de sangue de 281 indivíduos (20 a 59 anos), oriundos de um estudo de base populacional (ISA-Capital). A partir do plasma, foram determinadas as concentrações de IL1, IL6, IL8, IL10, TNF, IL12p70, adiponectina, PCR, proteína quimiotática para macrófagos solúvel (sMCP)1, molécula de adesão intercelular solúvel (sICAM)1 e molécula de adesão celular vascular solúvel (sVCAM)1 por meio da técnica multiplex de imunoensaio e o perfil de ácidos graxos por cromatografia gasosa. O DNA genômico foi extraído e realizada a genotipagem dos SNP presentes no gene da PCR (rs1205, rs1417938, rs2808630), TNF (rs1799964, rs1799724, rs1800629 e rs361525) e IL10 (rs1800871, rs1800896 e rs1800872) pela ténica TaqMan Open Array. Foi realizada análise multivariada de cluster com base nos 11 biomarcadores inflamatórios, permitindo agrupar os indivíduos em grupo inflamado e cluster não inflamado. Resultados: Os indivíduos que possuíam os genótipos GA+AA do SNP -238 G>A (rs361525) do gene do TNF- apresentaram concentrações plasmáticas de TNF-, IL-1, IL-6, IL-10 e IL-12 aumentadas quando comparados com indivíduos homozigotos dominantes. Além disso, homozigotos recessivos do SNP e/i boundary C>T (rs1554286) do gene da IL-10 apresentaram maior concentração plasmática de IL-1 e de TNF- e menor de MCP-1 em relação aos indivíduos homozigotos dominantes. O grupo inflamado apresentou idade, circunferência da cintura, pressão arterial significantemente maiores que o grupo não inflamado. Em relação aos AG do plasma, o grupo inflamado apresentou concentração plasmática de AG palmítico (C16:0), razões AG saturados (SFA)/AG ômega-6 (n-6) e SFA/ AG poli-insaturados (PUFA) e atividade estimada da enzima estearoil CoA desaturase (SCD) aumentadas e concentrações plasmática de PUFA, n- 6 e AG araquidônico (AA) e atividade estimada da enzima delta-5-dessaturase (D5D) reduzidas em comparação com o grupo não inflamado. Interações SNP-AG plasmáticos estatisticamente significante foram detectadas entre o SNP +1919 A>T (rs1417938) do gene da PCR e C16:1n-7, SFA/n-6 e SFA/PUFA; entre o SNP +3872 G>A (rs1205) do gene da PCR e C16:1n-7; entre o SNP e/i boundary C>T (rs1554286) do gene da IL-10 e atividade estimada da enzima D6D; e entre o SNP -1082 A>G (rs1800896) do gene da IL-10 e C18:0, C14:0 e atividade estimada da enzima D5D. Conclusão: Os SNP analisados possuem associações com biomarcadores inflamatórios e os ácidos graxos plasmáticos palmítico, SFA/n-6, SFA/PUFA, SCD-18 foram associados positivamente com um padrão inflamatório, enquanto PUFA, n-6, ácido araquidônico e D5D foram negativamente associados. Dentre as interações encontradas, o AG palmitoleico e a razão SFA/PUFA interagiram com +1919 A>T (rs1417938), e os AG esteárico e mirístico e D5D com -1082 A>G.. / Introduction: Genetics variation can influence the relation between fatty acids (FA) and inflammatory biomarkers levels. Objective: To verify the association between Single Nucleotide Polymorphisms (SNP) in adiponectin, C-Reactive Protein (CRP), Tumor Necrosis Factor (TNF)- and Interleukin (IL)-10 genes and plasma fatty acids and their effects to a systemic inflammatory pattern at a population-based study. Methods: Sociodemographics information, life style, physical activity (IPAQ long form), smoking and drinking habits, as well as blood samples of 281 individuals (20 years 59 years) participants of a population based study (ISA-Capital). Plasma IL1, IL6, IL8, IL10, TNF, IL12p70, adiponectin, CRP, soluble monocyte chemoattractant protein-1 (sMCP-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) levels were measured using a multiplex immunoassay and the fatty acid profile was measured by gas chromatography. The DNA was extracted and genotyping of SNP in CPR gene (rs1205, rs1417938, rs2808630), TNF (rs1799964, rs1799724, rs1800629 e rs361525) and IL10 (rs1800871, rs1800896 e rs1800872) was analyzed by TaqMan Open Array. Multivariate cluster analysis was applied on 11 inflammatory biomarkers, allowing to group individuals in inflammatory (INF) or non-inflammatory (NINF) group. Results: Individuals with GA+AA genotypes of SNP -238 G>A (rs361525) of TNF- gene had higher levels of TNF-, IL-1, IL-6, IL-10 and IL-12 compared to GG genotype. Besides that, recessive homozygous of SNP e/i boundary C>T (rs1554286) of IL-10 gene presented higher level of IL-1 and TNF- and lower level of sMCP-1 in relation to dominant homozygous. The INF group had significantly higher age, waist circumference, blood pressure, and total cholesterol than NINF group. Concerning fatty acid profile, INF group had palmitic acid (C16:0), saturated fatty acid (SFA)/omega-6 (n-6) polyunsaturated fatty acid (PUFA) ratio, SFA/PUFA and estimated enzyme activity of stearoyl-CoA desaturase (SCD) levels higher and PUFA, n-6, arachidonic acid and estimated enzyme activity of delta-5 desaturase (D5D) levels lower than NINF group. Significantly interactions were found between of SNP +1919 A>T (rs1417938) of PCR and C16:1n-7, SFA/n-6 and SFA/PUFA; between SNP +3872 G>A (rs1205) of PCR gene and C16:1n-7; between SNP e/i boundary C>T (rs1554286) of IL-10 and estimated enzyme activity of delta-6 desaturase (D6D); and between SNP -1082 A>G (rs1800896) of IL-10 gene and C18:0, C14:0 and estimated D5D activity. Conclusion: The SNP analyzed have associations with inflammatory biomarkers, and plasma palmitic, SFA/n-6, SFA/PUFA, SCD- 18 were positively associated with inflammatory pattern, while PUFA, n-6, arachidonic acid and D5D were negatively associated. Interactions were founded with palmitoleic and SFA/PUFA with +1919.A>T (rs1417938), and stearic and myristic acids and D5D with 1082 A>G.

To help mitigate the escalating prevalence of Type 2 Diabetes (T2D) and alleviate society of its associated morbidity and economic burden on health care, it is crucial to understand its aetiology. Both genetic and the environmental risk factors are known to be involved. Healthy diets have been proven to reduce the risk of T2D in primary prevention trials, however, which components and exact mechanisms are involved is not fully understood, in particular, the role of macronutrient intake. Body weight, glycaemic markers and T2D are all to some extent genetically regulated. There may also be genetic influences on how people digest, absorb or metabolise macronutrients. This poses the possibility that the interplay between genes and our diet may help us unravel T2D’s aetiology. The aim of this PhD was to investigate gene-diet interactions on the risk of incident T2D, focusing primarily on macronutrient intake as the dietary factor. First, I systematically evaluated the current evidence before taking a step-wise approach (hypothesis driven to hypothesis-free) to interrogate gene-macronutrient interactions. This identified 13 publications, with 8 unique interactions reported between macronutrients (carbohydrate, fat, saturated fat, dietary fibre, and glycaemic load derived from self-report of dietary intake and circulating n-3 polyunsaturated fatty acids) and genetic variants in or near TCF7L2, GIPR, CAV2 and PEPD (p < 0.05) on T2D. All studies were observational with moderate to serious risk of bias and limitations that included lack of adequate adjustment for confounders, lack of reported replication and insufficient correction for multiple testing. Second, these reported interactions did not replicate in a large European multi-centre prospective T2D case-cohort study called EPIC-InterAct. We concluded that the heterogeneity between our results and those published could be explained by methodological differences in dietary measurement, population under study, study design and analysis but also by the possibility of spurious interactions. Third, given the paucity of gene-macronutrient interaction research using genetic risk scores (GRS), we examined the interaction between three GRS (for BMI (97 SNPs), insulin resistance (53 SNPs) and T2D (48 SNPs)) and macronutrient intake (quantity and quality indicators) in EPIC-InterAct. We did not identify any statistically significant interactions that passed multiple testing corrections (p≥0.20, with a p value threshold for rejecting the null hypothesis of 0.0015 (based on 0.05/33 tests)). We also examined 15 foods and beverages identified as being associated with T2D, and no significant interactions were detected. Lastly, we applied a hypothesis-free method to examine gene-macronutrient interactions and T2D risk by using a genome-environment-wide-interaction-study. Preliminary findings showed no significant interactions for total carbohydrate, protein, saturated fat, polyunsaturated fat and cereal fibre intake on T2D. In conclusion, the consistently null findings in this thesis using a range of statistical approaches to examine interactions between genetic variants and macronutrient intake on the risk of developing T2D have two key implications. One, based on the specific interactions examined, this research does not confirm evidence for gene-diet interactions in the aetiology of T2D and two, this research suggests that the association between macronutrient intake and the risk of developing T2D does not differ by genotype.

Introdução: Variações genéticas podem influenciar a relação entre ácidos graxos (AG) do plasma e concentração plasmática de biomarcadores inflamatórios. Objetivo: Verificar a associação entre polimorfismos de nucleotídeo único (SNP) presentes nos genes da proteína C reativa (PCR), fator de necrose tumoral (TNF) e interleucina (IL)-10 e AG do plasma e seus efeitos sobre a concentração plasmática de biomarcadores inflamatórios em um estudo de base populacional ISACapital. Métodos: Foram coletadas informações sociodemográficas, de estilo de vida, de atividade física (IPAQ longo), hábito de fumar e beber, bem como amostras de sangue de 281 indivíduos (20 a 59 anos), oriundos de um estudo de base populacional (ISA-Capital). A partir do plasma, foram determinadas as concentrações de IL1, IL6, IL8, IL10, TNF, IL12p70, adiponectina, PCR, proteína quimiotática para macrófagos solúvel (sMCP)1, molécula de adesão intercelular solúvel (sICAM)1 e molécula de adesão celular vascular solúvel (sVCAM)1 por meio da técnica multiplex de imunoensaio e o perfil de ácidos graxos por cromatografia gasosa. O DNA genômico foi extraído e realizada a genotipagem dos SNP presentes no gene da PCR (rs1205, rs1417938, rs2808630), TNF (rs1799964, rs1799724, rs1800629 e rs361525) e IL10 (rs1800871, rs1800896 e rs1800872) pela ténica TaqMan Open Array. Foi realizada análise multivariada de cluster com base nos 11 biomarcadores inflamatórios, permitindo agrupar os indivíduos em grupo inflamado e cluster não inflamado. Resultados: Os indivíduos que possuíam os genótipos GA+AA do SNP -238 G>A (rs361525) do gene do TNF- apresentaram concentrações plasmáticas de TNF-, IL-1, IL-6, IL-10 e IL-12 aumentadas quando comparados com indivíduos homozigotos dominantes. Além disso, homozigotos recessivos do SNP e/i boundary C>T (rs1554286) do gene da IL-10 apresentaram maior concentração plasmática de IL-1 e de TNF- e menor de MCP-1 em relação aos indivíduos homozigotos dominantes. O grupo inflamado apresentou idade, circunferência da cintura, pressão arterial significantemente maiores que o grupo não inflamado. Em relação aos AG do plasma, o grupo inflamado apresentou concentração plasmática de AG palmítico (C16:0), razões AG saturados (SFA)/AG ômega-6 (n-6) e SFA/ AG poli-insaturados (PUFA) e atividade estimada da enzima estearoil CoA desaturase (SCD) aumentadas e concentrações plasmática de PUFA, n- 6 e AG araquidônico (AA) e atividade estimada da enzima delta-5-dessaturase (D5D) reduzidas em comparação com o grupo não inflamado. Interações SNP-AG plasmáticos estatisticamente significante foram detectadas entre o SNP +1919 A>T (rs1417938) do gene da PCR e C16:1n-7, SFA/n-6 e SFA/PUFA; entre o SNP +3872 G>A (rs1205) do gene da PCR e C16:1n-7; entre o SNP e/i boundary C>T (rs1554286) do gene da IL-10 e atividade estimada da enzima D6D; e entre o SNP -1082 A>G (rs1800896) do gene da IL-10 e C18:0, C14:0 e atividade estimada da enzima D5D. Conclusão: Os SNP analisados possuem associações com biomarcadores inflamatórios e os ácidos graxos plasmáticos palmítico, SFA/n-6, SFA/PUFA, SCD-18 foram associados positivamente com um padrão inflamatório, enquanto PUFA, n-6, ácido araquidônico e D5D foram negativamente associados. Dentre as interações encontradas, o AG palmitoleico e a razão SFA/PUFA interagiram com +1919 A>T (rs1417938), e os AG esteárico e mirístico e D5D com -1082 A>G.. / Introduction: Genetics variation can influence the relation between fatty acids (FA) and inflammatory biomarkers levels. Objective: To verify the association between Single Nucleotide Polymorphisms (SNP) in adiponectin, C-Reactive Protein (CRP), Tumor Necrosis Factor (TNF)- and Interleukin (IL)-10 genes and plasma fatty acids and their effects to a systemic inflammatory pattern at a population-based study. Methods: Sociodemographics information, life style, physical activity (IPAQ long form), smoking and drinking habits, as well as blood samples of 281 individuals (20 years 59 years) participants of a population based study (ISA-Capital). Plasma IL1, IL6, IL8, IL10, TNF, IL12p70, adiponectin, CRP, soluble monocyte chemoattractant protein-1 (sMCP-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) levels were measured using a multiplex immunoassay and the fatty acid profile was measured by gas chromatography. The DNA was extracted and genotyping of SNP in CPR gene (rs1205, rs1417938, rs2808630), TNF (rs1799964, rs1799724, rs1800629 e rs361525) and IL10 (rs1800871, rs1800896 e rs1800872) was analyzed by TaqMan Open Array. Multivariate cluster analysis was applied on 11 inflammatory biomarkers, allowing to group individuals in inflammatory (INF) or non-inflammatory (NINF) group. Results: Individuals with GA+AA genotypes of SNP -238 G>A (rs361525) of TNF- gene had higher levels of TNF-, IL-1, IL-6, IL-10 and IL-12 compared to GG genotype. Besides that, recessive homozygous of SNP e/i boundary C>T (rs1554286) of IL-10 gene presented higher level of IL-1 and TNF- and lower level of sMCP-1 in relation to dominant homozygous. The INF group had significantly higher age, waist circumference, blood pressure, and total cholesterol than NINF group. Concerning fatty acid profile, INF group had palmitic acid (C16:0), saturated fatty acid (SFA)/omega-6 (n-6) polyunsaturated fatty acid (PUFA) ratio, SFA/PUFA and estimated enzyme activity of stearoyl-CoA desaturase (SCD) levels higher and PUFA, n-6, arachidonic acid and estimated enzyme activity of delta-5 desaturase (D5D) levels lower than NINF group. Significantly interactions were found between of SNP +1919 A>T (rs1417938) of PCR and C16:1n-7, SFA/n-6 and SFA/PUFA; between SNP +3872 G>A (rs1205) of PCR gene and C16:1n-7; between SNP e/i boundary C>T (rs1554286) of IL-10 and estimated enzyme activity of delta-6 desaturase (D6D); and between SNP -1082 A>G (rs1800896) of IL-10 gene and C18:0, C14:0 and estimated D5D activity. Conclusion: The SNP analyzed have associations with inflammatory biomarkers, and plasma palmitic, SFA/n-6, SFA/PUFA, SCD- 18 were positively associated with inflammatory pattern, while PUFA, n-6, arachidonic acid and D5D were negatively associated. Interactions were founded with palmitoleic and SFA/PUFA with +1919.A>T (rs1417938), and stearic and myristic acids and D5D with 1082 A>G.

No description available.

Introdução: Fatores genéticos estão entre os determinantes de obesidade, podendo influenciar a resposta a intervenções em estilo de vida. O impacto de polimorfismos de nucleotídeo único (SNPs) na resposta de biomarcadores a intervenções não é claro. Objetivo: Este estudo examinou as associações de seis SNPs FTO T/A, PPAR Pro12Ala, Apo A1 -75G/A, TNF- -308G/A, IL-6 - 174G/C e AdipoQ 45T/G com mudanças induzidas por uma intervenção em amostra de brasileiros de risco cardiometabólico. Métodos: Em um programa de nove meses de orientações em hábitos alimentares e atividade física, 180 indivíduos com prediabetes ou síndrome metabólica foram genotipados e agrupados segundo a presença do alelo variante de cada SNP e comparados quanto a variáveis antropométricas, metabólicas e inflamatórias. Resultados: A intervenção resultou em redução do consumo calórico, aumento da atividade física, melhora na antropometria e outros biomarcadores. Estratificando pelos SNPs, os principais achados estão contidos em dois artigos. Artigo 1: Houve melhor resposta do perfil glicêmico após a intervenção nos portadores do alelo variante do SNP TNF -308 G/A. Observou-se melhora das variáveis lipídicas nos portadores do alelo variante do SNP IL-6 -174 G/C, enquanto que aqueles com o genótipo referência obtiveram melhora no metabolismo da glicose. Carreadores do SNP AdipoQ 45T/G não obtiveram melhora no perfil lipídico nem no glicêmico.Artigo 2: O alelo variante do FTO T/A associou-se a melhores perfis 9 inflamatório e glicêmico em resposta à intervenção. Portadores do alelo variante do SNP PPAR Pro12Ala obtiveram melhora na pressão arterial, enquanto que indivíduos com o genótipo referência melhoraram o metabolismo lipídico. Carreadores do alelo variante do SNP Apo A1 -75G/A apresentaram melhora no perfil lipídico que, após ajuste para medicação, não se manteve significante. Conclusões: SNPs relacionados à obesidade e comorbidades podem influenciar a resposta de marcadores metabólicos e inflamatórios a intervenções em hábitos de vida em brasileiros. O SNP TNF -308G/A parece favorecer um melhor perfil glicêmico. O SNP IL-6 -174G/C pode conferir efeito benéfico no perfil lipídico, mas não na glicemia. O SNP AdipoQ 45T/G compromete a resposta à intervenção em indivíduos de risco cardiometabólico no nosso meio. O SNP FTO T/A pode favorecer a resposta do metabolismo da glicose e a atenuação da inflamação. O SNP PPAR Pro12Ala pode ter impacto benéfico na pressão arterial, mas não no metabolismo lipídico. Em contraste com a literatura, o SNP Apo A1 -75G/A não parece influenciar resposta dos lípides à intervenção. Mais estudos envolvendo estes SNPs são necessários para possível direcionamento de intervenções a subgrupos específicos de indivíduos de risco. / Introduction: Genetic factors are one of the determinants of obesity and may influence the response to interventions. The impact of single nucleotide polymorphisms (SNPs) in weight loss and inflammatory response to interventions is not clear. Objective: This study examined associations of six polymorphisms FTO T/A, PPAR Pro12Ala, Apo A1 -75G/A, TNF- -308G/A, IL-6 -174G/C and AdipoQ 45T/G with changes induced by lifestyle intervention in Brazilians at cardiometabolic risk. Methods: In a 9-month intervention on diet and physical activity, 180 individuals with prediabetes or metabolic syndrome were genotyped and compared according the presence of variant allele of the SNPs and antrophometric, metabolic and inflammatory variables. Results: The intervention resulted in lower energy intake and greater total physical activity as well as improvement in anthropometry and several biomarkers. Stratified by SNPs, the main findings are covered in two articles. Article 1: Variant allele carriers of TNF -308 G/A SNP decreased plasma glucose after intervention. Lipid profile improved after intervention in variant allele carriers of IL-6 -174 G/C, while individuals with reference genotype had better plasma glucose response. Variant allele carriers of AdipoQ 45T/G did not improve lipid and glycemic profile. Article 2: Only variant allele carriers of FTO T/A decreased fasting plasma glucose and C-reactive protein concentration after intervention. Blood pressure reduced after intervention in variant allele carriers of the PPAR Pro12Ala, while the reference genotype increased Apo A1. Apparent favorable response of lipid profile to intervention in variant allele carriers of Apo A1 -75G/A was not maintained after adjustments for lipid-lowering medication. Conclusions: SNPs associated with obesity and comorbidities may influence the response of metabolic and inflammatory markers after lifestyle intervention. The TNF -308G/A may predispose a better response of glucose metabolism. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid profile but not in glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45T/G SNP in lipid and glucose metabolism after lifestyle intervention in Brazilians at cardiometabolic risk. FTO T/A SNP induces a favorable impact on inflammatory status and glucose metabolism. The reference genotype of PPAR Pro12Ala seems to favor a better lipid profile, while the variant allele to decrease blood pressure. In contrast to literature, our data did not support benefits on lipid profile of the variant allele of Apo A1 -75G/A SNP. Further studies of these SNPs are needed to direct interventions to specific subgroups of at-risk individuals.

Introdução: Fatores genéticos estão entre os determinantes de obesidade, podendo influenciar a resposta a intervenções em estilo de vida. O impacto de polimorfismos de nucleotídeo único (SNPs) na resposta de biomarcadores a intervenções não é claro. Objetivo: Este estudo examinou as associações de seis SNPs FTO T/A, PPAR Pro12Ala, Apo A1 -75G/A, TNF- -308G/A, IL-6 - 174G/C e AdipoQ 45T/G com mudanças induzidas por uma intervenção em amostra de brasileiros de risco cardiometabólico. Métodos: Em um programa de nove meses de orientações em hábitos alimentares e atividade física, 180 indivíduos com prediabetes ou síndrome metabólica foram genotipados e agrupados segundo a presença do alelo variante de cada SNP e comparados quanto a variáveis antropométricas, metabólicas e inflamatórias. Resultados: A intervenção resultou em redução do consumo calórico, aumento da atividade física, melhora na antropometria e outros biomarcadores. Estratificando pelos SNPs, os principais achados estão contidos em dois artigos. Artigo 1: Houve melhor resposta do perfil glicêmico após a intervenção nos portadores do alelo variante do SNP TNF -308 G/A. Observou-se melhora das variáveis lipídicas nos portadores do alelo variante do SNP IL-6 -174 G/C, enquanto que aqueles com o genótipo referência obtiveram melhora no metabolismo da glicose. Carreadores do SNP AdipoQ 45T/G não obtiveram melhora no perfil lipídico nem no glicêmico.Artigo 2: O alelo variante do FTO T/A associou-se a melhores perfis 9 inflamatório e glicêmico em resposta à intervenção. Portadores do alelo variante do SNP PPAR Pro12Ala obtiveram melhora na pressão arterial, enquanto que indivíduos com o genótipo referência melhoraram o metabolismo lipídico. Carreadores do alelo variante do SNP Apo A1 -75G/A apresentaram melhora no perfil lipídico que, após ajuste para medicação, não se manteve significante. Conclusões: SNPs relacionados à obesidade e comorbidades podem influenciar a resposta de marcadores metabólicos e inflamatórios a intervenções em hábitos de vida em brasileiros. O SNP TNF -308G/A parece favorecer um melhor perfil glicêmico. O SNP IL-6 -174G/C pode conferir efeito benéfico no perfil lipídico, mas não na glicemia. O SNP AdipoQ 45T/G compromete a resposta à intervenção em indivíduos de risco cardiometabólico no nosso meio. O SNP FTO T/A pode favorecer a resposta do metabolismo da glicose e a atenuação da inflamação. O SNP PPAR Pro12Ala pode ter impacto benéfico na pressão arterial, mas não no metabolismo lipídico. Em contraste com a literatura, o SNP Apo A1 -75G/A não parece influenciar resposta dos lípides à intervenção. Mais estudos envolvendo estes SNPs são necessários para possível direcionamento de intervenções a subgrupos específicos de indivíduos de risco. / Introduction: Genetic factors are one of the determinants of obesity and may influence the response to interventions. The impact of single nucleotide polymorphisms (SNPs) in weight loss and inflammatory response to interventions is not clear. Objective: This study examined associations of six polymorphisms FTO T/A, PPAR Pro12Ala, Apo A1 -75G/A, TNF- -308G/A, IL-6 -174G/C and AdipoQ 45T/G with changes induced by lifestyle intervention in Brazilians at cardiometabolic risk. Methods: In a 9-month intervention on diet and physical activity, 180 individuals with prediabetes or metabolic syndrome were genotyped and compared according the presence of variant allele of the SNPs and antrophometric, metabolic and inflammatory variables. Results: The intervention resulted in lower energy intake and greater total physical activity as well as improvement in anthropometry and several biomarkers. Stratified by SNPs, the main findings are covered in two articles. Article 1: Variant allele carriers of TNF -308 G/A SNP decreased plasma glucose after intervention. Lipid profile improved after intervention in variant allele carriers of IL-6 -174 G/C, while individuals with reference genotype had better plasma glucose response. Variant allele carriers of AdipoQ 45T/G did not improve lipid and glycemic profile. Article 2: Only variant allele carriers of FTO T/A decreased fasting plasma glucose and C-reactive protein concentration after intervention. Blood pressure reduced after intervention in variant allele carriers of the PPAR Pro12Ala, while the reference genotype increased Apo A1. Apparent favorable response of lipid profile to intervention in variant allele carriers of Apo A1 -75G/A was not maintained after adjustments for lipid-lowering medication. Conclusions: SNPs associated with obesity and comorbidities may influence the response of metabolic and inflammatory markers after lifestyle intervention. The TNF -308G/A may predispose a better response of glucose metabolism. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid profile but not in glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45T/G SNP in lipid and glucose metabolism after lifestyle intervention in Brazilians at cardiometabolic risk. FTO T/A SNP induces a favorable impact on inflammatory status and glucose metabolism. The reference genotype of PPAR Pro12Ala seems to favor a better lipid profile, while the variant allele to decrease blood pressure. In contrast to literature, our data did not support benefits on lipid profile of the variant allele of Apo A1 -75G/A SNP. Further studies of these SNPs are needed to direct interventions to specific subgroups of at-risk individuals.

Metabolic syndrome (MetS) is a complex condition with a number of interacting genes, epigenetic and environmental factors underlying its pathogenesis. The analysis of genetic component of MetS showed that number of defining parameters of the syndrome is linked to regions of rat chromosome 4. In order to verify these quantitative trait loci (QTL), a double congenic strain was derived with parts of chromosome 4 of spontaneously hypertensive rat (SHR, an inbred MetS model) origin introgressed onto genomic background of congenic Brown Norway strain (BN-Lx). The aim of the proposed thesis is comprise detail genetic mapping of differential segments of the above mentioned double congenic strain BN-Lx.SHR4 and comparison of its metabolic profile under different dietary conditions with varying carbohydrate and fat content. Utilizing DNA sequence and gene expression comparisons, candidate genes or polymorphisms for the MetS aspects and potential nutrigenetic interactions will be identified. Key words: nutrigenetics, experimental models, metabolic syndrome, congenic strain, genotyping, rat

Submitted by Ricardo Cedraz Duque Moliterno (ricardo.moliterno@uefs.br) on 2017-11-27T20:53:26Z No. of bitstreams: 1 edilenemqa-tese.pdf: 4986958 bytes, checksum: 98721b3ed915b46fe60ca445665ea3ca (MD5) / Made available in DSpace on 2017-11-27T20:53:26Z (GMT). No. of bitstreams: 1 edilenemqa-tese.pdf: 4986958 bytes, checksum: 98721b3ed915b46fe60ca445665ea3ca (MD5) Previous issue date: 2016-09-26 / Metabolic syndrome (MS) is a complex disorder with a strong genetic basis and multifactorial etiology. Insulin resistance (IR) causes MS and it can be triggered by intestinal inflammation like the use of lactose in patients intolerant of this carbohydrate. It was found that variants in the lactase gene are associated with lactase non persistence LNP and MS in a population sample of Salvador/Bahia; and whether these variants are modifying the response to diet-therapeutic intervention in patients with this syndrome; also compared the biochemical test of lactose tolerance (LTT) with genetic diagnosis; and tested the association of mutations in the lactase gene with cofactors SM (TGL, HDL-C, blood pressure, glucose levels, waist circumference), with anthropometric variables (Arm Circumference, Body Mass Index, Hip Circumference, hip-waist ratio,lean massand fat mass percentages) and other factors associated with MS: insulin, total cholesterol, LDL-C, VLDL-C, C-reactive protein, HOMA-IR, renal function (creatinine, urea, uric acid, microalbuminuria) and vitamin D. There were two studies: a case-control with 257 cases (MS) and 210 controls and other clinical trial study, which was conducted with three types of diet in patients with metabolic syndrome: diet 1 - No lactose; Diet 2 - Lactose and energy restriction; Diet 3 - Only energy restriction. In all groups were also evaluated for nine SNPs in the lactase (LCT) gene. The genotyping of SNPs was carried out by TaqMan assays. Data were analyzed using SPSS, 20.0, and the Hardy-Weinberg Equilibriumhaplotype frequencies were calculated using Arlequin, 2000 program. The results showed that all diets improve several MSaspects after two months of intervention, especially in the diet 1, that also decreased inflammation, insulin resistance and dyslipidemia (LDL-C). In addition,it was the diet that most took out patients of the MS: 2.72 times more likely to get out of MS than diet 3. LNP was high in both cases and controls. There was compatibility between clinical diagnosis for LNP by Lactose Tolerance Test and two of the studied SNPs, they were rs4988253 and rs182549, those that have proved functional studies. Thus, it is suggested the analysis of LCT gene polymorphisms before the nutritional therapeutics for patients with MS, as well as to take out the lactose in their diet. / A S?ndrome Metab?lica (SM) ? uma desordem complexa, de forte base gen?tica e de etiologia multifatorial. Dentre as suas causas, encontra-se a Resist?ncia ? Insulina (RI) que pode ser desencadeada pela inflama??o intestinal, pelo uso de lactose em pacientes intolerantes a este carboidrato. Verificou-se quais variantes no gene da lactase est?o associados ? IL e SM em amostra da popula??o de Salvador/Bahia; e tamb?m se estas variantes s?o modificadoras da resposta ? interven??o dietoter?pica em portadores desta s?ndrome; comparou-se tamb?m o teste bioqu?mico de toler?ncia ? lactose (TTL) com o diagn?stico gen?tico; e testou-se a associa??o das muta??es no gene da lactase com os cofatores da SM (TGL, HDL-c, press?o arterial, glicemia, circunfer?ncia da cintura), com vari?veis antropom?tricas (circunfer?ncia do bra?o, ?ndice de massa corporal, circunfer?ncia do quadril, raz?o cintura quadril, percentual de massa magra e massa gorda) e com outros fatores associados ? SM: insulina, colesterol total, LDL-C, VLDL, Prote?na C reativa, HOMA-IR, fun??o renal (creatinina, ur?ia, ?cido ?rico, microalbumin?ria) e vitamina D. Foram realizados dois estudos: um caso-controle com 257 casos (SM) e 210 controles e outro estudo de tipo ensaio cl?nico, que foi realizado com tr?s tipos de dieta com os pacientes com SM: dieta 1 ? sem lactose; dieta 2 ? sem lactose e com restri??o energ?tica; Dieta 3 ? apenas restri??o energ?tica. Em ambos os grupos tamb?m foram avaliados 9 SNPs no gene da lactase. A genotipagem dos SNPs foi realizada pela tecnologia de ensaios TaqMan. Os dados foram analisados pelo programa SPSS ver 20.0 e a adequa??o das frequ?ncias genot?picas ao Equilibrio de Hardy-Weinberg e c?lculo da frequ?ncia dos hapl?tipos formados pelos polimorfismos foram obtidos atrav?s do programa Arlequin ver 2000. Os resultados mostraram que todas as dietas melhoram o quadro da SM ap?s dois meses de interven??o, com destaque para a dieta 1, que tamb?m diminuiu a inflama??o, resist?ncia ? insulina e a dislipidemia (LDL-C). Al?m disso foi a dieta que mais tirou paciente da SM: apresentou 2,72 vezes mais chances de sair da SM que a dieta 3. A intoler?ncia ? lactose foi alta tanto em casos como em controles. Houve compatibilidade do TTL com os SNPsrs4988253 e rs182549, os ?nicos que possuem estudos funcionais. Assim, sugere-se an?lise de polimorfismos do gene da lactase antes da prescri??o nutricional para pacientes com SM, bem como, a retirada da lactose da dieta.

Increasing level of public concerns about ageing and obesity problems accompanied by the advent of more and more health conscious consumers have put a priority on the health and wellness industry development which has started transformation from a niche category towards the mainstream. As a human being is an individual with unique known characteristics (like age, gender, health state, lifestyle) and less known characteristics like a genetic predisposition, the nutrition plan should be designed around these characteristics. Being aware of genetic predisposition of an individual allows to develop the appropriate health strategy for the particular individual. A systematization of these individual programs would support the development of a new generation of health practitioners. Russia is experiencing serious demographic problems with decreasing population and low life expectancy; high mortality rate from heart diseases and quite high obesity rates. It is expected that nutrigenomics concepts can be successfully developed in Russia due to its solid scientific base, relatively high level of medicine and the ever increasing awareness of the need for a healthy quality life especially within young generation. The goal of the thesis therefore is to analyze the key trends in the global and Russian food industries and develop a business idea of commercializing the personalized nutrition concept in the Russian food service market.