Plant sterols (PS) share a similar chemical structure to cholesterol, differing only in side chains and double bond placement. PS are naturally found in plants and are typically ingested in the 400mg/day range. Consumption of 1-3 g of PS a day has been repeatedly shown to lower total and LDL cholesterol. However, data from nutritional trials involving plant sterols demonstrate considerable inter-individual variations in response to PS consumption. The objective of this research was to investigate the metabolic and genetic factors that underlie this heterogeneity of responsiveness of LDL cholesterol to PS consumption. A study was conducted to test the effectiveness of lathosterol to cholesterol ratio (L/C), a surrogate marker of cholesterol synthesis, as a predictor of LDL cholesterol lowering in response to plant sterol consumption. 63 mildly hypercholesterolemic adults, with high (n=24, L/C = 2.03 ± 0.39umol/mmol) or low (n=39, L/C =0.99±0.28 umol/mmol) L/C ratio at baseline, consumed either 0 or 2g/d of PS for 28 days in a dual-center, single-blind, randomized, crossover design. Plasma lipid and non-cholesterol sterol concentrations were measured at the end of each phase. Single nucleotide polymorphisms (SNPs) in candidate genes involved in cholesterol metabolism were investigated for potential gene by nutrient interactions. Plant sterol consumption lowered total and LDL cholesterol concentrations overall, but only individuals with low L/C ratio responded to plant sterol treatment by lowering TC and LDL-C, while individuals with high L/C ratio showed no marked improvement. The rs3808607 T-allele in the promoter of the CYP7A1 gene was associated with decreased LDL-C responsiveness to PS consumption. The rs3808607 G-allele and ApoE ε4 were associated with increased LDL-C responsiveness to PS consumption. PS consumption did not lower TG overall (p=0.0506), but had an interaction with rs5882 in CETP (p=0.0080). Baseline L/C predicts LDL-C lowering due to PS consumption, which is associated with rs3808607 genotype in the promoter of the CYP7A1 gene. rs5882 in CETP is associated with TG lowering due to PS consumption. rs3808607, rs5882 and ApoE variant are potential genetic markers which could identify individuals who would derive maximum benefit from PS consumption.

Previously, ADH1Cc.-64T>C was shown to have an association with intramuscular fat (IMF) in the longissimus thoracis (LT) muscle when vitamin A was limited in finishing rations of beef steers. The purpose of the current study was to determine the optimum vitamin A supplementation level, in combination with ADH1C genotype, to increase IMF of the LT muscle. Forty-five TT, 45 CT and 27 CC cross-bred steers, black in colour, were backgrounded on a commercial ration containing 3360 IU vitamin A/kg DM. During finishing the steers were randomly assigned to one of three vitamin A treatments at 25, 50 and 75% of the NRC recommendation of 2200 IU/kg DM. Treatments were administered via an oral bolus. Carcass quality was evaluated and a sample from the LT muscle was collected for analysis of IMF. A treatment x genotype interaction (P=0.04) was observed for IMF; TT steers on the 75% treatment had higher IMF relative to CT and CC steers on the same treatment. Intramuscular fat was also higher for TT steers on the 75% treatment in comparison to TT steers on the 25% treatment. Eighty-four percent of the steers graded Canada AAA. Western blot analysis showed that TT steers had higher (P=0.02) ADH1C levels in hepatic tissue. Previously, TT steers had increased IMF when fed limited vitamin A. In the current study the lack of variation between treatments and genotypes at the lower vitamin A treatment levels was likely due to the majority of the steers grading Canada AAA (USDA Choice). However, the western blot data supports that TT steers are expected to have higher IMF deposition, due to an increase production of ADH1C.

Fishy-egg tainting has long been a problem associated with feeding canola meal (CM) to brown-shelled laying hens. It is a classical example of nutrigenetics, as both dietary and genetic factors must be present for a hen to lay fishy-tainted eggs. Trimethylamine (TMA), the compound responsible for the fishy smell, is produced by bacterial fermentation of choline in the lower gut. CM contains large amounts of choline in the form of sinapine. Choline must first be hydrolyzed from sinapine before it can be absorbed or converted to TMA. Normally, the malodourous TMA is metabolized to the odourless trimethylamine N-oxide (TMAO) by flavin-containing monooxygenase 3 (FMO3). A mutation in FMO3 (c.984A>T) prevents TMA from being oxidized to TMAO, and subsequently TMA accumulates in the developing egg yolks. Our objective was to determine the inheritance pattern of fishy-egg tainting when hens are fed canola meal, reflecting typical industry conditions. In the first of two trials, hens of a commercial brown-shelled strain were genotyped at FMO3 c.984A>T and fed graded levels of CM (0, 6, 12, or 18%). These hens were bred to produce a second generation of hens, which were also genotyped and fed graded levels of CM (0, 6, 12, 18, or 24%) or choline chloride (0, 0.055, 0.110, 0.165, or 0.220%). Choline chloride, at levels up to 0.220%, does not lead to the production of fishy tainted-eggs. When fed CM, TT hens laid fishy-tainted eggs. Mean yolk TMA concentration was not significantly different between hens of the AA and AT genotypes, with means from both genotypes remaining below the human detection threshold for all of the dietary treatments. Large day-to-day variations in yolk TMA concentration were seen in hens of all three genotypes. We concluded that fishy-egg tainting is recessive when hens are fed CM at levels reflecting typical commercial practices.

Fishy-egg tainting has long been a problem associated with feeding canola meal (CM) to brown-shelled laying hens. It is a classical example of nutrigenetics, as both dietary and genetic factors must be present for a hen to lay fishy-tainted eggs. Trimethylamine (TMA), the compound responsible for the fishy smell, is produced by bacterial fermentation of choline in the lower gut. CM contains large amounts of choline in the form of sinapine. Choline must first be hydrolyzed from sinapine before it can be absorbed or converted to TMA. Normally, the malodourous TMA is metabolized to the odourless trimethylamine N-oxide (TMAO) by flavin-containing monooxygenase 3 (FMO3). A mutation in FMO3 (c.984A>T) prevents TMA from being oxidized to TMAO, and subsequently TMA accumulates in the developing egg yolks. Our objective was to determine the inheritance pattern of fishy-egg tainting when hens are fed canola meal, reflecting typical industry conditions. In the first of two trials, hens of a commercial brown-shelled strain were genotyped at FMO3 c.984A>T and fed graded levels of CM (0, 6, 12, or 18%). These hens were bred to produce a second generation of hens, which were also genotyped and fed graded levels of CM (0, 6, 12, 18, or 24%) or choline chloride (0, 0.055, 0.110, 0.165, or 0.220%). Choline chloride, at levels up to 0.220%, does not lead to the production of fishy tainted-eggs. When fed CM, TT hens laid fishy-tainted eggs. Mean yolk TMA concentration was not significantly different between hens of the AA and AT genotypes, with means from both genotypes remaining below the human detection threshold for all of the dietary treatments. Large day-to-day variations in yolk TMA concentration were seen in hens of all three genotypes. We concluded that fishy-egg tainting is recessive when hens are fed CM at levels reflecting typical commercial practices.

Yes / Background: Commercial technology-enabled personalised nutrition is undergoing 19 rapid growth, yet uptake in dietetics practice remains low. This survey sought the opinions 20 of dietetics practitioners on personalised nutrition and related technologies to understand 21 facilitators and barriers to its application in practice. 22 Method: A cross-section of Registered Dietitians were recruited in the US, UK, 23 Australia, Canada, Israel, Mexico, Portugal, Spain and South Africa. The questionnaire 24 sought views on risk of genetic technology, ethics of genetic testing, usefulness of new 25 personalised nutrition technologies, entrepreneurism and the perceived importance of 26 new technologies to dietetics. Validated scales were included to assess personality (Big 27 5) and self-efficacy (NGSEI). The survey was available in English, Spanish and 28 Portuguese. Regression analyses were performed to identify factors associated with 29 integration of nutrigenetic testing into practice, and to identify factors associated with the 30 perceived importance of bio, information and mobile technologies to dietetic practice. 31 Results: A total of 323 responses (response rate 19.7%) were analysed. Dietetic 32 practitioners who had integrated personalised nutrition technology into practice perceived 33 technologies to be less risky (P=0.02), biotechnology to be more important (P<0.01), and 34 professional skills to be less important (P=0.04) than those who had not. They were also 35 more likely to see themselves as entrepreneurs (P<0.01) and to perceive lower risks to be 36 associated with technology (P<0.01). Practitioners of nutrigenetics were lower on 37 neuroticism (P<0.01) and higher on self-efficacy (P<0.01), extraversion (P<0.01) and 38 agreeableness (P<0.01). Higher perceived importance of biotechnology to dietetic 39 practice was associated with higher perceived usefulness of omics tests (P<0.01). 40 Perceived importance of information technology was associated with perceived 41 importance of biotechnology (P<0.01). Mobile technologies were perceived as important 42 by dietitians with the highest level of education (P=0.02). 43 Conclusions: For dietitians to practice technology-enabled personalised nutrition, 44 training will be required to enhance self-efficacy, address risk perceived to be associated 45 with new technologies and to instil an entrepreneurial mindset.

The micronutrient selenium is essential to human physiology. As the amino acid selenocysteine, it is inserted into selenoproteins with a wide range of functions including antioxidant capacity, thyroid hormone metabolism, improvement of immune system, brain function, fertility and reproduction. Low selenium status has been associated with increased risk for chronic diseases, such as cancer, type-2 diabetes and cardiovascular disease. In this context, several studies have been conducted in order to investigate if selenium supplementation could reduce the risk of such diseases. However, genetic variations may interfere in the response of individuals to a dietary intervention and must be considered as a important source of inter-individual variation. Therefore, this study was conducted was conducted to investigate the influence of genetic variations in selenoproteins genes on the response to an intervention with Brazil nuts, the richest source of selenium known in nature. The study included 130 healthy volunteers with both genders, aged 20 to 60 years old selected in University of São Paulo. They received nuts for 8 weeks, eating one nut a day, and did a washout period for more 8 weeks. All volunteers had a blood sampling collection every 4 weeks during 4 months, in a total of 5. The following analysis were done: anthropometric measurements, lipid profile, plasma malondialdehyde, plasma and erythrocyte Se, selenoprotein P, plasma and erythrocyte GPx activity, gene expression of GPX1, SEPP1, SELS and SEP15. The volunteers were also genotyped for SNPs rs1050450, rs3811699, rs1800699, rs713041, rs3877899, rs7579, rs34713741 and rs5845. Each unit of Brazil nut provided an average of 300 &#181;g of selenium. All 130 volunteers completed the protocol. The concentrations of total cholesterol and glucose decreased after 8 weeks of supplementation. Moreover, HDL concentrations were higher for carriers of the variant T allele for GPX4_rs713041. The frequencies of the variant genotypes were 5,4% for rs1050450, rs3811699 e rs1088668, 10% for rs3877899, 19,2% for rs713041 e rs7579, 11,5% for rs5845 and 8,5% for rs34713741. The levels of the five biomarkers increased significantly after supplementation. In addition, erythrocyte GPx activity was influenced by rs1050450, rs713041 and rs5845; erythrocyte selenium was influenced by rs5845 and plasma selenium by rs3877899. Gene expression of GPX1, SEPP1 and SEP15 were higher after supplementation. The SNP rs1050450 influenced GPX1 mRNA expression and rs7579 influenced SEPP1 mRNA expression. Therefore, it can be concluded that the supplementation with one of Brazil nut for 8 weeks was efficient to reduce total cholesterol and glucose levels and to increase the concentrations of the main biomarkers of selenium status in healthy adults. Furthermore, our results suggest that GPX4_rs713041 might interfere on HDL concentrations and GPx1 activity, GPX1_rs1050450 might interfere on GPx1 activity, SEP15_rs5845 might interfere on GPx1 activity and erythrocyte selenium and SEPP1_3877899 might interfere on plasma Se levels. Therefore, the effect of genetic variations should be considered in future nutritional interventions evaluating the response to Brazil nut supplementation. / O micronutriente selênio é essencial para a fisiologia humana, inserido nas selenoproteínas na forma do aminoácido selenocisteína. As selenoproteínas são importantes para a função antioxidante, controle do metabolismo dos hormônios tireoidianos, melhora do sistema imune, função cerebral, fertilidade e reprodução. O estado nutricional de selênio deficiente ou marginal está associado com aumento do risco de doenças crônicas, como câncer, diabetes e doença cardiovascular. Sendo assim, diversos estudos procuraram investigar se a suplementação com selênio poderia reduzir o risco dessas doenças. Entretanto, as variações genéticas podem afetar a resposta dos indivíduos a uma intervenção dietética. Portanto, esse estudo foi conduzido para investigar a influência de variações genéticas em genes de selenoproteínas na resposta à suplementação com castanha-do-brasil, melhor fonte de selênio da natureza. Participaram do estudo 130 adultos de ambos os gêneros, com idade de 20 a 60 anos, selecionados na Universidade de São Paulo. Os indivíduos receberam castanhas suficientes para 8 semanas, ingerindo uma unidade por dia e, após o período de suplementação realizaram um período de washout também por 8 semanas. Todos realizaram cinco coletas de material biológico a cada quatro semanas. Foram realizadas medidas antropométricas, perfil lipídico, malondialdeído (MDA), concentração de selênio e selenoproteína P no plasma, eritrócitos, atividade da GPx eritrocitária e plasmática, expressão gênica da GPX1, SEPP1, SELS e SEP15. Além disso, os participantes foram genotipados para os SNPs rs1050450, rs3811699, rs1800699, rs713041, rs3877899, rs7579, rs34713741 e rs5845. Cada unidade de castanha forneceu em média 350&#181;g de selênio. Todos os 130 voluntários concluíram o estudo. As concentrações de glicose e colesterol total diminuíram após 8 semanas de suplementação. Além disso, as concentrações de HDL-c foram influenciadas pelo SNP rs713041 no gene da GPX4, sendo os valores mais altos encontrados para os indivíduos com o alelo variante T (CT+TT). As frequências dos genótipos variantes foram 5,4% para rs1050450, rs3811699 e rs1088668, 10% para rs3877899, 19,2% para rs713041 e rs7579, 11,5% para rs5845 e 8,5% para rs34713741. Os níveis dos cinco biomarcadores aumentaram significativamente após a suplementação. Além disso, a atividade da GPx eritrocitária foi influenciada pelos rs1050450, rs713041 e rs5845, o selênio eritrocitário foi influenciado pelo rs5845 e o selênio plasmático pelo rs3877899. A expressão dos genes GPX1 e SEPP foram maiores após a suplementação. Tendo em vista esses resultados, conclui-se que a suplementação com uma unidade de castanha-do-brasil durante 8 semanas foi suficiente para reduzir as concentrações de colesterol e de glicose, e elevar as concentrações dos principais biomarcadores do estado nutricional de selênio. Além disso, observou-se que o polimorfismo rs713041 parece influenciar as concentrações de HDL-c e atividade da GPx1, o polimorfismo rs1050450 parece influenciar a atividade da GPx1, o polimorfismo rs5845 parece influenciar a atividade da GPx1 e o selênio eritrocitário e o polimorfismo rs3877899 parece influenciar a o selênio plasmático. Portanto, sugere-se considerar o perfil genético dos indivíduos em futuros estudos avaliando a resposta à suplementação com castanha-do-brasil no estado nutricional de selênio da população.

Introdução: Evidências experimentais, epidemiológicas e clínicas mostram o papel da inflamação na patogênese de desordens metabólicas, sendo a modulação da resposta inflamatória associada a quantidade e a qualidade dos ácidos graxos (AG) da dieta. Polimorfismos de nucleotídeo único (SNP) podem influenciar a relação entre AG e concentração plasmática de biomarcadores inflamatórios. Objetivo: Verificar a associação de SNP relacionados aos genes da adiponectina, Receptor do tipo Toll (TLR)-4, interleucina (IL)-1 e IL-6 e ingestão de lipídios com um padrão inflamatório sistêmico, baseado na concentração plasmática de onze biomarcadores inflamatórios em estudo de base populacional ISA-Capital. Metodologia: O presente estudo compreende adultos (20 a 59 anos) do estudo de base populacional, ISA-capital 2008-2010 (n=302). A coleta dos dados dietéticos foi realizada por meio de recordatório de 24 horas, aplicado em duplicata. A partir do plasma, foram determinadas as concentrações plasmáticas de adiponectina, proteína C reativa (PCR), IL-1, IL-6, IL-8, IL-10, fator de necrose tumoral-alfa, IL- 12p70, Quimiocina C-C motif ligante (CCL) 2, 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 (AG) do plasma por cromatografia gasosa. A partir do DNA genômico foi realizada a genotipagem dos SNP relacionados aos genes da adiponectina (rs266729, rs17300539, rs16861209, rs1501299 e rs2241766), TLR4 (rs4986790, rs4686791, rs5030728, rs11536889), IL-1 (rs1143623, rs16944, rs1143627, rs1143634 e rs1143643) e da IL-6 (rs1800795, rs1800796, rs1800797) pelo sistema Taqman Open Array. Uma análise multivariada de Cluster (k-means) foi realizada para separar os indivíduos legíveis entre grupo inflamado (INF), n=93, e grupo não inflamado (NINF),n=169, segundo a concentração plasmática dos onze 8 biomarcadores inflamatórios avaliados. Resultados: Todos os SNP estavam em equilíbrio de Hardy-Wienberg (n=301). O INF apresentou idade, circunferência da cintura, pressão arterial e concentrações de triacilgliceróis sanguíneo estatisticamente maiores que aqueles observados para o NINF. O INF apresentou concentração plasmática de AG palmítico (C16:0), razões AG saturados (AGS)/AG ômega-6 (n-6) e AGS/ AG poli-insaturados (AGPI) e atividade estimada da enzima estearoil CoA desaturase aumentadas e concentrações plasmática de AGPI, n-6 e AG araquidônico (AA) e atividade estimada da enzima delta-5-dessaturase (D5D) reduzidas em comparação com o NINF. Interações SNP-AG plasmáticos estatisticamente significantes para predisposição ao padrão inflamatório sistêmico foram detectadas entre o SNP +6054 G>A (rs1143643) do gene da IL-1 e os AG esteárico, AA e AGPI e atividade estimada da enzima delta-6-desaturase (D6D); entre o SNP +3725 G>C (rs11536889) do gene do TLR-4 e a razão AA/AG eicosapentaenoico (EPA); entre o SNP +45 T>G (rs2241766) do gene da adiponectina e o AG ômega-3 (n-3); entre o SNP -7734 C>A (rs16861209) do gene da adiponectina e AA; e entre o SNP -11391 G>A (rs17300539) do gene da adiponectina e AGS. Conclui-se que algumas frações dos AG do plasma podem modular a inflamação e que SNP localizados nos genes da adiponectina, TLR-4, IL- 1 e IL-6 podem interagir com as frações de AG do plasma influenciando a chance de desenvolver uma inflamação sistêmica. / Introduction: Experimental, epidemiological and clinical evidences point to a pathogenic role of inflammation on metabolic disorders development, and to the relationship between this inflammatory response and the quantity and quality of dietary fatty acids. Single Nucleotide Polymorphisms (SNP) can modulate the relationship between fatty acids and plasma inflammatory biomarkers levels. Objective: To verify the association between SNP in the genes of adiponectin, TLR- 4, IL-1 and IL-6 and dietary fatty acids and their effects to a systemic inflammatory pattern at a population-based study ISA-Capital. Methods: This study sample was composed by adults (20 to 59 years), participants of the population-based study ISAcapital 2008-2010 (n=302). Dietary data was collected using two 24 hours dietary recall. Plasma concentration of adiponectin, C reactive protein, IL-1, IL-6, IL-8, IL- 10, tumor necrosis factor-alfa, IL-12p70, Chemokine C-C motif ligand (CCL) 2, soluble intercellular adhesion molecule (sICAM)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 was determined by multiplex immunoassay. Plasma FA profile was determined by gas chromatography. SNP from adiponectin (rs266729, rs17300539, rs16861209, rs1501299 e rs2241766), TLR4 (rs4986790, rs4686791, rs5030728, rs11536889), IL-1 (rs1143623, rs16944, rs1143627, rs1143634 e rs1143643) and IL-6 (rs1800795, rs1800796, rs1800797) gene were genotyped by Taqman Open Array system. A Cluster multivariate analysis (k-means) was conducted to separate individual into inflammatory group (INF), n=93, and noninflammatory group (NINF), n=169, according to eleven inflammatory biomarkers plasma levels. Results: All the SNP were in Hardy-Weinberg equilibrium (n=301). INF had statistically higher age, waist circumference, blood pressure and plasma tryglicerides concentration than NINF. INF presented statistically higher plasma palmitic acid (C16:0) levels, saturated fatty acid (SFA)/omega-6 fatty acid (n-6) ratio and SFA/polyunsaturated fatty acid (PUFA) ratio and estimated stearoil CoA 10 desaturase activity, and statistically lower plasma PUFA, n-6 and arachidonic acid e (AA) and estimate delta-5-desaturase (D5D) activity in comparison to NINF. Statistically significant SNP-plasma fatty acid interactions were found between SNP +6054 G>A (rs1143643) of IL-1 gene and stearic acid, AA and PUFA and estimate delta-6-desaturase (D6D) activity; between SNP +3725 G>C (rs11536889) of TLR-4 gene and AA/eicosapentaenoic acid (EPA) ratio; between SNP +45 T>G (rs2241766) of adiponectin gene and omega-3 fatty acid (n-3); between SNP -7734 C>A (rs16861209) of adiponectin gene and AA; and between SNP -11391 G>A (rs17300539) of adiponectin gene and SFA. In conclusion, some plasma fatty acid subfractions can modulate inflammation and SNP of adiponectin, TLR-4, IL-1 and IL-6 genes can interact with plasma fatty acids to modulate the chance to develop systemic inflammation.

Introdução: Evidências experimentais, epidemiológicas e clínicas mostram o papel da inflamação na patogênese de desordens metabólicas, sendo a modulação da resposta inflamatória associada a quantidade e a qualidade dos ácidos graxos (AG) da dieta. Polimorfismos de nucleotídeo único (SNP) podem influenciar a relação entre AG e concentração plasmática de biomarcadores inflamatórios. Objetivo: Verificar a associação de SNP relacionados aos genes da adiponectina, Receptor do tipo Toll (TLR)-4, interleucina (IL)-1 e IL-6 e ingestão de lipídios com um padrão inflamatório sistêmico, baseado na concentração plasmática de onze biomarcadores inflamatórios em estudo de base populacional ISA-Capital. Metodologia: O presente estudo compreende adultos (20 a 59 anos) do estudo de base populacional, ISA-capital 2008-2010 (n=302). A coleta dos dados dietéticos foi realizada por meio de recordatório de 24 horas, aplicado em duplicata. A partir do plasma, foram determinadas as concentrações plasmáticas de adiponectina, proteína C reativa (PCR), IL-1, IL-6, IL-8, IL-10, fator de necrose tumoral-alfa, IL- 12p70, Quimiocina C-C motif ligante (CCL) 2, 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 (AG) do plasma por cromatografia gasosa. A partir do DNA genômico foi realizada a genotipagem dos SNP relacionados aos genes da adiponectina (rs266729, rs17300539, rs16861209, rs1501299 e rs2241766), TLR4 (rs4986790, rs4686791, rs5030728, rs11536889), IL-1 (rs1143623, rs16944, rs1143627, rs1143634 e rs1143643) e da IL-6 (rs1800795, rs1800796, rs1800797) pelo sistema Taqman Open Array. Uma análise multivariada de Cluster (k-means) foi realizada para separar os indivíduos legíveis entre grupo inflamado (INF), n=93, e grupo não inflamado (NINF),n=169, segundo a concentração plasmática dos onze 8 biomarcadores inflamatórios avaliados. Resultados: Todos os SNP estavam em equilíbrio de Hardy-Wienberg (n=301). O INF apresentou idade, circunferência da cintura, pressão arterial e concentrações de triacilgliceróis sanguíneo estatisticamente maiores que aqueles observados para o NINF. O INF apresentou concentração plasmática de AG palmítico (C16:0), razões AG saturados (AGS)/AG ômega-6 (n-6) e AGS/ AG poli-insaturados (AGPI) e atividade estimada da enzima estearoil CoA desaturase aumentadas e concentrações plasmática de AGPI, n-6 e AG araquidônico (AA) e atividade estimada da enzima delta-5-dessaturase (D5D) reduzidas em comparação com o NINF. Interações SNP-AG plasmáticos estatisticamente significantes para predisposição ao padrão inflamatório sistêmico foram detectadas entre o SNP +6054 G>A (rs1143643) do gene da IL-1 e os AG esteárico, AA e AGPI e atividade estimada da enzima delta-6-desaturase (D6D); entre o SNP +3725 G>C (rs11536889) do gene do TLR-4 e a razão AA/AG eicosapentaenoico (EPA); entre o SNP +45 T>G (rs2241766) do gene da adiponectina e o AG ômega-3 (n-3); entre o SNP -7734 C>A (rs16861209) do gene da adiponectina e AA; e entre o SNP -11391 G>A (rs17300539) do gene da adiponectina e AGS. Conclui-se que algumas frações dos AG do plasma podem modular a inflamação e que SNP localizados nos genes da adiponectina, TLR-4, IL- 1 e IL-6 podem interagir com as frações de AG do plasma influenciando a chance de desenvolver uma inflamação sistêmica. / Introduction: Experimental, epidemiological and clinical evidences point to a pathogenic role of inflammation on metabolic disorders development, and to the relationship between this inflammatory response and the quantity and quality of dietary fatty acids. Single Nucleotide Polymorphisms (SNP) can modulate the relationship between fatty acids and plasma inflammatory biomarkers levels. Objective: To verify the association between SNP in the genes of adiponectin, TLR- 4, IL-1 and IL-6 and dietary fatty acids and their effects to a systemic inflammatory pattern at a population-based study ISA-Capital. Methods: This study sample was composed by adults (20 to 59 years), participants of the population-based study ISAcapital 2008-2010 (n=302). Dietary data was collected using two 24 hours dietary recall. Plasma concentration of adiponectin, C reactive protein, IL-1, IL-6, IL-8, IL- 10, tumor necrosis factor-alfa, IL-12p70, Chemokine C-C motif ligand (CCL) 2, soluble intercellular adhesion molecule (sICAM)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 was determined by multiplex immunoassay. Plasma FA profile was determined by gas chromatography. SNP from adiponectin (rs266729, rs17300539, rs16861209, rs1501299 e rs2241766), TLR4 (rs4986790, rs4686791, rs5030728, rs11536889), IL-1 (rs1143623, rs16944, rs1143627, rs1143634 e rs1143643) and IL-6 (rs1800795, rs1800796, rs1800797) gene were genotyped by Taqman Open Array system. A Cluster multivariate analysis (k-means) was conducted to separate individual into inflammatory group (INF), n=93, and noninflammatory group (NINF), n=169, according to eleven inflammatory biomarkers plasma levels. Results: All the SNP were in Hardy-Weinberg equilibrium (n=301). INF had statistically higher age, waist circumference, blood pressure and plasma tryglicerides concentration than NINF. INF presented statistically higher plasma palmitic acid (C16:0) levels, saturated fatty acid (SFA)/omega-6 fatty acid (n-6) ratio and SFA/polyunsaturated fatty acid (PUFA) ratio and estimated stearoil CoA 10 desaturase activity, and statistically lower plasma PUFA, n-6 and arachidonic acid e (AA) and estimate delta-5-desaturase (D5D) activity in comparison to NINF. Statistically significant SNP-plasma fatty acid interactions were found between SNP +6054 G>A (rs1143643) of IL-1 gene and stearic acid, AA and PUFA and estimate delta-6-desaturase (D6D) activity; between SNP +3725 G>C (rs11536889) of TLR-4 gene and AA/eicosapentaenoic acid (EPA) ratio; between SNP +45 T>G (rs2241766) of adiponectin gene and omega-3 fatty acid (n-3); between SNP -7734 C>A (rs16861209) of adiponectin gene and AA; and between SNP -11391 G>A (rs17300539) of adiponectin gene and SFA. In conclusion, some plasma fatty acid subfractions can modulate inflammation and SNP of adiponectin, TLR-4, IL-1 and IL-6 genes can interact with plasma fatty acids to modulate the chance to develop systemic inflammation.

The micronutrient selenium is essential to human physiology. As the amino acid selenocysteine, it is inserted into selenoproteins with a wide range of functions including antioxidant capacity, thyroid hormone metabolism, improvement of immune system, brain function, fertility and reproduction. Low selenium status has been associated with increased risk for chronic diseases, such as cancer, type-2 diabetes and cardiovascular disease. In this context, several studies have been conducted in order to investigate if selenium supplementation could reduce the risk of such diseases. However, genetic variations may interfere in the response of individuals to a dietary intervention and must be considered as a important source of inter-individual variation. Therefore, this study was conducted was conducted to investigate the influence of genetic variations in selenoproteins genes on the response to an intervention with Brazil nuts, the richest source of selenium known in nature. The study included 130 healthy volunteers with both genders, aged 20 to 60 years old selected in University of São Paulo. They received nuts for 8 weeks, eating one nut a day, and did a washout period for more 8 weeks. All volunteers had a blood sampling collection every 4 weeks during 4 months, in a total of 5. The following analysis were done: anthropometric measurements, lipid profile, plasma malondialdehyde, plasma and erythrocyte Se, selenoprotein P, plasma and erythrocyte GPx activity, gene expression of GPX1, SEPP1, SELS and SEP15. The volunteers were also genotyped for SNPs rs1050450, rs3811699, rs1800699, rs713041, rs3877899, rs7579, rs34713741 and rs5845. Each unit of Brazil nut provided an average of 300 &#181;g of selenium. All 130 volunteers completed the protocol. The concentrations of total cholesterol and glucose decreased after 8 weeks of supplementation. Moreover, HDL concentrations were higher for carriers of the variant T allele for GPX4_rs713041. The frequencies of the variant genotypes were 5,4% for rs1050450, rs3811699 e rs1088668, 10% for rs3877899, 19,2% for rs713041 e rs7579, 11,5% for rs5845 and 8,5% for rs34713741. The levels of the five biomarkers increased significantly after supplementation. In addition, erythrocyte GPx activity was influenced by rs1050450, rs713041 and rs5845; erythrocyte selenium was influenced by rs5845 and plasma selenium by rs3877899. Gene expression of GPX1, SEPP1 and SEP15 were higher after supplementation. The SNP rs1050450 influenced GPX1 mRNA expression and rs7579 influenced SEPP1 mRNA expression. Therefore, it can be concluded that the supplementation with one of Brazil nut for 8 weeks was efficient to reduce total cholesterol and glucose levels and to increase the concentrations of the main biomarkers of selenium status in healthy adults. Furthermore, our results suggest that GPX4_rs713041 might interfere on HDL concentrations and GPx1 activity, GPX1_rs1050450 might interfere on GPx1 activity, SEP15_rs5845 might interfere on GPx1 activity and erythrocyte selenium and SEPP1_3877899 might interfere on plasma Se levels. Therefore, the effect of genetic variations should be considered in future nutritional interventions evaluating the response to Brazil nut supplementation. / O micronutriente selênio é essencial para a fisiologia humana, inserido nas selenoproteínas na forma do aminoácido selenocisteína. As selenoproteínas são importantes para a função antioxidante, controle do metabolismo dos hormônios tireoidianos, melhora do sistema imune, função cerebral, fertilidade e reprodução. O estado nutricional de selênio deficiente ou marginal está associado com aumento do risco de doenças crônicas, como câncer, diabetes e doença cardiovascular. Sendo assim, diversos estudos procuraram investigar se a suplementação com selênio poderia reduzir o risco dessas doenças. Entretanto, as variações genéticas podem afetar a resposta dos indivíduos a uma intervenção dietética. Portanto, esse estudo foi conduzido para investigar a influência de variações genéticas em genes de selenoproteínas na resposta à suplementação com castanha-do-brasil, melhor fonte de selênio da natureza. Participaram do estudo 130 adultos de ambos os gêneros, com idade de 20 a 60 anos, selecionados na Universidade de São Paulo. Os indivíduos receberam castanhas suficientes para 8 semanas, ingerindo uma unidade por dia e, após o período de suplementação realizaram um período de washout também por 8 semanas. Todos realizaram cinco coletas de material biológico a cada quatro semanas. Foram realizadas medidas antropométricas, perfil lipídico, malondialdeído (MDA), concentração de selênio e selenoproteína P no plasma, eritrócitos, atividade da GPx eritrocitária e plasmática, expressão gênica da GPX1, SEPP1, SELS e SEP15. Além disso, os participantes foram genotipados para os SNPs rs1050450, rs3811699, rs1800699, rs713041, rs3877899, rs7579, rs34713741 e rs5845. Cada unidade de castanha forneceu em média 350&#181;g de selênio. Todos os 130 voluntários concluíram o estudo. As concentrações de glicose e colesterol total diminuíram após 8 semanas de suplementação. Além disso, as concentrações de HDL-c foram influenciadas pelo SNP rs713041 no gene da GPX4, sendo os valores mais altos encontrados para os indivíduos com o alelo variante T (CT+TT). As frequências dos genótipos variantes foram 5,4% para rs1050450, rs3811699 e rs1088668, 10% para rs3877899, 19,2% para rs713041 e rs7579, 11,5% para rs5845 e 8,5% para rs34713741. Os níveis dos cinco biomarcadores aumentaram significativamente após a suplementação. Além disso, a atividade da GPx eritrocitária foi influenciada pelos rs1050450, rs713041 e rs5845, o selênio eritrocitário foi influenciado pelo rs5845 e o selênio plasmático pelo rs3877899. A expressão dos genes GPX1 e SEPP foram maiores após a suplementação. Tendo em vista esses resultados, conclui-se que a suplementação com uma unidade de castanha-do-brasil durante 8 semanas foi suficiente para reduzir as concentrações de colesterol e de glicose, e elevar as concentrações dos principais biomarcadores do estado nutricional de selênio. Além disso, observou-se que o polimorfismo rs713041 parece influenciar as concentrações de HDL-c e atividade da GPx1, o polimorfismo rs1050450 parece influenciar a atividade da GPx1, o polimorfismo rs5845 parece influenciar a atividade da GPx1 e o selênio eritrocitário e o polimorfismo rs3877899 parece influenciar a o selênio plasmático. Portanto, sugere-se considerar o perfil genético dos indivíduos em futuros estudos avaliando a resposta à suplementação com castanha-do-brasil no estado nutricional de selênio da população.

Animal studies have shown that chronic high consumption of saturated fat (SF) leads to hypothalamic inflammation and ultimately, alters appetite control. This has been shown to be partly due to an increase in the activity of the transcription factor Nuclear Factor-κB (NF-κB), a major regulator of the inflammatory response. The goal of the study was to first confirm the association between SF measurements and anthropometric traits, then to determine the association between single nucleotide polymorphisms (SNPs) in the NF-κB1 gene and body mass index (BMI) and waist circumference (WC), and finally, to test the interaction between variants in this gene and dietary SF and circulating saturated fatty acids (CSFA) on these anthropometric traits in young adults. A significant positive association was identified between quartiles of CSFA and anthropometric measurements in the total sample (BMI: p = 0.0003, WC: p = 0.0001) and in South Asians (BMI: p = 0.004, WC: p = 0.01), but only marginally among Caucasians (BMI: p = 0.08, WC: p = 0.051) and East Asians (BMI: p = 0.13, WC: p = 0.053). After correcting for false discovery rate, carriers of the T allele in SNP rs4648022 had higher BMI and WC compared to those with the dominant CC genotype (p = 0.0003 and p = 0.0001, respectively). Among Caucasians, there was a significant interaction between SNPs in the NF-κB1 gene and quartiles of CSFA on WC for rs4648095 (p = 0.002). Thus, certain SNPs in the NF-κB1 gene appear to influence BMI and WC and also to modify the association between CSFA and anthropometric traits.