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1.
Lifestyle Genom ; : 1-10, 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30472712

RESUMO

BACKGROUND: Metabolic syndrome (MetS) comprises a cluster of risk factors including central obesity, hypertension, dyslipidemia, and impaired glucose homeostasis. Lifestyle interventions that promote improvements in diet quality and physical activity represent a first line of therapy for MetS. However, varying responses to lifestyle interventions are well documented and may be partially explained by underlying genetic differences. The aim of this study was to investigate if variants in genes previously associated with MetS influence the magnitude of change in MetS risk during a 1-year lifestyle intervention. METHODS: The present study used data collected from the Canadian Health Advanced by Nutrition and Graded Exercise study cohort (n = 159 men and women) to investigate the effect of 17 candidate single nucleotide polymorphisms (SNPs) on response to a 1-year lifestyle intervention. Associations between SNPs and the continuous MetS (cMetS) score, as well as individual MetS components, were examined. RESULTS: Reductions in cMetS score at both 3 months and 1 year were significantly associated with 2 variants: rs662799 (A/G) in apolipoprotein A5 (APOA5) and rs1501299 (G/T) in adiponectin (ADIPOQ). Individuals carrying a minor T allele in rs1501299 experienced a greater reduction in cMetS score at both 3 months and 1 year, whereas major allele AA homozygotes in rs662799 experienced greater reductions in cMetS score during the intervention. No associations were identified between the aforementioned SNPs and individual components of MetS. Both un-weighted and weighted genetic risk scores (GRS) using these 2 SNPs revealed that individuals carrying none of the risk alleles experienced significantly greater reductions in cMetS score after 1 year. CONCLUSIONS: The findings from the current study suggest that individuals with certain genotypes may benefit more from a lifestyle intervention for MetS and that specific variants, either independently or as part of a GRS, could be used as a nutrigenomic tool to tailor the intervention to reduce the risk of MetS.

2.
Can J Diet Pract Res ; 79(3): 106-112, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29546765

RESUMO

PURPOSE: To assess awareness of omega-3 fatty acids (FAs) and their possible health effects among young adults. METHODS: An online survey was deployed to young adults. Questionnaire development involved identification of topic areas by content experts and adaptation of questions from previous consumer surveys. Focus groups and cognitive interviews ensured face validity, feasibility, and clarity of survey questions. Degrees of awareness and self-reported consumption were assessed by descriptive statistics and associations by Cochran's Q tests, Pearson's χ2 tests, Z-tests, and logistic regression. RESULTS: Of the 834 survey completers (aged 18-25 years), more respondents recognized the abbreviations EPA (∼51%) and DHA (∼66%) relative to ALA (∼40%; P ≤ 0.01). Most respondents (∼83%) recognized that EPA and DHA have been linked to heart and brain health. Respondents who used academic/reputable sources, healthcare professionals, and/or social media to obtain nutritional information were more likely to report awareness of these health effects (P ≤ 0.01). Finally, 48% of respondents reported purchasing or consuming omega-3 foods, while 21% reported taking omega-3 supplements. CONCLUSIONS: This baseline survey suggests a high level of awareness of some aspects of omega-3 fats and health in a sample of young adults, and social media has become a prominent source of nutrition and health information.

3.
Lipids ; 52(12): 969-980, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29080057

RESUMO

Blood lipids are associated with cardiovascular disease (CVD) risk. Moreover, circulating lipid and fatty acid levels vary between men and women, and evidence demonstrates these traits may be influenced by single nucleotide polymorphisms (SNP). Sex-genotype interactions related to blood lipids and fatty acids have been poorly investigated and may help elucidate sex differences in CVD risk. The goal of this study was to investigate if the influence of SNPs previously associated with blood lipids and fatty acids varies in a sex-specific manner. Lipids and fatty acids were measured in serum and red blood cells (RBC), respectively, in 94 adults (18-30 years) from the GONE FISHIN' cohort and 118 age-matched individuals from the GOLDN cohort. HDL-c levels were higher and the total cholesterol/HDL-c (TC/HDL-c) ratio was lower in women versus men (p < 0.01). RBC palmitoleic acid and the stearoyl-CoA desaturase index were both higher in women (p < 0.01). Fatty acid desaturase (FADS) pathway activity (estimated using the ratio of eicosapentaenoic acid/alpha-linolenic acid) was higher in men (p < 0.01). The AA genotype for rs1800775 in CETP had a lower TC/HDL-c ratio in men, but not women (p int = 0.03). Independent of sex, major alleles for rs174537 in FADS1 (GG) and rs3211956 in CD36 (TT) had higher arachidonic acid, lower dihomo-γ-linoleic acid, and a higher FADS1 activity compared to minor alleles. The current study showed that blood lipid and fatty acid levels vary between healthy young men and women, but that the observed sex differences are not associated with common variants in candidate lipid metabolism genes.


Assuntos
HDL-Colesterol/sangue , Colesterol/sangue , Ácidos Graxos Monoinsaturados/sangue , Redes Reguladoras de Genes , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Antígenos CD36/genética , Proteínas de Transferência de Ésteres de Colesterol/genética , Estudos de Coortes , Ácidos Graxos Dessaturases/genética , Feminino , Humanos , Masculino , Caracteres Sexuais , Estearoil-CoA Dessaturase/genética , Adulto Jovem
4.
Nutrients ; 9(3)2017 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-28272299

RESUMO

Nutrigenetics research is anticipated to lay the foundation for personalized dietary recommendations; however, it remains unclear if providing individuals with their personal genetic information changes dietary behaviors. Our objective was to evaluate if providing information for a common variant in the fatty acid desaturase 1 (FADS1) gene changed omega-3 fatty acid (FA) intake and blood levels in young female adults (18-25 years). Participants were randomized into Genetic (intervention) and Non-Genetic (control) groups, with measurements taken at Baseline and Final (12 weeks). Dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was assessed using an omega-3 food frequency questionnaire. Red blood cell (RBC) FA content was quantified by gas chromatography. Implications of participation in a nutrigenetics study and awareness of omega-3 FAs were assessed with online questionnaires. Upon completion of the study, EPA and DHA intake increased significantly (p = 1.0 × 10-4) in all participants. This change was reflected by small increases in RBC %EPA. Participants in the Genetic group showed increased awareness of omega-3 terminology by the end of the study, reported that the dietary recommendations were more useful, and rated cost as a barrier to omega-3 consumption less often than those in the Non-Genetic group. Providing participants FADS1 genetic information did not appear to influence omega-3 intake during the 12 weeks, but did change perceptions and behaviors related to omega-3 FAs in this timeframe.


Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Dessaturases/genética , Nutrigenômica , Adolescente , Adulto , Alelos , Dieta , Eritrócitos/química , Feminino , Técnicas de Genotipagem , Humanos , Polimorfismo de Nucleotídeo Único , Inquéritos e Questionários , Adulto Jovem
5.
Appl Physiol Nutr Metab ; 42(3): 333, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28186827

RESUMO

From a global health perspective, increased intake of omega-3 fatty acids (FAs), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for human health. However, the consumption of EPA- and DHA-rich foods such as fatty fish is low in the Western diet. Therefore, finding new ways to motivate people to increase their consumption of omega-3 FAs is essential. To find effective ways to motivate individuals, understanding people's awareness of omega-3 FAs and how they obtain their knowledge about nutrition and health is critical. Consequently, we developed an online survey to assess awareness and self-reported intake of omega-3 FAs and supplements in young adults. EPA and DHA are also produced endogenously to a limited extent through a pathway regulated by fatty acid desaturase 1 and 2 (FADS1 and FADS2) genes. Of relevance, single nucleotide polymorphisms (SNPs) in the FADS genes influence levels of omega-3 FAs, where minor allele carriers have lower levels compared with major allele carriers. Accordingly, we conducted a clinical trial to investigate FA levels in response to dietary EPA and DHA supplementation in young adults stratified by SNPs in FADS1 and FADS2. The level of reported awareness of omega-3 terminology varied depending on an individual's field of study and thus providing all participants with the same set of nutrition information could be an effective tool to increase knowledge and motivate behaviour change. Additionally, the variation in FA levels in accordance to SNPs in FADS1 and FADS2 could be used to create tailored nutritional recommendations which may improve lifestyle habits. The results discovered in the first 2 studies regarding awareness of omega-3 FAs and genetic variation were subsequently used to design a nutrigenetics intervention in young adults. Individuals who received their FADS1 genetic information were more aware of different omega-3 FAs and reported fewer barriers to their consumption by the end of the study, compared with those who did not receive their personal genetic information. All participants increased their intake of EPA and DHA, which was reflected in the analyses of red blood cells. Overall, this thesis demonstrates the power of combining nutritional and genetic information as motivators to increase omega-3 consumption.

6.
PLoS One ; 12(2): e0172576, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28212390

RESUMO

Fish oil (FO) has been shown to have beneficial effects in the body via incorporation into the membranes of many tissues. It has been proposed that omega-3 fatty acids in FO may increase whole body resting metabolic rate (RMR) and fatty acid (FA) oxidation in human subjects, but the results to date are equivocal. The purpose of this study was to investigate the effects of a 12 week FO supplementation period on RMR and substrate oxidation, in comparison to an olive oil (OO) control group, in young healthy males (n = 26; 22.8 ± 2.6 yr). Subjects were matched for age, RMR, physical activity, VO2max and body mass, and were randomly separated into a group supplemented with either OO (3 g/d) or FO containing 2 g/d eicosapentaenoic acid (EPA) and 1 g/d docosahexaenoic acid (DHA). Participants visited the lab for RMR and substrate oxidation measurements after an overnight fast (10-12 hr) at weeks 0, 6 and 12. Fasted blood samples were taken at baseline and after 12 weeks of supplementation. There were significant increases in the EPA (413%) and DHA (59%) levels in red blood cells after FO supplementation, with no change of these fatty acids in the OO group. RMR and substrate oxidation did not change after supplementation with OO or FO after 6 and 12 weeks. Since there was no effect of supplementation on metabolic measures, we pooled the two treatment groups to determine whether there was a seasonal effect on RMR and substrate oxidation. During the winter season, there was an increase in FA oxidation (36%) with a concomitant decrease (34%) in carbohydrate (CHO) oxidation (p < 0.01), with no change in RMR. These measures were unaffected during the summer season. In conclusion, FO supplementation had no effect on RMR and substrate oxidation in healthy young males. Resting FA oxidation was increased and CHO oxidation reduced over a 12 week period in the winter, with no change in RMR. TRIAL REGISTRATION: ClinicalTrials.gov NCT02092649.


Assuntos
Metabolismo Basal/efeitos dos fármacos , Óleos de Peixe/farmacologia , Adulto , Metabolismo dos Carboidratos/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Ácidos Graxos/sangue , Voluntários Saudáveis , Humanos , Masculino , Azeite de Oliva/farmacologia , Oxirredução , Estações do Ano
7.
Appl Physiol Nutr Metab ; 41(7): 791-4, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27144909

RESUMO

Considerable evidence supports an association between fatty acid desaturase 2 (FADS2) polymorphisms and the efficiency of converting alpha-linolenic acid (ALA) into eicosapentaenoic acid (EPA) via the desaturation-elongation pathway. However, ALA conversion into EPA represents only 1 of the metabolic fates for this essential fatty acid, as ALA is also highly oxidized. This study demonstrates for the first time that genetic variation in FADS2 (rs174576) is not only associated with the activity of the desaturation-elongation pathway, but also whole-body fat oxidation.


Assuntos
Ácidos Graxos Dessaturases/genética , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Descanso/fisiologia , Ácido Eicosapentaenoico/química , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Adulto Jovem , Ácido alfa-Linoleico/química
8.
Mol Nutr Food Res ; 60(3): 631-41, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26679630

RESUMO

SCOPE: Increased consumption of fish oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with improved cardiometabolic health and inflammatory status; however, age-related responses remain poorly described. METHODS AND RESULTS: In a placebo-controlled study, healthy young and older men consumed five fish oil capsules daily, providing 2.0 g/d EPA and 1.0g/d DHA, for three months. Both young and older men experienced a ∼30% reduction in blood triglycerides with fish oil supplementation. A significant group × time interaction was observed for DHA, with young men experiencing a ∼twofold increase in DHA in serum and RBCs, while older men showed negligible increases. Other fatty acids were differentially regulated between young and older men, most notably osbond acid and several saturates. Small changes were observed in serum oxylipins, with both groups of men responding similarly: 5-HETE was reduced, while PGF2α and 17-HDoHE were increased. Changes in oxylipins occurred independent of changes in whole blood expression of key genes regulating oxylipin production. CONCLUSION: Our study suggests that both young and older men experience the triglyceride-lowering benefits associated with fish oil supplements, but show differential responses in blood fatty acids. Additionally, fish oil promotes an improved oxylipin profile in both groups of men.


Assuntos
Ácidos Graxos/sangue , Óleos de Peixe/farmacologia , Oxilipinas/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Nutr Metab (Lond) ; 12: 14, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25914723

RESUMO

BACKGROUND: There is great interest in the relationship between polyunsaturated fatty acids and health. Yet, the combinatory effect of factors such as sex, ethnicity, genetic polymorphisms and hormonal contraceptives (HC) on the concentrations of these fatty acids is unknown. Therefore, we sought to determine the effects of FADS polymorphisms, and HC use in females, on aggregate desaturase indices (ADI), and plasma docosahexaenoic acid (DHA) concentrations in Caucasian and East Asian males and females. METHODS: Fasting plasma samples were collected from subjects (Caucasian males: 113 and females: 298; East Asian males: 98 and females: 277) from the Toronto Nutrigenomics and Health Study. Fatty acid concentrations were measured by gas chromatography. ADI were estimated by dividing concentrations of arachidonic acid by linoleic acid (n-6 ADI) and eicosapentaenoic acid (EPA) by α-linolenic acid (n-3 ADI). [DHA/EPA] desaturase index was used to determine effects of FADS2 polymorphisms and HC use on EPA conversion to DHA. RESULTS: In Caucasians, associations between n-6 ADI and multiple SNP (FADS1 rs174547, FADS2 rs174576, and rs174611 in males; FADS1 rs174547, FADS2 rs174570, rs174576, rs174679, rs174611, rs174593, rs174626, rs2072114, rs2845573, and rs2851682 in females) withstood multiple testing. In East Asian females, 5 SNP-n-6 ADI associations (FADS2 rs174602, rs174626, rs2072114, rs2845573, and rs2851682) withstood multiple testing. One FADS2 SNP was associated with altered [DHA/EPA] desaturase index in Caucasian females only (rs174576, p < 0.0001). HC use had a significant effect on DHA concentrations in Caucasian females only (P < 0.0001). CONCLUSIONS: We demonstrate ethnic- and sex-specific effects of FADS polymorphisms on desaturase indices, and ethnic-specific effect of HC use on plasma DHA concentrations.

10.
Nutrients ; 6(6): 2290-304, 2014 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-24936800

RESUMO

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3) fatty acids (FAs) known to influence cardiometabolic markers of health. Evidence suggests that single nucleotide polymorphisms (SNPs) in the fatty acid desaturase 1 and 2 (FADS1/2) gene cluster may influence an individual's response to n-3 FAs. This study examined the impact of a moderate daily dose of EPA and DHA fish oil supplements on cardiometabolic markers, FA levels in serum and red blood cells (RBC), and whether these endpoints were influenced by SNPs in FADS1/2. Young adults consumed fish oil supplements (1.8 g total EPA/DHA per day) for 12 weeks followed by an 8-week washout period. Serum and RBC FA profiles were analyzed every two weeks by gas chromatography. Two SNPs were genotyped: rs174537 in FADS1 and rs174576 in FADS2. Participants had significantly reduced levels of blood triglycerides (-13%) and glucose (-11%) by week 12; however, these benefits were lost during the washout period. EPA and DHA levels increased significantly in serum (+250% and +51%, respectively) and RBCs (+132% and +18%, respectively) within the first two weeks of supplementation and remained elevated throughout the 12-week period. EPA and DHA levels in RBCs only (not serum) remained significantly elevated (+37% and +24%, respectively) after the washout period. Minor allele carriers for both SNPs experienced greater increases in RBC EPA levels during supplementation; suggesting that genetic variation at this locus can influence an individual's response to fish oil supplements.


Assuntos
Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos/sangue , Óleos de Peixe/farmacologia , Adolescente , Adulto , Biomarcadores , Suplementos Nutricionais , Ácidos Graxos Dessaturases/genética , Óleos de Peixe/administração & dosagem , Regulação da Expressão Gênica , Genótipo , Humanos , Masculino , Polimorfismo Genético , Adulto Jovem
11.
Lipids ; 49(3): 255-63, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24338596

RESUMO

Inflammation is a recognized risk factor for the development of chronic diseases, such as type 2 diabetes and atherosclerosis. Evidence suggests that individual fatty acids (FA) may have distinct influences on inflammatory processes. The goal of this study was to conduct a cross-sectional analysis to examine the associations between circulating FA and markers of inflammation in a population of young healthy Canadian adults. FA, high-sensitivity C-reactive protein (hsCRP), and cytokines were measured in fasted plasma samples from 965 young adults (22.6 ± 0.1 years). Gas chromatography was used to measure FA. The following cytokines were analyzed with a multiplex assay: regulated upon activation normal T cell expressed and secreted (RANTES/CCL5), interleukin 1-receptor antagonist (IL-1Ra), interferon-γ (IFN-γ), interferon-γ inducible protein 10 (IP-10), and platelet-derived growth factor ß (PDGF-ßß). Numerous statistically significant associations (p < 0.05, corrected for multiple testing) were identified between individual FA and markers of inflammation using linear regression. Myristic (14:0), palmitic (16:0), palmitoleic (16:1n-7), and dihomo-γ-linolenic (20:3n-6) acids were positively associated with all markers of inflammation. In contrast, stearic acid (18:0) was inversely associated with hsCRP and RANTES, and linoleic acid (18:2n-6) was inversely associated with hsCRP, RANTES and PDGF-ßß. In conclusion, our results indicate that specific FA are distinctly correlated with various markers of inflammation. Moreover, the findings of this study suggest that FA profiles in young adults may serve as an early indicator for the development of future complications comprising an inflammatory component.


Assuntos
Biomarcadores/sangue , Inflamação/sangue , Lipídeos/sangue , Adulto , Cromatografia Gasosa , Feminino , Humanos , Masculino , Adulto Jovem
12.
Artigo em Inglês | MEDLINE | ID: mdl-23867726

RESUMO

INTRODUCTION: Past research has reported that single nucleotide polymorphisms (SNPs) in fatty acid desaturase 1 and 2 (FADS1/2) can influence plasma fatty acid (FA) profiles. Changes in FA profiles are known to influence inflammatory processes; therefore both FA and SNPs in FADS1/2 may affect inflammation. The goals of this study were to (i) examine the relationships between individual n-6 FA and estimates of FA desaturation with circulating high sensitivity C-reactive protein (hsCRP) levels, and (ii) determine whether SNPs in FADS1/2 are associated with changes in hsCRP. METHODS: FA and hsCRP were measured in fasted plasma samples from 878 healthy young adults (20-29yrs). Circulating levels of plasma linoleic (LA), γ-linolenic (GLA), dihomo-γ-linolenic (DGLA) and arachidonic (AA) acids were measured by gas chromatography and used to calculate desaturase indices for FADS1/2. Nineteen SNPs in FADS1/2 were genotyped in all subjects and six (rs174579, rs174593, rs174626, rs526126, rs968567 and rs17831757) were further analyzed. RESULTS: Significant inverse associations were found between LA and hsCRP (p=8.55×10(-9)) and the FADS1 desaturase index and hsCRP (p=4.41×10(-6)). A significant positive association was found between DGLA and hsCRP (p=9.10×10(-11)). Several SNPs were associated with circulating levels of individual FA and desaturase indices, with minor allele carriers having lower AA levels and reduced desaturase indices. A single SNP in FADS2 (rs526126) was weakly associated with hsCRP (p=0.05). CONCLUSIONS: This study highlights the relationships between FA and hsCRP, and confirms that FA are strongly influenced by SNPs in FADS1/2. Furthermore, we found weak evidence that SNPs in FADS1/2 may influence hsCRP levels in young adults.


Assuntos
Proteína C-Reativa/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Ômega-6/sangue , Adulto , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Voluntários Saudáveis , Humanos , Masculino , Família Multigênica , Polimorfismo de Nucleotídeo Único , Adulto Jovem
13.
Nutr Metab (Lond) ; 10: 50, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23866021

RESUMO

BACKGROUND: The conjugated linoleic acid isomer cis9trans11 CLA can be endogenously synthesized from trans vaccenic acid (C18:1 t11) via desaturation at the delta 9 position catalyzed by the stearoyl-CoA desaturase 1 (SCD1), also known as delta-9 desaturase (D9D). Diet, hormonal regulation of gene expression and single nucleotide polymorphisms (SNPs) have been implicated in altering circulating levels of fatty acids. Hormonal contraceptives (HC) have also been shown to influence levels of some fatty acids. SNPs in SCD1 have been associated with altered levels of palmitoleic and oleic acids; however, associations between SCD1 SNPs and D9D desaturation index have not been previously examined in relation to CLA. Herein, we investigated the effects of sex and HC use on circulating concentrations of c9t11 CLA and D9D desaturation index. Furthermore, we determined the effects of ten SCD1 SNPs on D9D desaturation indices estimated by product to precursor ratio of c9t11 CLA to C18:1 t11. METHODS: PLASMA SAMPLES WERE COLLECTED FROM SUBJECTS (CAUCASIAN MALES: n = 113; Caucasian females: n = 298; Asian males: n = 98; Asian females: n = 277) from the Toronto Nutrigenomics and Health Study. Circulating fatty acids levels were measured by gas chromatography. RESULTS: Results show that circulating c9t11 CLA concentrations are significantly higher in females than males and they are further elevated in females using HC. In addition, a significant sex- and ethnic-specific association was found between SCD1 SNP rs10883463 (p = 0.0014) and altered D9D activity in Caucasian males. CONCLUSION: Findings from the present study identify SCD1 SNPs and hormonal contraceptives as factors altering endogenous c9t11 CLA levels in a sex- and ethnic-specific manner.

14.
Nutr Metab (Lond) ; 9(1): 102, 2012 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-23158971

RESUMO

BACKGROUND: Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. METHODS: Participants (n = 1,007) from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson's correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates. RESULTS: We observed weak micronutrient-cytokine correlations, moderate correlations between certain cytokines, and strong correlations between specific cytokines, particularly interleukin 1- receptor antagonist (IL-1RA), interferon-γ (IFN-γ), and platelet-derived growth factor BB (PDGF-bb). After full covariate adjustment, circulating α-tocopherol was inversely associated with IFN-γ and regulated upon activation normal T-cell expressed and secreted (RANTES). We observed an unexpected positive association between ascorbic acid and IFN-γ. 25(OH)D was not associated with altered concentrations of any inflammatory biomarkers. CONCLUSIONS: These findings suggest that α-tocopherol, but not ascorbic acid or 25(OH)D, is inversely associated with inflammation in healthy young adults.

15.
Mol Genet Metab ; 105(3): 421-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22209225

RESUMO

Fatty acids (FA) represent a diverse class of molecules known to regulate inflammatory pathways. Therefore enzymes that regulate FA metabolism are attractive candidates to better understand the relationship between FA and inflammation. Stearoyl-CoA desaturase 1 (SCD1) is rate limiting for the conversion of saturated FA (SFA) to monounsaturated FA (MUFA). Evidence suggests that SCD1 activity may be positively associated with inflammation. Moreover, genetic variation in SCD1 may alter enzyme activity; however, it is unknown whether this affects inflammatory status. The goal of this study was to examine the relationships between plasma FA, SCD1 activity, and SCD1 polymorphisms with C-reactive protein (CRP) levels in young adults. SFA, MUFA, and CRP were measured in fasted plasma samples from European (n=279, 198 female and 81 male) and Asian (n=249, 179 female and 70 male) subjects, 20-29 years old. Circulating levels of palmitic (16:0), palmitoleic (16:1), stearic (18:0), and oleic acids (18:1) were measured by gas chromatography and SCD1 activity was estimated by the ratio of product to precursor (16:1/16:0; 18:1/18:0). Positive associations were identified between CRP levels and 16:0 (p<2.0×10(-4)), 16:1 (p<0.05), and the SCD1 index (18:1/18:0; p<6.0×10(-3)) in European and Asian females, while 18:0 was inversely associated with CRP (p<2.0×10(-4)) in both groups. Ten single nucleotide polymorphisms (SNPs) in SCD1 were genotyped in all subjects. One SNP (rs2060792) was associated (p<0.05) with 16:0 and 18:0 levels in females of European descent. This same SNP was also associated with CRP levels in both groups of females (p<0.05). Overall, SCD1 activity and genetic variation have an important role in modulating the relationship between FA and inflammation in young adults.


Assuntos
Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Inflamação/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Adulto , Proteína C-Reativa/análise , Ácidos Graxos/imunologia , Ácidos Graxos Monoinsaturados/sangue , Feminino , Variação Genética , Genótipo , Humanos , Inflamação/imunologia , Metabolismo dos Lipídeos/genética , Masculino , Ácido Oleico/sangue , Ácido Palmítico/sangue , Polimorfismo de Nucleotídeo Único , Ácidos Esteáricos/sangue , Adulto Jovem
16.
Mol Genet Metab ; 103(2): 171-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21414826

RESUMO

Recent evidence indicates that genetic variation in fatty acid desaturases 1 and 2 (FADS1 and FADS2) is associated with changes in plasma fatty acid profiles; however, the association with altered desaturase activity has not been examined in different ethnic populations. The present study examined whether genetic variation in the FADS gene cluster regulates desaturase activity in two populations of young Canadian adults (Caucasian and Asian) and whether altered desaturase activity was reflected in both n-3 and n-6 fatty acid profiles. FADS1 and FADS2 were genotyped in a random subset of participants (Caucasian, n=78; Asian, n=69) from the Toronto Nutrigenomics and Health study using MALDI-TOF mass spectrometry, and plasma fatty acids were measured by gas chromatography. Desaturase activities were estimated using the following fatty acid ratios: γ-linoleic acid to linoleic acid (GLA:LA), arachidonic acid to linoleic acid (AA:LA), arachidonic acid to dihomo-γ-linoleic acid (AA:DGLA), and eicosapentaneoic acid to α-linolenic acid (EPA:ALA). Nineteen single nucleotide polymorphisms (SNPs) were examined, and several SNPs (9 in Caucasians and 8 in Asians) were associated with various desaturase activities. The most significant association detected was between the FADS1 rs174547 SNP and AA:LA in both Caucasians (p=4.0 × 10(-8)) and Asians (p=5.0 × 10(-5)). Although the minor allele for this SNP differed between Caucasians (T) and Asians (C), carriers of the C allele had a lower desaturase activity than carriers of the T allele in both groups. To determine whether rs174547 was a dominant SNP in the FADS gene cluster, we constructed an additional model which included this SNP as a covariate. Only one SNP (rs498793 in FADS2) remained associated with the EPA:ALA ratio (p=1.1 × 10(-5)) in Asians. This study shows that genetic variation in the FADS gene cluster (in particular rs174547) can alter desaturase activity in subjects of Caucasians and Asian descent.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Ativação Enzimática/genética , Ácidos Graxos Dessaturases/sangue , Ácidos Graxos/sangue , Feminino , Regulação Enzimológica da Expressão Gênica , Frequência do Gene/genética , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Adulto Jovem
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