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FADS1 genotype is distinguished by human subcutaneous adipose tissue fatty acids, but not inflammatory gene expression
SL. Klingel, A. Valsesia, A. Astrup, M. Kunesova, WHM. Saris, D. Langin, N. Viguerie, DM. Mutch,
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
Free Medical Journals
od 2005 do Před 5 lety
ProQuest Central
od 2005-01-01 do Před 1 rokem
Open Access Digital Library
od 1997-01-01
Health & Medicine (ProQuest)
od 2005-01-01 do Před 1 rokem
Psychology Database (ProQuest)
od 2005-01-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
- MeSH
- buněčná diferenciace genetika MeSH
- desaturasy mastných kyselin genetika metabolismus MeSH
- dospělí MeSH
- exprese genu MeSH
- genotyp MeSH
- imunitní systém MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- mastné kyseliny genetika MeSH
- metabolismus lipidů genetika MeSH
- multigenová rodina genetika MeSH
- multivariační analýza MeSH
- obezita genetika MeSH
- podkožní tuk metabolismus MeSH
- zánět genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Single nucleotide polymorphisms (SNPs) in FADS1/FADS2 genes are associated with changes in serum and tissue polyunsaturated fatty acid (PUFA) content. PUFA regulate inflammatory signaling pathways in adipose tissue; however, the effect of SNPs in FADS1/FADS2 on adipose tissue inflammation is equivocal. The present study examined if SNPs in FADS1/FADS2 modify human subcutaneous adipose tissue (SAT) fatty acid profiles and the expression of genes associated with inflammation/immune function, lipid metabolism, and cellular differentiation. METHODS: SAT fatty acids and the expression of 117 genes were measured in 174 men and women from the DiOGenes Study using gas chromatography and qRT-PCR, respectively. Associations between fatty acids, gene expression, and SNPs in FADS1/FADS2 were investigated by linear regression and multivariate analysis. RESULTS: Four SNPs (rs174537, rs174546, rs174556, rs174601) in FADS1/FADS2 were significantly associated with SAT fatty acids. All SNPs were in high linkage disequilibrium with the commonly reported rs174537 SNP in FADS1. Minor allele carriers for rs174537 (GT+TT) had reduced 20:4n-6 (p = 1.74E-5), lower delta-5 desaturase enzyme activity (p = 2.09E-9), and lower FADS1 gene expression (p = 0.03) compared to major GG carriers. Multivariate analysis revealed that 20:4n-6 and 20:3n-6 explained ~19% of the variance between rs174537 genotypes, while gene expression explained <7%. Receiver operating characteristic (ROC) curves indicated that rs174537 genotype can be distinguished with SAT fatty acids (AUC = 0.842), but not gene expression (AUC = 0.627). No differences in SAT inflammatory gene expression were observed between rs174537 genotypes. SAT 20:3n-6 levels were positively correlated with the expression of several inflammatory genes, and inversely correlated with FADS1 expression. CONCLUSION: This study showed that FADS1 genotype is distinguished by SAT fatty acid profiles, but not inflammatory gene expression.
Department of Human Health and Nutritional Sciences University of Guelph Guelph ON N1G 2W1 Canada
Department of Nutrition Exercise and Sports University of Copenhagen Copenhagen Denmark
Institute of Endocrinology Obesity Management Centre Prague Czech Republic
Citace poskytuje Crossref.org
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- $a Klingel, Shannon L $u Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, N1G 2W1, Canada.
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- $a FADS1 genotype is distinguished by human subcutaneous adipose tissue fatty acids, but not inflammatory gene expression / $c SL. Klingel, A. Valsesia, A. Astrup, M. Kunesova, WHM. Saris, D. Langin, N. Viguerie, DM. Mutch,
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- $a BACKGROUND: Single nucleotide polymorphisms (SNPs) in FADS1/FADS2 genes are associated with changes in serum and tissue polyunsaturated fatty acid (PUFA) content. PUFA regulate inflammatory signaling pathways in adipose tissue; however, the effect of SNPs in FADS1/FADS2 on adipose tissue inflammation is equivocal. The present study examined if SNPs in FADS1/FADS2 modify human subcutaneous adipose tissue (SAT) fatty acid profiles and the expression of genes associated with inflammation/immune function, lipid metabolism, and cellular differentiation. METHODS: SAT fatty acids and the expression of 117 genes were measured in 174 men and women from the DiOGenes Study using gas chromatography and qRT-PCR, respectively. Associations between fatty acids, gene expression, and SNPs in FADS1/FADS2 were investigated by linear regression and multivariate analysis. RESULTS: Four SNPs (rs174537, rs174546, rs174556, rs174601) in FADS1/FADS2 were significantly associated with SAT fatty acids. All SNPs were in high linkage disequilibrium with the commonly reported rs174537 SNP in FADS1. Minor allele carriers for rs174537 (GT+TT) had reduced 20:4n-6 (p = 1.74E-5), lower delta-5 desaturase enzyme activity (p = 2.09E-9), and lower FADS1 gene expression (p = 0.03) compared to major GG carriers. Multivariate analysis revealed that 20:4n-6 and 20:3n-6 explained ~19% of the variance between rs174537 genotypes, while gene expression explained <7%. Receiver operating characteristic (ROC) curves indicated that rs174537 genotype can be distinguished with SAT fatty acids (AUC = 0.842), but not gene expression (AUC = 0.627). No differences in SAT inflammatory gene expression were observed between rs174537 genotypes. SAT 20:3n-6 levels were positively correlated with the expression of several inflammatory genes, and inversely correlated with FADS1 expression. CONCLUSION: This study showed that FADS1 genotype is distinguished by SAT fatty acid profiles, but not inflammatory gene expression.
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