Compensatory induction of Fads1 gene expression in heterozygous Fads2-null mice and by diet with a high n-6/n-3 PUFA ratio.
J Lipid Res
; 57(11): 1995-2004, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27613800
ABSTRACT
In mammals, because they share a single synthetic pathway, n-6/n-3 ratios of dietary PUFAs impact tissue arachidonic acid (ARA) and DHA content. Likewise, SNPs in the human fatty acid desaturase (FADS) gene cluster impact tissue ARA and DHA. Here we tested the feasibility of using heterozygous Fads2-null-mice (HET) as an animal model of human FADS polymorphisms. WT and HET mice were fed diets with linoleate/α-linolenate ratios of 11, 71, and 441 at 7% of diet. In WT liver, ARA and DHA in phospholipids varied >2× among dietary groups, reflecting precursor ratios. Unexpectedly, ARA content was only <10% lower in HET than in WT livers, when fed the 441 diet, likely due to increased Fads1 mRNA in response to reduced Fads2 mRNA in HET. Consistent with the RNA data, C203n-6, which is elevated in minor FADS haplotypes in humans, was lower in HET than WT. Diet and genotype had little effect on brain PUFAs even though brain Fads2 mRNA was low in HET. No differences in cytokine mRNA were found among groups under unstimulated conditions. In conclusion, differential PUFA profiles between HET mice and human FADS SNPs suggest low expression of both FADS1 and 2 genes in human minor haplotypes.
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MEDLINE
Assunto principal:
Ácidos Graxos Ômega-3
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Ácidos Graxos Dessaturases
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Ácidos Graxos Insaturados
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article