TY - JOUR
T1 - Compensatory induction of Fads1 gene expression in heterozygous Fads2-null mice and by diet with a high n-6/n-3 PUFA ratio
AU - Su, Hang
AU - Zhou, Dan
AU - Pan, Yuan Xiang
AU - Wang, Xingguo
AU - Nakamura, Manabu T.
N1 - Publisher Copyright:
Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.
PY - 2016
Y1 - 2016
N2 - 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 1:1, 7:1, and 44:1 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 44:1 diet, likely due to increased Fads1 mRNA in response to reduced Fads2 mRNA in HET Consistent with the RNA data, C20:3n-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.
AB - 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 1:1, 7:1, and 44:1 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 44:1 diet, likely due to increased Fads1 mRNA in response to reduced Fads2 mRNA in HET Consistent with the RNA data, C20:3n-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.
KW - Brain lipids
KW - Cytokines
KW - Diet and dietary lipids
KW - Fatty acid desaturase 1
KW - Fatty acid desaturase 2
KW - Fatty acid/desaturases
KW - Fatty acid/elongases
KW - Inflammation
KW - Liver
KW - Muscle
KW - Omega-3 fatty acids
KW - Polyunsaturated fatty acid
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U2 - 10.1194/jlr.M064956
DO - 10.1194/jlr.M064956
M3 - Article
C2 - 27613800
AN - SCOPUS:84993983923
SN - 0022-2275
VL - 57
SP - 1995
EP - 2004
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 11
ER -