Compensatory induction of Fads1 gene expression in heterozygous Fads2-null mice and by diet with a high n-6/n-3 PUFA ratio

Hang Su, Dan Zhou, Yuan Xiang Pan, Xingguo Wang, Manabu T. Nakamura

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)1995-2004
Number of pages10
JournalJournal of Lipid Research
Volume57
Issue number11
DOIs
StatePublished - 2016

Keywords

  • Brain lipids
  • Cytokines
  • Diet and dietary lipids
  • Fatty acid desaturase 1
  • Fatty acid desaturase 2
  • Fatty acid/desaturases
  • Fatty acid/elongases
  • Inflammation
  • Liver
  • Muscle
  • Omega-3 fatty acids
  • Polyunsaturated fatty acid

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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