Compensatory induction of Fads1 gene expression in heterozygous Fads2-null mice and by diet with a high n-6/n-3 PUFA ratio.
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.
State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, People's Republic of China.|Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Hang
H
Su
Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Dan
D
Zhou
Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
Yuan-Xiang
YX
Pan
State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, People's Republic of China mtnakamu@illinois.edu wxg1002@qq.com.
Xingguo
X
Wang
Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801 mtnakamu@illinois.edu wxg1002@qq.com.
Manabu T
MT
Nakamura
D000818:Animals; D016718:Arachidonic Acid; D000090943:Delta-5 Fatty Acid Desaturase; D004032:Diet; D004281:Docosahexaenoic Acids; D044943:Fatty Acid Desaturases / Q000096:biosynthesis / Q000235:genetics*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis
D000090943:Delta-5 Fatty Acid Desaturase; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human
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