Tags

Type your tag names separated by a space and hit enter

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. 2016 11; 57(11):1995-2004.JL

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.

Authors+Show Affiliations

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.Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801.Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801.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.Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801 mtnakamu@illinois.edu wxg1002@qq.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

27613800

Citation

Su, Hang, et al. "Compensatory Induction of Fads1 Gene Expression in Heterozygous Fads2-null Mice and By Diet With a High N-6/n-3 PUFA Ratio." Journal of Lipid Research, vol. 57, no. 11, 2016, pp. 1995-2004.
Su H, Zhou D, Pan YX, et al. 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. 2016;57(11):1995-2004.
Su, H., Zhou, D., Pan, Y. X., Wang, X., & Nakamura, M. T. (2016). Compensatory induction of Fads1 gene expression in heterozygous Fads2-null mice and by diet with a high n-6/n-3 PUFA ratio. Journal of Lipid Research, 57(11), 1995-2004.
Su H, et al. 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. 2016;57(11):1995-2004. PubMed PMID: 27613800.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2016/09/09/ PY - 2015/11/04/received PY - 2016/11/3/pubmed PY - 2017/8/15/medline PY - 2016/9/11/entrez 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 SP - 1995 EP - 2004 JF - Journal of lipid research JO - J. Lipid Res. VL - 57 IS - 11 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. SN - 1539-7262 UR - https://www.unboundmedicine.com/medline/citation/27613800/Compensatory_induction_of_Fads1_gene_expression_in_heterozygous_Fads2_null_mice_and_by_diet_with_a_high_n_6/n_3_PUFA_ratio_ L2 - http://www.jlr.org/cgi/pmidlookup?view=long&amp;pmid=27613800 DB - PRIME DP - Unbound Medicine ER -