The FADS1 rs174550 Genotype Modifies the n-3 and n-6 PUFA and Lipid Mediator Responses to a High Alpha-Linolenic Acid and High Linoleic Acid Diets

Abstract

Scope: The fatty acid composition of plasma lipids, which is associated with biomarkers and risk of non-communicable diseases, is regulated by dietary polyunsaturated fatty acids (PUFAs) and variants of fatty acid desaturase (FADS). We investigated the interactions between dietary PUFAs and FADS1 rs174550 variant.

Methods and results: Participants (n = 118), homozygous for FADS1 rs174550 variant (TT and CC) followed a high alpha-linolenic acid (ALA, 5 percent of energy (E-%)) or a high linoleic acid (LA, 10 E-%) diet during an 8-week randomized controlled intervention. Fatty acid composition of plasma lipids and PUFA-derived lipid mediators were quantified by gas and liquid chromatography mass spectrometry, respectively. The high-LA diet increased the concentration of plasma LA, but not its lipid mediators. The concentration of plasma arachidonic acid decreased in carriers of CC and remained unchanged in the TT genotype. The high-ALA diet increased the concentration of plasma ALA and its cytochrome P450-derived epoxides and dihydroxys, and cyclooxygenase-derived monohydroxys. Concentrations of plasma eicosapentaenoic acid and its mono- and dihydroxys increased only in TT genotype carriers.

Conclusions: These findings suggest the potential for genotype-based recommendations for PUFA consumption, resulting in modulation of bioactive lipid mediators which can exert beneficial effects in maintaining health.

Keywords: FADS; alpha-linolenic acid; eicosanoid; eicosapentaenoic acid; linoleic acid; octadecanoid.

Figure 1

A) Metabolic pathway of n‐6 and n‐3 PUFAs. B) Study design and the main results of the study. Participants with FADS1 rs174550 TT and CC genotypes were randomized to receive either high‐LA or high‐ALA diet for 8 weeks. Direction of the changes in the concentration of plasma cholesteryl ester and phospholipid PUFAs and lipid mediator concentrations are illustrated with arrows, genotype (TT or CC) specific changes and shared changes in response to diets are separated.

Figure 2

Consort flow diagram.

Figure 3

Changes (%) in PUFA concentrations in plasma cholesteryl esters in the A) high‐LA and B) high‐ALA diets and plasma phospholipids in the C) high‐LA and D) high‐ALA diets. The dotted red line is set to 0% in each graph. Black asterisk (*) shows FDR corrected p‐values <0.05 within the study group changes (0 wk vs 8 wk) and p‐value on the right side the FDR corrected p‐values for genotype–diet interaction.

Figure 4

Changes in plasma A) EDA, B) DGLA, C) LA, and D) AA derived lipid mediator concentrations. Values are Cohen D values (0 wk vs 8 wk) and red and blue colors indicate increased and decreased concentrations, respectively. Black asterisk (*) shows FDR corrected p‐values <0.05 within the study group changes (0 wk vs 8 wk). Structural isomers of 11‐OH‐9,10‐epoxy‐LA are annotated as 1 and 2 and 9,10,13‐ and 9,12,13‐TriHOMEs as in ref. [30].

Figure 5

Changes in plasma A) ALA, B) EPA, and C) DHA derived lipid mediator concentrations. Values are Cohen D values (0 wk vs 8 wk) and red and blue colors indicate increased and decreased concentrations, respectively. Black asterisk (*) shows FDR corrected p‐values < 0.05 within the study group changes (0 wk vs 8 wk).