Abstract

IntroductionFatty acid desaturase 1 (FADS1) gene encodes for delta-5 desaturase enzyme which is needed in conversion of linoleic acid (LA) to arachidonic acid (AA). Recent studies have shown that response to dietary PUFAs differs between the genotypes in circulating fatty acids. However, interactions between the FADS1 genotype and dietary LA on overall metabolism have not been studied.ObjectivesWe aimed to examine the interactions of FADS1 rs174550 genotypes (TT and CC) and high-LA diet to identify plasma metabolites that respond differentially to dietary LA according to the FADS1 genotype.MethodsA total of 59 men (TT n = 26, CC n = 33) consumed a sunflower oil supplemented diet for 4 weeks. Daily dose of 30, 40, or 50 ml was calculated based on body mass index. It resulted in 17–28 g of LA on top of the usual daily intake. Fasting plasma samples at the beginning and at the end of the intervention were analyzed with LC–MS/MS non-targeted metabolomics method.ResultsAt the baseline, the carriers of FADS1 rs174550-TT genotype had higher abundance of long-chain PUFA phospholipids compared to the FADS1 rs174550-CC one. In response to the high-LA diet, LA phospholipids and long-chain acylcarnitines increased and lysophospholipids decreased in fasting plasma similarly in both genotypes. LysoPE (20:4), LysoPC (20:4), and PC (16:0_20:4) decreased and cortisol increased in the carriers of rs174550-CC genotype; however, these genotype–diet interactions were not significant after correction for multiple testing.ConclusionOur findings show that both FADS1 rs174550 genotype and high-LA diet modify plasma phospholipid composition.Trial registrationThe study was registered to ClinicalTrials: NCT02543216, September 7, 2015 (retrospectively registered).

Highlights

  • Fatty acid desaturase 1 (FADS1) gene encodes for delta-5 desaturase enzyme which is needed in conversion of linoleic acid (LA) to arachidonic acid (AA)

  • We have recently shown that the impact of dietary LA on high-sensitivity C-reactive protein concentration depends on the rs174550 variant of FADS1 [16]

  • Identified metabolites which differed between the metabolic profiles of FADS1 rs174550 TT and CC genotypes at baseline are shown in Fig. 1 and listed in Online Resources 3 and 4

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Summary

Introduction

Fatty acid desaturase 1 (FADS1) gene encodes for delta-5 desaturase enzyme which is needed in conversion of linoleic acid (LA) to arachidonic acid (AA). Recent studies have shown that response to dietary PUFAs differs between the genotypes in circulating fatty acids. In response to the high-LA diet, LA phospholipids and long-chain acylcarnitines increased and lysophospholipids decreased in fasting plasma in both genotypes. We aimed to investigate how genetic variation in a polyunsaturated fatty acid (PUFA) metabolism-related fatty acid desaturase 1 gene (FADS1) affects subjects’ metabolic profiles and responses to a high linoleic acid (LA, 18:2n6) diet. Fatty acid delta-6 desaturase (D6D) converts LA and ALA, both from dietary sources, to gamma-linolenic acid (GLA, 18:3n6) and stearidonic acid (SA, 18:4n3), respectively. Estimated enzyme activity of D5D is modified by genetic variants in FADS1, and the conversion rate of LA to AA differs between the carriers of different genotypes [7, 8]

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