Inflammatory response to dietary linoleic acid depends on FADS1 genotype

• Published in: The American journal of clinical nutrition Vol. 109; no. 1; pp. 165 - 175
• Main Authors: Lankinen, Maria A, Fauland, Alexander, Shimizu, Bun-ichi, Ågren, Jyrki, Wheelock, Craig E, Laakso, Markku, Schwab, Ursula, Pihlajamäki, Jussi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2019; Oxford University Press; American Society for Clinical Nutrition, Inc
• Subjects: Aged; Arachidonic acid; biochemical pathways; Blood Glucose - analysis; blood lipids; blood serum; C-reactive protein; C-Reactive Protein - analysis; cholesteryl esters; Cross-Sectional Studies; Delta-5 Fatty Acid Desaturase; Desaturase; Diet; diet counseling; Dietary intake; dietary intervention; Eicosanoids; Esters; FADS1; Fasting; fatty acid; Fatty acid composition; Fatty Acid Desaturases - genetics; Fatty Acids; Fatty Acids, Omega-6 - blood; Fatty Acids, Unsaturated - blood; Finland; food intake; gene–diet interaction; Genotype; Genotype & phenotype; Glucose; homozygosity; Homozygote; Homozygotes; human; Humans; Inflammation; Inflammation - blood; Inflammation - chemically induced; Inflammation - genetics; Inflammatory response; Linoleic acid; Linoleic Acid - administration & dosage; Linoleic Acid - blood; lipid; Lipids; Lipids - blood; Male; men; Metabolic disorders; Metabolic Syndrome; Metabolism; Middle Aged; multigene family; oxylipin; Phospholipids; Polymorphism, Single Nucleotide - genetics; Polyunsaturated fatty acids; Proteins; saturated fatty acids; stearoyl-CoA desaturase; Finland; AA; oxylipin; fatty acid; linoleic acid; lipid; COX; genotype; D5D; D6D; LOX; SNP; LA; gene–diet interaction; hsCRP; diet; CYP; human; FADS1; dietary intervention
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.1093/ajcn/nqy287

The health benefits of substituting dietary polyunsaturated fatty acids (PUFAs) for saturated fatty acids are well known. However, limited information exists on how the response to dietary intake of linoleic acid (LA; 18:2n–6) is modified by polymorphisms in the fatty acid desaturase (FADS) gene cluster. The aim of the current study was to test the hypothesis that the FADS1 rs174550 genotype modifies the effect of dietary LA intake on the fatty acid composition of plasma lipids, fasting glucose, and high-sensitivity C-reactive protein (hsCRP). Associations were investigated between genotype, plasma PUFAs, fasting glucose, and hsCRP concentrations in the cross-sectional, population-based Metabolic Syndrome in Men cohort (n = 1337). In addition, 62 healthy men from the cohort who were homozygotes for the TT or CC genotype of the FADS1 rs174550 were recruited to a 4-wk intervention (FADSDIET) with an LA-enriched diet. The fatty acid composition of plasma PUFAs and concentrations of plasma fasting glucose, serum hsCRP, and plasma lipid mediators (eicosanoids and related analogs) were measured at the beginning and end of the 4-wk intervention period. In the FADSDIET trial, the plasma LA proportion increased in both genotype groups in response to an LA-enriched diet. Responses in concentrations of serum hsCRP and plasma fasting glucose and the proportion of arachidonic acid (20:4n–6) in plasma phospholipids and cholesteryl esters differed between genotype groups (interaction of diet × genotype, P < 0.05). In TT homozygous subjects, plasma eicosanoid concentrations correlated with the arachidonic acid proportion in plasma and with hsCRP (r = 0.4–0.7, P < 0.05), whereas in the CC genotype there were no correlations. Our findings show that the FADS1 genotype modifies metabolic responses to dietary LA. The emerging concept that personalized dietary counseling should be modified by the FADS1 genotype needs to be tested in larger randomized trials. The study was registered at clinicaltrials.gov as NCT02543216.