The FADS1 genotypes modify the effect of linoleic acid-enriched diet on adipose tissue inflammation via pro-inflammatory eicosanoid metabolism

• Published in: European journal of nutrition Vol. 61; no. 7; pp. 3707 - 3718
• Main Authors: Vaittinen, Maija, Lankinen, Maria A., Käkelä, Pirjo, Ågren, Jyrki, Wheelock, Craig E., Laakso, Markku, Schwab, Ursula, Pihlajamäki, Jussi
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2022; Springer Nature B.V
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; biosynthesis; Body fat; Chemistry; Chemistry and Materials Science; Delta-5 Fatty Acid Desaturase - genetics; Desaturase; Diet; Eicosanoids; Eicosanoids - metabolism; fatty acid desaturase; Fatty acids; Female; Gene expression; Genotype; Genotype & phenotype; Genotypes; homozygosity; Homozygotes; Humans; Inflammation; Inflammation - metabolism; interleukins; Linoleic acid; Linoleic Acid - administration & dosage; Linoleic Acid - metabolism; Male; Metabolic syndrome; Metabolism; Nutrition; nutrition-genotype interaction; obesity; Original Contribution; Polymorphism, Single Nucleotide; protective effect; Staphylococcal enterotoxin H; surgery; Inflammation; Adipose tissue; Arachidonic acid; Eicosanoid; FADS1; Linoleic acid
• ISSN: 1436-6207; 1436-6215; 1436-6215
• DOI: 10.1007/s00394-022-02922-y

Purpose Fatty acid desaturase ( FADS ) variants associate with fatty acid (FA) and adipose tissue (AT) metabolism and inflammation. Thus, the role of FADS1 variants in the regulation of dietary linoleic acid (LA)-induced effects on AT inflammation was investigated. Methods Subjects homozygotes for the TT and CC genotypes of the FADS1 -rs174550 (TT, n  = 25 and CC, n  = 28) or -rs174547 (TT, n  = 42 and CC, n  = 28), were either recruited from the METabolic Syndrome In Men cohort to participate in an intervention with LA-enriched diet (FADSDIET) or from the Kuopio Obesity Surgery (KOBS) study. GC and LC–MS for plasma FA proportions and eicosanoid concentrations and AT gene expression for AT inflammatory score (AT-InSc) was determined. Results We observed a diet-genotype interaction between LA-enriched diet and AT-InSc in the FADSDIET. In the KOBS study, interleukin (IL)1 beta mRNA expression in AT was increased in subjects with the TT genotype and highest LA proportion. In the FADSDIET, n-6/LA proportions correlated positively with AT-InSc in those with the TT genotype but not with the CC genotype after LA-enriched diet. Specifically, LA- and AA-derived pro-inflammatory eicosanoids related to CYP450/sEH-pathways correlated positively with AT-InSc in those with the TT genotype, whereas in those with the CC genotype, the negative correlations between pro-inflammatory eicosanoids and AT-InSc related to COX/LOX-pathways. Conclusions LA-enriched diet increases inflammatory AT gene expression in subjects with the TT genotype, while CC genotype could play a protective role against LA-induced AT inflammation. Overall, the FADS1 variant could modify the dietary LA-induced effects on AT inflammation through the differential biosynthesis of AA-derived eicosanoids.