Plasma fatty acid ratios affect blood gene expression profiles--a cross-sectional study of the Norwegian Women and Cancer Post-Genome Cohort

• Published in: PloS one Vol. 8; no. 6; p. e67270
• Main Authors: Olsen, Karina Standahl, Fenton, Christopher, Frøyland, Livar, Waaseth, Marit, Paulssen, Ruth H, Lund, Eiliv
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-06-2013; Public Library of Science (PLoS)
• Subjects: Arachidonic acid; Asthma; Autophagy; Basale medisinske, odontologiske og veterinærmedisinske fag: 710; Basic medical, dental and veterinary science disciplines: 710; Biology; Blood; Cancer; Cancer genetics; Cancer research; Cardiovascular diseases; Cell death; Clinical medicine; Cohort Studies; Cross-Sectional Studies; Development and progression; Diabetes; Diet; Disease; DNA binding proteins; Eicosapentaenoic acid; Epidemiology; Fatty acids; Fatty Acids - blood; Female; Foams; Gene expression; Genes; Genetic aspects; Genome, Human - genetics; Genomes; Genomics; Heart diseases; Humans; Hypotheses; Inflammation; Inflammatory diseases; Insulin; Linoleic acid; Linolenic acid; Linolenic acids; Lipid metabolism; Lipids; Medical disciplines: 700; Medical genetics: 714; Medicine; Medisinsk genetikk: 714; Medisinske Fag: 700; Metabolism; MicroRNAs; Middle Aged; miRNA; Neoplasms - blood; Neoplasms - epidemiology; Neoplasms - genetics; Norway - epidemiology; Nutrition research; Pathogenesis; Phagocytosis; Physiology; Population; Quality; Ratios; Signal transduction; Signaling; Studies; Transcription (Genetics); Transcription factors; Transcriptome; VDP; Womens health; Norway
• DOI: 10.1371/journal.pone.0067270
• EISSN: 1932-6203

High blood concentrations of n-6 fatty acids (FAs) relative to n-3 FAs may lead to a "physiological switch" towards permanent low-grade inflammation, potentially influencing the onset of cardiovascular and inflammatory diseases, as well as cancer. To explore the potential effects of FA ratios prior to disease onset, we measured blood gene expression profiles and plasma FA ratios (linoleic acid/alpha-linolenic acid, LA/ALA; arachidonic acid/eicosapentaenoic acid, AA/EPA; and total n-6/n-3) in a cross-section of middle-aged Norwegian women (n = 227). After arranging samples from the highest values to the lowest for all three FA ratios (LA/ALA, AA/EPA and total n-6/n-3), the highest and lowest deciles of samples were compared. Differences in gene expression profiles were assessed by single-gene and pathway-level analyses. The LA/ALA ratio had the largest impact on gene expression profiles, with 135 differentially expressed genes, followed by the total n-6/n-3 ratio (125 genes) and the AA/EPA ratio (72 genes). All FA ratios were associated with genes related to immune processes, with a tendency for increased pro-inflammatory signaling in the highest FA ratio deciles. Lipid metabolism related to peroxisome proliferator-activated receptor γ (PPARγ) signaling was modified, with possible implications for foam cell formation and development of cardiovascular diseases. We identified higher expression levels of several autophagy marker genes, mainly in the lowest LA/ALA decile. This finding may point to the regulation of autophagy as a novel aspect of FA biology which warrants further study. Lastly, all FA ratios were associated with gene sets that included targets of specific microRNAs, and gene sets containing common promoter motifs that did not match any known transcription factors. We conclude that plasma FA ratios are associated with differences in blood gene expression profiles in this free-living population, and that affected genes and pathways may influence the onset and progression of disease.