Key Findings:
ALA represents the main n3 fatty acid in the Western diet with intakes averaging 1.5 g. Intakes of n6 fatty acid LA is about 10 times higher. A ratio of about 10:1 n6 to n3, pro-inflammatory/aggregatory eicosanoids from LA is favored over those from n3 fatty acids which have anti inflammatory/aggregatory effects. A human hepatoma cell line (HepG2) was used as a model system to investigate the impact of varying ratios of n6/n3 fatty acids on the conversion of ALA to EPA and DHA. Different levels of LA and ALA affected transcript levels of a portfolio of genes encoding regulating proteins involved in several stages of fatty acid metabolism. Higher oxidation rates as indicated by high transcript levels of PPAR alpha were found when ALA levels were very low. Administration of LA/ALA at a ratio of 1 to 1 led to the highest formation of EPA and DHA.
Abstract:
Background: Conversion of linoleic acid (LA) and alpha linolenic acid (ALA) to their higher chain homologues in humans depends on the ratio of ingested n6 and n3 fatty acids. Design and methods: In order to determine the most effective ratio with regard to the conversion of ALA to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), human hepatoma cells were incubated with varying ratios of [13C] labeled linoleic acid ([13C]LA) and alpha linolenic acid ([13C]ALA) methylesters. Regulative cellular signal transduction pathways involved were studied by determinations of transcript levels of the genes encoding delta 5 desaturase (D5D) and delta 6 desaturase (D6D), peroxisome proliferator-activated receptor alpha (PPARα) and sterol regulatory element binding protein 1c (SREBP 1c). Mitogen-activated protein kinase kinase 1 (MEK1) and mitogen-activated protein kinase kinase kinase 1 (MEKK1) were also examined. Results: Maximum conversion was observed in cells incubated with the mixture of [13C]LA [13C]ALA at a ratio of 1:1, where 0.7 percent and 17 percent of the recovered [13C]ALA was converted to DHA and EPA, respectively. Furthermore, differential regulation of enzymes involved in the conversion at the transcript level, dependent on the ratio of administered n6 to n3 fatty acids in human hepatocytes was demonstrated. Conclusion: Formation of EPA and DHA was highest at an administered LA/ALA ratio of 1 to 1, although gene expression of PPARα, SREBP 1c and D5D involved in ALA elongation were higher in the presence of ALA solely. Also, our findings suggest that a diet induced enhancement of the cell membrane content of highly unsaturated fatty acids is only possible up to a certain level. (Authors abstract)
This is a free article, click below to view:
Link to Full Text