Dietary essential α-linolenic acid and linoleic acid differentially modulate TNFα-induced NFκB activity in FADS2-deficient HEK-293 cells.

Key Findings

It has not yet been clarified whether LA and ALA need to be metabolized to become bioactive or whether LA and ALA themselves might also exert an impact on inflammatory processes by influencing the NFκB response. The NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls cytokine production and cell survival. NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases. The objective of the present study was to test if application of LA or ALA is able to modulate the NFκB activity status independent of an apparent Delta-6 desaturase (D6D) activity. The results show that the anti-inflammatory bioactivity of essential PUFA LA or ALA might not exclusively implicate a D6D activity. It would appear to involve distinct targeting and modulation of NFκB activity. This D6D-independent bioactivity may represent an important mechanism during processes of declined D6D activity as a result of ageing or progressing insulin resistance.

ABSTRACT

The pro- or anti-inflammatory bioactivity of dietary essential linoleic acid (LA) and alpha-linolenic acid (ALA) is mainly attributed to rate-limiting delta-6 desaturase (D6D) activity. The aim of this study was to analyze mechanisms of D6D-substrates ALA, LA and D6D-product gamma-linolenic acid (GLA) under D6D-deficient conditions. Fatty acid profiles (GC-MS), D6D gene expression (real-time RT-PCR) and NFκB activity (luciferase assay) were assessed in HEK293 cells. FADS2 gene expression was approved being marginal. Incubation with ALA or LA did not increase D6D products but their elongase products C20:3n-3 and C20:2n-6. Bypassing the D6D, GLA elevated C20:3n-6 and C20:4n-6. LA significantly increased (+18% at 60 μM; p < .001), ALA reduced (-32% at 100 μM; p < .001) and GLA did not specifically change NFκB activity. Our data indicate that D6D might not be essential for the distinct effects of LA and ALA on NFκB activity.