title: Dietary essential α-linolenic acid and linoleic acid differentially modulate TNFα-induced NFκB activity in FADS2-deficient HEK-293 cells.
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.
authors.affiliation: a Department of Physiology and Biochemistry of Nutrition , Karlsruhe , Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Schübel
authors.affiliation: a Department of Physiology and Biochemistry of Nutrition , Karlsruhe , Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Jaudszus
authors.affiliation: a Department of Physiology and Biochemistry of Nutrition , Karlsruhe , Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Krüger
authors.affiliation: a Department of Physiology and Biochemistry of Nutrition , Karlsruhe , Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roth
authors.affiliation: b Department of Quality and Safety of Milk and Fish , Federal Research Institute of Nutrition and Food, Max Rubner-Institut , Kiel , Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Klempt
authors.affiliation: a Department of Physiology and Biochemistry of Nutrition , Karlsruhe , Germany.
authors.forename: Stephan Wilhelm
authors.initials: SW
authors.lastname: Barth
mesh_terms: D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D017962:alpha-Linolenic Acid / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D017962:alpha-Linolenic Acid; D044943:Fatty Acid Desaturases; C533241:FADS2 protein, human
keywords: Delta-6 desaturase; fatty acid desaturase; inflammation; polyunsaturated fatty acids