Dietary alpha-linolenic acid increases TNF-alpha, and decreases IL-6, IL-10 in response to LPS: effects of sesamin on the delta-5 desaturation of omega6 and omega3 fatty acids in mice.
Sesamin (a non-fat portion of sesame seed oil) inhibits delta-5 desaturase activity resulting in an accumulation of dihomo-gamma-linolenic acid (DGLA) which can displace arachidonic acid (AA) and decrease the formation of pro-inflammatory mediators. We investigated the effects of consumption of diets containing 0.25wt% sesamin and 15 wt% safflower oil (SO) (providing 12% of the added fat as linoleic acid) or a 15 wt% 2:1 mixture of linseed oil and SO (LOSO) (providing 6% alpha-linolenic acid and 6% linoleic acid) for 3 weeks on the liver membrane fatty acid composition and on the production of prostaglandin (PG) E2, TNF-alpha, IL-6 and IL10 in mice. Consumption of sesamin-supplemented SO and LOSO diets resulted in a significant increase in the levels of 20:3omega6 (DGLA), suggesting that sesamin inhibited delta-5 desaturation of omega6 fatty acids. In animals fed LOSO diets, the levels of alpha-linolenic acid, eicosapentaenoic acid (EPA) and of docosahexaenoic acid (DHA) were elevated with a concomitant decrease of arachidonic acid (AA) in the liver membrane phospholipids. Further, in animals fed LOSO diets with or without sesamin, an increase in the circulating levels of TNF-alpha was associated with a concomitant decrease in PGE2. Despite a lack of differences in the levels of AA, the PGE2 levels were significantly lower in mice fed sesamin-supplemented SO compared to those fed SO alone. Thus, these data suggest that irrespective of the availability of a specific fatty acid as a substrate, through regulating the PGE2 synthesis, the production of TNF-alpha could be modulated.
Chavali
S R
SR
Department of Surgery, Harvard Institute of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Zhong
W W
WW
Forse
R A
RA
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000090943:Delta-5 Fatty Acid Desaturase; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D015232:Dinoprostone / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D044943:Fatty Acid Desaturases / Q000187:drug effects / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D017705:Lignans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000008:administration & dosage*
D000924:Anticholesteremic Agents; D000090943:Delta-5 Fatty Acid Desaturase; D004042:Dietary Fats, Unsaturated; D004149:Dioxoles; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D015850:Interleukin-6; D017705:Lignans; D008070:Lipopolysaccharides; D008563:Membrane Lipids; D014409:Tumor Necrosis Factor-alpha; D017962:alpha-Linolenic Acid; D016753:Interleukin-10; D044943:Fatty Acid Desaturases; D015232:Dinoprostone; C054125:sesamin