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Fatty Acids and the Immune System

Fatty Acids and the Immune System. What Are Fatty Acids. Long Chain Hydrocarbons with a carboxyl group Long Chain Fatty Acids are typically even numbered Variable Saturation Polyunsaturated/Monounsaturated Ex. Docosahexaenoic Acid, Oleic Acid Fully Saturated Ex. Palmitic Acid

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Fatty Acids and the Immune System

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  1. Fatty Acids and the Immune System

  2. What Are Fatty Acids • Long Chain Hydrocarbons with a carboxyl group • Long Chain Fatty Acids are typically even numbered • Variable Saturation • Polyunsaturated/Monounsaturated • Ex. Docosahexaenoic Acid, Oleic Acid • Fully Saturated • Ex. Palmitic Acid • Omega-3, omega-6 and omega-9

  3. Linoleic Acid (LA): C18:2, n-6 or -6. Essential Fatty Acid Alpha Linolenic Acid (ALA): C18-3, n-3 or -3. Essential Fatty Acid Good source: Flaxseed Oleic Acid (OA): C18:1, n-9 or -9 Good source: Olive oil, Peanut oil, Soy oil

  4. Docosahexaenoic Acid (DHA): C22:6, n-3 or -3. Essential Fatty Acid. Good Source: Fish oil Eicosapentaenoic Acid (EPA): C20:5, n-3 or -3. Essential Fatty Acid. Good source: Fish oil Arachidonic Acid (AA): C20:4, n-6 or -6. Good source: Liver, Beef.

  5. Fatty Acids in Blood • Fatty acids are bound to albumin when in blood • Can also link to glycerol as triglycerides • Can also be part of phospholipids

  6. How Can Fatty Acids Modulate the Immune System? • Why do we need immune modulation in the first place? • Answer: Similar to avoid excessive, chronic inflammation which leads to tissue destruction. • FAs such as DHA and EPA can reduce production of inflammatory cytokines (IL-6, IL-12, IL-23) • FAs can increase phagocytic activity • FAs can decrease lymphocytic proliferation • FAs can influence immune cell migration

  7. Plasma Membrane

  8. Phospholipids and Fatty Acids + Fatty Acid (both saturated and unsaturated Phospho Group Phosphatidylserine

  9. Fatty Acids and Plasma Membrane • Depending on diet, fatty acids end up in plasma membrane • Consumption of hydrogenated oils results in reduction of PUFAs in plasma membrane • PS is a recognition marker for apoptotic cells • It is highly prevalent in Brain tissue • Made up of predominantly Stearic Acid (C18:0) and DHA (C22:6) • PS predominantly resides on the interior (cytoplasmic side of plasma membrane) • Flippase is responsible for the assymetry • Upon apoptosis, more of PS translocates to the exterior facilitating uptake by scavenger cells such as macrophages and neutrophils. • Reduced levels of PS with DHA, may decrease efficiency uptake by scavenger cells. • Anecdotal evidence for preventing dementia

  10. DHA PS DHA and PS

  11. PS flips to Extracytoplasmic Side VIABLE CELL MEMBRANE APOPTOTIC CELL MEMBRANE PS predominantly on cytosolic side PS distribution becomes symmetrical Recognition of Apoptotic Cells

  12. Detecting PS on Extracellular Side LPS Medium 7 9 85 85 4 5 LPS+PGE2 PGE2 5 5 91 90 2 4

  13. Cytokines, Growth Factors, Lipid Metabolites ??? M M M APOPTOTIC CELL MEMBRANE Apoptotic Engulfment

  14. Positional Distribution of Fatty Acids in PS 1. Wood, R. and Harlow, R.D. Arch. Biochem. Biophys., 135, 272-281 (1969).2. Yabuuchi, H. and O'Brien, J.S. J. Lipid Res., 9, 65-67 (1968).

  15. Arachidonic Acid (AA): C20:4, n-6 or -6. Good source: Liver, Beef. Arachidonic Acid Metabolism • Esterified onto phospholipids • Cleaved by phospholipases • Free AA in cytosol is metabolized by numerous enzymes • The COX pathway generates several prostanoids • PGE2 is the cause of pain and inflammation • NSAIDs inhibit the COX pathway

  16. Prostaglandin Synthesis Harris S. et al., 2002

  17. Hydrogenation Plant • Hydrogenation involves: • Heating oil • Pressurizing oil • hydrogen gas • Using platinum catalyst • Trans fats are a by product of hydrogenation • 0 g trans fats does not mean zero • It means <0.5 g per serving!

  18. Effect of DHA on IB • NF-B/IkB dimer resides in cytosol • Upon stimulation, IkB is phosphorylated/degraded • NF-B translocates to nucleus facilitating transcription of cytokines • Western blot shows reduction in IkB degradation when DHA is present Kong W. et al, 2010

  19. Effect of DHA on NF-B • DHA reduces translocation of NF-B to nucleus • Reduction is likely due to increased stability of IB in cytosol • Heterodimer does not translocate to nucleus • Rosiglitazone is a PPAR agonist (has no effect) on NF-B translocation Kong W. et al, 2010

  20. Effect of DHA on Cytokine Production ELISA Assays show: • Reduction in IL-12 • Reduction in IL-23 • Reduction in IL-27 • Effect diminishes below 1 M Kong W. et al, 2010

  21. IUPAC, 2001

  22. IUPAC, 2001

  23. IUPAC, 2001

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