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Bioactive dietary long-chain fatty acids: emerging mechanisms of action

  • Robert S. Chapkin (a1) (a2) (a3), David N. McMurray (a1) (a2) (a4), Laurie A. Davidson (a1) (a2), Bhimanagouda S. Patil (a1) (a3), Yang-Yi Fan (a1) and Joanne R. Lupton (a1) (a2)...

Abstract

The plasma membranes of all eukaryotic cells contain heterogeneous self-organising intrinsically unstable liquid ordered domains or lipid assemblies in which key signal transduction proteins are localised. These assemblies are classified as ‘lipid rafts’ (10–200 nm), which are composed mostly of cholesterol and sphingolipid microdomains and therefore do not integrate well into the fluid phospholipid bilayers. In addition, caveolae represent a subtype of lipid raft macrodomain that form flask-shaped membrane invaginations containing structural proteins, i.e. caveolins. With respect to the diverse biological effects of long-chain PUFA, increasing evidence suggests that n-3 PUFA and perhaps conjugated fatty acids uniquely alter the basic properties of cell membranes. Because of its polyunsaturation, DHA and possibly conjugated linoleic acid are sterically incompatible with sphingolipid and cholesterol and, therefore, appear to alter lipid raft behaviour and protein function. The present review examines the evidence indicating that dietary sources of n-3 PUFA can profoundly alter the biochemical make up of lipid rafts/caveolae microdomains, thereby influencing cell signalling, protein trafficking and cell cytokinetics.

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Corresponding author

*Corresponding author: Dr Robert S. Chapkin, fax +1 979 862 2378, email r-chapkin@tamu.edu

References

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1Karin, M (2006) Nuclear factor-kB in cancer development and progression. Nature 441, 431436.
2Rollins, BJ (2006) Inflammatory chemokines in cancer growth and progression. Eur J Cancer 42, 760767.
3Hong, MY, Lupton, JR, Morris, JS, Wang, N, Carroll, RJ, Davidson, LA, Elder, RH & Chapkin, RS (2000) Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation. Cancer Epidemiol Biomarkers Prev 9, 819826.
4Chapkin, RS, McMurray, DN & Lupton, JR (2007) Colon cancer, fatty acids and anti-inflammatory compounds. Curr Opin Gastroenterol 23, 4854.
5Fowler, KH, Chapkin, RS & McMurray, DN (1993) Effects of purified dietary n-3 ethyl esters on murine T-lymphocyte function. J Immunol 151, 51865197.
6Serhan, CN, Yacoubian, S & Yang, R (2008) Anti-inflammatory and proresolving lipid mediators. Annu Rev Pathol Mech Dis 3, 279312.
7Ariel, A & Serhan, CN (2007) Resolvins and protectins in the termination program of acute inflammation. Trends Immunol 28, 176183.
8Bazan, NG (2007) Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Curr Opin Clin Nutr Metab Care 10, 136141.
9deUrquiza, AM, Liu, S, Sjoberg, M, Zetterström, RH, Griffiths, W, Sjövall, J & Perlmann, T (2000) Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 290, 21402144.
10Fan, YY, Spencer, TE, Wang, N, Moyer, MP & Chapkin, RS (2003) Chemopreventive n-3 fatty acids activate RXRα in colonocytes. Carcinogenesis 4, 15411548.
11Davidson, LA, Nguyen, DV, Hokanson, RM, et al. (2004) Chemopreventive n-3 polyunsaturated fatty acids reprogram genetic signatures during colon cancer initiation and progression in the rat. Cancer Res 64, 67976804.
12Jump, DB, Botolin, D, Wang, Y, Xu, J, Christian, B & Demeure, O (2005) Fatty acid regulation of hepatic gene transcription. J Nutr 135, 25032506.
13Ma, DW, Seo, J, Switzer, KC, Fan, YY, McMurray, DN, Lupton, JR & Chapkin, RS (2004) n-3 PUFA and membrane microdomains: a new frontier in bioactive lipid research. J Nutr Biochem 15, 700706.
14Seo, J, Barhoumi, R, Johnson, AE, Lupton, JR & Chapkin, RS (2006) Docosahexaenoic acid selectively inhibits plasma membrane targeting of lipidated proteins. FASEB J 20, 770772.
15Kolar, SS, Barhoumi, R, Lupton, JR & Chapkin, RS (2007) Docosahexaenoic acid and butyrate synergistically induce colonocyte apoptosis by enhancing mitochondrial Ca2+ accumulation. Cancer Res 67, 55615568.
16Kolar, SS, Barhoumi, R, Callaway, ES, Fan, YY, Wang, N, Lupton, JR & Chapkin, RS (2007) Synergy between docosahexaenoic acid and butyrate elicits p53-independent apoptosis via mitochondrial Ca2+ accumulation in colonocytes. Am J Physiol Gastrointest Liver Physiol 293, G935G943.
17Chapkin, RS, Wang, N, Fan, YY, Lupton, JR & Prior, IA (2008) Docosahexaenoic acid alters the size and distribution of cell surface microdomains. Biochim Biophys Acta 1778, 466471.
18Biscione, F, Pignalberi, C, Totteri, A, Messina, F & Altamura, G (2007) Cardiovascular effects of omega-3 free fatty acids. Curr Vasc Pharmacol 5, 163172.
19Harris, WS, Poston, WC & Haddock, CK (2007) Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis 193, 110.
20Ou, L, Ip, C, Lisafeld, B & Ip, MM (2007) Conjugated linoleic acid induces apoptosis of murine mammary tumor cells via Bcl-2 loss. Biochem Biophys Res Commun 356, 10441049.
21Bozzo, F, Bocca, C, Colombatto, S & Miglietta, A (2007) Antiproliferative effect of conjugated linoleic acid in Caco-2 cells: involvement of PPARγ and APC/β-catenin pathways. Chem Biol Interact 169, 110121.
22Song, HJ, Sneddon, AA, Heys, SD & Wahle, KW (2006) Induction of apoptosis and inhibition of NF-κB activation in human prostate cancer cells by the cis-9, trans-11 but not the trans-10, cis-12 isomer of conjugated linoleic acid. Prostate 66, 839846.
23Chung, S, Brown, JM, Provo, JN, Hopkins, R & McIntosh, MK (2005) Conjugated linoleic acid promotes human adipocyte insulin resistance through NF-κB dependent cytokine production. J Biol Chem 280, 3844538456.
24Liu, LF, Purushotham, A, Wendel, AA & Belury, MA (2007) Combined effects of rosiglitazone and conjugated linoleic acid on adiposity, insulin sensitivity, and hepatic steatosis in high-fat-fed mice. Am J Physiol Liver Physiol 292, G1671G1682.
25Pérez-Matute, P, Marti, A, Martínez, JA, Fernández-Otero, MP, Stanhope, KL, Havel, PJ & Moreno-Aliaga, MJ (2007) Conjugated linoleic acid inhibits glucose metabolism, leptin and adiponectin-secretion in primary cultured rat adipocytes. Mol Cell Endocrinol 268, 5058.
26Navarro, V, Fernandez-Quintela, A, Churruca, I & Portillo, MP (2006) The fat-lowering effect of conjugated linoleic acid: a comparison between animal and human studies. J Physiol Biochem 62, 137148.
27Tricon, S & Yaqoob, P (2006) Conjugated linoleic acid and human health: a critical evaluation of the evidence. Curr Opin Nutr Metab Care 9, 105110.
28Close, RN, Schoeller, DA, Watras, AC & Nora, EH (2007) Conjugated linoleic acid supplementation alters the 6-mo change in fat oxidation during sleep. Am J Clin Nutr 86, 797804.
29Whigham, LD, Watras, AC & Schoeller, DA (2007) Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. Am J Clin Nutr 85, 12031211.
30Laude, AJ & Prior, IA (2004) Plasma membrane microdomains: organization, function and trafficking. Mol Membr Biol 21, 193205.
31Hancock, JF (2006) Lipid rafts: contentious only from simplistic standpoints. Nat Rev Mol Cell Biol 7, 456462.
32Anderson, RGW (1998) The caveolae membrane system. Annu Rev Biochem 67, 199225.
33Simons, K & Ikonen, E (1997) Functional rafts in cell membranes. Nature 387, 569572.
34Prior, IA, Muncke, C, Parton, RG & Hancock, JF (2003) Direct visualization of Ras proteins in spatially distinct cell surface microdomains. J Cell Biol 160, 165170.
35Stillwell, W & Wassall, SR (2003) Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem Phys Lipids 126, 127.
36Fan, YY, Ly, LH, Barhoumi, R, McMurray, DN & Chapkin, RS (2004) Dietary docosahexaenoic acid suppresses T-cell protein kinase C-theta lipid raft recruitment and interleukin-2 production. J Immunol 173, 61516160.
37Ma, DW, Seo, J, Davidson, LA, Callaway, ES, Fan, YY, Lupton, JR & Chapkin, RS (2004) n-3 PUFA alter caveolae lipid composition and resident protein localization in mouse colon. FASEB J 18, 10401042.
38Zeyda, M, Säemann, MD, Stuhlmeier, KM, Mascher, DG, Nowotny, PN, Zlabinger, GJ, Waldhäusl, W & Stulnig, TM (2005) Polyunsaturated block dendritic cell activation and function independently of NF-κB activation. J Biol Chem 280, 1429314301.
39Geyeregger, R, Zeyda, M, Zlabinger, GJ, Waldhäusl, W & Stulnig, TM (2005) Polyunsaturated fatty acids interfere with formation of the immunological synapse. J Leuk Biol 77, 680688.
40Stulnig, TM, Berger, M, Sigmund, T, Raederstorff, D, Stockinner, H & Waldhäusl, W (1998) Polyunsaturated fatty acids inhibit T cell signal transduction by modification of detergent-insoluble membrane domains. J Cell Biol 143, 637644.
41Stulnig, TM, Huber, J, Leitinger, N, Imre, E-M, Angelisová, P, Nowotny, P & Waldhäusl, W (2001) Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition. J Biol Chem 276, 3733537340.
42Fowler, KH, McMurray, DN, Fan, YY, Aukema, HM & Chapkin, RS (1993) Purified dietary n-3 polyunsaturated fatty acids alter diacylglycerol mass and molecular species composition in concanavalin A stimulated murine splenocytes. Biochim Biophys Acta 1210, 8996.
43Switzer, KC, McMurray, DN, Morris, JS & Chapkin, RS (2003) Dietary n-3 polyunsaturated fatty acids selectively promote activation-induced cell death in T-lymphocytes. J Nutr 133, 496503.
44Fan, YY, McMurray, DN, Ly, LH & Chapkin, RS (2003) Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts. J Nutr 133, 19131920.
45Switzer, KC, Fan, YY, Wang, N, McMurray, DM & Chapkin, RS (2004) Dietary n-3 polyunsaturated fatty acids promote activation-induced cell death in the Th1-polarized murine CD4+T-cells. J Lipid Res 45, 14821492.
46Leitenberg, D, Balamuth, F & Bottomly, K (2001) Changes in the T cell receptor macromolecular signaling complex and membrane microdomains during T cell development and activation. Sem Immunol 13, 129138.
47Gaus, K, Chklovskaia, E, Fazekas de St Groth, B, Jessup, W & Harder, T (2005) Condensation of the plasma membrane at the site of T lymphocyte activation. J Cell Biol 171, 121131.
48Harder, T, Rentero, C, Zech, T & Gaus, K (2007) Plasma membrane segregation during T cell activation: probing the order of domains. Curr Opin Immunol 19, 470475.
49Shaikh, SR & Edidin, M (2007) Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules. J Lipid Res 48, 127138.
50Huot, PS & Ma, WL (2007) CLA incorporates into caveolae phospholipids and reduces caveolin-1 expression in MCF-7 cells. Presented at the 98th American Oil Chemists' Society (AOCS) Annual Meeting, Quebec, Canada, May 2007, p. 81. Urbana, IL: AOCS Press..
51Yin, JJ, Kramer, JK, Yurawecz, MP, Eynard, AR, Mossoba, MM & Yu, L (2006) Effects of conjugated linoleic acid (CLA) isomers on oxygen diffusion-concentration products in liposomes and phospholipids solutions. J Agric Food Chem 54, 72877293.
52Huster, D, Arnold, K & Gawrisch, K (1998) Influence of docosahexaenoic acid and cholesterol on lateral lipid organization in phospholipid mixtures. Biochemistry 37, 1729917308.
53Mitchell, DC & Litman, BJ (1998) Effect of cholesterol on molecular order and dynamics in highly polyunsaturated phospholipid bilayers. Biophys J 75, 896908.
54Pasenkiewicz-Gierula, M, Subczynski, WK & Kusumi, A (1991) Influence of phospholipid unsaturation on the cholesterol distribution in membranes. Biochimie 73, 13111316.
55Niu, SL & Litman, BJ (2002) Determination of membrane cholesterol partition coefficient using a lipid vesicle-cyclodextrin binary system: effect of phospholipid acyl chain unsaturation and headgroup composition. Biophys J 83, 34083415.
56Zerouga, M, Jenski, LJ & Stillwell, W (1995) Comparison of phosphatidylcholines containing one or two docosahexaenoic acyl chains on properties of phospholipid monolayers and bilayers. Biochim Biophys Acta 1236, 266272.
57Kariel, N, Davidson, E & Keough, KM (1991) Cholesterol does not remove the gel-liquid crystalline phase transition of phosphatidylcholines containing two polyenoic acyl chains. Biochim Biophys Acta 1062, 7076.
58Needham, D & Nunn, RS (1990) Elastic deformation and failure of lipid bilayer membranes containing cholesterol. Biophys J 58, 9971009.
59Mitchell, DC & Litman, BJ (1998) Molecular order and dynamics in bilayers consisting of highly polyunsaturated phospholipids. Biophys J 74, 879891.
60Brzustowicz, MR, Cherezov, V, Caffrey, M, Stillwell, W & Wassall, SR (2002) Molecular organization of cholesterol in polyunsaturated membranes: microdomain formation. Biophys J 82, 285298.
61Brzustowicz, MR, Cherezov, V, Zerouga, M, Caffrey, M, Stillwell, W & Wassall, SR (2002) Controlling membrane cholesterol content. A role for polyunsaturated (docosahexaenoate) phospholipids. Biochemistry 41, 1250912519.
62Pasenkiewicz-Gierula, M, Subczynski, WK & Kusumi, A (1990) Rotational diffusion of a steroid molecule in phosphatidylcholine-cholesterol membranes: fluid-phase microimmiscibility in unsaturated phosphatidylcholine-cholesterol membranes. Biochemistry 29, 40594069.
63Huang, J & Feigenson, GW (1999) A microscopic interaction model of maximum solubility of cholesterol in lipid bilayers. Biophys J 76, 21422157.
64Shaikh, SR, Cherezov, V, Caffrey, M, Stillwell, W & Wassall, SR (2003) Interaction of cholesterol with a docosahexaenoic acid-containing phosphatidylethanolamine: trigger for microdomain/raft formation? Biochemistry 42, 1202812037.
65Danbara, N, Yuri, T, Tsujita-Kyutoku, M, Sato, M, Senzaki, H, Takada, H, Hada, T, Miyazawa, T, Okazaki, K & Tsubura, A (2004) Conjugated docosahexaenoic acid is a potent inducer of cell cycle arrest and apoptosis and inhibits growth of Colo 201 human colon cancer cells. Nutr Cancer 50, 7179.
66Kimura, Y & Sumiyoshi, M (2005) Antitumor and antimetastatic actions of eicosapentaenoic acid ethylester and its by-products formed during accelerated stability testing. Cancer Sci 96, 441450.
67Yonezawa, Y, Tsuzuki, T, Eitsuka, T, et al. (2005) Inhibitory effect of conjugated eicosapentaenoic acid on human DNA topoisomerases I and II. Arch Biochem Biophys 435, 197206.
68Tsuzuki, T, Tanaka, K, Kuwahara, S & Miyazawa, T (2005) Synthesis of the conjugated trienes 5E,7E,9E,14Z,17Z-eiocospentaenoic acid and 5Z,7E,9E,14Z,17Z-eiocsapentaenoic acid and their induction of apoptosis in DLD-1 colorectal adenocarcinoma cells. Lipids 40, 147154.
69Tsuzuki, T, Kambe, T, Shibata, A, Kawakami, Y, Nakagawa, K & Miyazawa, T (2007) Conjugated EPA activates mutant p53 via lipid peroxidation and induces p53-dependent apoptosis in DLD-1 colorectal adenocarcinoma human cells. Biochim Biophys Acta 1771, 2030.
70Tsuzuki, T, Kawakami, Y, Nakagawa, K & Miyazawa, T (2006) Conjugated docosahexaenoic acid inhibits lipid accumulation in rats. J Nutr Biochem 17, 518524.
71Tsuzuki, T, Shibata, A, Kawakami, Y, Nakagaya, K & Miyazawa, T (2007) Anti-angiogenic effects of conjugated docosahexaenoic acid in vitro and in vivo. Biosci Biotechnol Biochem 71, 19021910.

Keywords

Bioactive dietary long-chain fatty acids: emerging mechanisms of action

  • Robert S. Chapkin (a1) (a2) (a3), David N. McMurray (a1) (a2) (a4), Laurie A. Davidson (a1) (a2), Bhimanagouda S. Patil (a1) (a3), Yang-Yi Fan (a1) and Joanne R. Lupton (a1) (a2)...

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