Study of the effects of dietary polyunsaturated fatty acids: Molecular mechanisms involved in intestinal inflammation


  • Bianca Knoch Food, Metabolism & Microbiology Section, Food & Textiles Group, AgResearch Grasslands and Institute of Food, Nutrition & Human Health, Massey University
  • Matthew P.G. Barnett Food, Metabolism & Microbiology Section, Food & Textiles Group, AgResearch Grasslands
  • Nicole C. Roy Food, Metabolism & Microbiology Section, Food & Textiles Group, AgResearch Grasslands
  • Warren C. McNabb Food, Metabolism & Microbiology Section, Food & Textiles Group, AgResearch Grasslands



Dietary n-3 and n-6 polyunsaturated fatty acid, Gene, Intestinal inflammation


The use of “omics” techniques in combination with model systems and molecular tools allows to understand how foods and food components act on metabolic pathways to regulate transcriptional processes. Polyunsaturated fatty acids have distinctive nutritional and metabolic effects because they give rise to lipid mediated products and affect the expression of various genes involved in intestinal inflammation. The present review focuses on the molecular effects of dietary polyunsaturated fatty acids on intestinal inflammation.


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Andoh A, Tsujikawa T, Ishizuka I, Araki Y, Sasaki M, Koyama S, Fujiyama Y. 2003. N-3 fatty acid-rich diet prevents early response of interleukin-6 elevation in trinitrobenzene sulfonic acid-induced enteritis. Int. J. Mol. Med. 12, 721-725.

Balish E, Warner T. 2002. Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am. J. Pathol. 160, 2253-2257.

Bannenberg G, Arita M, Serhan CN. 2007. Endogenous receptor agonists: resolving inflammation. The Scientific World Journal 7, 1440-1462. doi:10.1100/tsw.2007.188 PMid:17767360

Bassaganya-Riera, J, Hontecillas R. 2006. CLA and n-3 PUFA differentially modulate clinical activity and colonic PPAR-responsive gene expression in a pig model of experimental IBD. Clin. Nutr. 25, 454-465. doi:10.1016/j.clnu.2005.12.008 PMid:16698153

Belluzzi A. 2002. N-3 Fatty acids for the treatment of inflammatory bowel disease. Proc. Nutr. Soc. 61, 391- 395. doi:10.1079/PNS2002171 PMid:12296296

Berg DJ, Davidson N, Kühn R, Müller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, Rennick D. 1996. Enterocolitis and colon cancer in interleukin- 10-deficient mice are associated with aberrant cytokine production and CD4+ TH1-like responses. J. Clin. Invest. 98, 1010-1020. doi:10.1172/JCI118861 PMid:8770874 PMCid:507517

Bünger M, Van Den Bosch HM, Van Der Meijde J, Kersten S, Hooiveld G, Müller M. 2007. Genome-wide analysis of PPAR alpha activation in murine small intestine. Physiol. Genomics 30, 192-204. doi:10.1152/physiolgenomics.00198.2006 PMid:17426115

Calder PC. 2003. N-3 polyunsaturated fatty acids and inflammation: From molecular biology to the clinic. Lipids 38, 343-352. doi:10.1007/s11745-003-1068-y PMid:12848278

Calder PC. 2006. N-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am. J. Clin. Nutr. 83, 1505S-1519S.

Calder PC. 2008. Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol. Nutr. Food Res. 52, 885-897. doi:10.1002/mnfr.200700289

Campos FG, Waitzberg DL, Habr-Gama A, Logullo AF, Noronha IL, Jancar S, Torrinhas RSM, Furst P. 2002. Impact of parenteral n-3 fatty acids on experimental acute colitis. Brit. J. Nutr. 87, S83-S88. doi:10.1079/BJN2001460

Caplan MS, Russell T, Xiao Y, Amer M, Kaup S, Jilling, T. 2001. Effect of polyunsaturated fatty acid (PUFA) supplementation on intestinal inflammation and necrotizing enterocolitis (NEC) in a neonatal rat model. Pediatr. Res. 49, 647-652. doi:10.1203/00006450-200105000-00007 PMid:11328947

Chapkin RS, Davidson LA, Ly L, Weeks BR, Lupton JR, McMurray DN. 2007. Immunomodulatory effects of (n- 3) fatty acids: Putative link to inflammation and colon cancer. J. Nutr. 137, 200S-204S.

De Vogel-Van Den Bosch HM, Bu.nger M, De Groot PJ, Bosch-Vermeulen H, Hooiveld GJEJ, Müller M. 2008. PPARalpha-mediated effects of dietary lipids on intestinal barrier gene expression. BMC Genomics 9, 231. doi:10.1186/1471-2164-9-231 PMid:18489776 PMCid:2408604

Deckelbaum RJ, Worgall TS, Seo T. 2006. N-3 fatty acids and gene expression. Am. J. Clin. Nutr. 83, 1520S- 1525S.

Dommels YEM, Alink GM, Van Bladeren PJ, Van Ommen B. 2002. Dietary n-6 and n-3 polyunsaturated fatty acids and colorectal carcinogenesis: results from cultured colon cells, animal models and human studies. Environ Toxicol Pharmacol. 12, 233-244. doi:10.1016/S1382-6689(02)00095-9

Dommels EM, Butts CA, Zhu S, Davy M, Martell S, Hedderley D, Barnett MPG, McNabb WC, Roy NC. 2007. Characterization of intestinal inflammation and identification of related gene expression changes in mdr1a-/- mice. Genes Nutr. 2, 209-223. doi:10.1007/s12263-007-0051-4

Dulpus E, Glorian M, Forest C. 2000. Fatty acid regulation of gene transcription. J. Biol. Chem. 275, 30749- 30752. doi:10.1074/jbc.R000015200 PMid:10934217

Empey LR, Jewell LD, Garg ML, Thomson AB, Clandidin MT, Fedorak RN. 1991. Fish-oil enriched diet is mucosal protective against acetic acid-induced colitis in rats Can. J. Physiol. Pharm. 69, 480-487.

Ewaschuk JB, Dieleman LA. 2006. Probiotics and prebiotics in chronic inflammatory bowel diseases. World J. Gastroenterol. 12, 5941-5950.

Favier C, Neut C, Mizon C, Cortot A, Colombel JF, Mizon J. 1997. Fecal beta-D-galactosidase production and Bifidobacteria are decreased in Crohn’s disease. Dig. Dis. Sci. 42, 817-822. doi:10.1023/A:1018876400528 PMid:9125655

Ferguson LR, Shelling AN, Browning BL, Huebner C, Petermann I. 2007. Genes, diet and inflammatory bowel disease. Mutat. Res. 622, 70-83. doi:10.1016/j.mrfmmm.2007.05.011

Geerling BJ, Van Houwelingen AC, Badart-Smook A, Stockbrugger RW, Brummer JM. 1999. Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn’s disease, compared with controls. Am. J. Gastroenterol. 94, 410-417. doi:10.1111/j.1572-0241.1999.869_a.x PMid:10022638

Gill HS, Shu Q, Lin H, Rutherfurd KJ, Cross ML. 2001. Protection against translocating Salmonella typhimurium infection in mice by feeding the immunoenhancing probiotic Lactobacillus rhamnosus strain HN001. Med. Microbiol. Immunol. 190, 97-104.

Goodwin JS, Ceuppens J. 1983. Regulation of the immune-response by prostaglandins. J. Clin. Immunol 3, 295-315. doi:10.1007/BF00915791 PMid:6140268

Goudriaan JR, Dahlmans VEH, Febbraio M, Teusink B, Romijn JA, Havekes LM, Voshol PJ. 2002. Intestinal lipid absorption is not affected in CD36 deficient mice. Mol. Cell. Biochem. 239, 199-202. doi:10.1023/A:1020575412789 PMid:12479586

Grammatikos SI, Subbaiah PV, Victor TA, Miller WM. 1994. Diverse effects of essential (n-6 and n-3) fatty acids on cultured cells. Cytotechnology 15, 31-50. doi:10.1007/BF00762377 PMid:7765945

Hansen Petrik MB, McEntee MF, Chiu CH, Whelan J. 2000. Antagonism of arachidonic acid is linked to the antitumorigenic effect of dietary eicosapentaenoic acid in ApcMin/+ mice. J. Nutr. 130, 1153-1158.

Hegazi RAF, Saad RS, Mady H, Matarese LE, O’keefe S, Kandil HM. 2006. Dietary fatty acids modulate chronic colitis, colitis-associated colon neoplasia and COX-2 expression in IL-10 knockout mice. Nutrition 22, 275- 282. doi:10.1016/j.nut.2005.06.006 PMid:16500554

Heimerl S, Moehle C, Zahn A, Boettcher A, Stremmel W, Langmann T, Schmitz G. 2006. Alterations in intestinal fatty acid metabolism in inflammatory bowel disease. Biochim. Biophys. Acta-Mol. Basis Dis. 1762, 341- 350.

Hudert CA, Weylandt KH, Lu Y, Wang JD, Hong S, Dignass A, Serhan CN, Kang JX. 2006. Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis. Proc. Natl. Acad. Sci. U. S. A. 103, 11276-11281. doi:10.1073/pnas.0601280103

Jurjus AR, Khoury NH, Reimund JM. 2004. Animal models of inflammatory bowel disease. J. Pharmacol. Toxicol. Methods 50, 81-92. doi:10.1016/j.vascn.2003.12.002 PMid:15385082

Kankaanpää PE, Salminen SJ, Isolauri E, Lee YK. 2001. The influence of polyunsaturated fatty acids on probiotic growth and adhesion. FEMS Microbiol. Lett. 194, 149-153.

Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. 1993. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75, 263-274. doi:10.1016/0092-8674(93)80068-P PMid:8402911

Kuroki F, Iida M, Matsumoto T, Aoyagi K, Kanamoto K, Fujishima M. 1997. Serum n-3 polyunsaturated fatty acids are depleted in Crohn’s disease. Dig. Dis. Sci. 42, 1137-1141. doi:10.1023/A:1018873217192 PMid:9201073

Kussmann M, Raymond F, Affolter M. 2006. OMICSdriven biomarker discovery in nutrition and health. J. Biotechnol. 124, 758-787. doi:10.1016/j.jbiotec.2006.02.014 PMid:16600411

Langmann T, Moehle C, Mauerer R, Scharl M, Liebisch G, Zahn A, Stremmel W, Schmitz G. 2004. Loss of detoxification in inflammatory bowel disease: Dysregulation of pregnane X receptor target genes. Gastroenterol. 127, 26-40. doi:10.1053/j.gastro.2004.04.019 PMid:15236169 Lu J, Jilling T, Li D, Caplan MS. 2007. Polyunsaturated fatty acid supplementation alters proinflammatory gene expression and reduces the incidence of necrotizing enterocolitis in a neonatal rat model. Pediatr. Res. 61, 427-432. doi:10.1203/pdr.0b013e3180332ca5 PMid:17515866

Maeda S, Hsu LC, Liu H, Bankston LA, Iimura M, Kagnoff MF, Eckmann L, Karin M. 2005. Nod2 mutation in Crohn’s disease potentiates NF-kappaB activity and IL-1beta processing. Science 307, 734-738. doi:10.1126/science.1103685 PMid:15692052

Mills SC, Windsor AC, Knight SC. 2005. The potential interactions between polyunsaturated fatty acids and colonic inflammatory processes. Clin. Exp. Immunol 142, 216-228. doi:10.1111/j.1365-2249.2005.02851.x

Mitsuyama K, Suzuki A, Tomiyasu N, Takaki K, Toyonaga A, Sata M. 2001. Transcription factor-targeted therapies in inflammatory bowel disease. Digestion 63, 68-72. doi:10.1159/000051914 PMid:11173913

Müller M, Kersten S. 2003. Nutrigenomics: goals and strategies. Nat. Rev. Genet 4, 315-322. doi:10.1038/nrg1047 PMid:12671662

Mutch DM, Grigorov M, Berger A, Fay LB, Roberts MA, Watkins SM, Williamson G, German JB. 2005. An integrative metabolism approach identifies stearoyl- CoA desaturase as a target for an arachidonateenriched diet. FASEB J. 19, 599-601. doi:10.1096/fj.05-3911rev PMid:16195369

Niess JH, Reinecker HC. 2006. Dendritic cells: the commanders-in-chief of mucosal immune defenses. Curr. Opin. Gastroenterol. 22, 354-360. doi:10.1097/01.mog.0000231807.03149.54 PMid:16760749

Nieto N, Torres MI, Rios A, Gil A. 2002. Dietary polyunsaturated fatty acids improve histological and biochemical alterations in rats with experimental ulcerative colitis. J. Nutr. 132, 11-19.

Nones K, Dommels YEM, Martell S, Butts C, McNabb WC, Park ZA, Zhu S, Hedderley D, Barnett MPG, Roy NC. 2008. The effects of dietary curcumin and rutin on colonic inflammation and gene expression in multiple drug resistance gene-deficient (mdr1a-/-) mice, a model of inflammatory bowel diseases. Brit. J. Nutr. Sep2 (ahead of publication), 1-13.

Podolsky DK. 2002. Inflammatory bowel disease. N. Engl. J. Med. 347, 417-429. doi:10.1056/NEJMra020831 PMid:12167685

Pru.fer K, Muetzel B, Do HH, Weiss G, Khaitovich P, Rahm E, Pääbo S, Lachmann M, Enard W. 2007. FUNC: a package for detecting significant associations between gene sets and ontological annotations.BMC Bioinformatics 8, 41.

Ramakers JD, Mensink RP, Verstege MI, Te Velde AA, Plat, J. 2008. An arachidonic acid-enriched diet does not result in more colonic inflammation as compared with fish oil- or oleic acid-enriched diets in mice with experimental colitis. Brit. J. Nutr. 100, 347-354. doi:10.1017/S0007114507901257 PMid:18205994 PMCid:2564112

Rivera E, Flores I, Rivera E, Appleyard CB. 2006. Molecular profiling of a rat model of colitis: Validation of known inflammatory genes and identification of novel disease-associated targets. Inflamm. Bowel Dis. 12, 950-966. doi:10.1097/01.mib.0000231575.11678.8c PMid:17012966

Roberts RL, Gearry RB, Hollis-Moffatt JE, Miller AL, Reid J, Abkevich V, Timms KM, Gutin A, Lanchbury JS, Merriman TR, Barclay ML, Kennedy MA. 2007. IL23R R381Q and ATG16L1 T300A are strongly associated with Crohn’s disease in a study of New Zealand Caucasians with inflammatory bowel disease. Am. J. Gastroenterol. 102, 2754-61. doi:10.1111/j.1572-0241.2007.01525.x PMid:17894849

Roy N, Barnett M, Knoch B, Dommels Y, McNabb W. 2007. Nutrigenomics applied to an animal model of inflammatory bowel diseases: Transcriptomic analysis of the effects of eicosapentaenoic acid and arachidonic acid-enriched diets. Mutat. Res.: Fundam. Mol. Mech. Mutagen 622, 103-116. doi:10.1016/j.mrfmmm.2007.04.003

Salter A, Tarling E. 2007. Regulation of gene transcription by fatty acids. Animal 1, 1314–1320. doi:10.1017/S1751731107000675

Sampath H, Ntambi J. M. 2005. Polyunsaturated fatty acid regulation of genes of lipid metabolism. Annu. Rev. Nutr. 25, 317-340. doi:10.1146/annurev.nutr.25.051804.101917 PMid:16011470

Sanderson LM, De Groot PJ, Hooiveld GJEJ, Koppen A, Kalkhoven E, Müller M, Kersten S. 2008. Effect of synthetic dietary triglycerides: A novel research paradigm for nutrigenomics. PLoS ONE 3, e1681.

Schmitz G, Ecker J. 2008. The opposing effects of n-3 and n-6 fatty acids. Prog. Lipid Res. 47, 147-155. doi:10.1016/j.plipres.2007.12.004 PMid:18198131

Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, Rennick DM, Sartor RB. 1998. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect. Immun. 66, 5224-5231.

Serhan CN, Chiang N. 2008. Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Brit. J. Pharmacol. 153, S200- S215. doi:10.1038/sj.bjp.0707489 PMid:17965751

Sheehan AL, Warren BF, Gear MWL, Shepherd NA. 1992. Fat-wrapping in Crohn’s disease - Pathological basis and relevance to surgical practice. Brit. J. Surg. 79, 955-958. doi:10.1002/bjs.1800790934 PMid:1422768

Shimizu T, Fujii T, Suzuki R, Igarashi J, Ohtsuka Y, Nagata S, Yamashiro Y. 2003. Effects of highly purified eicosapentaenoic acid on erythrocyte fatty acid composition and leukocyte and colonic mucosa leukotriene B4 production in children with ulcerative colitis. J. Pediatr. Gastroenterol. Nutr. 37, 581-585. doi:10.1097/00005176-200311000-00015 PMid:14581801

Shoda R, Matsueda K, Yamato S, Umeda N. 1995. Therapeutic Efficacy of n-3 polyunsaturated fatty-acid in experimental Crohn’s disease. J. Gastroenterol. 30, 98-101.

Simopoulos AP. 2002. Omega-3 fatty acids in inflammation and autoimmune diseases. J. Am. Coll. Nutr. 21, 495 - 505.

Soupene E, Kuypers FA. 2008. Mammalian long-chain Acyl-CoA synthetases. Exp. Biol. Med. 233, 507-521. Stahl A. 2004. A current review of fatty acid transport proteins (SLC27). Pflueg. Arch. Eur. J. Physiol 447, 722-727.

Stulnig TM. 2003. Immunomodulation by polyunsaturated fatty acids: Mechanisms and effects. Int. Arch. Allergy Immunol. 132, 310-321. doi:10.1159/000074898 PMid:14707462

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. 2005. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U. S. A 102, 15545-15550. doi:10.1073/pnas.0506580102

Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandezsueiro JL, Balish E, Hammer RE. 1994. The germ-free state prevents development of gut and joint inflammatory disease in Hla-B27 transgenic rats. J. Exp. Med. 180, 2359-2364. doi:10.1084/jem.180.6.2359 PMid:7964509 PMCid:2191772

Torres MI, Ríos A. 2008. Current view of the immunopathogenesis in inflammatory bowel disease and its implications for therapy.World J. Gastroenterol. 14, 1972-1980. doi:10.3748/wjg.14.1972 PMid:18395894 Vilaseca J, Salas A, Guarner F, Rodriguez R, Martinez M, Malagelada JR. 1990. Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis. Gut 31, 539-544. doi:10.1136/gut.31.5.539 PMid:2161781 PMCid:1378570

Whiting CV, Bland PW, Tarlton JE. 2005. Dietary n-3 polyunsaturated fatty acids reduce disease and colonic proinflammatory cytokines in a mouse model of colitis. Inflamm. Bowel Dis. 11, 340-349. doi:10.1097/01.MIB.0000164016.98913.7c PMid:15803023

Wiercinska-Drapalo A, Jaroszewicz J, Siwak E, Pogorzelska J, Prokopowicz D. 2008. Intestinal fatty acid binding protein (I-FABP) as a possible biomarker of ileitis in patients with ulcerative colitis. Regul. Pept. 147, 25-28. doi:10.1016/j.regpep.2007.12.002 PMid:18201778

Wu TC. 2007. The role of vascular cell adhesion molecule-1 in tumor immune evasion. Cancer Res. 67, 6003-6006. doi:10.1158/0008-5472.CAN-07-1543 PMid:17616653

Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, Mckenzie B, Kleinschek MA, Owyang A, Mattson J, Blumenschein W, Murphy E, Sathe M, Cua DJ, Kastelein RA, Rennick D. 2006. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J. Clin. Invest. 116, 1310-1316. doi:10.1172/JCI21404 PMid:16670770 PMCid:1451201

Yuceyar H, Ozutemiz O, Huseyinov A, Saruc M, Alkanat M, Bor S, Coker I, Batur Y. 1999. Is administration of n-3 fatty acids by mucosal enema protective against trinitrobenzene-induced colitis in rats? Prostaglandins Leukot. Essent. Fatty Acids 61, 339-345. doi:10.1054/plef.1999.0111




How to Cite

Knoch B, Barnett MP, Roy NC, McNabb WC. Study of the effects of dietary polyunsaturated fatty acids: Molecular mechanisms involved in intestinal inflammation. grasasaceites [Internet]. 2009Mar.30 [cited 2022Dec.7];60(1):8-21. Available from: