, Volume 45, Issue 9, pp 843–854 | Cite as

Potential of Magnetic Resonance Spectroscopy in Assessing the Effect of Fatty Acids on Inflammatory Bowel Disease in an Animal Model

  • Sonal Varma
  • Michael N. A. Eskin
  • Ranjana Bird
  • Brion Dolenko
  • Jayadev Raju
  • Omkar B. Ijare
  • Tedros Bezabeh
Original Article


People with inflammatory bowel disease (IBD) are at risk for developing colorectal cancer, and this risk increases at a rate of 1% per year after 8–10 years of having the disease. Saturated and ω-6 polyunsaturated fatty acids (PUFAs) have been implicated in its causation. Conversely, ω-3 PUFAs may have the potential to confer therapeutic benefit. Since proton magnetic resonance spectroscopy (1H MRS) combined with pattern recognition methods could be a valuable adjunct to histology, the objective of this study was to analyze the potential of 1H MRS in assessing the effect of dietary fatty acids on colonic inflammation. Forty male Sprague-Dawley rats were administered one of the following dietary regimens for 2 weeks: low-fat corn oil (ω-6), high-fat corn oil (ω-6), high-fat flaxseed oil (ω-3) or high-fat beef tallow (saturated fatty acids). Half of the animals were fed 2% carrageenan to induce colonic inflammation similar to IBD. 1H MRS and histology were performed on ex vivo colonic samples, and the 1H MR spectra were analyzed using a statistical classification strategy (SCS). The histological and/or MRS studies revealed that different dietary fatty acids modulate colonic inflammation differently, with high-fat corn oil being the most inflammatory and high-fat flaxseed oil the least inflammatory. 1H MRS is capable of identifying the biochemical changes in the colonic tissue as a result of inflammation, and when combined with SCS, this technique accurately differentiated the inflamed colonic mucosa based on the severity of the inflammation. This indicates that MRS could serve as a valuable adjunct to histology in accurately assessing colonic inflammation. Our data also suggest that both the type and the amount of fatty acids in the diet are critical in modulating IBD.


Beef tallow Corn oil Flaxseed oil Inflammatory bowel disease Proton magnetic resonance spectroscopy Statistical classification strategy 



Free induction decay


Genetic-algorithm-based optimal region selection


Gas chromatography


Hematoxylin and eosin


High-fat beef tallow


High-fat corn oil


High-fat flaxseed oil


High-performance liquid chromatography


High-resolution magic angle spinning


Inflammatory bowel disease


Linear discriminant analysis


Low-fat corn oil




Magnetic resonance spectroscopy


Platelet activating factor


Phosphate-buffered saline in deuterium oxide


Polyunsaturated fatty acids


Statistical classification strategy


3-Trimethylsilylpropionic acid-d4 sodium salt

List of symbols









We would like to thank Saro Bascaramurty, who was the key resource for tissue sectioning and staining for histological assessment. We thank the Natural Sciences and Engineering Research Council of Canada (NSERC) for the strategic project grant to R.P. Bird, M. Eskin and T. Bezabeh.

Conflict of interest

There are no conflicts of interest to report.


  1. 1.
    Loftus EV (2004) Clinical epidemiology of inflammatory bowel disease: incidence, prevalence and environmental influences. Gastroenterology 126:1504–1517CrossRefPubMedGoogle Scholar
  2. 2.
    Shoda R, Matsueda K, Yamato S, Umeda N (1996) Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr 63:741–745PubMedGoogle Scholar
  3. 3.
    Stenson WF, Cort D, Rodgers J, Burakoff R, DeSchryver-Kecskemeti K, Gramlich TL, Beeken W (1992) Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med 116:609–614PubMedGoogle Scholar
  4. 4.
    Lands WE (1992) Biochemistry and physiology of n-3 fatty acids. FASEB J 6:2530–2536PubMedGoogle Scholar
  5. 5.
    Eaden JA, Abrams KR, Mayberry JF (2001) The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48:526–535CrossRefPubMedGoogle Scholar
  6. 6.
    Bezabeh T, Somorjai RL, Smith ICP, Nikulin AE, Dolenko B, Bernstein CN (2001) The use of 1H magnetic resonance spectroscopy in inflammatory bowel diseases: distinguishing ulcerative colitis from Crohn’s disease. Am J Gastroenterol 96:442–448CrossRefPubMedGoogle Scholar
  7. 7.
    Varma S, Bird R, Eskin M, Dolenko B, Raju J, Bezabeh T (2007) Detection of inflammatory bowel disease by proton magnetic resonance spectroscopy (1H MRS) using an animal model. J Inflamm (Lond) 4:24CrossRefGoogle Scholar
  8. 8.
    Kriat M, Vion-Dury J, Confort-Gouny S, Favre R, Viout P, Sciaky M, Sari H, Cozzone PJ (1993) Analysis of plasma lipids by NMR spectroscopy: application to modifications induced by malignant tumors. J Lipid Res 34:1009–1019PubMedGoogle Scholar
  9. 9.
    Adosraku RK, Choi GT, Constantinou-Kokotos V, Anderson MM, Gibbons WA (1994) NMR lipid profiles of cells, tissues, and body fluids: proton NMR analysis of human erythrocyte lipids. J Lipid Res 35:1925–1931PubMedGoogle Scholar
  10. 10.
    Singer S, Sivaraja M, Souza K, Millis K, Corson JM (1996) 1H-NMR detectable fatty acyl chain unsaturation in excised leiomyosarcoma correlate with grade and mitotic activity. J Clin Invest 98:244–250CrossRefPubMedGoogle Scholar
  11. 11.
    Gunstone FD (1994) High resolution 13C NMR. A technique for the study of lipid structure and composition. Prog Lipid Res 33:19–28CrossRefPubMedGoogle Scholar
  12. 12.
    Martin FP, Wang Y, Sprenger N, Holmes E, Lindon JC, Kochhar S, Nicholson JK (2007) Effects of probiotic Lactobacillus paracasei treatment on the host gut tissue metabolic profiles probed via magic-angle-spinning NMR spectroscopy. J Proteome Res 6:1471–1481CrossRefPubMedGoogle Scholar
  13. 13.
    Sands CJ, Coen M, Maher AD, Ebbels TM, Holmes E, Lindon JC, Nicholson JK (2009) Statistical total correlation spectroscopy editing of 1H NMR spectra of biofluids: application to drug metabolite profile identification and enhanced information recovery. Anal Chem 81:6458–6466CrossRefPubMedGoogle Scholar
  14. 14.
    Bjerrum JT, Nielsen OH, Hao F, Tang H, Nicholson JK, Wang Y, Olsen J (2010) Metabonomics in ulcerative colitis: diagnostics, biomarker identification, and insight into the pathophysiology. J Proteome Res 9:954–962CrossRefPubMedGoogle Scholar
  15. 15.
    Nikulin AE, Dolenko B, Bezabeh T, Somorjai RL (1998) Near-optimal region selection for feature space reduction: novel preprocessing methods for classifying MR spectra. NMR Biomed 11:209–217CrossRefPubMedGoogle Scholar
  16. 16.
    Somorjai RL, Alexander M, Baumgartner R, Booth S, Bowman C, Demko A, Dolenko B, Mandelzweig M, Nikulin AE, Pizzi N, Pranckeviciene E, Summers R, Zhilkin P (2004) A data-driven, flexible machine learning strategy for the classification of biomedical data. In: Azuaje F, Dubitsky W (eds) Computational biology, vol 5: artificial intelligence methods and tools for systems biology. Kluwer Academic Publishers, Boston, pp 67–85Google Scholar
  17. 17.
    Briere KM, Kuesel AC, Bird RP, Smith ICP (1995) 1H MR visible lipids in colon tissue from normal and carcinogen-treated rats. NMR Biomed 8:33–40CrossRefPubMedGoogle Scholar
  18. 18.
    Kuesel AC, Kroft T, Saunders JK, Prefontaine M, Mikhael N, Smith ICP (1992) A simple procedure for obtaining high-quality NMR spectra of semiquantitative value from small tissue specimens: cervical biopsies. Magn Reson Med 27:349–355CrossRefPubMedGoogle Scholar
  19. 19.
    AOCS Official Method Ce 1–62. (1998) Fatty acid composition by packed column gas chromatography, American Oil Chemist’s Society—official methods and recommended protocols. AOCS Press, ChampaignGoogle Scholar
  20. 20.
    Righi V, Durante C, Cocchi M, Calabrese C, Di Febo G, Lecce F, Pisi A, Tugnoli V, Mucci A, Schenetti L (2009) Discrimination of healthy and neoplastic human colon tissues by ex vivo HR-MAS NMR spectroscopy and chemometric analyses. J Proteome Res 8:1859–1869CrossRefPubMedGoogle Scholar
  21. 21.
    Lean CL, Newland RC, Ende DA, Bokey EL, Smith ICP, Mountford CE (1993) Assessment of human colorectal biopsies by 1H MRS: correlation with histopathology. Magn Reson Med 30:525–533CrossRefPubMedGoogle Scholar
  22. 22.
    Smith ICP, Blandford DE (1998) Diagnosis of cancer in humans by 1H NMR of tissue biopsies. Biochem Cell Biol 76:472–476CrossRefPubMedGoogle Scholar
  23. 23.
    Bezabeh T, Smith ICP, Krupnik E, Somorjai RL, Kitchen DG, Bernstein CN, Pettigrew NM, Bird RP, Lewin KJ, Briere KM (1996) Diagnostic potential for cancer via 1H magnetic resonance spectroscopy of colon tissue. Anticancer Res 16:1553–1558PubMedGoogle Scholar
  24. 24.
    Ende D, Rutter A, Russell P, Mountford CE (1996) Chemical shift imaging of human colorectal tissue (ex vivo). NMR Biomed 9:179–183CrossRefPubMedGoogle Scholar
  25. 25.
    Jockers-Wretou E, Giebel W, Pfleiderer G (1977) Immunohistochemical localization of creatinkinase isoenzymes in human tissue. Histochemistry 54:83–95CrossRefPubMedGoogle Scholar
  26. 26.
    Graeber GM, Cafferty PJ, Wolf RE, Harmon JW (1984) An analysis of creatine phosphokinase in the mucosa and the muscularis of the gastrointestinal tract. J Surg Res 37:376–382CrossRefPubMedGoogle Scholar
  27. 27.
    Clandinin MT, Cheema S, Field CJ, Garg ML, Venkatraman J, Clandinin TR (1991) Dietary fat: exogenous determination of membrane structure and cell function. FASEB J 5:2761–2769PubMedGoogle Scholar
  28. 28.
    Simopoulos AP (2002) Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 21:495–505PubMedGoogle Scholar
  29. 29.
    Nishida T, Miwa H, Shigematsu A, Yamamoto M, Iida M, Fujishima M (1987) Increased arachidonic acid composition of phospholipids in colonic mucosa from patients with active ulcerative colitis. Gut 28:1002–1007CrossRefPubMedGoogle Scholar
  30. 30.
    Nieto N, Giron MD, Suarez MD, Gil A (1998) Changes in plasma and colonic mucosa fatty acid profiles in rats with ulcerative colitis induced by trinitrobenzene sulfonic acid. Dig Dis Sci 43:2688–2695CrossRefPubMedGoogle Scholar
  31. 31.
    Rashid A, Pizer ES, Moga M, Milgraum LZ, Zahurak M, Pasternack GR, Kuhajda FP, Hamilton SR (1997) Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia. Am J Pathol 150:201–208PubMedGoogle Scholar
  32. 32.
    Robblee NM, Farnworth ER, Bird RP (1998) Phospholipid profile and production of prostanoids by murine colonic epithelium: effect of dietary fat. Lipids 23:334–339CrossRefGoogle Scholar
  33. 33.
    Robblee NM, Bird RP (1994) Effects of high corn oil diet on preneoplastic murine colons: prostanoid production and lipid composition. Lipids 29:67–71CrossRefPubMedGoogle Scholar
  34. 34.
    Hawthorne AB, Daneshmend TK, Hawkey CJ, Belluzzi A, Everitt SJ, Holmes GK, Malkinson C, Shaheen MZ, Willars JE (1992) Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. Gut 33:922–928CrossRefPubMedGoogle Scholar
  35. 35.
    Bartolí R, Fernández-Bañares F, Navarro E, Castellà E, Mañé J, Alvarez M, Pastor C, Cabré E, Gassull MA (2000) Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E(2) synthesis. Gut 46:191–199CrossRefPubMedGoogle Scholar
  36. 36.
    James LA, Lunn PG, Elia M (1998) Glutamine metabolism in the gastrointestinal tract of the rat assess by the relative activities of glutaminase (EC and glutamine synthetase (EC Br J Nutr 79:365–372CrossRefPubMedGoogle Scholar
  37. 37.
    James LA, Lunn PG, Middleton S, Elia M (1998) Distribution of glutaminase and glutamine synthetase activities in the human gastrointestinal tract. Clin Sci 94:313–319PubMedGoogle Scholar
  38. 38.
    Giaroni C, Zanetti E, Chiaravalli AM, Albarello L, Dominioni L, Capella C, Lecchini S, Frigo G (2003) Evidence for a glutamatergic modulation of the cholinergic function in the human enteric nervous system via NMDA receptors. Eur J Pharmacol 476:63–69CrossRefPubMedGoogle Scholar
  39. 39.
    Wang FY, Zhu RM, Maemura K, Hirata I, Katsu K, Watanabe M (2006) Expression of gamma-aminobutyric acid and glutamic acid decarboxylases in rat descending colon and their relation to epithelial differentiation. Chin J Dig Dis 7:103–108CrossRefPubMedGoogle Scholar
  40. 40.
    Cullis PR, Hope MJ (1992) Physical properties and functional roles of lipids in membranes. In: Vance DE (ed) Biochemistry of lipids, lipoproteins and membranes. Elsevier Science publishers, Amsterdam, pp 1–41Google Scholar
  41. 41.
    White DA (1973) The phospholipid composition of mammalian tissue. In: Ansell GB, Hawthorne JN, Dawson RMC (eds) Form and function of phospholipids. Elsevier Scienctific publishing Co, Amsterdam, pp 441–482Google Scholar
  42. 42.
    Snyder F (1997) CDP-choline:alkylacetylglycerol cholinephosphotransferase catalyzes the final step in the de novo synthesis of platelet-activating factor. Biochim Biophys Acta 4(1348):111–116Google Scholar
  43. 43.
    Henneberry AL, Wistow G, McMaster CR (2000) Cloning, genomic organization, and characterization of a human cholinephosphotransferase. J Biol Chem 275:29808–29815CrossRefPubMedGoogle Scholar
  44. 44.
    Thyssen E, Turk J, Bohrer A, Stenson WF (1996) Quantification of distinct molecular species of platelet activating factor in ulcerative colitis. Lipids 31:255–259CrossRefGoogle Scholar
  45. 45.
    Hocke M, Richter L, Bosseckert H, Eitner K (1999) Platelet activating factor in stool from patients with ulcerative colitis and Crohn’s disease. Hepatogastroenterology 46:2333–2337PubMedGoogle Scholar
  46. 46.
    Sharma U, Singh RR, Ahuja V, Makharia GK, Jagannathan NR (2010) Similarity in the metabolic profile in macroscopically involved and un-involved colonic mucosa in patients with inflammatory bowel disease: an in vitro proton (1H) MR spectroscopy study. Magn Reson Imaging 28:1022–1029CrossRefPubMedGoogle Scholar
  47. 47.
    Balasubramanian K, Kumar S, Singh RR, Sharma U, Ahuja V, Makharia GK, Jagannathan NR (2009) Metabolism of the colonic mucosa in patients with inflammatory bowel diseases: an in vitro proton magnetic resonance spectroscopy study. Magn Reson Imaging 27:79–86CrossRefPubMedGoogle Scholar
  48. 48.
    Bamba T, Shimoyama T, Sasaki M, Tsujikawa T, Fukuda Y, Koganei K, Hibi T, Iwao Y, Munakata A, Fukuda S, Matsumoto T, Oshitani N, Hiwatashi N, Oriuchi T, Kitahora T, Utsunomiya T, Saitoh Y, Suzuki Y, Nakajima M (2003) Dietary fat attenuates the benefits of an elemental diet in active Crohn’s disease: a randomized, controlled trial. Eur J Gastroenterol Hepatol 15:151–157CrossRefPubMedGoogle Scholar
  49. 49.
    Reddy BS, Narisawa T, Vukusich D, Weisburger JH, Wynder EL (1976) Effect of quality and quantity of dietary fat and dimethylhydrazine in colon carcinogenesis in rats. Proc Soc Exp Biol Med 151:237–239PubMedGoogle Scholar
  50. 50.
    Rao CV, Hirose Y, Indranie C, Reddy BS (2001) Modulation of experimental colon tumorigenesis by types and amounts of dietary fatty acids. Cancer Res 61:1927–1933PubMedGoogle Scholar

Copyright information

© Her Majesty the Queen in Right of Canada 2010

Authors and Affiliations

  • Sonal Varma
    • 1
    • 2
    • 5
  • Michael N. A. Eskin
    • 2
  • Ranjana Bird
    • 3
  • Brion Dolenko
    • 1
  • Jayadev Raju
    • 4
  • Omkar B. Ijare
    • 1
  • Tedros Bezabeh
    • 1
    • 2
  1. 1.National Research Council Institute for BiodiagnosticsWinnipegCanada
  2. 2.Department of Human Nutritional SciencesUniversity of ManitobaWinnipegCanada
  3. 3.Department of Biological SciencesUniversity of WindsorWindsorCanada
  4. 4.Department of BiologyUniversity of WaterlooWaterlooCanada
  5. 5.Department of Pathology and Molecular MedicineQueen’s UniversityKingstonCanada

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