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2003 Fiscal Year Final Research Report Summary

Prevention of inflammatory diseases by regulating the production of lipid mediators-basic and clinical studies

Research Project

Project/Area Number 13470500
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionNagoya City University, Graduate School Pharmaceutical Sciences

Principal Investigator

OKUYAMA Harumi  Nagoya City University, Grad.Sch.Pharm.Sci., Professor, 大学院・薬学研究科, 教授 (90080176)

Co-Investigator(Kenkyū-buntansha) ICHIKAWA Yuko  Nagoya City University, Grad.Sch.Pharm.Sci., Research Associate, 大学院・薬学研究科, 助手 (80173441)
FUJII Yoichi  Nagoya City University, Grad.Sch.Pharm.Sci., Assoc.Professor, 大学院・薬学研究科, 助教授 (50165346)
Project Period (FY) 2001 – 2003
Keywordsinflammation / atopic dermatitis / cancer / prevention / linoleic acid / alpha-linolenic acid / arachidonic acid / lipid mediator
Research Abstract

Inflammatory diseases include allergy, cancers of the Western type and many kinds of so-called intractable diseases. We interpreted that persistent inflammation is a major cause for the increased incidence of these diseases in Japan in the past half a century, and that these inflammatory diseases could be prevented by regulating the production of inflammatory mediators. At present, no safe means has been found to regulate the production of peptide mediators. However, the amounts and activities of lipid mediators can be modified safely by reducing the intake of n-6 fatty acids and increasing that of n-3 fatty acids in foods.
In animal experiments, reducing the content of linoleic acid (n-6) and increasing that of α-linolenic acid (n-3) or fish oil enriched with EPA (n-3) and DHA (n-3) were shown to suppress the productions and activites of lipid kidney was suppressed similarly, and some results from animal experiments are collected in this report.
On the other hand, we collaborated with clinicians to perform clinical trials aimed at treating atopic dermatitis and colorectal tumors by lowering the n-6/-3 ratio of fatty acids in foods. Subjects with atopic dermatitis (n=76) were advised to select foods so as to lower the n-6/n-3 ratio of ingested fatty acids, and were followed for 2 years to find that this means is very promising for the improvement of hyper-allergic constitution. In the randomized control trial for the suppression of recurrence of colorectal polyps after polypectomy, the number of subjects participating in the trial has been increasing. When the number of subjects was 20 in each group, this method seemed to be promising, too.
These results support our interpretation that increased linoleic acid intake (>2.5 times high compared with the level of 40 years ago, several-fold higher than the essential amount) and relative n-3 fatty acid deficiency are the major causes for the increases in the incidence of these diseases.

  • Research Products

    (49 results)

All Other

All Publications (49 results)

  • [Publications] Yoshida, S., Miyazaki, M., Zhang, QZ, Sakaki, K., Fujimoto, I., Ikenaka, K., Ikemoto, A., Watanabe, S., Okuyama, H.: "Change of oligosaccharides of rat brain microsomes depending on dietary fatty acids and learning task."J.Neurosci.Res.. 63. 185-195 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Du, C., Sato, A., Watanabe, S., Ikemoto, A., Fujii, Y., Okuyama, H.: "Effect of dietary oils enriched with n-3 fatty acids on survival of mice."J.Nutr.Biochem.. 12. 474-480 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikemoto, A., Ohishi, M., Sato, Y., Hata, N., Misawa, Y., Fujii, Y., Okuyama, H.: "Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat: level of n-6 fatty acids as another critical factor."J.Lipid Res.. 42. 1655-1663 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hatama, S., Otake, K., Ohta, M., Kobayashi, M., Imakawa, K., Ikemoto, A., Okuyama, H., Mochizuki, M., Miyazawa, T., Tohya, Y., Fujii, Y., Takahashi, E.: "Reactivation of feline foamy virus from a chronically infected feline renal cell line by Trichostatin A."Virology.. 283. 315-323 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takemura, N., Takahashi, K., Tanaka, H., Ihara, Y., Ikemoto, A., Fujii, Y., Okuyama, H.: "Dietary, but not topical, alpha-linolenic acid suppresses UVB-induced skin injury in hairless mice when compared with linoleic acid."J.Photochem.Photobiol.. 76. 657-663 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tokudome, S., Imaeda, N., Tokudome, Y., Kuriki, K., Cheng, J., Fujii, T., Goto, C., Nagaya, T., Ichikawa, H., Okuyama, H.: "Correspondence re: Terry et al., No association between fat and fatty acid intake and risk of colorectal cancer."Cancer Epidemiol.Biomark.Prev.. 11. 217-218 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tokudome, S., Yokoyama, Y., Kamiya, T., Seno, K., Okuyama, H., Kuriki, K., Cheng, J., Nakamura, T., Fujii, T., Ichikawa, H., Itoh, M.: "Rationale and study design of dietary intervention in patients polypectomized for tumors of the colorectum."Jpn.J.Clin.Oncol.. 32. 550-553 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto, T., Omoto, S., Mizuguchi, M., Mizukami, H., Okuyama, H., Okada, N., Saksena, N.K., Brisibe, E.A., Otake, K., Fujii, R.Y: "Double-stranded nef RNA interferes with human immunodeficiency virus type 1 replication."Microbiol.Immunol.. 46(11). 809-817 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyazawa, D., Ikemoto, A., Fujii, Y., Okuyama, H.: "Partial purification and characterization of phosphatidic acid-specitic phospholipase A1 in porcine platelet membranes."Biochim.Biophys.Acta.. 1631. 17-25 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Umezawa, M., Tatematsu, K., Korenaga, T., Fu, X., Matsushita, T., Okuyama, H., Hosokawa, M., Takeda, T., Higuchi, K.: "Dietary fat modulation of apoA-II metabolism and prevention of senile amyloidosis in the senescence-accelerated mouse."J.Lipid Res.. 44. 762-769 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyazawa, D., Ikemoto, A., Fujii, Y., Okuyama, H.: "Dietary alpha-linolenic acid suppresses the formation of lysophosphatidic acid, a lipid mediator, in rat platelets compared with linoleic acid."Life Sci.. 73. 2083-2090 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Du, C., Sato, S., Watanabe, S., Wu, C-Z., Ikemoto, A., Ando, K., Kikugawa, K., Fujii, Y.and Okuyama, H.: "Cholesterol synthesis in mice is suppressed but lipofuscin formation is not affected by long-term feeding of n-3 fatty acid-enriched oils compared with lard and n-6 fatty acid-enriched oils."Biol.Pharm.Bull.. 26(6). 766-770 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujii, Y., Murase, Y., Otake, K., Yokota, Y., Omoto, S., Hayashi, H., Okada, H., Okada, N., Kawai, M.Okuyama, H., Imakawa, K.: "A potential live vector, foamy virus, directed intra-cellular expression of ovine interferon-t exhibited the resistance to HIV infection."J.Vet.Med.Sci.. 66(2). 115-121 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Brisibe, EA., Okada, N., Mizukami, H., Okuyama, H., Fujii, RY.: "RNA interference: potentials for the prevention of HIV infections and the challenges ahead."trends in Biotec.. 21(7). 306-311 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tatematsu, K., Hirose, N., Ichikawa, Y., Fujii, Y, Takami, A., Okuyama, H.: "Nutritional Evaluation of an Inter-Esterified Perilla Oil and Lard in Comparison with Butter and Margarine Based on the Survival of Stroke-Prone Spontaneously Hypertensive (SHRSP) Rats."J.Health Sci.. 50(1). 108-111 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Du, C., Fujii, Y., Ito, M., Harada, M., Moriyama, E., Shimada, R., Ikemoto, A., Okuyama, H.: "Dietary polyunsaturated fatty acids suppress acute hepatitis, alter gene expression and prolong survival of Long-Evans Cinnamon rats, a model of Wilson Disease."J.Nutr.Biochem.. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tokudome, S., Kuriki, K., Suzuki, S., Imaeda, N., Goto, C., Tokudome, Y., Takeda, E., Ichikawa, Y., Okuyama.H.: "n-6 Polyunsaturated fatty acids and breast cancer."Nutr.Cancer. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tokudome, S., Ichikawa, Y., Okuyama, H., Tokudome, Y., Goto, C., Imaeda, N., Kuriki, K., Suzuki, S., Shibata, K., Jiang, J., Wang, J., Takeda, E.: "The Mediterranean vs the Japanese diet."Eur.J.Clin.Nutr.. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tatematsu, K., Fuma, S., Satoh, J., Ichikawa, Y., Fujii, Y., Okuyama, H.: "Dietary canola oil and soybean oil fed to SHRSP rat dams differently affect the growth and survival of their male pups."J.Nutr.. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tatematsu, K., Fuma, S., Nagase, T., Ichikawa, Y., Fujii, Y., Okuyama, H.: "Factors other than phytosterols in vegetable oils affect the survival of SHRSP rats."Food Chem.Toxicol.. (accepted). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuyama, H., Ohishi, M., Fukuma, A., Sato, Y., Ikemoto, A., Fujii, Y.: "α-Linolenate-deficiencyinduced alterations in brightness-discrimination learning behavior and retinal functions in rats."Fatty Acids and Lipids - New Findings.. 8. (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuyama, H.: "High n-6 to n-3 ratio of dietary fatty acids rather than serum cholesterol as a major risk factor for coronary heart disease."Eur.J.Lipid Sci.Technol.. 103. (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuyama, H., Fujii, Y., Ikemoto, A.: "Brightness-Discrimination learning behavior and retinal function affected by long-term a-linolenic acie deficiency in rat."Fatty Acids: Physiological and Behavioral Functions.. (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuyama, H., Tatematsu, K., Hirose, N., Kato, T., Chiba, S., Nagata, Y.: "Suppression of allergic hyper reactivity by lowering the n-6/n-3 ratio of dietary fatty acids: basic and clinical studies."1st International Congress on the Columbus Concept. (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hamazaki, T., Okuyama, H.: "World Rev.Nutr.Diet, The Japan Society for Lipid Nutrition recommends to reduce the intake of linoleic acid."Basel, Karger. 24 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida, S., Miyazaki, M., Zhang, QZ, Sakaki, K., Fujimoto, I., Ikenaka, K., Ikemoto, A., Watanabe, S., Okuyama, H.: "Change of oligosaccharides of rat brain microsomes depending on dietary fatty acids and learning task."J.Neurosci.Res.. 63. 185-195 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Du, C., Sato, A., Watanabe, S., Ikemoto, A., Fujii, Y., Okuyama, H.: "Effect of dietary oils enriched with n-3 fatty acids on survival of mice."J.Nutr.Biochem.. 12. 474-480 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikemoto, A., Ohishi, M., Sato, Y., Hata, N., Misawa, Y., Fujii, Y., Okuyama, H.: "Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat : level of n-6 fatty acids as another critical factor."J.Lipid Res.. 42. 1655-1663 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hatama, S., Otake, K., Ohta, M., Kobayashi, M., Imakawa, K., Ikemoto, A., Okuyama, H., Mochizuki, M., Miyazawa, T., Tohya, Y., Fujii, Y., Takahashi, E.: "Reactivation of feline foamy virus from a chronically infected feline renal cell line by Trichostatin A."Virology.. 283. 315-323

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takemura, N., Takahashi, K., Tanaka, H., Ihara, Y., Ikemoto, A., Fujii, Y., Okuyama, H.: "Dietary, but not topical, alpha-linolenic acid suppresses UVB-induced skin injury in hairless mice when compared with linoleic acid."J.Photochem.Photobiol.. 76. 657-663 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokudome, S., Imaeda, N., Tokudome, Y., Kuriki, K., Cheng, J., Fujii, T., Goto, C., Nagaya, T., Ichikawa, H., Okuyama, H.: "Correspondence re : Terry et al., No association between fat and fatty acid intake and risk of colorectal cancer."Cancer Epidemiol.Biomark.Prev.. 11. 217-218 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokudome, S., Yokoyama, Y., Kamiya, T., Seno, K., Okuyama, H., Kuriki, K., Cheng, J., Nakamura, T., Fujii, T., Ichikawa, H., Itoh, M.: "Rationale and study design of dietary intervention in patients polypectomized for tumors of the colorectum."Jpn.J.Clin.Oncol.. 32. 550-553 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto, T., Omoto, S., Mizuguchi, M., Mizukami, H., Okuyama, H., Okada, N., Saksena, N.K., Brisibe, E.A., Otake, K., Fujii, R.Y.: "Double-stranded nef RNA interferes with human immunodeficiency virus type 1 replication."Microbiol.Immunol.. 6(11). 809-817 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyazawa, D., Ikemoto, A., Fujii, Y., Okuyama, H.: "Partial purification and characterization of phosphatidic acid-specific phospholipase A1 in porcine platelet membranes."Biochim.Biophys.Acta.. 1631. 17-25 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Umezawa, M., Tatematsu, K., Korenaga, T., Fu, X., Matsushita, T., Okuyama, H., Hosokawa, M., Takeda, T., Higuchi, K.: "Dietary fat modulation of apoA-II metabolism and prevention of senile amyloidosis in the senescence-accelerated mouse."J.Lipid Res.. 44. 762-769 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyazawa, D., Ikemoto, A., Fujii, Y., Okuyama, H.: "Dietary alpha-Linolenic acid suppresses the formation of lysophosphatidic acid, a lipid mediator, in rat platelets compared with linoleic acid."Life Sci.. 73. 2083-2090 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Du, C., Sato, S., Watanabe, Sl, Wu, C-Z., Ikemoto, A., Ando, K., Kikugawa, K., Fujii, Y., Okuyama, H.: "Cholesterol synthesis in mice is suppressed but lipofuscin formation is not affected by long-term feeding of n-3 fatty acid-enriched oils compared with lard and n-6 fatty acid-enrich oils."Biol.Pharm.Bull.. 6(6). 766-770 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujii, Y., Murase, Y., Otake, K., Yokota, Y., Omoto, S., Hayashi, H., Okada, H., Okada, N., Kawai, M., Okuyama, H., Imakawa, K.: "A potential live vector, foamy virus, directed Intra-Cellular expression of ovine Interferon-τ exhibited the resistance to HIV infection."J.Vet.Med.Sci.. 66(2). 115-121 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatematsu, K., Hirose, N., Ichikawa, Y., Fujii, Y., Takami, A., Okuyama, H.: "Nutritional Evaluation of an Inter-Esterified Perilla Oil and Lard in Comparison with Butter and Margarine Based on the Survival of Stroke-Prone Spontaneously Hypertensive (SHRSP) Rats."J.Health Sci.. 50(1). 108-111 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Du, C., Fujii, Y., Ito, M., Harada, M., Moriyama, E., Shimada, R., Ikemoto, A., Okuyama, H.: "Dietary polyunsaturated fatty acids suppress acute hepatitis, alter gene expression and prolong survival of Long-Evans Cinnamon rats, a model of Wilson Disease."J.Nutr.Biochem.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokudome, S., Kuriki, K., Suzuki, S., Imaeda, N., Goto, C., Tokudome, Y., Takeda, E., Ichikawa, Y., Okuyama, H.: "n-6 Polyunsaturated fatty acids and breast cancer."Nutr.Cancer. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokudome, S., Ichikawa, Y., Okuyama, H., Tokudome, Y., Goto, C., Imaeda, N., Kuriki, K., Suzuki, S., Shibata, K., Jiang, J., Wang, J., Takeda, E.: "The Mediterranean vs the Japanese diet."Eur.J.Clin.Nutr.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatematsu, K., Fuma, S., Satoh, J., Ichikawa, Y., Fujii, Y., Okuyama, H.: "Dietary canola oil and soybean oil fed to SHRSP rat dams differently affect the growth and survival of their male pups."J.Nutr.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatematsu, K., Fuma, S., Nagase, T., Ichikawa, Y., Fujii, Y., Okuyama, H.: "Factors other than phytosterol in vegetable oils affect the survival of SHRSP rats."Food Chem.Toxicol.. (accepted). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okuyama, H., Ohishi, M., Fukuma, A., Sato, Y., Ikemoto, A., Fujii, Y.: "α-Linolenate-deficiency-induced alterations in brightness-discrimination learning behavior and retinal functions in rats."Fatty Acids and Lipids -New Findings.. 88. 35-40 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okuyama, H: "High n-6 to n-3 ratio of dietary fatty acids rather fatty acids rather than serum cholesterol as a major risk factor for coronary heart disease."Eur.J.Lipid Sci.Technol.. 103. 418-422 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okuyama, H., Fujii, Y., Ikemoto, A.: "Brightness-Discrimination learning behavior and retinal function affected by long-term α-linolenic acie deficiency in rat."Fatty Acids : Physiological and Behavioral Functions.. 103. 418-422 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okuyama, H., Tatematsu, K., Hirose, N., Kato, T., Ohiba, S., Nagata, Y.: "Suppression of allergic hyper reactivity by lowering the n-6/n-3 ratio of dietary fatty acids : Basic and clinical studies."1st International Congress on the Columbus Concept.(Belovo S.A., Belgium). 119-126 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hamazaki, T., Okuyama, H.: "The Japan Society for Lipid Nutrition recommends to reduce the intake of linoleic acid."World Rev.Nutr.Diet.(Karger, Basel, Switzerland). 109-132 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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