糖尿病予防効果を及ぼすオメガ3系多価不飽和脂肪酸活性化ペプチドの探索と機能解析

• Project/Area Number: 11J10925
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 国内
• Research Field: Applied health science
• Research Institution: Kitasato University
• Principal Investigator: 川島 祐介 北里大学, 理学部, 特別研究員(PD)
• Project Period (FY): 2011 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,400,000 (Direct Cost: ¥2,400,000); Fiscal Year 2013: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2012: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2011: ¥800,000 (Direct Cost: ¥800,000)
• Keywords: オメガ3系脂肪酸 / 糖尿病 / プロテオミクス / オメガ3系多価不飽和脂肪酸 / fat-1マウス

Research Abstract

食文化の欧米化や運動不足に伴い、糖尿病は、年々増加の一途をたどっている。現在、我が国の成人の5人に1人、40歳以上では3人に1人が糖尿病とその予備軍をいわれている。これによる死亡率の上昇や、医療費の増大は社会的な問題となっている。近年、魚油に豊富に含まれるオメガ3系多価不飽和脂肪酸が循環器疾患をはじめ糖尿病などに予防効果をもたらすという報告が数多くされ注目されている。しかしながら、その作用メカニズムは未だに不明な点が多い。そこで、本研究では、実験動物を用いてオメガ3系多価不飽和脂肪酸の糖尿病に対する予防効果を検証し、プロテオミクス・ペプチドミクスの手法を用いて、その作用メカニズム解明を目指し研究を進めている。昨年度までに、55%脂肪含有食で誘導した糖尿病に対するオメガ3系不飽和脂肪酸の効果を調べ、オメガ3系不飽和脂肪酸による明確な糖尿病抑制作用を確認することに成功した。本年度は、このマウスの肝臓を用いて、大規模なプロテオーム・ペプチドーム解析を行った。その結果、合計で3469種類のタンパク質が同定され、その内の287種類のタンパク質がオメガ3系不飽和脂肪酸によって変動した。さらに、変動したタンパク質のパスウェイ解析を行い、糖尿病抑制に関与する脂肪酸分解経路、PPARシグナル経路のタンパク質が増加し、糖尿病の進行に関与する糖新生経路、脂肪酸合成経路のタンパク質が減少していることを明らかにした。これにより、オメガ3系不飽和脂肪酸による糖尿病予防効果を分子レベルで明らかにすることに成功した。

Strategy for Future Research Activity

(抄録なし)

Research Products

• [Journal Article] Efficient extraction of proteins from formalin-fixed paraffin-embedded tissues requires higher concentration of tris (hydroxymethyl) aminomethane (2014)
  • Author(s): Kawashima Y, Kodera Y, Singh A, Matsumoto M, Matsumoto H
  • Journal Title: Clinical Proteomics Volume: Vol.11 Issue: 1 Pages: 1-6
  • DOI: 10.1186/1559-0275-11-4
  • Peer Reviewed / Open Access
• [Journal Article] Nutritional Proteomics : Investigating molecular mechanisms underlying the health beneficial effect of functional foods (2013)
  • Author(s): Kawashima Y, Singh A, Kodera Y, Matsumoto H
  • Journal Title: Functional Foods in Health and Disease Volume: Vol.3 Pages: 300-309
  • Peer Reviewed
• [Journal Article] Application of quantitative proteomic analysis using tandem mass tags for discovery and identification of novel biomarkers in periodontal disease. (2013)
  • Author(s): Tsuchida S, Satoh M, Kawashima Y, Sogawa K, Kado S, Sawai S, Nishimura M, Ogita M, Takeuchi Y, Kobyashi H, Aoki A, Kodera Y, Matsushita K. Izumi Y. Nomura F
  • Journal Title: Proteomics Volume: Vol.13 Issue: 15 Pages: 2339-2350
  • DOI: 10.1002/pmic.201200510
  • Peer Reviewed
• [Journal Article] Serum monomeric α2-macroglobulin as a clinical biomarker in diabetes (2013)
  • Author(s): Takada T, Kodera Y, Matsubara M, Kawashima Y, Maeda T, Fujita Y, Shichiri M
  • Journal Title: Atherosclerosis Volume: 228 Pages: 270-276
  • Peer Reviewed
• [Journal Article] Cyclic sample pooling using two-dimensional liquid chromatography system enhances coverage in shotgun proteomics (2013)
  • Author(s): Kawashiraa Y, Satoh M, Saito T, Matsui T, Nomura F, Matsumoto H, Kodera Y
  • Journal Title: Biomedical Chromatography Volume: 27 Issue: 6 Pages: 691-694
  • DOI: 10.1002/bmc.2864
  • Peer Reviewed
• [Journal Article] Establishment and application of a high-quality comparative analysis strategy for the discovery and small-scale validation of low-abundance biomarker peptides in serum based on an optimized novel peptide extraction method (2013)
  • Author(s): Saito T, Kawashima Y, Minamida S, Matsumoto K, Araki K, Matsui T, Satoh M, Nomura F, Iwamura M, Maeda T, Baba S, Kodera Y
  • Journal Title: Journal of Electrophoresis Volume: 57 Issue: 1 Pages: 1-9
  • DOI: 10.2198/jelectroph.57.1
  • NAID: 130003364779
  • ISSN: 1349-9394, 1349-9408
  • Peer Reviewed
• [Journal Article] Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy (2013)
  • Author(s): Ichimura K, Kawashima Y, Nakamura T, Powell R, Hidoh Y, Terai S, Sakaida l, Kodera Y, T suji T, Ma JX, Sakai T, Matsumoto H, Obara T
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 431 Issue: 4 Pages: 712-717
  • DOI: 10.1016/j.bbrc.2013.01.053
  • Peer Reviewed
• [Journal Article] Enhanced recovery of lyophilized peptides in shotgun proteomics by using an LC-ESI-MS compatible surfactant (2013)
  • Author(s): Kawashima Y, Takahashi N, Satoh M, Saito T, Kado S, Nomura F, Matsumoto H, Kodera Y
  • Journal Title: Proteomics Volume: 13 Issue: 5 Pages: 751-755
  • DOI: 10.1002/pmic.201200462
  • Peer Reviewed
• [Journal Article] 14-3-3 protein beta/alpha as a urinary biomarker for renal cell carcinoma : proteomic analysis of cyst fluid (2011)
  • Author(s): Minamida S, Iwamura M, Kodera Y, Kawashima Y, Tabata K, Matsumoto K, Fujita T, Satoh T, Maeda T, Baba S
  • Journal Title: Anal Bioanal Chem Volume: 401 Pages: 245-252
  • Peer Reviewed
• [Journal Article] Profilin 1 overexpression in renal cell carcinoma (2011)
  • Author(s): Minamida S, Iwamura M, Kodera Y, Kawashima Y, Ikeda M, Okusa H, Fujita T, Maeda T, Baba S
  • Journal Title: Int J Urol Volume: 18 Issue: 1 Pages: 63-71
  • DOI: 10.1111/j.1442-2042.2010.02670.x
  • Peer Reviewed
• [Journal Article] Increased serum levels of pigment epithelium-derived factor by excessive alcohol consumption-detection and identification by a three-step serum proteome analysis (2011)
  • Author(s): Sogawa K, Kodera Y, Satoh M, Kawashima Y, Umemura H, Maruyama K, Takizawa H, Yokosuka O, Nomura F
  • Journal Title: Alcohol Clin Exp Res Volume: 35 Issue: 2 Pages: 211-217
  • DOI: 10.1111/j.1530-0277.2010.01336.x
  • Peer Reviewed
• [Presentation] Nutritional Proteomics for the Study of the Suppression of High Fat Diet-Induced Pre-Diabetes by Omega-3 Polyunsaturated Fatty Acids (2013)
  • Author(s): Kawashima Y, Kodera Y, Matsumoto H
  • Organizer: HUPO 2013 Congress
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市西区)
• [Presentation] Discovery of a Urinary Biomarker for Renal Cell Carcinoma Based on a Proteomic Analysis of Cyst Fluid (2013)
  • Author(s): Kaneko S, Minamida S, Kawashima Y, Tabata K, Matsumoto K, Fujita T, Satoh T, Maeda T, Kodera Y, Iwamura M
  • Organizer: HUPO 2013 Congress
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市西区)
• [Presentation] Application of Quantitative Proteomic Analysis Using Tandem Mass Tags for Discovery and Identification of Novel Biomarkers in Periodontal Disease (2013)
  • Author(s): Tsuchida S, Satoh M, Kawashima Y, Sogawa K, Kado S, Sawai S, Nishimura M, Ogita M, Takeuchi Y, Kobyashi H, Aoki A, Kodera Y, Matsushita K, Izumi Y, Nomura F
  • Organizer: HUPO 2013 Congress
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市西区)
• [Presentation] Establishment and Application of a High-Quality Comparative Analysis Strategy of Low-Abundance Biomarker Peptide in Serum Based on Optimized Novel Peptide Extraction Method (2013)
  • Author(s): Saito T, Kawashima Y, Minamida S, Matsumoto K, Matsui T, Satoh M, Nomura F, Iwamura M, Maeda T, Baba S, Kodera Y
  • Organizer: HUPO 2013 Congress
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市西区)
• [Presentation] Discovery of Subnanomolar Serum/Plasma Biomarkers Inclusive of Albumin-Bound Molecules by Novel Sample Pretreatment and High Quality Comparative Analysis (2013)
  • Author(s): Kodera Y, Hidoh Y, Saito T, Kawashim Y, Sogawa K, Minamida S, Matsumoto K, Iwarnura M, Shiro Baba S, Maeda T, Tomonaga T, Nomura F
  • Organizer: HUPO 2013 Congress
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市西区)
• [Presentation] Differential Solublization Method to Extract Low-Molecular-Weight Proteins/Peptides for Successful Serum SRM Analyses (2013)
  • Author(s): Satoh M, Kawashima Y, Saito T, Ishibashi M, Sogawa K, Kado S, Kodera Y, Nomura F
  • Organizer: HUPO 2013 Congress
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市西区)
• [Presentation] Comprehensive approach to develop diagnostic biomarker peptides in serum-Establishment of discovery and validation methods targeting low-abundance peptides (2012)
  • Author(s): Kodera Y, Saitoh T, Kawashima Y, Sogawa K ; Minamida S, Matsumoto K, lwamura M, Baba S, Maeda T, Tomonaga T, Nomura F
  • Organizer: HUPO 2012 Congress
  • Place of Presentation: ボストン
  • Year and Date: 2012-09-09
• [Presentation] 診断マーカー探索を目指した血中ペプチド抽出法の開発 (2011)
  • Author(s): 川島祐介
  • Organizer: 日本プロテオーム学会(JHUPO)
  • Place of Presentation: 朱鷺メッセ新潟コンベンションセンター(奨励賞受賞講演)
  • Year and Date: 2011-07-29