Visualization of lipid metabolism and its application to molecular pathology

• Project/Area Number: 24590457
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Sasaki Foundation (2015-2016); National Defense Medical College (2012-2014)
• Principal Investigator: Iwaya Keiichi 公益財団法人佐々木研究所, 附属研究所, 研究員(移行) (50312012)
• Co-Investigator(Kenkyū-buntansha): 小田 美規 東京医科大学, 医学部, 助教 (50527942) ; 石川 孝 東京医科大学, 医学部, 主任教授 (80275049)
• Project Period (FY): 2012-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 質量分析 / レスベラトロール / 脂質 / 脂肪肝 / マクロファージ / 中性脂肪 / 脂肪酸 / 可視化 / 構造解析

Outline of Final Research Achievements

Lipids are important biological substances that are involved in signaling roles and energy storages. Among them triacylglycerol (TG) is a major component of food and animal fats. Excess amount of TG storages induce metabolic diseases such as type 2 diabetes and coronary heart disease. Because visceral TG significantly affects human health, we analyzed TG in fatty liver.
TG species in fatty liver can be detected by imaging mass spectrometry (IMS) and the results provided a reliable distribution map of the TG peaks. Compared with histological analyses, IMS provided better semi-quantitative visualisation of preferred TG peaks in liver specimens and would thus serve as a useful tool for clinical and other estimations of fatty liver. Analysis using MS/MS showed a structural change between liver TG and dietary TG. These findings suggest that MALDI-SpiralTOF is a powerful tool for clinical screening and estimating fatty liver, and that resveratrol improves fatty liver.

Research Products

• [Journal Article] High-Temperature-Required Protein A2 as a Predictive Marker for Response to Chemotherapy and Prognosis in Patients with High-Grade Serous Ovarian Cancers. (2017)
  • Author(s): Miyamoto, M., M. Takano, K. Iwaya, N. Shinomiya, T. Goto, M. Kato, A. Suzuki, T. Aoyama, J. Hitrata, I. Nagaoka, H. Tsuda and K. Furuya
  • Journal Title: Br J Cancer Volume: 116, no. 6 Issue: 6 Pages: e2-e2
  • DOI: 10.1038/bjc.2016.371
  • Peer Reviewed / Open Access
• [Journal Article] Up-Regulation of Antioxidant Proteins in the Plasma Proteome During Saturation Diving: Unique Coincidence under Hypobaric Hypoxia (2016)
  • Author(s): Domoto, H., K. Iwaya, F. Ikomi, H. Matsuo, Y. Tadano, S. Fujii, K. Tachi, Y. Itoh, M. Sato, K. Inoue and N. Shinomiya
  • Journal Title: PLoS One Volume: 11, no. 10 Issue: 10 Pages: e0163804-e0163804
  • DOI: 10.1371/journal.pone.0163804
  • Peer Reviewed / Open Access
• [Journal Article] Association between Breast Cancer Recurrence and Cellular Dissociation Assessed Using Fine-Needle Aspiration. (2016)
  • Author(s): Koike E, Iwaya K, Watanabe A, Miyake S, Sato E, Ishikawa T
  • Journal Title: Acta Cytol Volume: 60 Pages: 413-420
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Fluorescence Multispectral Imaging-Based Diagnostic System for Atherosclerosis. (2016)
  • Author(s): Ho, C. S., T. Horiuchi, H. Taniguchi, A. Umetsu, K. Hagisawa, K. Iwaya, K. Nakai, A. Azmi, N. Zulaziz, A. Azhim, N. Shinomiya and Y. Morimoto
  • Journal Title: Biomed Eng Online Volume: 15, no. 1 Issue: 1 Pages: 98-98
  • DOI: 10.1186/s12938-016-0220-z
  • NAID: 130005163581
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Resveratrol increases CD68+ Kupffer cells colocalized with adipose differentiation-related protein and ameliorates high-fat-diet-induced fatty liver in mice. (2015)
  • Author(s): Nishikawa K, Iwaya K, Kinoshita M, Fujiwara Y, Akao M, Sonoda M, Thiruppathi S, Suzuki T, Hiroi S, Seki S, Sakamoto T.
  • Journal Title: Mol Nutr Food Res Volume: 12 Issue: 6 Pages: 564-564
  • DOI: 10.1002/mnfr.201400564
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] High levels of DJ-1 protein and isoelectric point 6.3 isoform in sera of breast cancer patients. (2015)
  • Author(s): Kawate T, Iwaya K, Koshikawa K, Moriya T, Yamasaki T, Hasegawa S, Kaise H, Fujita T, Matsuo H, Nakamura T, Ishikawa T, Hiroi S, Iguchi-Ariga SM, Ariga H, Murota K, Fujimori M, Yamamoto J, Matsubara O, Kohno N
  • Journal Title: Cancer Sci Volume: １０６ Issue: 7 Pages: 938-43
  • DOI: 10.1111/cas.12673
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes. (2015)
  • Author(s): Matsuo H, et al.
  • Journal Title: Ann Rheum Dis. Volume: 印刷中 Issue: 4 Pages: 652-659
  • DOI: 10.1136/annrheumdis-2014-206191
  • Peer Reviewed / Open Access
• [Journal Article] The influence of dietary restriction on hepatic mononuclear cell numbers and functions in mice (2015)
  • Author(s): Moriya T, Fukatsu K, Iwaya K, Noguchi M, Saitoh D, Miyazaki M, Hase K, Yamamoto J
  • Journal Title: J Surg Res Volume: １９８ Issue: 1 Pages: 120-6
  • DOI: 10.1016/j.jss.2015.05.061
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Detection of changes in the structure and distribution map of triacylglycerol in fatty liver model by MALDI-Spiral TOF (2014)
  • Author(s): Nishikawa K, Hashimoto M, Itoh Y, Hiroi S, Kusai A, Hirata F, Sakamoto T, Iwaya K
  • Journal Title: FEBS Open Bop Volume: 19 Issue: 1 Pages: 179-84
  • DOI: 10.1016/j.fob.2014.02.005
  • Peer Reviewed / Open Access
• [Journal Article] DJ-1 protein expression as a predictor of pathological complete (2013)
  • Author(s): Kawate T, Iwaya K, Kikuchi R, Kaise H, Oda M, Sato E, Hiroi S, Matsubara O,Kohno N
  • Journal Title: Breast Cancer Res Treat Volume: 17 Pages: 51-59
  • Peer Reviewed
• [Journal Article] A simple immunohistochemical panel comprising 2 conventional markers, Ki67 and p53, is a powerful tool for predicting patient outcome in luminal-type breast cancer. (2013)
  • Author(s): Kobayashi T, Iwaya K, Moriya T, Yamasaki T, Tsuda H, Yamamoto J, Matsubara O.
  • Journal Title: BMC Clin Pathol Volume: 13 Issue: 1 Pages: 5-16
  • DOI: 10.1186/1472-6890-13-5
  • Peer Reviewed
• [Journal Article] Application of poly-L-lactic acid nanosheet as a material for wound dressing. (2013)
  • Author(s): Aoki, S
  • Journal Title: Plast Reconstr Surg. Volume: 131 Issue: 2 Pages: 236-240
  • DOI: 10.1097/prs.0b013e3182789c79
  • Peer Reviewed
• [Presentation] 乳癌患者の血中に高濃度に検出されるDJ-1 isoform pI 6.3:癌と酸化ストレスの邂逅 (2015)
  • Author(s): 岩屋啓一
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] Fatty acid xynthase overexpression in testicular germ cell tumors (2013)
  • Author(s): Miyai K, Iwaya K, Matsubara O
  • Organizer: USCAP
  • Place of Presentation: Baltimore