Kyushu University Academic Staff Educational and Research Activities Database
Researcher information (To researchers) Need Help? How to update
Yoshihiro Izumi Last modified date:2021.10.28

Graduate School
Other Organization

 Reseacher Profiling Tool Kyushu University Pure
HP: Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University .
Academic Degree
Ph.D in Engineering
Field of Specialization
Metabolomics, Analytical chemistry, Mass spectrometry, Chromatography
ORCID(Open Researcher and Contributor ID)
Outline Activities
With the recent breakthrough in metabolomics technologies, application of metabolomics has been increasing in the medical field. Identification and semiquantitation of the compounds in the metabolome is defined as metabolic profiling, and it is applied to define metabolic changes related to genetic differences, environmental influences and disease or drug perturbations. Medical metabolomics are two major purposes for its use; the first is to acquire knowledge on the mechanisms of drug action or the disease itself, and another is biomarker detection and disease diagnosis. Our group has developed a novel high-sensitivity and absolute quantitative metabolomics methodology based on gas chromatography, liquid chromatography, and supercritical fluid chromatography coupled to mass spectrometry. Advances in metabolic profiling offer comprehensive coverage of a metabolome as well as provide valuable insight towards understanding the different biochemical profiles of a biosystem.
Research Interests
  • Development of basic technologies for single-cell metabolomics
    keyword : Single-cell metabolomics
  • Next-generation metabolomics: Technological development and medical application
    keyword : Metabolomics, Metabolome analysis, Widely-targeted Quantitaive metabolomics, Non-target metabolomics
Academic Activities
1. Tatsuya Fushimi, Yoshihiro Izumi*, Masatomo Takahashi, Kosuke Hata, Yoshihiro Murano, and Takeshi Bamba, Dynamic metabolome analysis reveals the metabolic fate of medium-chain fatty acid in AML12 cells, Journal of Agricultural and Food Chemistry, org/10.1021/acs.jafc.0c04723, 68, 43, 11997-12010, 2020.10, Several studies in hepatocyte cell lines reported that medium-chain fatty acids (MCFAs) with 6–12 carbons showed different metabolic properties from long-chain fatty acids (LCFAs). However, these studies reported unclear effects of different fatty acid molecules on hepatocyte metabolism. This study is aimed to capture the metabolic kinetics of MCFA assimilation in AML12 cells treated with octanoic acid (FA 8:0), decanoic acid (FA 10:0), or lauric acid (FA12:0) [LCFA; oleic acid (FA 18:1)] via metabolic profiling and dynamic metabolome analysis with 13C-labeling. The concentrations of total ketone bodies in the media of cells treated with FA 8:0 or FA 10:0 were 3.22- or 3.69-fold higher than those obtained with FA 18:1 treatment, respectively. FA 12:0 treatment did not significantly increase ketone body levels compared to DMSO treatment (control), whereas FA 12:0 treatment increased intracellular triacylglycerol (TG) levels 15.4 times compared to the control. Metabolic profiles of FA 12:0-treated samples differed from those of the FA 8:0-treated and FA 10:0-treated samples, suggesting that metabolic assimilation of MCFAs differed significantly depending on the MCFA type. Furthermore, the dynamic metabolome analysis clearly revealed that FA 8:0 was rapidly and quantitatively oxidized to acetyl-CoA and assimilated into ketone bodies, citrate cycle intermediates, and glucogenic amino acids but not readily into TGs..
2. Hiroaki Takeda, Yoshihiro Izumi*, Shohei Tamura, Tomonari Koike, Yui Koike, Masashi Shiomi, Takeshi Bamba, Lipid Profiling of Serum and Lipoprotein Fractions in Response to Pitavastatin Using an Animal Model of Familial Hypercholesterolemia, Journal of Proteome Research, 10.1021/acs.jproteome.9b00602, 19, 3, 1100-1108, 2020.03, Statins are widely used for the treatment of atherosclerotic cardiovascular diseases. They inhibit cholesterol biosynthesis in the liver and cause pleiotropic effects, including anti-inflammatory and antioxidant effects. To develop novel therapeutic drugs, the effect of blood-borne lipid molecules on the pleiotropic effects of statins must be elucidated. Myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for hypercholesterolemia, are suitable for the determination of lipid molecules in the blood in response to statins because their lipoprotein metabolism is similar to that of humans. Herein, lipid molecules were investigated by lipidome analysis in response to pitavastatin using WHHLMI rabbits. Various lipid molecules in the blood were measured using a supercritical fluid chromatography triple quadrupole mass spectrometry. Cholesterol and cholesterol ester blood concentrations decreased by reducing the secretion of very low density lipoproteins from the liver. Independent of the inhibition effects of cholesterol biosynthesis, the concentrations of some lipids with anti-inflammation and antioxidant effects (phospholipid molecules with n-6 fatty acid side chains, lysophosphatidylcholines, phosphatidylethanolamine plasmalogens, and ceramide molecules) were significantly altered. These findings may lead to further investigation of the mechanism of statin action..
3. Kosuke Hata, Yoshihiro Izumi*, Takeshi Hara, Masaki Matsumoto*, Takeshi Bamba, In-Line Sample Processing System with an Immobilized Trypsin-Packed Fused-Silica Capillary Tube for the Proteomic Analysis of a Small Number of Mammalian Cells, Analytical chemistry, 10.1021/acs.analchem.9b03993, 92, 4, 2997-3005, 2020.02, Omics analysis at single-cell resolution has helped to demonstrate the shaping of cellular heterogeneity on the basis of the expression of various molecules. However, in-depth proteomic analysis of low-quantity samples has remained challenging because of difficulties associated with the measurement of large numbers of proteins by shotgun proteomics using nanoflow liquid chromatography tandem mass spectrometry (nano-LC/MS/MS). To meet such a demand, we developed a method called in-line sample preparation for efficient cellular proteomics (ISPEC) in which cells were captured, directly lysed, and digested with immobilized trypsin within fused-silica capillaries. ISPEC minimized sample loss during the sample preparation processes with a relatively small number of mammalian cells (<1000 cells) and improved the stability and efficiency of digestion by immobilized trypsin, compared to a conventional preparation method. Using our optimized ISPEC method with nano-LC/MS/MS analysis, we identified 1351, 351, and 60 proteins from 100 cells, 10 cells, and single cells, respectively. The linear response of the signal intensity of each peptide to the introduced cell number indicates the quantitative recovery of the proteome from a very small number of cells. Thus, our ISPEC strategy facilitates quantitative proteomic analysis of small cell populations..
4. Nao Nishida-Aoki, Yoshihiro Izumi*, Hiroaki Takeda, Masatomo Takahashi, Takahiro Ochiya*, Takeshi Bamba, Lipidomic analysis of cells and extracellular vesicles from high-and low-metastatic triple-negative breast cancer, Metabolites, 10.3390/metabo10020067, 10, 2, Article number: 67, 2020.02, Extracellular vesicles (EVs) are lipid bilayer nanovesicles secreted from almost all cells including cancer. Cancer-derived EVs contribute to cancer progression and malignancy via educating the surrounding normal cells. In breast cancer, epidemiological and experimental observations indicated that lipids are associated with cancer malignancy. However, lipid compositions of breast cancer EVs and their contributions to cancer progression are unexplored. In this study, we performed a widely targeted quantitative lipidomic analysis in cells and EVs derived from high-and low-metastatic triple-negative breast cancer cell lines, using supercritical fluid chromatography fast-scanning triple-quadrupole mass spectrometry. We demonstrated the differential lipid compositions between EVs and cells of their origin, and between high-and low-metastatic cell lines. Further, we demonstrated EVs from highly metastatic breast cancer accumulated unsaturated diacylglycerols (DGs) compared with EVs from lower-metastatic cells, without increasing the amount in cells. The EVs enriched with DGs could activate the protein kinase D signaling pathway in endothelial cells, which can lead to stimulated angiogenesis. Our results indicate that lipids are selectively loaded into breast cancer EVs to support tumor progression..
5. Kohta Nakatani, Yoshihiro Izumi*, Kosuke Hata, Takeshi Bamba, An analytical system for single-cell metabolomics of typical mammalian cells based on highly sensitive nano-liquid chromatography tandem mass spectrometry, Mass Spectrometry, 10.5702/massspectrometry.A0080, 9, 1, 2020.01, The rapid development of next-generation sequencing techniques has enabled single-cell genomic and transcriptomic analyses, which have revealed the importance of heterogeneity in biological systems. However, analytical methods to accurately identify and quantify comprehensive metabolites from single mammalian cells with a typical diameter of 10–20 µm are still in the process of development. The aim of this study was to develop a single-cell metabolomic analytical system based on highly sensitive nanoliquid chromatography tandem mass spectrometry (nano-LC-MS/MS) with multiple reaction monitoring. A packed nano-LC column (3-µm particle-size pentafluorophenylpropyl Discovery HSF5 of dimensions 100 µm i.d.×180 mm) was prepared using a slurry technique. The optimized nano-LC-MS/MS method showed 3–132-fold (average value, 26-fold) greater sensitivity than semimicro-LC-MS/MS, and the detection limits for several hydrophilic metabolites, including amino acids and nucleic acid related metabolites were in the sub-fmol range. By combining live single-cell sampling and nano-LC-MS/MS, we successfully detected 18 relatively abundant hydrophilic metabolites (16 amino acids and 2 nucleic acid related metabo-lites) from single HeLa cells (n=22). Based on single-cell metabolic profiles, the 22 HeLa cells were classified into three distinct subclasses, suggesting differences in metabolic function in cultured HeLa cell populations. Our single-cell metabolomic analytical system represents a potentially useful tool for in-depth studies focused on cell metabolism and heterogeneity..
6. Yoshihiro Izumi, Fumio Matsuda*, Akiyoshi Hirayama, Kazutaka Ikeda, Yoshihiro Kita, Kanta Horie, Daisuke Saigusa, Kosuke Saito, Yuji Sawada, Hiroki Nakanishi, Nobuyuki Okahashi, Masatomo Takahashi, Motonao Nakao, Kosuke Hata, Yutaro Hoshi, Motohiko Morihara, Kazuhiro Tanabe, Takeshi Bamba*, Yoshiya Oda, Inter-laboratory comparison of metabolite measurements for metabolomics data integration, Metabolites, 10.3390/metabo9110257, 9, 11, Article number: 257, 2019.11, Background: One of the current problems in the field of metabolomics is the difficulty in integrating data collected using different equipment at different facilities, because many metabolomic methods have been developed independently and are unique to each laboratory. Methods: In this study, we examined whether different analytical methods among 12 different laboratories provided comparable relative quantification data for certain metabolites. Identical samples extracted from two cell lines (HT-29 and AsPc-1) were distributed to each facility, and hydrophilic and hydrophobic metabolite analyses were performed using the daily routine protocols of each laboratory. Results: The results indicate that there was no difference in the relative quantitative data (HT-29/AsPc-1) for about half of the measured metabolites among the laboratories and assay methods. Data review also revealed that errors in relative quantification were derived from issues such as erroneous peak identification, insufficient peak separation, a difference in detection sensitivity, derivatization reactions, and extraction solvent interference. Conclusion: The results indicated that relative quantification data obtained at different facilities and at different times would be integrated and compared by using a reference materials shared for data normalization..
7. Masatomo Takahashi, Yoshihiro Izumi*, Fukumatsu Iwahashi, Yasumune Nakayama, Mitsuhiko Iwakoshi, Motonao Nakao, Seiji Yamato, Eiichiro Fukusaki, Takeshi Bamba*, Highly Accurate Detection and Identification Methodology of Xenobiotic Metabolites Using Stable Isotope Labeling, Data Mining Techniques, and Time-Dependent Profiling Based on LC/HRMS/MS, Analytical Chemistry, 10.1021/acs.analchem.8b01388, 90, 15, 9068-9076, 2018.08, A generally applicable method to discover xenobiotic metabolites is important to safely and effectively develop xenobiotics. We propose an advanced method to detect and identify comprehensive xenobiotic metabolites using stable isotope labeling, liquid chromatography coupled with benchtop quadrupole Orbitrap high-resolution tandem mass spectrometry (LC/HRMS/MS), data mining techniques (alignment, peak picking, and paired-peaks filtering), in silico metabolism prediction, and time-dependent profiling. The LC/HRMS analysis was carried out using Arabidopsis T87 cultured cells treated with unlabeled, or 13C- or 2H-labeled 2,4-dichlorophenoxyacetic acid (2,4-D). Paired-peak filtering enabled accurate detection of 83 candidates for 2,4-D metabolites without any false positive peaks derived from solvents or the biological matrix. We confirmed 10 previously reported 2,4-D metabolites and identified 16 novel 2,4-D metabolites. Our method provides accurate detection and identification of comprehensive xenobiotic metabolites and represents a potentially useful tool to elucidate xenobiotic metabolism..
8. Hiroaki Takeda, Yoshihiro Izumi, Masatomo Takahashi, Thanai Paxton, Shohei Tamura, Tomonari Koike, Ying Yu, Noriko Kato, Katsutoshi Nagase, Masashi Shiomi, Takeshi Bamba*, Widely-targeted quantitative lipidomics method by supercritical fluid chromatography triple quadrupole mass spectrometry, Journal of Lipid Research, 10.1194/jlr.D083014, 59, 7, 1283-1293, 2018.01, Lipidomics, the mass spectrometry-based comprehensive analysis of lipids, has attracted attention as an analytical approach to provide novel insight into lipid metabolism and to search for biomarkers. However, an ideal method for both comprehensive and quantitative analysis of lipids has not been fully developed. Here, we have proposed a practical methodology for widely targeted quantitative lipidome analysis using supercritical fluid chromatography fast-scanning triple-quadrupole mass spectrometry (SFC/ QqQMS) and theoretically calculated a comprehensive lipid multiple reaction monitoring (MRM) library. Lipid classes can be separated by SFC with a normal-phase diethylaminebonded silica column with high resolution, high throughput, and good repeatability. Structural isomers of phospholipids can be monitored by mass spectrometric separation with fatty acyl-based MRM transitions. SFC/QqQMS analysis with an internal standard-dilution method offers quantitative information for both lipid class and individual lipid molecular species in the same lipid class. Additionally, data acquired using this method has advantages, including reduction of misidentification and acceleration of data analysis. Using the SFC/QqQMS system, alteration of plasma lipid levels in myocardial infarction-prone rabbits to the supplementation of EPA was first observed. Our developed SFC/QqQMS method represents a potentially useful tool for in-depth studies focused on complex lipid metabolism and biomarker discovery..
1. ○Yoshihiro Izumi, Eiichiro Fukusaki, Takeshi Bamba, Supercritical fluid chromatography fast-scanning triple-quadrupole mass spectrometry: An alternative to LC/MS/MS for highly-sensitive and high-throughput analysis of multiresidue pesticides

, SHIMADZU GLOBAL INNOVATION SUMMIT 2017, 2017.07, Recently, a generally applicable screening method for multiresidue pesticide analysis, which is simple, quick, accurate, and has a reliable performance, is becoming increasingly important for food safety and international trade. Herein, we established a high-throughput screening methodology that enables the detection of multiresidue pesticides using supercritical fluid chromatography coupled to a fast-scanning triple-quadrupole mass spectrometry (SFC/MS/MS). A total of 509 chemicals covering a wide polarity range (logPow from ‒4.6 to 8.1) and a wide molecular range (from 99.0 to 1052.0) were analyzed simultaneously through a combination of fast-speed multiple reaction monitoring (MRM) with positive/negative polarity switching and highly efficient separation by SFC. The developed analytical system is a potentially useful tool for practical multiresidue pesticide screening with high-sensitivity and -throughput..
2. ○Takato Uchikata, Hidetoshi Terada, Yasuhiro Funada, Yoshihiro Izumi, Takeshi Bamba, Automatically extraction and analysis using on-line supercritical fluid extraction (SFE) / supercritical fluid chromatography (SFC) system, SFC 2015, 9th International Conference on Packed-Column SFC, 2015.07.
Membership in Academic Society
  • The Mass Spectrometry Society of Japan
  • The Society for Biotechnology, Japan
  • The Society for Chromatographic Sciences
  • Japan Society for Bioscience, Biotechnology, and Agrochemistry
  • Japan Society for SFC
  • Supercritical fluid chromatography/triple-quadrupole mass spectrometry-based method for highly sensitive and high-throughput analysis of multiresidue pesticides
Educational Activities
Division of Metabolomics, Graduate School of Systems Life Sciences, Kyushu University