Serum metabolomics analysis of patients with fatty liver due to undernutrition

• Project/Area Number: 15K00849
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Tokyo Medical University
• Principal Investigator: Iwamoto Junichi 東京医科大学, 医学部, 准教授 (10384950)
• Co-Investigator(Kenkyū-buntansha): 本多 彰 東京医科大学, 医学部, 教授 (10468639) ; 宮崎 照雄 東京医科大学, 医学部, 講師 (60532687)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 低栄養性脂肪肝 / 脂肪肝 / 低栄養 / 脂肪酸代謝 / アミノ酸代謝 / 糖代謝

Outline of Final Research Achievements

To study the pathophysiology of fatty liver due to undernutrition, new LC-MS/MS methods were developed for metabolomics analysis of patients’ serum. By use of the methods, we analyzed serum from Crohn’s disease and citrin deficiency that are often accompanied by fatty liver due to undernutrition. Activation of LXR and deactivation of FXR were detected in Crohn’s disease while stimulation of fatty acid biosynthesis by oversupply of citrate was observed in citrin deficiency. Thus, serum metabolomics analysis is a useful method to explore the mechanism of fatty liver due to unknown origin.

Research Products

• [Journal Article] Detection of Gut Dysbiosis due to Reduced Clostridium Subcluster XIVa Using the Fecal or Serum Bile Acid Profile. (2018)
  • Author(s): Murakami M, Iwamoto J, Honda A, Tsuji T, Tamamushi M, Ueda H, Monma T, Konishi N, Yara S, Hirayama T, Miyazaki T, Saito Y, Ikegami T, Matsuzaki Y.
  • Journal Title: Inflamm Bowel Dis Volume: 24 Issue: 5 Pages: 1035-1044
  • DOI: 10.1093/ibd/izy022
  • Peer Reviewed
• [Journal Article] Serum Amino Acid Profiling in Citrin-Deficient Children Exhibiting Normal Liver Function During the Apparently Healthy Period. (2018)
  • Author(s): Miyazaki T, Nagasaka H, Komatsu H, Inui A, Morioka I, Tsukahara H, Kaji S, Hirayama S, Miida T, Kondou H, Ihara K, Yagi M, Kizaki Z, Bessho K, Kodama T, Iijima K, Yorifuji T, Matsuzaki Y, Honda A.
  • Journal Title: JIM Rep. Volume: － Pages: 53-61
  • DOI: 10.1007/8904_2018_99
  • ISBN: 9783662586136, 9783662586143
  • Peer Reviewed / Open Access
• [Journal Article] Circulating tricarboxylic acid cycle metabolite levels in citrin-deficient children with metabolic adaptation, with and without sodium pyruvate treatment. (2017)
  • Author(s): Nagasaka H, Komatsu H, Inui A, Nakacho M, Morioka I, Tsukahara H, Kaji S, Hirayama S, Miida T, Kondou H, Ihara H, Yagi M, Kizaki Z, Bessho K, Kodama T, Iijima K, Saheki T, Yorifuji T, Honda A
  • Journal Title: Mol. Genet. Metab. Volume: 120 Issue: 3 Pages: 207-212
  • DOI: 10.1016/j.ymgme.2016.12.011
  • Peer Reviewed / Open Access
• [Journal Article] Retention of acetylcarnitine in chronic kidney disease causes insulin resistance in skeletal muscle (2016)
  • Author(s): Miyamoto Y, Miyazaki T, Honda A, Shimohata H, Hirayama K, Kobayashi M
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 59 Issue: 3 Pages: 199-206
  • DOI: 10.3164/jcbn.15-146
  • NAID: 130005268805
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Simultaneous quantification of salivary hydroxybutyrates as possible markers of amino acid and fatty acid catabolic pathways by LC-ESI-MS/MS (2015)
  • Author(s): Miyazaki T, Honda A, Ikegami T, Iwamoto J, Monma T, Hirayama T, Saito Y, Yamashita K, Matsuzaki Y. . . .
  • Journal Title: Springerplus Volume: 4 Issue: 1 Pages: 494-494
  • DOI: 10.1186/s40064-015-1304-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Detection of gut dysbiosis due to reduced Clostridium subcluster XIVa based on the serum bile acid profile. (2017)
  • Author(s): Murakami M, Iwamoto J, Miyazaki T, Monma T, Shoichiro Y, Ikegami T, Matsuzaki Y, Honda A.
  • Organizer: Digestive Disease Week
  • Int'l Joint Research
• [Presentation] 肝臓内脂質代謝の老化とアンチエイジング (2017)
  • Author(s): 本多 彰，池上 正，宮﨑照雄，松﨑靖司.
  • Organizer: 第17回日本抗加齢医学会総会（シンポジウム）
• [Presentation] 脂肪性肝炎進展過程における酸化ステロールの質的変化 (2016)
  • Author(s): 屋良昭一郎, 池上 正，本多 彰，岩本淳一，宮﨑照雄，松﨑靖司.
  • Organizer: 第20回日本肝臓学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2016-11-03
• [Presentation] 核内受容体を介した胆汁酸の脂質代謝制御による脂肪肝改善作用 (2016)
  • Author(s): 宮崎照雄, 本多 彰，松崎靖司
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: 千葉
  • Year and Date: 2016-05-19
• [Presentation] Dysregulation of hepatic 27-hydroxycholesterol in steatohepatitis model mice with hyperglycemia (2016)
  • Author(s): Yara S, Ikegami T, Honda A, Miyazaki T, Monma T, Murakami M, Konishi N, Iwamoto J, Saito Y, Matsuzaki Y
  • Organizer: 25th Conference of the APASL
  • Place of Presentation: Tokyo
  • Year and Date: 2016-02-23
  • Int'l Joint Research
• [Presentation] 肝代謝代償能を評価する骨格筋分岐鎖アミノ酸異化バイオマーカー (2015)
  • Author(s): 宮崎照雄, 本多 彰，松崎靖司
  • Organizer: 日本肝臓学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-05-21