Development of a new method for improving physical ability of chronic renal failure patients by correcting mitochondrial metabolism using electron carriers

• Project/Area Number: 15K19465
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: Mitsuishi Masanori 慶應義塾大学, 医学部(信濃町), 特任助教 (50468485)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 骨格筋ミトコンドリア / サルコペニア / 慢性腎不全 / 身体能力 / グレリン / アミノレブリン酸 / 内分泌学 / ミトコンドリア / IGF-1

Outline of Final Research Achievements

Ghrelin administration on 5/6 nephrectomized mice improved skeletal muscle mitochondrial function, increased skeletal muscle mass, and improved physical performance. Ghrelin administration improved mitochondrial biogenesis through epigenomic modification of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and it was suggested that increasing both muscle mass and mitochondrial content by ghrelin would improve sarcopenia associated with CKD efficiently.On the other hand, amino levulinic acid (ALA) administration increased skeletal muscle mitochondrial function, muscle mass and physical function. ALA administration increased mitochondrial biogenesis. In metabolome studies, branched chain amino acids in skeletal muscle were increased by administration of ALA. It was thought that ALA increased skeletal muscle mass through the metabolic changes in skeletal muscle.

Research Products

• [Journal Article] Improvement of physical performance in 5/6 nephrectomized CKD model mice by a gastric hormone ghrelin. (2015)
  • Author(s): Tamaki M, Miyashita K, Wakino S, Hagiwara A, Inoue H, Fujii K, Fujii C, Mitsuishi M, Muraki A, Hayashi K, Doi T, Itoh H.
  • Journal Title: Endocrinology Volume: 156 Issue: 10 Pages: 3638-3648
  • DOI: 10.1210/en.2015-1353
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 電子キャリア前駆体アミノレブリン酸を用いたミトコンドリア活性化によるサルコペニア治療の試み (2016)
  • Author(s): 藤井 千華子, 宮下 和季, 藤井 健太郎, 井上 博之, 萩原 あいか, 田蒔 昌憲, 河合 俊英, 伊藤 裕
  • Organizer: 日本抗加齢医学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-06-10
• [Presentation] ミトコンドリア活性化分子であるアミノレブリン酸を用いたサルコペニア治療の試み (2016)
  • Author(s): 藤井千華子、宮下和季、藤井健太郎、井上博之、萩原あいか、田蒔昌憲、三石正憲、村木絢子、河合俊英、伊藤裕
  • Organizer: 日本肥満治療学会学術集会
  • Place of Presentation: 東京スクエアガーデン
• [Presentation] 高血圧における臓器代謝異常 ホルモンによるミトコンドリア制御と身体能力 (2015)
  • Author(s): 宮下和季, 三石正憲, 田蒔昌憲, 萩原あいか, 井上博之, 藤井健太郎, 藤井千華子, 伊藤裕
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: ひめぎんホール(愛媛県松山市)
  • Year and Date: 2015-10-10
  • Invited
• [Presentation] Improvement of physical decline through combined effects of muscle enhancement and mitochondrial activation by a gastric hormone ghrelin in male 5/6Nx CKD model mice. (2015)
  • Author(s): 田蒔昌憲, 宮下和季, 三石正憲, 村木絢子, 藤井千華子, 萩原あいか, 井上博之, 藤井健太郎, 伊藤裕
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: ひめぎんホール(愛媛県松山市)
  • Year and Date: 2015-10-10
• [Presentation] Improvement of physical performance in 5/6 nephrectomized CKD model mice through epigenetic modulation of PGC-1 expression by a gastric hormone ghrelin. (2015)
  • Author(s): M Tamaki, K Miyashita, M. Mitsuishi, M Sato, A Hagiwara, H Inoue, K Fujii, H Itoh
  • Organizer: 52nd ERA-EDTA congress
  • Place of Presentation: ロンドン(イギリス)
  • Year and Date: 2015-05-28
  • Int'l Joint Research
• [Presentation] 高蛋白食によるサルコペニア治療のピットフォールとグレリン・IGF-1の治療効果 (2015)
  • Author(s): 宮下和季, 三石正憲, 村木絢子, 田蒔昌憲, 藤井千華子, 萩原あいか, 井上博之, 藤井健太郎, 伊藤裕
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ホテルニューオータニ(東京都千代田区)
  • Year and Date: 2015-04-23