GH plays a role in the protective effect of BCAA against muscle atrophy

• Project/Area Number: 26500021
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrated Nutrition Science
• Research Institution: Kobe Women's University
• Principal Investigator: OKIMURA Yasuhiko 神戸女子大学, 家政学部, 教授 (30204100)
• Research Collaborator: NISHIDA Hikaru 神戸女子大学, 大学院・家政学研究科, 院生 ; YAMAMOTO Yu 神戸女子大学, 大学院・家政学研究科, 院生 ; WAKE Ikumi 神戸女子大学, 大学院・家政学研究科, 院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 分岐鎖アミノ酸 / 骨格筋 / 成長ホルモン / mTOR / 筋委縮 / IGF-I / 筋萎縮 / グルココルチコイド / LAT1

Outline of Final Research Achievements

Branched-chain amino acid (BCAA) prevents muscle atrophy. mTOR complex 1 (mTORC1) plays a pivotal role in the protective actions of BCAA. GH is also known to have a protective effect against muscle atrophy. We examined whether BCAA exerts a protective effect against dexamethasone (Dex)-induced muscle atrophy independently of GH using GH-deficient spontaneous dwarf rats (SDRs). BCAA did not increase cross-sectional area (CSA) of the muscle fibers and did not stimulate the phosphorylation of p70S6K and 4E-BP1, both of which are phosphorylated by mTORC1 and stimulate protein synthesis. In contrast, after GH supplementation, muscle fiber CSA was decreased by Dex and BCAA prevented the Dex-induced decrease in CSA. BCAA increased p70S6K phosphorylation. These findings suggest that GH increases mTORC1 activity to recover the action of BCAA in SDRs and that GH is required for the actions of BCAA in muscles.

Research Products

• [Journal Article] Glucose-mediated inactivation of AMP-activated protein kinase reduces the levels of L-type amino acid transporter 1 mRNA in C2C12 cells (2017)
  • Author(s): Yu Yamamoto, Ran Sawa, Ikumi Wake, Ayaka Morimoto, Yasuhiko Okimura
  • Journal Title: Nutrition Research Volume: 47 Pages: 13-20
  • DOI: 10.1016/j.nutres.2017.08.003
  • Peer Reviewed
• [Journal Article] Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats. (2015)
  • Author(s): Nishida H, Ikegami A, Kaneko C, Kakuma H, Nishi H, Tanaka N, Aoyama M, Usami M, Okimura Y.
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: 1-20
  • DOI: 10.1371/journal.pone.0128805
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Insulin-like growth factor-I decreased mRNA levels of sestrin1. 2. and 3, but did not influence mTOR1 activation by leucine in C2C12 myotubes (2017)
  • Author(s): Ikumi Wake, Ran Sawa, Yu Yamamoto, Yasuhiko Okimura
  • Organizer: 2017年度生命科学系学会合同年次大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県神戸市)
  • Year and Date: 2017-12-06
• [Presentation] C2C12細胞においてグルコースはAMPK 活性を抑制してLAT1mRNA量を減少させる (2017)
  • Author(s): 山本 優、澤 蘭、森元 彩馨、和気 郁実、置村 康彦
  • Organizer: 第90回日本内分泌学会学術総会
  • Place of Presentation: みやこめっせ（京都府・京都市）
  • Year and Date: 2017-04-20
• [Presentation] GH/IGF-I系は、筋におけるデキサメサゾン(Dex)および分岐鎖アミノ酸(BCAA)の作用に関与している (2016)
  • Author(s): 西田ひかる、池上彩香、金子千晶、角間瞳、西寿野、田中紀子、青山倫子、宇佐美眞、置村康彦
  • Organizer: 第８９回日本内分泌学会学術総会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-21
• [Presentation] 新規アディポカイン、ケマリンは副腎髄質を介して褐色脂肪機能を調節する (2016)
  • Author(s): 高橋路子、置村康彦、小武由紀子、吉田健一、松本隆作、坂東弘教、隅田健太郎、西沢衡、福岡秀規、井口元三、北沢理子、小川渉、高橋裕
  • Organizer: 第８９回日本内分泌学会学術総会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-21
• [Presentation] 分岐鎖アミノ酸経口投与の筋萎縮抑制作用における成長ホルモンの関与 (2014)
  • Author(s): 西田ひかる、相原愛、梶原絵美，池上彩香，角間瞳，金子千晶，西寿野、田中紀子、置村康彦
  • Organizer: 日本内分泌学会
  • Place of Presentation: 福岡国際会議場（福岡市）
  • Year and Date: 2014-04-24 – 2014-04-26