PMID- 32234320
OWN - NLM
STAT- MEDLINE
DCOM- 20200505
LR  - 20200505
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 250
DP  - 2020 Jun 1
TI  - Branched-chain amino acid supplementation ameliorates angiotensin II-induced 
      skeletal muscle atrophy.
PG  - 117593
LID - S0024-3205(20)30341-6 [pii]
LID - 10.1016/j.lfs.2020.117593 [doi]
AB  - AIMS: Sarcopenia is characterized by muscle mass and strength loss and reduced 
      physical activity. Branched-chain amino acids (BCAAs) were recently described as 
      an activator of protein synthesis via mammalian target of rapamycin (mTOR) 
      signaling for muscle atrophy. In cardiovascular diseases, excessive activation of 
      the renin-angiotensin system may induce an imbalance of protein synthesis and 
      degradation, and this plays a crucial role in muscle atrophy. We investigated the 
      effects of BCAAs on angiotensin II (Ang II)-induced muscle atrophy in mice. 
      MATERIALS AND METHODS: We administered Ang II (1000 ng/kg/min) or vehicle to 
      10-12-week-old male C57BL/6J mice via subcutaneous osmotic minipumps for 4 weeks 
      with or without BCAA supplementation (3% BCAA in tap water). KEY FINDINGS: The 
      skeletal muscle weight/tibial length and cross-sectional area were smaller in the 
      Ang II mice than the vehicle mice; these changes were induced by an imbalance of 
      protein synthesis and degradation signaling such as Akt/mTOR and 
      MuRF-1/Atrogin-1. Compared to the Ang II mice, the mTOR signaling was 
      significantly activated and Ang II-induced muscle atrophy was ameliorated in the 
      Ang II + BCAA mice, and this attenuated the reduction of exercise capacity. 
      Notably, the decrease of muscle weight/tibial length in the fast-twitch dominant 
      muscles (e.g., the extensor digitorum longus) was significantly ameliorated 
      compared to that in the slow-twitch dominant muscles (e.g., soleus). 
      Histologically, the effect of BCAA was larger in fast-twitch than slow-twitch 
      fibers, which may be related to the difference in BCAA catabolism. SIGNIFICANCE: 
      BCAA supplementation could contribute to the prevention of skeletal muscle 
      atrophy induced by Ang II.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Yamanashi, Katsuma
AU  - Yamanashi K
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo 0608638, Japan.
FAU - Kinugawa, Shintaro
AU  - Kinugawa S
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo 0608638, Japan. Electronic address: 
      tuckahoe@w6.dion.ne.jp.
FAU - Fukushima, Arata
AU  - Fukushima A
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo 0608638, Japan.
FAU - Kakutani, Naoya
AU  - Kakutani N
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo 0608638, Japan; Research Fellow of the 
      Japan Society for the Promotion of Science, Japan.
FAU - Takada, Shingo
AU  - Takada S
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo 0608638, Japan; Faculty of Lifelong Sport, 
      Department of Sports Education, Hokusho University, Ebetsu 0698511, Japan.
FAU - Obata, Yoshikuni
AU  - Obata Y
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo 0608638, Japan.
FAU - Nakano, Ippei
AU  - Nakano I
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo 0608638, Japan.
FAU - Yokota, Takashi
AU  - Yokota T
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo 0608638, Japan.
FAU - Kitaura, Yasuyuki
AU  - Kitaura Y
AD  - Laboratory of Nutritional Biochemistry, Department of Applied Molecular 
      Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, 
      Nagoya 4648601, Japan.
FAU - Shimomura, Yoshiharu
AU  - Shimomura Y
AD  - Laboratory of Nutritional Biochemistry, Department of Applied Molecular 
      Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, 
      Nagoya 4648601, Japan.
FAU - Anzai, Toshihisa
AU  - Anzai T
AD  - Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of 
      Medicine, Hokkaido University, Sapporo 0608638, Japan.
LA  - eng
PT  - Journal Article
DEP - 20200328
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Amino Acids, Branched-Chain)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Amino Acids, Branched-Chain/*administration & dosage
MH  - Angiotensin II
MH  - Animals
MH  - Blood Pressure
MH  - Echocardiography
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle Fibers, Skeletal/metabolism
MH  - Muscle, Skeletal/*drug effects/pathology
MH  - Muscular Atrophy/*drug therapy
MH  - Phosphorylation
MH  - Physical Conditioning, Animal
MH  - Renin-Angiotensin System
MH  - Signal Transduction
OTO - NOTNLM
OT  - Angiotensin II
OT  - BCAA
OT  - Muscle atrophy
OT  - Muscle fiber type
COIS- Declaration of competing interest None declared.
EDAT- 2020/04/03 06:00
MHDA- 2020/05/06 06:00
CRDT- 2020/04/03 06:00
PHST- 2019/10/22 00:00 [received]
PHST- 2020/03/25 00:00 [revised]
PHST- 2020/03/26 00:00 [accepted]
PHST- 2020/04/03 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2020/04/03 06:00 [entrez]
AID - S0024-3205(20)30341-6 [pii]
AID - 10.1016/j.lfs.2020.117593 [doi]
PST - ppublish
SO  - Life Sci. 2020 Jun 1;250:117593. doi: 10.1016/j.lfs.2020.117593. Epub 2020 Mar 
      28.