Branched-chain amino acid supplementation ameliorates angiotensin II-induced skeletal muscle atrophy

Life Sci. 2020 Jun 1:250:117593. doi: 10.1016/j.lfs.2020.117593. Epub 2020 Mar 28.


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.

Keywords: Angiotensin II; BCAA; Muscle atrophy; Muscle fiber type.

MeSH terms

  • Amino Acids, Branched-Chain / administration & dosage*
  • Angiotensin II
  • Animals
  • Blood Pressure
  • Echocardiography
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / drug therapy*
  • Phosphorylation
  • Physical Conditioning, Animal
  • Renin-Angiotensin System
  • Signal Transduction


  • Amino Acids, Branched-Chain
  • Angiotensin II