Branched-Chain Amino Acids Reduce Hindlimb Suspension-Induced Muscle Atrophy and Protein Levels of Atrogin-1 and MuRF1 in Rats
Abstract
Atrogin-1 and MuRF1, muscle-specific ubiquitin ligases, and autophagy play a role in protein degradation in muscles. We hypothesized that branched-chain amino acids (BCAAs) may decrease atrogin-1, MuRF1, and autophagy, and may have a protective effect on disuse muscle atrophy. To test this hypothesis, we selected hindlimb suspension (HS)-induced muscle atrophy as a model of disuse muscle atrophy because it is an established model to investigate the effects of decreased muscle activity. Sprague-Dawley male rats were assigned to 4 groups: control, HS (14 days), oral BCAA administration (600 mg/[kg day], 22.9% L-isoleucine, 45.8% L-leucine, and 27.6% L-valine), and HS and BCAA administration. After 14 days of the treatment, muscle weights and protein concentrations, cross-sectional area (CSA) of the muscle fibers, atrogin-1 and MuRF1 proteins, and microtubule-associated protein 1 light chain 3 II/I (ratio of LC3 II/I) were measured. Hindlimb suspension significantly reduced soleus muscle weight and CSA of the muscle fibers. Branched-chain amino acid administration partly but significantly reversed the HS-induced decrease in CSA. Hindlimb suspension increased atrogin-1 and MuRF1 proteins, which play a pivotal role in various muscle atrophies. Branched-chain amino acid attenuated the increase in atrogin-1 and MuRF1 in soleus muscles. Hindlimb suspension significantly increased the ratio of LC3 II/I, an indicator of autophagy, whereas BCAA did not attenuate the increase in the ratio of LC3 II/I. These results indicate the possibility that BCAA inhibits HS-induced muscle atrophy, at least in part, via the inhibition of the ubiquitin-proteasome pathway. Oral BCAA administration appears to have the potential to prevent disuse muscle atrophy.
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Branched-chain amino acids inhibit hindlimb suspension-induced muscle atrophy in SD rats via suppressing MAFbx and MuRF1 in soleus muscles.
“Branched-chain amino acids (22.9% L-isoleucine, 45.8% L-leucine, and 27.6% L-valine) have been shown to inhibit hindlimb suspension-induced muscle atrophy in Sprague Dawley (SD) rats via, at least in part, suppressing the expression of MAFbx and MuRF1 in soleus muscles [28].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [28]
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- Authors
- Maki, T., Yamamoto, D., Nakanishi, S., Iida, K., Iguchi, G., Takahashi, Y., Kaji, H., Chihara, K., & Okimura, Y.
- Affiliations
- Kobe University (JP)
- University of Hyogo (JP)
- Kobe Women's University (JP)
- Venue
- Nutrition Research
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 32
- Issue
- 9
- Pages
- 676-683
- ISSN
- 0271-5317 (ISSN-L)
- OpenAlex
- W2039332129
- Cited by
- 85
- References
- 43
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 5 · 2022: 9 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 10 · 2015: 12 · 2014: 7 · 2013: 2
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nutrition Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Keywords
- branched-chain amino acids, disuse atrophy, hindlimb unloading, atrogin-1, MuRF1, ubiquitin-proteasome system, autophagy, LC3, soleus muscle, muscle protein degradation, muscle fiber cross-sectional area
- MeSH terms
- Tripartite Motif Proteins, Amino Acids, Branched-Chain, Animals, Isoleucine, Leucine, Male, Muscle Proteins, Muscular Atrophy, Organ Size, Valine, Blotting, Western, Rats, Sprague-Dawley, Muscle, Skeletal, Hindlimb Suspension, Muscular Disorders, Atrophic, Ubiquitin-Protein Ligases, SKP Cullin F-Box Protein Ligases, Rats
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