Skeletal Muscle Anti-Atrophic Effects of Leucine Involve Myostatin Inhibition

Abstract

Lack of mechanical load leads to skeletal muscle atrophy, and one major underlying mechanism involves the myostatin pathway that negatively regulates protein synthesis and also activates Atrogin-1/MAFbx and MuRF1 genes. In hindlimb immobilization, leucine was observed to attenuate the upregulation of the referred atrogenes, thereby shortening the impact on fiber cross-sectional area, nonetheless, the possible connection with myostatin is still elusive. This study sought to verify the impact of leucine supplementation on myostatin expression. Male Wistar rats were supplemented with leucine and hindlimb immobilized for 3 and 7 days, after which soleus muscles were removed for morphometric measurements and analyzed for gene and protein expression by realtime PCR and Western blotting, respectively. Muscle wasting was prominent 7 days after immobilization, as expected, leucine feeding mitigated this effect. Atrogin-1/MAFbx gene expression was upregulated only after 3 days of immobilization, and this effect was attenuated by leucine supplementation. Atrogin-1/MAFbx protein levels were elevated after 7 days of immobilization, which leucine supplementation was not able to lessen. On the other hand, myostatin gene expression was upregulated in immobilization for 3 and 7 days, which returned to normal levels after leucine supplementation. Myostatin protein levels followed gene expression at a 3-day time point only. Follistatin gene expression was upregulated during immobilization and accentuated by leucine after 3 days of supplementation. Concerning protein expression, follistatin was not altered neither by immobilization nor in immobilized animals treated with leucine. In conclusion, leucine protects against skeletal muscle mass loss during disuse, and the underlying molecular mechanisms appear to involve myostatin inhibition and Atrogin-1 normalization independently of follistatin signaling.

Evaluation of Variation on Myostatin (MSTN) Gene of Turkish Donkey Populations in Thrace Region of Turkey

“…As mentioned, silent mutations of G>A in leucine (Leu) amino acid were found in this study. The investigation about the Leucine effect on Myostatin expression on skeletal muscles of Wistar rats (Cruz et al;2020) demonstrated and confirm the importance of Leucine. They have found leucine prevents the loss of skeletal muscle mass and causes a decrement in the Myostatin expression, even block it in some circumstances (Cruz et al;2020).…”

“…The investigation about the Leucine effect on Myostatin expression on skeletal muscles of Wistar rats (Cruz et al;2020) demonstrated and confirm the importance of Leucine. They have found leucine prevents the loss of skeletal muscle mass and causes a decrement in the Myostatin expression, even block it in some circumstances (Cruz et al;2020). Since leucine alters the Myostatin expression and synonymous mutations can affect the amino acid and lead to several alterations as mentioned above, it can be interpretable that silent mutation in leucine in this study may affect the MSTN gene expression.…”

Effects of Soy Milk in Conjunction With Resistance Training on Physical Performance and Skeletal Muscle Regulatory Markers in Older Men

“…Leucine is able to stimulate the activation of proteins that are involved in regulating muscle protein synthesis. In this regard, Cruz et al (2020) evaluated the effect of leucine supplementation with hindlimb immobilized for 3 and 7 days, and reported significantly upgraded serum concentrations of follistatin and decreased serum concentrations of myostatin in male Wistar rats. Verhoeven et al (2009) found that 12 weeks of 3 gr of leucine supplementation did not significantly increase MPS in healthy elderly men.…”

“…The probable mechanism of soy milk on serum concentrations of follistatin, myostatin, GDF11, and also MFR, is yet unclear. Leucine, a component of soy milk, has an important role in maintaining and increasing muscle mass during the aging process (Cruz et al, 2020). Also, it has been indicated that leucine can minimize the muscle mass in injury, cachexia, cancer, and immobilization in older individuals (Cruz et al, 2020).…”

“…Leucine, a component of soy milk, has an important role in maintaining and increasing muscle mass during the aging process (Cruz et al, 2020). Also, it has been indicated that leucine can minimize the muscle mass in injury, cachexia, cancer, and immobilization in older individuals (Cruz et al, 2020). Leucine is able to stimulate the activation of proteins that are involved in regulating muscle protein synthesis.…”