Branched-Chain Amino Acids and Di-Alanine Supplementation Attenuates Muscle Atrophy in a Murine Model of Cancer Cachexia

Abstract

Aim

Cancer cachexia is a severe metabolic disorder leading to skeletal muscle atrophy. Muscle wasting is a major clinical problem in cachectic patients, as it limits the efficacy of chemotherapeutic treatments and worsens quality of life. Nutritional support based on branched-chain amino acids (BCAA) has been shown to be a promising approach to counteract cachexia-induced muscle atrophy, but its efficacy is still debated. Furthermore, the putative role of di-alanine (Di-Ala) supplementation has yet to be evaluated. The present study therefore sought to assess whether BCAA supplementation, alone or in combination with a Di-Ala peptide, could attenuate muscle wasting in a preclinical model of cancer cachexia.

Methods

To this end, C26 tumor-bearing mice were administered BCAA supplementation, with or without Di-Ala. Body and muscle weights, as well as molecular, biochemical, and morphological analysis, were carried out to characterize prospective changes of markers involved in cachexia and muscle atrophy.

Results

The main findings revealed that BCAA supplementation effectively prevented body weight loss and muscle atrophy. Of note, Di-Ala significantly amplified the effects of BCAA. These phenomena were found to be mediated by the suppression of pathways involved in protein catabolism.

Conclusions

Collectively, these results highlight that innovative formulations containing Di-Ala, capable of increasing BCAA bioavailability, may be efficacious in counteracting muscle atrophy, especially during mild-to-moderate cancer cachexia.