Effects of branched-chain amino acids on iron deficiency-induced muscle atrophy

TL;DR

Iron deficiency causes muscle atrophy, and BCAA only partially helps by affecting some muscle breakdown genes but not overall muscle size.

Contribution

This study reveals BCAA's limited effectiveness in preventing muscle atrophy caused by iron deficiency.

Findings

Iron deficiency reduces myotube diameter and activates atrogenes like Atrogin-1 and MuRF-1.

BCAA partially suppresses Atrogin-1 but does not prevent muscle atrophy or affect MuRF-1.

BCAA has limited efficacy in counteracting iron deficiency-induced muscle atrophy.

Abstract

Iron deficiency (ID) is a potential contributor to skeletal muscle atrophy through disruption of the balance between protein synthesis and degradation. This muscle loss is associated with sarcopenia and locomotive syndrome, conditions that impair mobility and reduce healthy life expectancy. While branched-chain amino acids (BCAA) are known to attenuate dexamethasone-induced muscle atrophy, its effectiveness against ID-induced atrophy has not been fully elucidated. This study aims to investigate the effects of BCAA on ID-induced muscle atrophy in C2C12 myotubes treated with the iron chelator deferoxamine (DFO). Results showed that DFO significantly reduced myotube diameter and upregulated atrogenes such as Atrogin-1 and MuRF-1, accompanied by increased p-AMPK and p-eEF2, and decreased p-Akt levels. BCAA supplementation partially suppressed Atrogin-1 expression but had no effect on MuRF-1 or myotube diameter. Additionally, p-p70S6K was significantly upregulated in the BCAA + DFO group, while p-eEF2 levels remained elevated, similar to the DFO group. These findings suggest that ID may activate alternative catabolic signaling, such as the NF-kB pathway, thereby counteracting the anabolic effects of BCAA via the Akt signaling pathway. Thus, BCAA has limited efficacy in preventing muscle atrophy under iron-deficient conditions. In conclusion, BCAA may partially promote muscle protein synthesis-related signaling pathways, but is insufficient to prevent muscle atrophy induced by ID.

•Iron deficiency leads to reduced myotube diameter and upregulation of atrogenes.•BCAA suppressed Atrogin-1 expression but had no effect on MuRF-1 or myotube diameter.•BCAA has limited efficacy in preventing muscle atrophy under iron-deficient conditions.

Iron deficiency leads to reduced myotube diameter and upregulation of atrogenes.

BCAA suppressed Atrogin-1 expression but had no effect on MuRF-1 or myotube diameter.

BCAA has limited efficacy in preventing muscle atrophy under iron-deficient conditions.

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