Protein Supplementation Enhances the Effects of Intermittent Loading on Skeletal Muscles by Activating the mTORC1 Signaling Pathway in a Rat Model of Disuse Atrophy

Abstract

Inactivity leads to skeletal muscle atrophy, whereas intermittent loading (IL) during hind limb unloading (HU) attenuates muscle atrophy. However, the combined effects of IL and protein supplementation on disuse muscle atrophy are unclear. Therefore, we investigated the effects of IL and a high-protein oral nutritional supplement (HP) during HU on skeletal muscle mass and protein synthesis/breakdown. Male F344 rats were assigned to the control (CON), 14-day HU (HU), IL during HU (HU + IL), and IL during HU followed by HP administration (2.6 g protein/kg/day; HU + IL + HP) groups. Soleus and gastrocnemius muscles were sampled 30 min after the last IL and HP supplementation. HU decreased relative soleus and gastrocnemius muscle masses. Relative muscle masses and p70 ribosomal protein S6 kinase/ribosomal protein S6 phosphorylation in soleus and gastrocnemius muscles were higher in the HU + IL group than the HU group and further higher in the HU + IL + HP group than the HU + IL group in gastrocnemius muscle. Therefore, protein administration plus IL effectively prevented skeletal muscle atrophy induced by disuse, potentially via enhanced activation of targets downstream of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway.

Molecular Regulation of Skeletal Muscle Growth and Organelle Biosynthesis: Practical Recommendations for Exercise Training

“…Importantly, the response of muscle hypertrophy did not differ between the groups [247], showing that disuse muscle atrophy does not alter muscle protein synthesis in response to acute resistance exercise and muscle hypertrophy in response to chronic resistance training. Consistent with these data, another study on disuse atrophy showed that intermittent loading with protein ingestion prevents atrophy during hindlimb unloading probably through mTORC1 signaling pathway [248].…”

Combination of Parenteral Amino Acid Infusion and Intermittent Loading Exercise Ameliorates Progression of Postoperative Sarcopenia in Rat Model

“…The ubiquitin–proteasome and autophagy–lysosome systems play key roles in protein degradation during muscle atrophy [ 14 , 15 , 16 ]. The upregulation of ubiquitin ligases and autophagy-related mRNA or protein expression was observed in animal models of muscle disuse and human bed rest conditions [ 15 , 29 , 35 , 36 , 37 , 38 ]. In this study, we measured mRNA expressions of atrogenes (Atrogin-1, MuRF1), autophagy-related genes (ULK1, LC3B, p62, Gabarap, and Bnip3), and FOXO transcription factors (Foxo1, Foxo3, and Gadd45a) which control both systems [ 17 , 39 , 40 ].…”

“…However, further evaluation is needed to confirm the fiber type-specific effect of AA and/or Exc. Second, the intermittent loading of Exc was conducted according to the methods proposed in previous studies [ 29 , 30 ]; however, it was difficult to obtain a unified Exc volume in individual animals. Hence, the combined effects of Exc itself may be altered depending on the individual and study.…”

“…HS was performed with their tail angled at approximately 30° head-down, and the rats were allowed to move freely in their cages using their forelimbs, as described in a previous report [ 28 ]. Rats in the AA (−)-Exc and AA (+)-Exc groups were released from HS for 1 h/d for the intermittent loading of Exc in accordance with previous studies [ 29 , 30 ]. During this period, the rats were allowed to move freely using their forelimbs and hindlimbs.…”

Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy

“…Protein, amino acid, and peptides supplementation (Table 1) is considered to be effective in increasing muscle anabolism and preventing muscle atrophy during extended periods of immobilization [19]. Oral administration of a high protein liquid nutritional supplement (milk protein, whey protein, leucine, and citrulline) inhibits intermittent loadinginduced muscle atrophy and increases muscle mass by activating the mTORC1 signaling pathway (Ribosomal protein S6 kinase (p70S6K) and ribosomal protein S6 (rpS6)) [20]. Shin et al reported that soluble whey protein hydrolysate increases grip strength, muscle mass, and cross-sectional area of muscle fiber and meliorates immobilization-induced C57BL/6 mice muscle atrophy via regulating the PI3K/Akt pathway [21].…”