A time course for markers of protein synthesis and degradation with hindlimb unloading and the accompanying anabolic resistance to refeeding

Roberson, Paul A.; Shimkus, Kevin L.; Welles, Jaclyn E.; Xu, Dandan; Whitsell, Abigale L.; Kimball, Eric M.; Jefferson, Leonard S.; Kimball, Scot R.

doi:10.1152/japplphysiol.00155.2020

Cited by 16 publications

(9 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is worth noting that rats drank and ate ad libitum until tissue collection, thus potentially impacting the interpretation of the findings herein, in particular, the signalling events related to mTORC1. However, the present findings that mTORC1 signalling is lower during disuse are consistent with previous studies 51, 53 . As disuse progresses, translational capacity (total RNA concentration or total RNA content) also decreases 50, 54 .…”

Section: Discussionsupporting

confidence: 93%

Ribosome biogenesis and degradation regulate translational capacity during muscle disuse and reloading

Figueiredo

D’Souza

Pelt

et al. 2020

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

Background Translational capacity (i.e. ribosomal mass) is a key determinant of protein synthesis and has been associated with skeletal muscle hypertrophy. The role of translational capacity in muscle atrophy and regrowth from disuse is largely unknown. Therefore, we investigated the effect of muscle disuse and reloading on translational capacity in middle‐aged men (Study 1) and in rats (Study 2). Methods In Study 1, 28 male participants (age 50.03 ± 3.54 years) underwent 2 weeks of knee immobilization followed by 2 weeks of ambulatory recovery and a further 2 weeks of resistance training. Muscle biopsies were obtained for measurement of total RNA and pre‐ribosomal (r)RNA expression, and vastus lateralis cross‐sectional area (CSA) was determined via peripheral quantitative computed tomography. In Study 2, male rats underwent hindlimb suspension (HS) for either 24 h (HS 24 h, n = 4) or 7 days (HS 7d, n = 5), HS for 7 days followed by 7 days of reloading (Rel, n = 5) or remained as ambulatory weight bearing (WB, n = 5) controls. Rats received deuterium oxide throughout the study to determine RNA synthesis and degradation, and mTORC1 signalling pathway was assessed. Results Two weeks of immobilization reduced total RNA concentration (20%) and CSA (4%) in men (both P ≤ 0.05). Ambulatory recovery restored total RNA concentration to baseline levels and partially restored muscle CSA. Total RNA concentration and 47S pre‐rRNA expression increased above basal levels after resistance training (P ≤ 0.05). In rats, RNA synthesis was 30% lower while degradation was ~400% higher in HS 7d in soleus and plantaris muscles compared with WB (P ≤ 0.05). mTORC1 signalling was lower in HS compared with WB as was 47S pre‐rRNA (P ≤ 0.05). With reloading, the aforementioned parameters were restored to WB levels while RNA degradation was suppressed (P ≤ 0.05). Conclusions Changes in RNA concentration following muscle disuse and reloading were associated with changes in ribosome biogenesis and degradation, indicating that both processes are important determinants of translational capacity. The pre‐clinical data help explain the reduced translational capacity after muscle immobilization in humans and demonstrate that ribosome biogenesis and degradation might be valuable therapeutic targets to maintain muscle mass during disuse.

show abstract

Section: Discussionsupporting

confidence: 93%

Ribosome biogenesis and degradation regulate translational capacity during muscle disuse and reloading

Figueiredo

D’Souza

Pelt

et al. 2020

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

“…Currently, in models of weightlessness-induced muscle atrophy, the tail suspension model with rats can simulate a series of physiological changes in hindlimb muscle during space flight and is one of the most extensively used animal models in studies of muscular dystrophy (29,30). Studies have shown that the soleus muscle exhibits significant atrophy after suspension for one week, and the muscle wet weight ratio decreases by approximately 50% after two weeks (31,32). In this study, RNA sequencing (RNAseq) analysis was used to analyze DEGs in rat soleus muscle at 12, 24, 36 hours, three days, and seven days after tail suspension.…”

Section: Introductionmentioning

confidence: 99%

RNA sequencing (RNA-seq) analysis of gene expression provides new insights into hindlimb unloading-induced skeletal muscle atrophy

Cui¹,

Yang²,

Gu³

et al. 2020

Ann Transl Med

View full text Add to dashboard Cite

Background: Weightlessness-induced skeletal muscle atrophy, accompanied by complex biochemical and physiological changes, has potentially damaged consequences. However, there is still an insufficient effective strategy to treat skeletal muscle atrophy. Therefore, exploring the molecular mechanisms regulating skeletal muscle atrophy and effective protection is necessary.Methods: RNA sequencing (RNA-seq) analysis was used to detect differentially expressed genes (DEGs) in the soleus muscle at 12, 24, 36 hours, three days, and seven days after hindlimb unloading in rats. Pearson correlation heatmaps and principal component analysis (PCA) were applied to analyze DEGs' expression profiles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for cluster analysis of DEGs. Ingenuity pathway analysis (IPA) was used to analyze specific biological processes further.

show abstract

“…DEPTOR knockdown, in vivo, resulted in an attenuation of immobilization-induced muscle atrophy associated with increased muscle protein synthesis (Kazi et al, 2011). The sensitivity of DEPTOR to atrophy conditions has been replicated by others showing DEPTOR expression increases with limb immobilization (Shimkus et al, 2018) and hind limb unloading (Roberson et al, 2020). The regulation of DEPTOR from nutrient availability does not appear as strong as mechanical loading, as fasting/refeeding did not alter DEPTOR protein expression (Shimkus et al, 2018).…”

Section: The Mtorc1 Complexmentioning

confidence: 91%

Amino Acid Trafficking and Skeletal Muscle Protein Synthesis: A Case of Supply and Demand

White

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Skeletal muscle protein synthesis is a highly complex process, influenced by nutritional status, mechanical stimuli, repair programs, hormones, and growth factors. The molecular aspects of protein synthesis are centered around the mTORC1 complex. However, the intricacies of mTORC1 regulation, both up and downstream, have expanded overtime. Moreover, the plastic nature of skeletal muscle makes it a unique tissue, having to coordinate between temporal changes in myofiber metabolism and hypertrophy/atrophy stimuli within a tissue with considerable protein content. Skeletal muscle manages the push and pull between anabolic and catabolic pathways through key regulatory proteins to promote energy production in times of nutrient deprivation or activate anabolic pathways in times of nutrient availability and anabolic stimuli. Branched-chain amino acids (BCAAs) can be used for both energy production and signaling to induce protein synthesis. The metabolism of BCAAs occur in tandem with energetic and anabolic processes, converging at several points along their respective pathways. The fate of intramuscular BCAAs adds another layer of regulation, which has consequences to promote or inhibit muscle fiber protein anabolism. This review will outline the general mechanisms of muscle protein synthesis and describe how metabolic pathways can regulate this process. Lastly, we will discuss how BCAA availability and demand coordinate with synthesis mechanisms and identify key factors involved in intramuscular BCAA trafficking.

show abstract

A time course for markers of protein synthesis and degradation with hindlimb unloading and the accompanying anabolic resistance to refeeding

Cited by 16 publications

References 57 publications

Ribosome biogenesis and degradation regulate translational capacity during muscle disuse and reloading

Ribosome biogenesis and degradation regulate translational capacity during muscle disuse and reloading

RNA sequencing (RNA-seq) analysis of gene expression provides new insights into hindlimb unloading-induced skeletal muscle atrophy

Amino Acid Trafficking and Skeletal Muscle Protein Synthesis: A Case of Supply and Demand

Contact Info

Product

Resources

About