Muscle Protein Metabolism Research Articles

The Regulatory Role of Nutrients in Muscle Protein Synthesis (MPS) and Muscle Protein Breakdown (MPB) with Resistance Exercise

With the improvement of living standards nowadays, the body’s health and physique have become a popular topic; the growth, maintenance, and health of muscles are achieved through the key process of muscle protein synthesis (MPS) and muscle protein breakdown (MPB). This paper discusses the important regulatory roles of macronutrients, amino acids, hormones, micronutrients, and vitamins in MPS and MPB, especially in the context of resistance exercise. Through a large review of the existing literature on the relationships between various nutrients and resistance exercise and muscle, this paper summarizes the complex interactions between all these nutrients and resistance exercise. This paper aims to provide comprehensive insights into the optimization of muscle hypertrophy and reduction of muscle atrophy, including an in-depth discussion of the importance of macronutrient intake during resistance exercise, the important role of amino acids, especially leucine, the associated effects of hormones such as insulin and testosterone, and the best timing and methods for the intake of these nutrients. This review demonstrates the indispensability and complementarity of each nutrient for muscle growth and building, provides practical advice for athletes such as powerlifters and bodybuilders, the declining elderly, and individuals seeking to enhance muscle health, fills existing research gaps, and provides valuable insights into the nutritional regulation of muscle protein metabolism.

Water deprivation induces a systemic pro-catabolic state that differentially affects oxidative and glycolytic skeletal muscles in male mice.

Dehydration, characterized by the loss of total body water and/or electrolytes due to diseases or inadequate fluid intake, is prevalent globally but often underestimated. Its contribution to long-term chronic diseases and sarcopenia is recognized, yet the mechanisms involved in systemic and muscle protein metabolism during dehydration remain unclear. This study investigated metabolic adaptations in a 36-hour water deprivation (WD) model of mice. Male C57BL/6 mice underwent 36-h WD or pair-feeding at rest, with assessments of motor skills along with biochemical, and metabolic parameters. Dehydration was confirmed by hypernatremia, body mass loss, hyporexia, and increased activity of vasopressinergic and oxytocinergic neurons compared to controls. These results were associated with liver mass loss, decreased glycaemia, and increased cholesterolemia. Additionally, increased VO2 and a decreased respiratory exchange ratio indicated reduced carbohydrate consumption and potentially increased protein use during dehydration. Thus, skeletal muscle protein metabolism was evaluated due to its high protein content. In the oxidative muscles of the WD group, total and proteasomal proteolysis increased, which was associated with decreased Akt-mediated intracellular signaling. Interestingly, there was an increase in fiber cross-sectional area, likely due to higher muscle water content caused by increased intracellular osmolality induced by protein catabolism products. Conversely, no changes were observed in protein turnover or water content in glycolytic muscles. These findings suggest that short-term WD imposes a pro-catabolic state, depleting protein content in skeletal muscle. However, skeletal muscle may respond differently to dehydration based on its phenotype and might adapt for a limited time.

Underpowered studies in muscle metabolism research: Determinants and considerations

Biomedical research frequently employs null hypothesis testing to determine whether an observed difference in a sample is likely to exist in the broader population. Null hypothesis testing generally assumes that differences between groups or interventions are non-existent, unless proven otherwise. Because biomedical studies with human subjects are often limited by financial and logistical resources, they tend to have low statistical power, i.e. a low probability of statistically confirming a true difference. As a result, small but potentially clinically important differences may be overseen or ignored simply due to the absence of a statistically significant difference. This absence is often misinterpreted as ‘equivalence’ of treatments. In this educational paper, we will use practical examples related to the effects of exercise and nutrition on muscle protein metabolism to illustrate the most important determinants of statistical power, as well as their implications for both investigators and readers of scientific articles.Changes in muscle mass occur at a relatively slow rate, making it practically challenging to detect differences between treatment groups in a long-term setting. One way to make it ‘easier’ to differentiate between groups and hence increase statistical power is to have a sufficiently long study duration to allow treatment effects to become apparent. This is especially relevant when comparing treatments with relatively small expected differences such as the effect of modest changes in daily protein intake. Secondly, one could try to minimize the variance and response heterogeneity within groups, for example by using strict inclusion criteria and standardization protocols (e.g., meal provision), by using cross-over designs, or even within-subject designs where two interventions are compared simultaneously (e.g., studying an exercised limb vs a contralateral control limb) although this might limit the generalizability of the findings (e.g. such single-limb exercise training is not common in practice). In terms of data interpretation, investigators should obviously refrain from drawing strong conclusions from underpowered studies. Yet, such studies still provide valuable data for meta-analyses. Finally, because muscle protein synthesis rates are highly responsive to anabolic stimuli, acute metabolic studies are more sensitive to detect potentially clinically relevant differences in the anabolic response between treatments. Apart from further elaborating on these topics, this educational article encourages readers to more critically question null findings and scientists to more clearly discuss limitations that may have compromised statistical power.

Fermented red ginseng extract improves sarcopenia-related muscle atrophy in old mice through regulation of muscle protein metabolism

Fermented red ginseng extract improves sarcopenia-related muscle atrophy in old mice through regulation of muscle protein metabolism

Effects of insect consumption on exercise performance, body composition and metabolism: a review

Abstract Insects contain a number of beneficial macronutrients, micronutrients, and bioactive compounds that play crucial roles for optimal bodily functions and exercise. This review aims to consolidate information from studies involving humans and animals that investigated the effect of insect consumption, either alone or in combination with exercise, on exercise performance, body composition, and metabolism. In humans, insect supplementation with exercise could improve strength. Insect supplementation, with or without exercise, could also improve body composition. However, the lack of dietary and physical activity control may have influenced these findings. Insect consumption alone caused increased blood amino acids, followed by activation of the mammalian target of rapamycin complex-1 (mTORC1) signalling and increased muscle protein synthesis, which is further elevated when combined with resistance exercise. In animals, insect consumption alone could improve endurance and fatigue biomarkers. It could also reduce fat mass and increase muscle mass. The reduction in fat mass was attributed to improvements in blood lipid profiles, while the increase in muscle mass is attributed to elevated blood amino acids and mTORC1. Interestingly, in combination with exercise, greater changes in these variables were observed, including increases in energy metabolism. Findings from animal studies, such as changes in muscle mass and protein metabolism, have been validated in humans, while outcomes regarding endurance, fat mass, and blood lipids have not been validated in humans. This encourages future research to focus on these parameters. Due to ethical constraints and impracticality, there has been a reliance on animal studies to elucidate certain mechanisms and parameters in humans. Overall, insect consumption, with or without exercise, in both humans and animals showed promising results in improving exercise performance, body composition, and metabolism and thus, could function as an alternative exercise supplement. Additionally, utilizing animal models has allowed researchers to better understand the key mechanisms behind these improvements.

Effects of Limosilactobacillus reuteri on ruminal microbiota, muscle protein metabolism, and flavor of Sunit lamb

To investigate the effects of dietary Limosilactobacillus reuteri (L. reuteri) supplementation on rumen microbiota, protein metabolism, and flavor, 12 three-month-old Sunit lambs were randomly divided into CG group (basal diet) and LG group (basal diet + L. reuteri) for 90 days. Each group of sheep had six replicates. Metagenomics, gas chromatography-mass spectrometry (GC-MS), real-time PCR, and electronic nose were used to measure the samples. The results showed that L. reuteri significantly increased muscle aromatic compounds (P < 0.05). In the rumen of the LG group, Prevotella, Bacteroides, Paraprevotella, Fibrobacter, and propionate abundance significantly increased (P < 0.05), with their function enriched in carbohydrate degradation (glycoside hydrolases and glycosyl transferases) based on CAZy analysis. Additionally, L. reuteri enhanced the expression of ZO-1, Occludins, and GPCR43 in the rumen epithelium. The mTOR and eIF4B genes were downregulated, while the TSC1 gene was upregulated in muscle (P < 0.05). Propionate was negatively correlated with g_Selenomonas, g_Schwartzia, mTOR, and eIF4B genes, while positively correlated with aromatic component receptor and TSC1 gene. In conclusion, dietary supplementation with L. reuteri can enhance rumen fermentation, regulate protein degradation, and optimize muscle aromatic compounds. These findings provide new perspectives for improving the quality of captive lambs.

Progress in physiologically based pharmacokinetic-pharmacodynamic models of amino acids in humans.

Amino acids are critical to health, serving both as constituents of proteins and in signaling and metabolism. Amino acids are consumed as nutrients, supplements, and nutraceuticals. Much remains to be learned about amino acid function. Physiologically based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling is an emerging tool for studying their complex biology. This review highlights recent PBPK-PD models developed to study amino acid physiology and metabolism and discusses their potential for addressing unresolved questions in the field. PBPK-PD models provided several insights. They revealed the interplay between the mechanisms by which leucine governs skeletal muscle protein metabolism in healthy adults. The models also identified optimal dosing regimens of amino acid supplementation to treat sickle-cell disease and recurrent hypoglycemia, and to minimize drug side effects in seizure disorders. Additionally, they characterized the effects of novel anticancer drugs that seek to deprive cancer cells of amino acids. Future models may inform treatment strategies for sarcopenia, characterize distinctions between animal- and plant-based nutrition, and inform nutrient-drug interactions in Parkinson's disease. PBPK-PD models are powerful tools for studying amino acid physiology and metabolism, with applications to nutrition, pharmacology, and their interplay.

A randomized translational study on protein- and glucose metabolism in skeletal muscles evaluated by gene-ontology, following preoperative oral carbohydrate loading compared to overnight peripheral parenteral nutrition (PPN) before major cancer surgery

BackgroundEffects of preoperative drinks on muscle metabolism are unclear despite general recommendations. The aim of the present study was therefore to compare metabolic effects of a preoperative oral nutrition drink, recommended by protocols for enhanced recovery after surgery (ERAS), compared to overnight preoperative peripheral total parenteral nutrition (PPN) on skeletal muscle metabolism in patients aimed at major gastrointestinal cancer surgery.MethodsPatients were randomized, based on diagnosis and clinical characteristics, to receive either a commercial carbohydrate-rich nutrition drink (Drink); or overnight (12 h) peripheral parenteral nutrition (PPN) as study regimens; compared to isotone Ringer-acetate as Control regimen. Arterial blood- and abdominal muscle tissue specimens were collected at start of surgery. Blood chemistry included substrate- and hormone concentrations. Muscle mRNA transcript analyses were performed by microarray and evaluated for changes in gene activities by Gene Ontology algorithms.ResultsPatient groups were comparable in all measured preoperative assessments. The Nutrition Drink had significant metabolic alterations on muscle glucose metabolism (p < 0.05), without any significant effects on amino acid- and protein metabolism. PPN showed similar significant effects on glucose metabolism as Drinks (p < 0.05), but indicated also major positive effects on amino acid- (p < 0.001) and protein anabolism (p < 0.05), particularly by inhibition of muscle protein degradation, related to both ubiquitination of proteins and autophagy/lysosome pathways (p < 0.05).ConclusionConventional overnight preoperative PPN seems effective to induce and support improved muscle protein metabolism in patients aimed at major cancer surgery while preoperative oral carbohydrate loading, according to ERAS-protocols, was ineffective to improve skeletal muscle catabolism and should therefore not be recommended before major cancer surgery.Trial registration Clinical trials.gov: NCT05080816, Registered June 10th 2021- Retrospectively registered. https://clinicaltrials.gov/study/NCT05080816

1 The role of gut microbiota on regulation of growth and metabolism by branched-chain amino acids

Abstract Branched-chain amino acids (BCAA) including leucine, isoleucine and valine are essential amino acids, which are involved in energy homeostasis and regulation of many physiological paradigms including growth. The BCAA serve not only as an essential substrate in the synthesis of body proteins, but also have an important role in regulation of protein turnover. The effects of BCAA on growth and metabolism are likely mediated through different pathways including shifts in metabolic profile in peripheral organs, oxidative capacity of muscle, gut development, and protein metabolism in muscle. Although it has not been appropriately studied or fully dissected, the impact of BCAA on growth and metabolism is thought to lie in the alteration of gut microbiota by BCAA. It has long been believed that gut microbiota, more specifically, the activity of the microbiome and its metabolic products, directly influence a variety of aspects in metazoan physiology. For example, deregulation of bacterial community structure has been linked with host longevity and stress resistance, the pathogenesis of several disorders, regulation of appetite. Multiple studies have demonstrated that modulation of dietary BCAA levels could elicit clear shifts in gut microbial community structure. As part of “Physiology Symposium: The Microbiome and the Host: Functional Role in Metabolism, Immunity, and Gut-Brain Axis”, the possible involvement of intestinal microbiota on regulatory roles of BCAA on growth and metabolism will be discussed.

Bed-rest and exercise remobilisation: concurrent adaptations in muscle glucose and protein metabolism

Bed rest (BR) of only a few days duration reduces muscle protein synthesis and induces skeletal muscle atrophy and insulin resistance, but the scale and juxtaposition of these events has not been investigated concurrently in the same individuals. Moreover, the impact of short-term exercise-supplemented remobilisation (ESR) on muscle volume, protein turnover and leg glucose uptake (LGU) in humans is unknown. Ten healthy males (24±1 years, body mass index (BMI) 22.7±0.6) underwent 3 days of BR, followed immediately by 3 days of ESR consisting of 5x30 maximal voluntary single leg isokinetic knee-extensions at 90o/sec each day. An isoenergetic diet was maintained throughout the study (30% fat,15% protein, 55% carbohydrate). Resting LGU was calculated from arteriovenous-venous difference across the leg and leg blood flow during the steady-state of a 3 hr hyperinsulinaemic euglycaemic clamp (60 mU/m2/min) measured pre BR, post BR and after remobilisation. Glycogen content was measured in Vastus Lateralis muscle biopsy samples obtained before and after each clamp. Leg muscle volume (LMV) was measured using magnetic resonance imaging pre BR, post BR and after remobilisation. Cumulative myofibrillar protein fractional synthesis rate (FSR), and whole-body muscle protein breakdown (MPB) were measured over the course of BR and remobilisation using deuterium oxide and 3-methylhistidine stable isotope tracers that were administered orally. Compared with pre BR, there was a 45% decline in insulin-stimulated LGU (p&lt;0.05) after BR, which was paralleled by a reduction in insulin stimulated leg blood flow (p&lt;0.01) and removal of insulin stimulated muscle glycogen storage. These events were accompanied by a 43% reduction in myofibrillar protein FSR (p&lt;0.05) and a 2.5% decrease in LMV (p&lt;0.01) during BR, along with a 30% decline in whole-body muscle myofibrillar protein breakdown after 2 days BR (p&lt;0.05). Myofibrillar protein FSR and LMV were restored by 3 days of ERS (p&lt;0.01, p&lt;0.01; respectively), but not by ambulation alone. However, insulin stimulated LGU and muscle glycogen storage were not restored by ESR. Three days of BR caused concurrent reductions in LMV, myofibrillar protein FSR, myofibrillar protein breakdown and insulin stimulated LGU, leg blood flow and muscle glycogen storage in healthy, young volunteers. Resistance ESR restored LMV and myofibrillar protein FSR, but LGU and muscle glycogen storage remained depressed, highlighting divergences in muscle fuel and protein metabolism. Furthermore, ambulation alone did not restore LMV and myofibrillar protein FSR in the non-exercised contralateral limb, emphasising the importance of exercise rehabilitation following even short-term BR. This study was supported by the Biotechnology and Biological Sciences Research Council (BB/P005004/1), the Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis (grant no. 21595), and the National Institute of Health Research (NIHR) Nottingham Biomedical Research Centre. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Maternal supplementation with mulberry-leaf flavonoids improves the development of skeletal muscle in the offspring of chickens

The development of skeletal muscle is a crucial factor in determining the meat yield and economic benefits of broiler production. Recent research has shown that mulberry leaves and their extracts can be used to significantly improve the growth performance of livestock and poultry. The present study aims to elucidate the mechanisms involved in the regulation of skeletal muscle development in broiler offspring by dietary mulberry-leaf flavonoids (MLF) supplementation from the perspective of maternal effect theory. A total of 270 Qiling broiler breeder hens were randomly assigned to 3 treatments with different doses of MLF (0, 30, 60 mg/kg) for 8 weeks before collecting their fertilized eggs. The chicken offspring at 13 and 19 d of embryonic stage, and from 1 to 28 d old after hatching were included in this study. The results showed that maternal supplementation increased the breast muscle weight and body weight of the offspring at the embryo and chick stages (P < 0.05). This was followed by increased cross-sectional area of pectoral muscle fibres at 14 d (P < 0.05). Further determination revealed a tendency towards increased serum levels of insulin-like growth factor 1 (IGF-1) (P = 0.092) and muscle fibre count (P = 0.167) at 1 d post-hatching following maternal MLF treatment, while serum uric acid (UA) was decreased at 14 d after hatching (P < 0.05). Moreover, maternal MLF supplementation significantly up-regulated the mRNA expression of the myogenic regulatory factor Myf5 in skeletal muscle at the both embryonic and growth stages (P < 0.05). The relative abundance of the downstream protein of BMPR2, Smad1 and p-Smad1/5/9 in the TGFβ signalling pathway was significantly increased by maternal MLF treatment. Meanwhile, the increased expression of the target protein p-mTOR in the breast muscle of the offspring chicks is in accordance with the improved growth rate of the breast and the body. In conclusion, maternal MLF supplementation can promote muscle protein metabolism and muscle fibre development of chick embryos through upregulation of Myf5 expression and BMP/p-Smad1/5/9 axis, thereby improving growth performance of slow growing broiler.

Identification and anti-oxidative potential of milk fat globule membrane (MFGM)-derived bioactive peptides released through in vitro gastrointestinal digestion

This study investigated the stability of milk fat globule membrane (MFGM) protein under simulated gastrointestinal conditions using an in vitro enzymatic digestion method. The optimal hydrolysis conditions were determined by monitoring the changes in particle size and zeta-potential of MFGM protein hydrolysates over time. Furthermore, the distribution of small molecular weight peptides with antioxidant activity was explored through DEAE-52 combined with in vitro cell experiments. Two novel antioxidant peptides (TGIIT and IITQ) were identified based on molecular docking technology and evaluated their potential scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS+) radicals. TGIIT and IITQ also demonstrated remarkable abilities in promoting mitochondrial biogenesis and activating Keap1/Nrf2 signaling pathway, which can effectively counteract skeletal muscle dysfunction induced by oxidative stress. Thus, MFGM-derived antioxidant peptides have the potential to be employed in food to regulate muscle protein metabolism and alleviate sarcopenia.

Bed-rest and exercise remobilization: Concurrent adaptations in muscle glucose and protein metabolism.

Bed-rest (BR) of only a few days duration reduces muscle protein synthesis and induces skeletal muscle atrophy and insulin resistance, but the scale and juxtaposition of these events have not been investigated concurrently in the same individuals. Moreover, the impact of short-term exercise-supplemented remobilization (ESR) on muscle volume, protein turnover and leg glucose uptake (LGU) in humans is unknown. Ten healthy males (24±1years, body mass index 22.7±0.6kg/m2) underwent 3days of BR, followed immediately by 3days of ESR consisting of 5×30 maximal voluntary single-leg isokinetic knee extensions at 90°/s each day. An isoenergetic diet was maintained throughout the study (30% fat, 15% protein and 55% carbohydrate). Resting LGU was calculated from arterialized-venous versus venous difference across the leg and leg blood flow during the steady-state of a 3-h hyperinsulinaemic-euglycaemic clamp (60mU/m2/min) measured before BR, after BR and after remobilization. Glycogen content was measured in vastus lateralis muscle biopsy samples obtained before and after each clamp. Leg muscle volume (LMV) was measured using magnetic resonance imaging before BR, after BR and after remobilization. Cumulative myofibrillar protein fractional synthetic rate (FSR) and whole-body muscle protein breakdown (MPB) were measured over the course of BR and remobilization using deuterium oxide and 3-methylhistidine stable isotope tracers that were administered orally. Compared with before BR, there was a 45% decline in insulin-stimulated LGU (P<0.05) after BR, which was paralleled by a reduction in insulin-stimulated leg blood flow (P<0.01) and removal of insulin-stimulated muscle glycogen storage. These events were accompanied by a 43% reduction in myofibrillar protein FSR (P<0.05) and a 2.5% decrease in LMV (P<0.01) during BR, along with a 30% decline in whole-body MPB after 2days of BR (P<0.05). Myofibrillar protein FSR and LMV were restored by 3days of ESR (P<0.01 and P<0.01, respectively) but not by ambulation alone. However, insulin-stimulated LGU and muscle glycogen storage were not restored by ESR. Three days of BR caused concurrent reductions in LMV, myofibrillar protein FSR, myofibrillar protein breakdown and insulin-stimulated LGU, leg blood flow and muscle glycogen storage in healthy, young volunteers. Resistance ESR restored LMV and myofibrillar protein FSR, but LGU and muscle glycogen storage remained depressed, highlighting divergences in muscle fuel and protein metabolism. Furthermore, ambulation alone did not restore LMV and myofibrillar protein FSR in the non-exercised contralateral limb, emphasizing the importance of exercise rehabilitation following even short-term BR.

The Effects of Glutamine Supplementation on Liver Inflammatory Response and Protein Metabolism in Muscle of Lipopolysaccharide-Challenged Broilers

The aim of our present study was to investigate the effects of Gln supplementation on liver inflammatory responses as well as protein synthesis and degradation in the muscle of LPS-challenged broilers. A total of 120 one-day-old male broiler chickens (Arbor Acres Plus) were randomly arranged in a 2 × 2 factorial design with five replicates per treatment and six broilers per replicate, containing two main factors: immune challenge (injected with LPS in a dose of 0 or 500 µg/kg of body weight) and dietary treatments (supplemented with 1.22% alanine or 1% Gln). After feeding with an alanine or Gln diet for 15 days, broilers were administrated an LPS or a saline injection at 16 and 21 days. The results showed that Gln supplementation alleviated the increased mRNA expressions of interleukin-6, interleukin-1β, and tumor necrosis factor-α induced by LPS in liver. Moreover, the increased activity of aspartate aminotransferase combined with the decreased expression of glutaminase in muscle were observed following Gln addition. In addition, in comparison with the saline treatment, LPS challenge altered the signaling molecules’ mRNA expressions associated with protein synthesis and degradation. However, Gln supplementation reversed the negative effects on protein synthesis and degradation in muscle of LPS-challenged broilers. Taken together, Gln supplementation had beneficial effects: alleviating inflammatory responses, promoting protein synthesis, and inhibiting protein degradation of LPS-challenged broilers.

β2-Adrenoceptors activation regulates muscle trophic-related genes following acute resistance exercise in mice.

Resistance exercise (RE) training and pharmacological stimulation of β2-Adrenoceptors (β2-ARs) alone can promote muscle hypertrophy and prevent muscle atrophy. Although the activation of the sympathetic nervous system (SNS) is a well-established response during RE, the physiological contribution of the endogenous catecholamines and β2-ARs to the RE-induced changes on skeletal muscle protein metabolism remains unclear. This study investigated the effects of the β2-ARs blockade on the acute molecular responses induced by a single bout of RE in rodent skeletal muscles. Male C57BL6/J mice were subjected to a single bout of progressive RE (until exhaustion) on a vertical ladder under β2-AR blockade with ICI 118,551 (ICI; 10mgkg-1, i. p.), or vehicle (sterile saline; 0.9%, i. p.), and the gene expression was analyzed in gastrocnemius (GAS) muscles by qPCR. We demonstrated that a single bout of RE acutely increased the circulating levels of stress-associated hormones norepinephrine (NE) and corticosterone (CORT), as well as the muscle phosphorylation levels of AMPK, p38 MAPK and CREB, immediately after the session. The acute increase in the phosphorylation levels of CREB was followed by the upregulation of CREB-target genes Sik1, Ppargc1a and Nr4a3 (a central regulator of the acute RE response), 3h after the RE session. Conversely, β2-AR blockade reduced significantly the Sik1 and Nr4a3 mRNA levels in muscles of exercised mice. Furthermore, a single bout of RE stimulated the mRNA levels of the atrophic genes Map1lc3b and Gabarapl1 (autophagy-related genes) and Mstn (a well-known negative regulator of muscle growth). Unexpectedly, the gene expression of Igf-1 or Il-6 were not affected by RE, while the atrophic genes Murf1/Trim63 and Atrogin-1/Mafbx32 (ubiquitin-ligases) were increased only in muscles of exercised mice under β2-AR blockade. Interestingly, performing a single bout of RE under β2-AR blockade increased the mRNA levels of Mstn in muscles of exercised mice. These data suggest that β2-ARs stimulation during acute RE stimulates the hypertrophic gene Nr4a3 and prevents the overexpression of atrophic genes such as Mstn, Murf1/Trim63, and Atrogin-1/Mafbx32 in the first hours of postexercise recovery, indicating that he SNS may be physiologically important to muscle adaptations in response to resistance training.

Kinetic modeling of leucine-mediated signaling and protein metabolism in human skeletal muscle

Skeletal muscle protein levels are governed by the relative rates of muscle protein synthesis (MPS) and breakdown (MPB). The mechanisms controlling these rates are complex, and their integrated behaviors are challenging to study through experiments alone. The purpose of this study was to develop and analyze a kinetic model of leucine-mediated mTOR signaling and protein metabolism in the skeletal muscle of young adults. Our model amalgamates published cellular-level models of the IRS1-PI3K-Akt-mTORC1 signaling system and of skeletal-muscle leucine kinetics with physiological-level models of leucine digestion and transport and insulin dynamics. The model satisfactorily predicts experimental data from diverse leucine feeding protocols. Model analysis revealed that total levels of p70S6K are a primary determinant of MPS, insulin signaling substantially affects muscle net protein balance via its effects on MPB, and p70S6K-mediated feedback of mTORC1 signaling reduces MPS in a dose-dependent manner.

Sarcopenia: no consensus, no diagnostic criteria, and no approved indication-How did we get here?

In addition to the role of skeletal muscle in movement and locomotion, muscle plays a critical role in a broad array of metabolic processes that can contribute to improved health or risk of disease. The age-associated loss of muscle has been termed sarcopenia. The muscle is the primary site of insulin-stimulated glucose disposal and the largest component of basal metabolic rate, directly and indirectly affects bone density, produces myokines with pleiotropic effect on muscle and other tissues including the brain, and stores essential amino acids essential for the maintenance of protein synthesis during periods of reduced food intake and stress. As such, not surprisingly deterioration of skeletal muscle health, typically operationalized as decline of muscle mass and muscle strength is both a powerful risk factor and main consequence of chronic diseases, disability, and loss of independence, and it is one of the strongest risk factors for mortality. However, skeletal muscle remains one of the most plastic of all tissues, with rapid changes in rates of protein synthesis and degradation in response to physical activity and inactivity, inflammation, and nutritional and hormonal status. This has made the development of pharmacological therapies to increase muscle mass (or prevent loss), an important goal for decades. However, while remarkable advances in the understanding of molecular and cellular regulation of muscle protein metabolism have occurred recently, there are no approved drugs for the treatment of sarcopenia, the loss of skeletal muscle affecting millions of older people. The goal of this paper is to describe the possible reasons for the lack of new and effective pharmacotherapies to treat one of the most important risk factors for age-associated disease and loss of independence.

Effects of Neuromuscular Electrical Stimulation in Combination with Glutamine Administration on Skeletal Muscle Atrophy in Colon-26 Tumor-Bearing Mice

The depressed protein synthetic response, a phenomenon termed anabolic resistance, has been shown to be involved in muscle wasting induced by cancer cachexia. Moreover, a positive relationship between the protein synthetic rate and intracellular glutamine (GLN) concentration has been found in skeletal muscles. This study investigated the effects of neuromuscular electrical stimulation (ES) and GLN administration on muscle wasting and GLN metabolism in colon-26 (C-26) tumor-bearing mice. CD2F1 mice were divided into 8 groups: control (CNT), CNT+ES, CNT+GLN, CNT+ES+GLN, C-26, C-26+ES, C-26+GLN, C-26+ES+GLN. Cancer cachexia was induced by subcutaneous injection of C-26 cells and developed for four weeks. ES was performed on the left plantar flexor muscles every other day, and GLN (1 g/kg) was administered daily intraperitoneally starting one day after the C-26 injection. Tumor-free body mass and fast-twitch gastrocnemius (Gas) muscle weight were lower in the C-26 group than in the CNT group (-19% and -17%, respectively). Neither ES training nor GLN administration, alone or in combination, ameliorated the loss of Gas muscle weight in the C-26 mice. However, ES training in combination with GLN administration inhibited the increased expression of GLN synthetase (GS) in the C-26 muscles. Thus, it is likely that GLN plays a critical role in muscle protein metabolism and, therefore, can be targeted as a tentative treatment of cancer cachexia.

Changes in Skeletal Muscle Protein Metabolism Signaling Induced by Glutamine Supplementation and Exercise.

To evaluate the effects of resistance exercise training (RET) and/or glutamine supplementation (GS) on signaling protein synthesis in adult rat skeletal muscles. The following groups were studied: (1) control, no exercise (C); (2) exercise, hypertrophy resistance exercise training protocol (T); (3) no exercise, supplemented with glutamine (G); and (4) exercise and supplemented with glutamine (GT). The rats performed hypertrophic training, climbing a vertical ladder with a height of 1.1 m at an 80° incline relative to the horizontal with extra weights tied to their tails. The RET was performed three days a week for five weeks. Each training session consisted of six ladder climbs. The extra weight load was progressively increased for each animal during each training session. The G groups received daily L-glutamine by gavage (one g per kilogram of body weight per day) for five weeks. The C group received the same volume of water during the same period. The rats were euthanized, and the extensor digitorum longus (EDL) muscles from both hind limbs were removed and immediately weighed. Glutamine and glutamate concentrations were measured, and histological, signaling protein contents, and mRNA expression analyses were performed. Supplementation with free L-glutamine increased the glutamine concentration in the EDL muscle in the C group. The glutamate concentration was augmented in the EDL muscles from T rats. The EDL muscle mass did not change, but a significant rise was reported in the cross-sectional area (CSA) of the fibers in the three experimental groups. The levels of the phosphorylated proteins (pAkt/Akt, pp70S6K/p70S6K, p4E-BP1/4E-BP1, and pS6/S6 ratios) were significantly increased in EDL muscles of G rats, and the activation of p4E-BP1 was present in T rats. The fiber CSAs of the EDL muscles in T, G, and GT rats were increased compared to the C group. These changes were accompanied by a reduction in the 26 proteasome activity of EDL muscles from T rats. Five weeks of GS and/or RET induced muscle hypertrophy, as indicated by the increased CSAs of the EDL muscle fibers. The increase in CSA was mediated via the upregulated phosphorylation of Akt, 4E-BP1, p70S6k, and S6 in G animals and 4E-BP1 in T animals. In the EDL muscles from T animals, a decrease in proteasome activity, favoring a further increase in the CSA of the muscle fibers, was reported.

Beta-hydroxy-β-methyl butyrate-supplemented diet for broiler chickens is more conducive to dietary protein reduction than a leucine-supplemented diet until 21 days old.

Dietary l-leucine or its metabolite 𝛽-hydroxy-𝛽-methylbutyrate (HMB) has a crucial role in the muscle protein metabolism of broilers during the first few-week growing period. The present study aimed to evaluate the effects of l-leucine (LLPD) or HMB (HLPD) supplementation in a low-protein diet (20%, LPD) until 21 days old on performance, carcass weight, muscle yield and meat quality, as well as intestinal morphometry, in broiler chickens. From days 1-42, LPD decreased body weight gain and feed intake (FI) and increased feed conversion ratio compared to a standard protein diet (22%, SPD). The LLPD and HLPD did not affect FI, but the LLPD decreased the body weight gain and increased the feed conversion ratio compared to the SPD. The LPD group had lower body and muscle weights than other groups. Compared to LPD, HLPD increased dressing percentage. The LPD decreased the serum insulin-like growth factor-1 content compared to the SPD and LLPD. The duodenal villus height of the LPD and LLPD broilers was smaller than those of the SPD and HLPD birds. The HLPD broilers had lower duodenal villus width than the SPD birds. The duodenal crypt depth and ileal mucosal thickness were higher in the HLPD group than in other groups. The HLPD and LLPD enhanced the ileal villus height compared to the SPD. The LLPD and HLPD treatments did not affect meat quality traits compared to the SPD treatment. Dietary HMB could be a conducive approach to reducing dietary protein for broilers until 21 days old. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.