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Muscle Protein Synthesis and Whole-Body Protein Turnover Responses to Ingesting Essential Amino Acids, Intact Protein, and Protein-Containing Mixed Meals with Considerations for Energy Deficit.
Gwin, JA, Church, DD, Wolfe, RR, Ferrando, AA, Pasiakos, SM
Nutrients. 2020;(8)
Abstract
Protein intake recommendations to optimally stimulate muscle protein synthesis (MPS) are derived from dose-response studies examining the stimulatory effects of isolated intact proteins (e.g., whey, egg) on MPS in healthy individuals during energy balance. Those recommendations may not be adequate during periods of physiological stress, specifically the catabolic stress induced by energy deficit. Providing supplemental intact protein (20-25 g whey protein, 0.25-0.3 g protein/kg per meal) during strenuous military operations that elicit severe energy deficit does not stimulate MPS-associated anabolic signaling or attenuate lean mass loss. This occurs likely because a greater proportion of the dietary amino acids consumed are targeted for energy-yielding pathways, whole-body protein synthesis, and other whole-body essential amino acid (EAA)-requiring processes than the proportion targeted for MPS. Protein feeding formats that provide sufficient energy to offset whole-body energy and protein-requiring demands during energy deficit and leverage EAA content, digestion, and absorption kinetics may optimize MPS under these conditions. Understanding the effects of protein feeding format-driven alterations in EAA availability and subsequent changes in MPS and whole-body protein turnover is required to design feeding strategies that mitigate the catabolic effects of energy deficit. In this manuscript, we review the effects, advantages, disadvantages, and knowledge gaps pertaining to supplemental free-form EAA, intact protein, and protein-containing mixed meal ingestion on MPS. We discuss the fundamental role of whole-body protein balance and highlight the importance of comprehensively assessing whole-body and muscle protein kinetics when evaluating the anabolic potential of varying protein feeding formats during energy deficit.
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2.
Intramuscular Mechanisms Mediating Adaptation to Low-Carbohydrate, High-Fat Diets during Exercise Training.
Howard, EE, Margolis, LM
Nutrients. 2020;(9)
Abstract
Interest in low-carbohydrate, high-fat (LCHF) diets has increased over recent decades given the theorized benefit of associated intramuscular adaptations and shifts in fuel utilization on endurance exercise performance. Consuming a LCHF diet during exercise training increases the availability of fat (i.e., intramuscular triglyceride stores; plasma free fatty acids) and decreases muscle glycogen stores. These changes in substrate availability increase reliance on fat oxidation for energy production while simultaneously decreasing reliance on carbohydrate oxidation for fuel during submaximal exercise. LCHF diet-mediated changes in substrate oxidation remain even after endogenous or exogenous carbohydrate availability is increased, suggesting that the adaptive response driving changes in fat and carbohydrate oxidation lies within the muscle and persists even when the macronutrient content of the diet is altered. This narrative review explores the intramuscular adaptations underlying increases in fat oxidation and decreases in carbohydrate oxidation with LCHF feeding. The possible effects of LCHF diets on protein metabolism and post-exercise muscle remodeling are also considered.
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3.
Muscle protein turnover and low-protein diets in patients with chronic kidney disease.
Garibotto, G, Picciotto, D, Saio, M, Esposito, P, Verzola, D
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(5):741-751
Abstract
Adaptation to a low-protein diet (LPD) involves a reduction in the rate of amino acid (AA) flux and oxidation, leading to more efficient use of dietary AA and reduced ureagenesis. Of note, the concept of 'adaptation' to low-protein intakes has been separated from the concept of 'accommodation', the latter term implying a decrease in protein synthesis, with development of wasting, when dietary protein intake becomes inadequate, i.e. beyond the limits of the adaptive mechanisms. Acidosis, insulin resistance and inflammation are recognized mechanisms that can increase protein degradation and can impair the ability to activate an adaptive response when an LPD is prescribed in a chronic kidney disease (CKD) patient. Current evidence shows that, in the short term, clinically stable patients with CKD Stages 3-5 can efficiently adapt their muscle protein turnover to an LPD containing 0.55-0.6 g protein/kg or a supplemented very-low-protein diet (VLPD) by decreasing muscle protein degradation and increasing the efficiency of muscle protein turnover. Recent long-term randomized clinical trials on supplemented VLPDs in patients with CKD have shown a very good safety profile, suggesting that observations shown by short-term studies on muscle protein turnover can be extrapolated to the long-term period.
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4.
Protein Distribution and Muscle-Related Outcomes: Does the Evidence Support the Concept?
Hudson, JL, Iii, REB, Campbell, WW
Nutrients. 2020;(5)
Abstract
There is a shift in thinking about dietary protein requirements from daily requirements to individual meal requirements. Per meal, stimulation of muscle protein synthesis has a saturable dose relationship with the quantity of dietary protein consumed. Protein intake above the saturable dose does not further contribute to the synthetic response; the "excess" amino acids are predominantly oxidized. Given that daily dietary protein intake is finite, finding protein distribution patterns that both reduce amino acid oxidation and maximize their contribution towards protein synthesis (in theory improving net balance) could be "optimal" and is of practical scientific interest to promote beneficial changes in skeletal muscle-related outcomes. This article reviews both observational and randomized controlled trial research on the protein distribution concept. The current evidence on the efficacy of consuming an "optimal" protein distribution to favorably influence skeletal muscle-related changes is limited and inconsistent. The effect of protein distribution cannot be sufficiently disentangled from the effect of protein quantity. Consuming a more balanced protein distribution may be a practical way for adults with marginal or inadequate protein intakes (<0.80 g·kg-1·d-1) to achieve a moderately higher total protein intake. However, for adults already consuming 0.8-1.3 g·kg-1·d-1, the preponderance of evidence supports that consuming at least one meal that contains sufficient protein quantity to maximally stimulate muscle protein synthesis, independent of daily distribution, is helpful to promote skeletal muscle health.
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5.
Myoferlin, a multifunctional protein in normal cells, has novel and key roles in various cancers.
Zhu, W, Zhou, B, Zhao, C, Ba, Z, Xu, H, Yan, X, Liu, W, Zhu, B, Wang, L, Ren, C
Journal of cellular and molecular medicine. 2019;(11):7180-7189
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Abstract
Myoferlin, a protein of the ferlin family, has seven C2 domains and exhibits activity in some cells, including myoblasts and endothelial cells. Recently, myoferlin was identified as a promising target and biomarker in non-small-cell lung cancer, breast cancer, pancreatic adenocarcinoma, hepatocellular carcinoma, colon cancer, melanoma, oropharyngeal squamous cell carcinoma, head and neck squamous cell carcinoma, clear cell renal cell carcinoma and endometrioid carcinoma. This evidence indicated that myoferlin was involved in the proliferation, invasion and migration of tumour cells, the mechanism of which mainly included promoting angiogenesis, vasculogenic mimicry, energy metabolism reprogramming, epithelial-mesenchymal transition and modulating exosomes. The roles of myoferlin in both normal cells and cancer cells are of great significance to provide novel and efficient methods of tumour treatment. In this review, we summarize recent studies and findings of myoferlin and suggest that myoferlin is a novel potential candidate for clinical diagnosis and targeted cancer therapy.
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The Muscle Protein Synthetic Response to Meal Ingestion Following Resistance-Type Exercise.
Trommelen, J, Betz, MW, van Loon, LJC
Sports medicine (Auckland, N.Z.). 2019;(2):185-197
Abstract
Protein ingestion following resistance-type exercise stimulates muscle protein synthesis rates and consequently enhances the skeletal muscle adaptive response to prolonged training. Ingestion of ~ 20 g of quickly digestible protein isolate optimizes muscle protein synthesis rates during the first few hours of post-exercise recovery. However, the majority of daily protein intake is consumed as slower digestible, nutrient-rich, whole-food protein sources as part of mixed meals. Therefore, the muscle protein synthetic response to the ingestion of protein supplements and typical foods or mixed meals may differ substantially. In addition, the muscle protein synthetic response to feeding is not only determined by acute nutrient intake but is also likely modulated by habitual energy and nutrient intake and nondietary factors such as habitual physical activity, body composition, age, and/or sex. Therefore, nutritional recommendations to maximize the muscle protein synthetic response to exercise depend on the type of meal (e.g., protein supplements vs. mixed meals) and the time until the next feeding opportunity (e.g., feeding before overnight sleep) and, therefore, need to be personalized to the individual athlete.
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Irreversible plasma and muscle protein oxidation and physical exercise.
Gorini, G, Gamberi, T, Fiaschi, T, Mannelli, M, Modesti, A, Magherini, F
Free radical research. 2019;(2):126-138
Abstract
The imbalance between the reactive oxygen (ROS) and nitrogen (RNS) species production and their handling by the antioxidant machinery (low molecular weight antioxidant molecules and antioxidant enzymes), also known as oxidative stress, is a condition caused by physiological and pathological processes. Moreover, oxidative stress may be due to an overproduction of free radicals during physical exercise. Excess of radical species leads to the modification of molecules, such as proteins - the most susceptible to oxidative modification - lipids and DNA. With regard to the oxidation of proteins, carbonylation is an oxidative modification that has been widely described. Several studies have detected changes in the total amount of protein carbonyls following different types of physical exercise, but only few of these identified the specific amino acidic residues targets of such oxidation. In this respect, proteomic approaches allow to identify the proteins susceptible to carbonylation and in many cases, it is also possible to identify the specific protein carbonylation sites. This review focuses on the role of protein oxidation, and specifically carbonyl formation, for plasma and skeletal muscle proteins, following different types of physical exercise performed at different intensities. Furthermore, we focused on the proteomic strategies used to identify the specific protein targets of carbonylation. Overall, our analysis suggests that regular physical activity promotes a protection against protein carbonylation, due to the activation of the antioxidant defence or of the turnover of protein carbonyls. However, we can conclude that from the comprehensive bibliography analysed, there is no clearly defined specific physiological role about this post-translational modification of proteins.
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Contraction and nutrition interaction promotes anabolism in cachectic muscle.
Di Girolamo, FG, Guadagni, M, Fiotti, N, Situlin, R, Biolo, G
Current opinion in clinical nutrition and metabolic care. 2019;(1):60-67
Abstract
PURPOSE OF REVIEW Cachexia is a disease-related multifactorial syndrome characterized by inflammation, massive muscle protein catabolism and carbohydrate and lipid metabolism disorder.Several studies tried to define the impact of either nutrition or physical exercise (single approach strategy) or their combination (multimodal approach strategy) on prevention and/or treatment of muscle wasting in cachectic patients. RECENT FINDINGS Single approach strategies (i.e. nutrition or physical exercise) have the potential of preventing and improving features of the cachexia syndrome possibly with a differential impact according to the underlying disease. Limited information is available on the beneficial effect of multimodal approach strategies. SUMMARY Multimodal approaches appear to be more effective than those based on single interventions in physiological condition and in cachectic patients with COPD or chronic kidney disease. Further studies, however, are required in cachexia induced by heart failure, cancer and critical illness.
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Effects of acute oral feeding on protein metabolism and muscle protein synthesis in individuals with cancer.
van der Meij, BS, De Groot, LM, Deutz, NEP, Engelen, MPKJ
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:110531
Abstract
Weight loss and muscle loss are common in individuals living with cancer, with ≤50% experiencing involuntary weight loss at any time point in their cancer journey, and between 11% and 74% having sarcopenia or significant muscle loss. These changes in body composition are related to poor outcomes such as increased treatment toxicity, impaired quality of life, and reduced survival duration. Poor outcomes are not restricted to those who are underweight with severe weight loss; sarcopenia alone has been shown to be a prognostic marker across all body mass index categories, ranging from underweight to obesity To understand the mechanism of nutrition interventions in cancer and to develop effective future interventions, it is necessary to look at the acute effects of feeding on the response of the body and the ability to reach an anabolic response. The aim of this study was to explore and summarize the emerging evidence on metabolic effects of acute oral interventions on whole body protein kinetics and muscle protein synthesis in individuals with cancer.
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Isolated branched-chain amino acid intake and muscle protein synthesis in humans: a biochemical review.
Santos, CS, Nascimento, FEL
Einstein (Sao Paulo, Brazil). 2019;(3):eRB4898
Abstract
Alongside a proper diet, ergogenic aids with potential direct and/or indirect physical performance enhancing effects are sought after for improved adaptation to physical training. Nutritional ergogenics include diet composition changes and/or dietary supplementation. Branched-chain amino acids valine, leucine and isoleucine are widely popular among products with ergogenic claims. Their major marketing appeal derives from allegations that branched-chain amino acids intake combined with resistance physical exercise stimulates muscle protein synthesis. Evidence supporting the efficacy of branched-chain amino acids alone for muscle hypertrophy in humans is somewhat equivocal. This brief review describes physiological and biochemical mechanisms underpinning the effects of complete protein source and branched-chain amino acid intake on skeletal muscle growth in the postabsorptive and post-exercise state. Evidence in favor of or against potential anabolic effects of isolated branched-chain amino acid intake on muscle protein synthesis in humans is also examined.