Essential Amino Acid-Enriched Diet Alleviates Dexamethasone-Induced Loss of Muscle Mass and Function through Stimulation of Myofibrillar Protein Synthesis and Improves Glucose Metabolism in Mice

Dexamethasone (DEX) induces dysregulation of protein turnover, leading to muscle atrophy and impairment of glucose metabolism. Positive protein balance, i.e., rate of protein synthesis exceeding rate of protein degradation, can be induced by dietary essential amino acids (EAAs). In this study, we investigated the roles of an EAA-enriched diet in the regulation of muscle proteostasis and its impact on glucose metabolism in the DEX-induced muscle atrophy model. Mice were fed normal chow or EAA-enriched chow and were given daily injections of DEX over 10 days. We determined muscle mass and functions using treadmill running and ladder climbing exercises, protein kinetics using the D2O labeling method, molecular signaling using immunoblot analysis, and glucose metabolism using a U-13C6 glucose tracer during oral glucose tolerance test (OGTT). The EAA-enriched diet increased muscle mass, strength, and myofibrillar protein synthesis rate, concurrent with improved glucose metabolism (i.e., reduced plasma insulin concentrations and increased insulin sensitivity) during the OGTT. The U-13C6 glucose tracing revealed that the EAA-enriched diet increased glucose uptake and subsequent glycolytic flux. In sum, our results demonstrate a vital role for the EAA-enriched diet in alleviating the DEX-induced muscle atrophy through stimulation of myofibrillar proteins synthesis, which was associated with improved glucose metabolism.

Damaging eccentric exercise attenuates disuse induced declines in daily myofibrillar protein synthesis and transiently prevents muscle atrophy in healthy men.

Introduction: Short-term disuse leads to muscle loss driven by lowered daily myofibrillar protein synthesis (MyoPS). However, disuse commonly results from muscle damage, and its influence on muscle deconditioning during disuse is unknown. Methods: 21 males (20±1 y, BMI=24±1 kg·m-2 (±SEM)) underwent 7 days of unilateral leg immobilization immediately preceded by 300 bilateral, maximal, muscle-damaging eccentric quadriceps contractions (DAM; n=10) or no exercise (CON; n=11). Participants ingested deuterated water and underwent temporal bilateral thigh MRI scans and vastus lateralis muscle biopsies of immobilized (IMM) and non-immobilized (N-IMM) legs. Results: N-IMM quadriceps muscle volume remained unchanged throughout in both groups. IMM quadriceps muscle volume declined after 2 days by 1.7±0.5% in CON (P=0.031; and by 1.3±0.6% when corrected to N-IMM; P=0.06) but did not change in DAM, and declined equivalently in CON (by 6.4±1.1% [5.0±1.6% when corrected to N-IMM]) and DAM (by 2.6±1.8% [4.0±1.9% when corrected to N-IMM]) after 7 days. Immobilization began to decrease MyoPS compared with N-IMM in both groups after 2 days (P=0.109), albeit with higher MyoPS rates in DAM compared with CON (P=0.035). Frank suppression of MyoPS was observed between days 2-7 in CON (IMM=1.04±0.12, N-IMM=1.86±0.10%·d-1; P=0.002) but not DAM (IMM=1.49±0.29, N-IMM=1.90±0.30%·d-1; P>0.05). Declines in MyoPS and quadriceps volume after 7 days correlated positively in CON (R2=0.403; P=0.035) but negatively in DAM (R2=0.483; P=0.037). Quadriceps strength declined following immobilization in both groups, but to a greater extent in DAM. Conclusion: Prior muscle damaging eccentric exercise increases MyoPS and prevents loss of quadriceps muscle volume after 2 (but not 7) days of disuse.

The Muscle Protein Synthetic Response to the Ingestion of a Plant-Based Protein Blend Is Not Different From Milk Protein in Healthy, Young Males

Objectives It has been reported that plant-based proteins are not as effective as animal-based proteins in their capacity to stimulate muscle protein synthesis rates. This has been attributed to the lower essential amino acid content and the selective deficiency in specific amino acids. It has been hypothesized that a blend of different plant-based proteins may complement each other and, as such, compensate for such deficits. This study compares post-prandial muscle protein synthesis rates following the ingestion of 30 g milk protein with the ingestion of a 30 g blend of wheat, corn, and pea protein in vivo, in healthy young males. Methods In a randomized, double blind, parallel-group design, 24 healthy young males (24 ± 4 y) received a primed continuous infusion of L-[ring-13C6]-phenylalanine and ingested 30 g milk protein (MILK), or a 30 g protein blend with 15 g wheat, 7.5 g corn, and 7.5 g pea protein (PLANT) in beverage form (n = 12 per group). Both interventional drinks were matched for leucine content. Blood and muscle biopsies were collected for 5 h following protein ingestion to assess post-prandial plasma amino acid profiles and myofibrillar protein synthesis rates. Data are expressed as mean ± SD. Results MILK increased plasma essential amino acid concentrations ∼2 fold more than PLANT over the 5 h post-prandial period (incremental area under curve (iAUC): 151 ± 31 vs 79 ± 12 mmol∙5 h∙L−1 respectively; P < 0.001). Similarly, the leucine iAUC was ∼16% greater for MILK vs PLANT (36 ± 7 vs 31 ± 4 mmol∙5 h∙L−1 respectively; P < 0.05). Ingestion of both MILK and PLANT increased myofibrillar protein synthesis rates when compared to basal post-absorptive values (P < 0.001), with no significant differences between treatments (0.053 ± 0.013 vs 0.064 ± 0.016%∙h−1, respectively; P > 0.05). Conclusions Ingestion of 30 g of a wheat, corn, and pea protein blend increases muscle protein synthesis rates in healthy, young males. The post-prandial muscle protein synthetic response to the ingestion of 30 g of a wheat, corn and pea protein blend does not differ from the ingestion of an equivalent amount of milk protein in healthy, young males. Funding Sources TiFN

Exercise Plus Presleep Protein Ingestion Increases Overnight Muscle Connective Tissue Protein Synthesis Rates in Healthy Older Men

Protein ingestion and exercise stimulate myofibrillar protein synthesis rates. When combined, exercise further increases the postprandial rise in myofibrillar protein synthesis rates. It remains unclear whether protein ingestion with or without exercise also stimulates muscle connective tissue protein synthesis rates. The authors assessed the impact of presleep protein ingestion on overnight muscle connective tissue protein synthesis rates at rest and during recovery from resistance-type exercise in older men. Thirty-six healthy, older men were randomly assigned to ingest 40 g intrinsically L-[1-13C]-phenylalanine and L-[1-13C]-leucine-labeled casein protein (PRO, n = 12) or a nonprotein placebo (PLA, n = 12) before going to sleep. A third group performed a single bout of resistance-type exercise in the evening before ingesting 40 g intrinsically-labeled casein protein prior to sleep (EX+PRO, n = 12). Continuous intravenous infusions of L-[ring-2H5]-phenylalanine and L-[1-13C]-leucine were applied with blood and muscle tissue samples collected throughout overnight sleep. Presleep protein ingestion did not increase muscle connective tissue protein synthesis rates (0.049 ± 0.013 vs. 0.060 ± 0.024%/hr in PLA and PRO, respectively; p = .73). Exercise plus protein ingestion resulted in greater overnight muscle connective tissue protein synthesis rates (0.095 ± 0.022%/hr) when compared with PLA and PRO (p < .01). Exercise increased the incorporation of dietary protein-derived amino acids into muscle connective tissue protein (0.036 ± 0.013 vs. 0.054 ± 0.009 mole percent excess in PRO vs. EX+PRO, respectively; p < .01). In conclusion, resistance-type exercise plus presleep protein ingestion increases overnight muscle connective tissue protein synthesis rates in older men. Exercise enhances the utilization of dietary protein-derived amino acids as precursors for de novo muscle connective tissue protein synthesis during overnight sleep.

No differences in muscle protein synthesis rates following ingestion of wheat protein, milk protein, and their protein blend in healthy, young males

ABSTRACT Plant-derived proteins have been suggested to have less anabolic properties when compared with animal-derived proteins. Whether blends of plant- and animal-derived proteins can compensate for their lesser anabolic potential has not been assessed. This study compares post-prandial muscle protein synthesis rates following the ingestion of milk protein with wheat protein or a blend of wheat plus milk protein in healthy, young males. In a randomized, double blind, parallel-group design, 36 males (23±3 y) received a primed continuous L-[ring-13C6]-phenylalanine infusion after which they ingested 30 g milk protein (MILK), 30 g wheat protein (WHEAT), or a 30 g blend combining 15 g wheat plus 15 g milk protein (WHEAT+MILK). Blood and muscle biopsies were collected frequently for 5 hours to assess post-prandial plasma amino acid profiles and subsequent myofibrillar protein synthesis rates. Ingestion of protein increased myofibrillar protein synthesis rates in all treatments (P<0.001). Post-prandial myofibrillar protein synthesis rates did not differ between MILK vs WHEAT (0.053±0.013 vs 0.056±0.012 %∙h-1, respectively; t-test P=0.56) or between MILK vs WHEAT+MILK (0.053±0.013 vs 0.059±0.025 %∙h-1, respectively; t-test P=0.46). In conclusion, ingestion of 30 g milk protein, 30 g wheat protein, or a blend of 15 g wheat plus 15 g milk protein increases muscle protein synthesis rates in young males. Furthermore, muscle protein synthesis rates following the ingestion of 30 g milk protein do not differ from rates observed after ingesting 30 g wheat protein or a blend with 15 g milk plus 15 g wheat protein in healthy, young males.

The Effect of Whole Egg Intake on Muscle Mass: Are the Yolk and Its Nutrients Important?

Whole egg may have potential benefits for enhancing muscle mass, independent of its protein content. The yolk comprises ∼40% of the total protein in an egg, as well as containing several nonprotein nutrients that could possess anabolic properties (e.g., microRNAs, vitamins, minerals, lipids, phosphatidic acid and other phospholipids). Therefore, the purpose of this narrative review is to discuss the current evidence as to the possible effects of egg yolk compounds on skeletal muscle accretion beyond those of egg whites alone. The intake of whole egg seems to promote greater myofibrillar protein synthesis than egg white intake in young men. However, limited evidence shows no difference in muscle hypertrophy when comparing the consumption of whole egg versus an isonitrogenous quantity of egg white in young men performing resistance training. Although egg yolk intake seems to promote additional acute increases on myofibrillar protein synthesis, it does not seem to further enhance muscle mass when compared to egg whites when consumed as part of a high-protein dietary patterns, at least in young men. This conclusion is based on very limited evidence and more studies are needed to evaluate the effects of egg yolk (or whole eggs) intake on muscle mass not only in young men, but also in other populations such as women, older adults, and individuals with muscle wasting diseases.

Improved recovery from skeletal muscle damage is largely unexplained by myofibrillar protein synthesis or inflammatory and regenerative gene expression pathways

The contribution of myofibrillar protein synthesis (MyoPS) to recovery from skeletal muscle damage in humans is unknown. Recreationally active males and females consumed a daily protein-polyphenol beverage targeted at increasing amino acid availability and reducing inflammation (PPB; n=9), both known to affect MyoPS, or an isocaloric placebo (PLA; n=9) during 168 h of recovery from 300 maximal unilateral eccentric contractions (EE). Muscle function was assessed daily. Muscle biopsies were collected 24, 27, 36, 72 and 168 h for MyoPS measurements using 2H2O and expression of 224 genes using RT-qPCR and pathway analysis. PPB improved recovery of muscle function, which was impaired for five days following EE in PLA (interaction; P<0.05). Acute postprandial MyoPS rates were unaffected by nutritional intervention (24-27 h). EE increased overnight (27-36 h) MyoPS versus control leg (PLA: 33±19%; PPB: 79±25%; leg P<0.01), and PPB tended to increase this further (interaction P=0.06). Daily MyoPS rates were greater with PPB between 72-168 h after EE, albeit after function had recovered. Inflammatory and regenerative signaling pathways were dramatically upregulated and clustered following EE but were unaffected by nutritional intervention. These results suggest that accelerated recovery from EE is not explained by elevated MyoPS or suppression of inflammation.

A mycoprotein-based high-protein vegan diet supports equivalent daily myofibrillar protein synthesis rates compared with an isonitrogenous omnivorous diet in older adults: a randomised controlled trial

Animal-derived dietary protein ingestion and physical activity stimulate myofibrillar protein synthesis rates in older adults. We determined whether a non-animal-derived diet can support daily myofibrillar protein synthesis rates to the same extent as an omnivorous diet. Nineteen healthy older adults (aged 66 (sem 1) years; BMI 24 (sem 1) kg/m2; twelve males, seven females) participated in a randomised, parallel-group, controlled trial during which they consumed a 3-d isoenergetic high-protein (1·8 g/kg body mass per d) diet, where the protein was provided from predominantly (71 %) animal (OMNI; n 9; six males, three females) or exclusively vegan (VEG; n 10; six males, four females; mycoprotein providing 57 % of daily protein intake) sources. During the dietary control period, participants conducted a daily bout of unilateral resistance-type leg extension exercise. Before the dietary control period, participants ingested 400 ml of deuterated water, with 50-ml doses consumed daily thereafter. Saliva samples were collected throughout to determine body water 2H enrichments, and muscle samples were collected from rested and exercised muscle to determine daily myofibrillar protein synthesis rates. Deuterated water dosing resulted in body water 2H enrichments of approximately 0·78 (sem 0·03) %. Daily myofibrillar protein synthesis rates were 13 (sem 8) (P = 0·169) and 12 (sem 4) % (P = 0·016) greater in the exercised compared with rested leg (1·59 (sem 0·12) v. 1·77 (sem 0·12) and 1·76 (sem 0·14) v. 1·93 (sem 0·12) %/d) in OMNI and VEG groups, respectively. Daily myofibrillar protein synthesis rates did not differ between OMNI and VEG in either rested or exercised muscle (P > 0·05). Over the course of a 3-d intervention, omnivorous- or vegan-derived dietary protein sources can support equivalent rested and exercised daily myofibrillar protein synthesis rates in healthy older adults consuming a high-protein diet.