-
1.
Impact of 3-week citrulline supplementation on postprandial protein metabolism in malnourished older patients: The Ciproage randomized controlled trial.
Bouillanne, O, Melchior, JC, Faure, C, Paul, M, Canouï-Poitrine, F, Boirie, Y, Chevenne, D, Forasassi, C, Guery, E, Herbaud, S, et al
Clinical nutrition (Edinburgh, Scotland). 2019;(2):564-574
Abstract
BACKGROUND Citrulline (CIT), is not extracted by the splanchnic area, can stimulate muscle protein synthesis and could potentially find clinical applications in conditions involving low amino acid (AA) intake, such as in malnourished older subjects. OBJECTIVE Our purpose was to research the effects of CIT supplementation on protein metabolism in particular on non-oxidative leucine disposal (NOLD, primary endpoint), and splanchnic extraction of amino acids in malnourished older patients. DESIGN This prospective randomized multicenter study determined whole-body and liver protein synthesis, splanchnic protein metabolism and appendicular skeletal muscle mass (ASMM) in 24 malnourished older patients [80-92 years; 18 women and 6 men] in inpatient rehabilitation units. All received an oral dose of 10 g of CIT or an equimolar mixture of six non-essential amino acids (NEAAs), as isonitrogenous placebo, for 3 weeks. RESULTS NOLD and albumin fractional synthesis rates were not different between the NEAA and CIT groups. Splanchnic extraction of dietary amino acid tended to decrease (p = 0.09) in the CIT group (45.2%) compared with the NEAA group (60.3%). Total differences in AA and NEAA area under the curves between fed-state and postabsorptive-state were significantly higher in the CIT than in the NEAA group. There were no significant differences for body mass index, fat mass (FM), lean mass (LM) or ASMM in the whole population except for a tendential decrease in FM for the citrulline group (p = 0.089). Compared with Day 1, lean mass and ASMM significantly increased (respectively p = 0.016 and p = 0.018) at Day 20 in CIT-treated women (mean respective increase of 1.7 kg and 1.1 kg), and fat mass significantly decreased (p = 0.001) at Day 20 in CIT-group women (mean decrease of 1.3 kg). CONCLUSIONS Our results demonstrate that CIT supplementation has no effect on whole-body protein synthesis or liver protein synthesis in malnourished older subjects. However, CIT supplementation was associated with a higher systemic AA availability. In the subgroup of women, CIT supplementation increased LM and ASMM, and decreased FM.
-
2.
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
-
-
Free full text
-
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.
-
3.
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.
-
4.
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.
-
5.
Differential Stimulation of Post-Exercise Myofibrillar Protein Synthesis in Humans Following Isonitrogenous, Isocaloric Pre-Exercise Feeding.
Davies, RW, Bass, JJ, Carson, BP, Norton, C, Kozior, M, Amigo-Benavent, M, Wilkinson, DJ, Brook, MS, Atherton, PJ, Smith, K, et al
Nutrients. 2019;(7)
Abstract
The aim of this study was to test the effects of two disparate isonitrogenous, isocaloric pre-exercise feeds on deuterium-oxide (D2O) derived measures of myofibrillar protein synthesis (myoPS) in humans. Methods: In a double-blind parallel group design, 22 resistance-trained men aged 18 to 35 years ingested a meal (6 kcal·kg-1, 0.8 g·kg-1 carbohydrate, 0.2 g·kg-1 fat) with 0.33 g·kg-1 nonessential amino acids blend (NEAA) or whey protein (WHEY), prior to resistance exercise (70% 1RM back-squats, 10 reps per set to failure, 25% duty cycle). Biopsies of M. vastus lateralis were obtained pre-ingestion (PRE) and +3 h post-exercise (POST). The myofibrillar fractional synthetic rate (myoFSR) was calculated via deuterium labelling of myofibrillar-bound alanine, measured by gas chromatography-pyrolysis-isotope ratio mass spectrometry (GC-Pyr-IRMS). Data are a mean percentage change (95% CI). Results: There was no discernable change in myoFSR following NEAA (10(-5, 25) %, p = 0.235), whereas an increase in myoFSR was observed after WHEY (28 (13, 43) %, p = 0.003). Conclusions: Measured by a D2O tracer technique, a disparate myoPS response was observed between NEAA and WHEY. Pre-exercise ingestion of whey protein increased post-exercise myoPS, whereas a NEAA blend did not, supporting the use of NEAA as a viable isonitrogenous negative control.
-
6.
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.
-
7.
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.
-
8.
Even effect of milk protein and carbohydrate intake but no further effect of heavy resistance exercise on myofibrillar protein synthesis in older men.
Reitelseder, S, Dideriksen, K, Agergaard, J, Malmgaard-Clausen, NM, Bechshoeft, RL, Petersen, RK, Serena, A, Mikkelsen, UR, Holm, L
European journal of nutrition. 2019;(2):583-595
Abstract
PURPOSE The responsiveness of older individuals' skeletal muscle to anabolic strategies may be impaired. However, direct comparisons within the same experimental setting are sparse. The aim of this study was to assess the resting and post-resistance exercise muscle protein synthesis rates in response to two types of milk protein and carbohydrate using a unilateral exercise leg model. METHODS Twenty-seven older (69 ± 1 year, mean ± SE) men were randomly assigned one of three groups: Whey hydrolysate (WH), caseinate (CAS), or carbohydrate (CHO). By applying stable isotope tracer techniques (L-[15N]phenylalanine), the fasted-rested (basal) myofibrillar fractional synthesis rate (FSR) was measured. Hereafter, FSR was measured in the postprandial phase (0.45 g nutrient/kg LBM) in both legs, one rested (fed-rest) and one exercised (10 × 8 reps at 70% 1RM; fed-exercise). In addition, the activity of p70S6K and venous plasma insulin, phenylalanine, and leucine concentrations were measured. RESULTS Insulin, phenylalanine, and leucine concentrations differed markedly after intake of the different study drinks. The basal FSR in WH, CAS, and CHO were 0.027 ± 0.003, 0.030 ± 0.003, and 0.030 ± 0.004%/h, the fed-rested FSR were 0.043 ± 0.004, 0.045 ± 0.003, and 0.035 ± 0.004%/h, and the fed-exercised FSR were 0.041 ± 0.004, 0.043 ± 0.004, and 0.034 ± 0.004%/h, respectively. No significant differences were observed at any state between the groups. Fed-rested- and fed-exercised FSR were higher than basal (P < 0.001). 3 h after exercise and feeding, no significant group differences were detected in the activity of p70S6K. CONCLUSIONS Milk protein and carbohydrate supplementation stimulate myofibrillar protein synthesis in older men, with no further effect of heavy resistance exercise within 0-3 h post exercise.
-
9.
Leucine coingestion augments the muscle protein synthetic response to the ingestion of 15 g of protein following resistance exercise in older men.
Holwerda, AM, Paulussen, KJM, Overkamp, M, Goessens, JPB, Kramer, IF, Wodzig, WKWH, Verdijk, LB, de Groot, LCPGM, van Loon, LJC
American journal of physiology. Endocrinology and metabolism. 2019;(3):E473-E482
Abstract
Older adults have shown an attenuated postexercise increase in muscle protein synthesis rates following ingestion of smaller amounts of protein compared with younger adults. Consequently, it has been suggested that older adults require the ingestion of more protein to increase postexercise muscle protein synthesis rates compared with younger adults. We investigated whether coingestion of 1.5 g of free leucine with a single 15-g bolus of protein further augments the postprandial muscle protein synthetic response during recovery from resistance-type exercise in older men. Twenty-four healthy older men (67 ± 1 yr) were randomly assigned to ingest 15 g of milk protein concentrate (MPC80) with (15G+LEU; n = 12) or without (15G; n = 12) 1.5 g of free leucine after performing a single bout of resistance-type exercise. Postprandial protein digestion and amino acid absorption kinetics, whole body protein metabolism, and postprandial myofibrillar protein synthesis rates were assessed using primed, continuous infusions with l-[ring-2H5]phenylalanine, l-[ring-2H2]tyrosine, and l-[1-13C]leucine combined with ingestion of intrinsically l-[1-13C]phenylalanine-labeled milk protein. A total of 70 ± 1% (10.5 ±0.2 g) and 75 ± 2% (11.2 ± 0.3 g) of the protein-derived amino acids were released in the circulation during the 6-h postexercise recovery phase in 15G+LEU and 15G, respectively (P < 0.05). Postexercise myofibrillar protein synthesis rates were 16% (0.058 ± 0.003 vs. 0.049 ± 0.002%/h, P < 0.05; based on l-[ring-2H5]phenylalanine) and 19% (0.071 ± 0.003 vs. 0.060 ± 0.003%/h, P < 0.05; based on l-[1-13C]leucine) greater in 15G+LEU compared with 15G. Leucine coingestion further augments the postexercise muscle protein synthetic response to the ingestion of a single 15-g bolus of protein in older men.
-
10.
Whey Protein Hydrolysate Increases Amino Acid Uptake, mTORC1 Signaling, and Protein Synthesis in Skeletal Muscle of Healthy Young Men in a Randomized Crossover Trial.
Moro, T, Brightwell, CR, Velarde, B, Fry, CS, Nakayama, K, Sanbongi, C, Volpi, E, Rasmussen, BB
The Journal of nutrition. 2019;(7):1149-1158
-
-
Free full text
-
Abstract
BACKGROUND Muscle protein synthesis (MPS) can be stimulated by ingestion of protein sources, such as whey, casein, or soy. Protein supplementation can enhance muscle protein synthesis after exercise and may preserve skeletal muscle mass and function in aging adults. Therefore, identifying protein sources with higher anabolic potency is of high significance. OBJECTIVE The aim of this study was to determine the anabolic potency and efficacy of a novel whey protein hydrolysate mixture (WPH) on mechanistic target of rapamycin complex 1 (mTORC1) signaling and skeletal MPS in healthy young subjects. METHODS Ten young men (aged 28.7 ± 3.6 y, 25.2 ± 2.9 kg/m2 body mass index [BMI]) were recruited into a double-blind two-way crossover trial. Subjects were randomized to receive either 0.08 g/kg of body weight (BW) of WPH or an intact whey protein (WHEY) mixture during stable isotope infusion experiments. Fractional synthetic rate, leucine and phenylalanine kinetics, and markers of amino acid sensing were assessed as primary outcomes before and 1-3 h after protein ingestion using a repeated measures mixed model. RESULTS Blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle and intracellular muscle leucine concentration significantly increased to a similar extent 1 h after ingestion of both mixtures (P < 0.05). Phosphorylation of S6K1 (i.e. a marker of mTORC1 activation) increased equally by ∼20% 1-h postingestion (P < 0.05). Ingestion of WPH and WHEY increased mixed MPS similarly in both groups by ∼43% (P < 0.05); however, phenylalanine utilization for synthesis increased in both treatments 1-h postingestion but remained elevated 3-h postingestion only in the WPH group (P < 0.05). CONCLUSIONS We conclude that a small dose of WPH effectively increases leucine transport into muscle, activating mTORC1 and stimulating MPS in young men. WPH anabolic potency and efficacy for promoting overall muscle protein anabolism is similar to WHEY, an intact protein source. This trial was registered at clinicaltrials.gov as NCT03313830.