Regulation of GLUT4 translocation in an in vitro cell model using postprandial human serum ex vivo.

NEW FINDINGS: What is the research question? This study used a new experimental model, in which culture medium is conditioned with human serum ex vivo, to investigate nutrient-mediated regulation of GLUT4 translocation in skeletal muscle cells in vitro. What is the main finding and importance? Human serum stimulated GLUT4 translocation, an effect differentially modulated by whether the culture medium was conditioned with serum from fasted subjects or with serum collected after feeding of intact or hydrolysed whey protein. Conditioning cell culture medium with human serum ex vivo represents a new approach to elucidate the effects of ingesting specific nutrients on skeletal muscle cell metabolism. ABSTRACT: Individual amino acids, amino acid mixtures and protein hydrolysates stimulate glucose uptake in many experimental models. To replicate better in vitro the dynamic postprandial response to feeding in vivo, in the present study we investigated the effects of culture media conditioned with fasted and postprandial human serum on GLUT4 translocation in L6-GLUT4myc myotubes. Serum samples were collected from healthy male participants (n = 8) at baseline (T0), 60 (T60) and 120 min (T120) after the ingestion of 0.33 g (kg body mass)-1 of intact (WPC) or hydrolysed (WPH) whey protein and an isonitrogenous non-essential amino acid (NEAA) control. L6-GLUT4myc myotubes were starved of serum and amino acids for 1 h before incubation for 1 h in medium containing 1% postprandial human serum, after which GLUT4 translocation was determined via colorimetric assay. Medium conditioned with fasted human serum at concentrations of 5-20% increased cell surface GLUT4myc abundance. Incubation with serum collected after the ingestion of WPH increased cell surface GLUT4myc at T60 relative to T0 [mean (lower, upper 95% confidence interval)]; [1.13 (1.05, 1.22)], whereas WPC [0.98 (0.90, 1.07)] or NEAA [1.02 (0.94, 1.11)] did not. The differential increases in cell surface GLUT4myc abundance were not explained by differences in serum concentrations of total, essential and branched-chain amino acids or insulin, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). Using a new ex vivo, in vitro approach, cell culture medium conditioned with postprandial serum after the ingestion of a whey protein hydrolysate increased GLUT4 translocation in skeletal muscle cells.

Comparison of time-matched aerobic, resistance, or concurrent exercise training in older adults.

A supervised 12-week intervention of time-matched aerobic vs resistance versus concurrent exercise training was employed to investigate mode- and time course-specific effects of exercise training in older adults. Community-dwelling men and women (n = 84; M/F, 45/39; 69.3 ± 3.5 years; 26.4 ± 3.8 kg m-2 ) were randomly assigned (n = 21 each) to either non-exercise control (CON), aerobic exercise only (AER), resistance exercise only (RES), or concurrent aerobic and resistance exercise (CEX). Training groups trained three times per week, each performing 72 minutes of active exercise time per week. Body composition, physical and cognitive function, and markers of metabolic health were assessed before (PRE), and after 6 (MID) and 12 (POST) weeks of exercise training. Hand-grip strength, 1RM chest press, and arm LBM were improved by both RES and CEX, but not AER. Aerobic fitness increased in AER and RES, but not CEX. Cognitive function improved in all groups, but occurred earlier (ie, at MID) in AER. CEX improved gait speed and lower limb strength and reduced trunk fat compared to either AER or RES. Leg LBM was unchanged in any group. Temporal patterns were observed as early as 6 weeks of training (gait speed, upper and lower limb strength, aerobic fitness), whereas others were unchanged until 12 weeks (hand-grip strength, timed up-and-go, sit-to-stand). Compared to either aerobic or resistance exercise training alone, concurrent exercise training is as efficacious for improving a range of health-related parameters and is more efficacious for increasing gait speed and lower limb strength, and decreasing trunk fat in older adults.

Effects of acute ingestion of whey protein with or without prior aerobic exercise on postprandial glycemia in type 2 diabetics.

PURPOSE: Acute protein co-ingestion or a single bout of aerobic exercise can attenuate postprandial glycemia, but their combined effect has not been investigated in type 2 diabetics. METHODS: Using a randomised crossover design, male type 2 diabetics (n = 8) [mean (95% CI); age, 55.0 (45.2, 64.8) year; BMI, 33.7 (25.6, 41.8) kg·m- 2; 2 h glucose 14.0 (12.5, 15.5) mM] completed (1) 75 g oral glucose tolerance test (OGTT) (CON); (2) OGTT supplemented with 0.33 g·kg BM- 1 of whey protein concentrate (PRO); or OGTT supplemented with PRO but preceded by a bout of aerobic cycling exercise (PRO + EX). Postprandial venous blood samples were collected for glucose, insulin, C-peptide and glucagon. RESULTS: Despite a fold-increase of 1.90 (1.26, 2.56; p < 0.05) in postprandial insulin compared to CON, PRO failed to attenuate postprandial glycemia measured by 2 h glucose area under the curve. During PRO + EX, plasma glucose was elevated by 1.51 (0.5, 2.5) mM and 1.3 (0.3, 2.3) mM at 15 and 30 min, respectively, compared to CON, but was lower by 1.60 (0.6, 2.6) mM and 1.5 (0.5, 2.5) mM at 90 and 120 min, respectively (all p < 0.01). The additive effect of exercise and protein ingestion resulted in a fold-increase of 1.67 (1.35, 2.00; p < 0.05) in postprandial glucagon compared to CON. CONCLUSION: In type 2 diabetics, prior aerobic exercise altered the humoral response to co-ingestion of whey protein with a carbohydrate load, but neither protein ingestion alone nor when preceded by prior exercise attenuated postprandial glycemia.

Co-ingestion of protein or a protein hydrolysate with carbohydrate enhances anabolic signaling, but not glycogen resynthesis, following recovery from prolonged aerobic exercise in trained cyclists.

PURPOSE: The effect of carbohydrate (CHO), or CHO supplemented with either sodium caseinate protein (CHO-C) or a sodium caseinate protein hydrolysate (CHO-H) on the recovery of skeletal muscle glycogen and anabolic signaling following prolonged aerobic exercise was determined in trained male cyclists [n = 11, mean ± SEM age 28.8 ± 2.3 years; body mass (BM) 75.0 ± 2.3 kg; VO2peak 61.3 ± 1.6 ml kg-1 min-1]. METHODS: On three separate occasions, participants cycled for 2 h at ~ 70% VO2peak followed by a 4-h recovery period. Isoenergetic drinks were consumed at + 0 and + 2 h of recovery containing either (1) CHO (1.2 g kg -1 BM), (2) CHO-C, or (3) CHO-H (1.04 and 0.16 g kg-1 BM, respectively) in a randomized, double-blind, cross-over design. Muscle biopsies from the vastus lateralis were taken prior to commencement of each trial, and at + 0 and + 4 h of recovery for determination of skeletal muscle glycogen, and intracellular signaling associated with protein synthesis. RESULTS: Despite an augmented insulin response following CHO-H ingestion, there was no significant difference in skeletal muscle glycogen resynthesis following recovery between trials. CHO-C and CHO-H co-ingestion significantly increased phospho-mTOR Ser2448 and 4EBP1 Thr37/46 versus CHO, with CHO-H displaying the greatest change in phospho-4EBP1 Thr37/46. Protein co-ingestion, compared to CHO alone, during recovery did not augment glycogen resynthesis. CONCLUSION: Supplementing CHO with intact sodium caseinate or an insulinotropic hydrolysate derivative augmented intracellular signaling associated with skeletal muscle protein synthesis following prolonged aerobic exercise.

Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation.

Optimising training and performance through nutrition strategies is central to supporting elite sportspeople, much of which has focused on manipulating the relative intake of carbohydrate and fat and their contributions as fuels for energy provision. The ketone bodies, namely acetoacetate, acetone and ß-hydroxybutyrate (ßHB), are produced in the liver during conditions of reduced carbohydrate availability and serve as an alternative fuel source for peripheral tissues including brain, heart and skeletal muscle. Ketone bodies are oxidised as a fuel source during exercise, are markedly elevated during the post-exercise recovery period, and the ability to utilise ketone bodies is higher in exercise-trained skeletal muscle. The metabolic actions of ketone bodies can alter fuel selection through attenuating glucose utilisation in peripheral tissues, anti-lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. Moreover, ketone bodies can act as signalling metabolites, with ßHB acting as an inhibitor of histone deacetylases, an important regulator of the adaptive response to exercise in skeletal muscle. Recent development of ketone esters facilitates acute ingestion of ßHB that results in nutritional ketosis without necessitating restrictive dietary practices. Initial reports suggest this strategy alters the metabolic response to exercise and improves exercise performance, while other lines of evidence suggest roles in recovery from exercise. The present review focuses on the physiology of ketone bodies during and after exercise and in response to training, with specific interest in exploring the physiological basis for exogenous ketone supplementation and potential benefits for performance and recovery in athletes.

Increased Leg Strength After Concurrent Aerobic and Resistance Exercise Training in Older Adults Is Augmented by a Whole Food-Based High Protein Diet Intervention.

Most studies in older adults have utilized powdered protein supplements or oral nutrition solutions as a source of additional dietary protein, but whole foods may provide a greater anabolic stimulus than protein isolated from food matrices. Therefore, the present study investigated a concurrent aerobic and resistance exercise training program in older adults, in the absence or presence of a high protein whole food-based dietary intervention, for effects on strength, physical function, and body composition. Community-dwelling older adults (n = 56; M/F, 28/28; age, 69.3 ± 4.0 years; BMI, 26.6 ± 3.7 kg m-2) participated in a 12-week intervention after randomization to either nutrition only (NUTR; n = 16), exercise only (EX, n = 19), or nutrition plus exercise (NUTR + EX, n = 21) groups. NUTR and NUTR + EX followed a dietary intervention targeting an increase in protein-rich meals at breakfast, lunch, and dinner. Exercise training in EX and NUTR + EX consisted of 24 min sessions of concurrent aerobic and resistance exercise performed three times per week. Daily protein intake increased in NUTR and NUTR + EX, but not EX. The increase in 1RM leg press strength was greater (Interaction effect, P = 0.012) in NUTR + EX [29.6 (18.1, 41.0) kg] than increases observed in NUTR [11.1 (-1.3, 23.6) kg] and EX [12.3 (0.9, 23.8) kg]. The increase in 1RM chest press strength was greater (interaction effect, P = 0.031) in NUTR + EX [6.3 (4.0, 8.6) kg] than the increase observed in NUTR [2.9 (0.3, 5.5) kg], but not EX [6.3 (3.9, 8.7) kg]. Hand-grip strength and sit-to-stand performance were each improved in all three groups, with no differences observed between groups (interaction effect, P = 0.382 and P = 0.671, respectively). An increase in percentage body fat was observed in NUTR, but not in EX or NUTR + EX (interaction effect, P = 0.018). No between-group differences were observed for change in lean body mass (interaction effect, P = 0.402). Concurrent aerobic and resistance exercise training improves strength and physical function in older adults, but combining this training with an increase in daily protein intake through whole foods may be advantageous to increase lower limb strength.

Exercise Maintenance in Older Adults 1 Year After Completion of a Supervised Training Intervention.

BACKGROUND/OBJECTIVE: Barriers and facilitators of exercise maintenance and residual effects of exercise training intervention on physical and cognitive function after the cessation of training are inadequately described in older adults. DESIGN AND SETTING: One year after the cessation of a supervised exercise training intervention, a mixed methods approach employed a quantitative phase that assessed body composition and physical and cognitive function and a qualitative phase that explored determinants of exercise maintenance after participation in the intervention. PARTICIPANTS: Community-dwelling older Irish adults (aged >65 years) who had completed 12 weeks of supervised exercise training 1 year previously. MEASUREMENTS: Fifty-three participants (male/female ratio = 30:23; age = 70.8 ± 3.9 years) completed the follow-up testing comprising body composition and physical and cognitive function. Semistructured interviews were conducted with 12 participants (male/female ratio = 6:6) using the Theoretical Domains Framework to inform the interview guide. RESULTS: At 1 year follow-up, body fat increased (mean = 4.3%; 95% confidence limit = 2.2% to 6.3%), while lean body mass (mean = -0.6%; 95% confidence limit = -1.2% to -0.1%), strength (leg press, mean = -5.6%; 95% confidence limit = -8.3% to -2.8%; chest press, mean = -11.0%; 95% confidence limit = -14.8% to -7.8%), and cognitive function (mean = -3.7%; 95% confidence limit = -5.7% to -1.8%) declined (all P < .05). Interviews revealed key facilitators (social aspects and beliefs about benefits of exercise) and barriers (affordability and general aversion to gyms) to exercise maintenance in this population. CONCLUSION: Key barriers and facilitators to exercise maintenance were identified, which will inform the development of future behavior change interventions to support exercise participation and maintenance in older adults to mitigate adverse changes in body composition and physical and cognitive function with advancing age. J Am Geriatr Soc 68:163-169, 2019.