Yi-Hung Liao

Postexercise carbohydrate-protein supplementation improves subsequent exercise performance and intracellular signaling for protein synthesis.

Ferguson-Stegall, L, McCleave, EL, Ding, Z, Doerner III, PG, Wang, B, Liao, Y-H, Kammer, L, Liu, Y, Hwang, J, Dessard, BM, and Ivy, JL. Postexercise carbohydrate-protein supplementation improves subsequent exercise performance and intracellular signaling for protein synthesis. J Strength Cond Res 25(5): 1210-1224, 2011-Postexercise carbohydrate-protein (CHO + PRO) supplementation has been proposed to improve recovery and subsequent endurance performance compared to CHO supplementation. This study compared the effects of a CHO + PRO supplement in the form of chocolate milk (CM), isocaloric CHO, and placebo (PLA) on recovery and subsequent exercise performance. Ten cyclists performed 3 trials, cycling 1.5 hours at 70% &OV0312;o2max plus 10 minutes of intervals. They ingested supplements immediately postexercise and 2 hours into a 4-hour recovery. Biopsies were performed at recovery minutes 0, 45, and 240 (R0, R45, REnd). Postrecovery, subjects performed a 40-km time trial (TT). The TT time was faster in CM than in CHO and in PLA (79.43 ± 2.11 vs. 85.74 ± 3.44 and 86.92 ± 3.28 minutes, p ≤ 0.05). Muscle glycogen resynthesis was higher in CM and in CHO than in PLA (23.58 and 30.58 vs. 7.05 μmol·g−1 wet weight, p ≤ 0.05). The mammalian target of rapamycin phosphorylation was greater at R45 in CM than in CHO or in PLA (174.4 ± 36.3 vs. 131.3 ± 28.1 and 73.7 ± 7.8% standard, p ≤ 0.05) and at REnd in CM than in PLA (94.5 ± 9.9 vs. 69.1 ± 3.8%, p ≤ 0.05). rpS6 phosphorylation was greater in CM than in PLA at R45 (41.0 ± 8.3 vs. 15.3 ± 2.9%, p ≤ 0.05) and REnd (16.8 ± 2.8 vs. 8.4 ± 1.9%, p ≤ 0.05). FOXO3A phosphorylation was greater at R45 in CM and in CHO than in PLA (84.7 ± 6.7 and 85.4 ± 4.7 vs. 69.2 ± 5.5%, p ≤ 0.05). These results indicate that postexercise CM supplementation can improve subsequent exercise performance and provide a greater intracellular signaling stimulus for PRO synthesis compared to CHO and placebo.

An amino acid mixture improves glucose tolerance and insulin signaling in Sprague-Dawley rats

The aims of this investigation were to evaluate the effect of an amino acid supplement on the glucose response to an oral glucose challenge (experiment 1) and to evaluate whether differences in blood glucose response were associated with increased skeletal muscle glucose uptake (experimental 2). Experiment 1 rats were gavaged with either glucose (CHO), glucose plus an amino acid mixture (CHO-AA-1), glucose plus an amino acid mixture with increased leucine concentration (CHO-AA-2), or water (PLA). CHO-AA-1 and CHO-AA-2 had reduced blood glucose responses compared with CHO, with no difference in insulin among these treatments. Experiment 2 rats were gavaged with either CHO or CHO-AA-1. Fifteen minutes after gavage, a bolus containing 2-[(3)H]deoxyglucose and [U-(14)C]mannitol was infused via a tail vein. Blood glucose was significantly lower in CHO-AA-1 than in CHO, whereas insulin responses were similar. Muscle glucose uptake was higher in CHO-AA-1 compared with CHO in both fast-twitch red (8.36 ± 1.3 vs. 5.27 ± 0.7 μmol·g(-1)·h(-1)) and white muscle (1.85 ± 0.3 vs. 1.11 ± 0.2 μmol·g(-1)·h(-1)). There was no difference in Akt/PKB phosphorylation between treatment groups; however, the amino acid treatment resulted in increased AS160 phosphorylation in both muscle fiber types. Glycogen synthase phosphorylation was reduced in fast-twitch red muscle of CHO-AA-1 compared with CHO, whereas mTOR phosphorylation was increased. These differences were not noted in fast-twitch white muscle. These findings suggest that amino acid supplementation can improve glucose tolerance by increasing skeletal muscle glucose uptake and intracellular disposal through enhanced intracellular signaling.

An amino acid mixture enhances insulin-stimulated glucose uptake in isolated rat epitrochlearis muscle

Protein and certain amino acids (AA) have been found to lower blood glucose. Although these glucose-lowering AA are important modulators of skeletal muscle metabolism, their impact on muscle glucose uptake remains unclear. We therefore examined how an AA mixture consisting of 2 mM isoleucine, 0.012 mM cysteine, 0.006 mM methionine, 0.0016 mM valine, and 0.014 mM leucine impacts skeletal muscle glucose uptake in the absence or presence of a submaximal (sINS) or maximal insulin (mINS) concentration. The AA mixture, sINS, and mINS significantly increased 2-[(3)H]deoxyglucose (2-DG) uptake by 63, 79, and 298% above basal, respectively. When the AA mixture was combined with sINS and mINS, 2-DG uptake was further increased significantly by 26% (P = 0.028) and 14% (P = 0.032), respectively. Western blotting analysis revealed that the AA mixture increased basal and sINS Akt substrate of 160 kDa (AS160) phosphorylation, while AA mixture did not change phosphorylation of Akt or mammalian target of rapamycin (mTOR) under these conditions. Interestingly, addition of the AA mixture to mINS increased phosphorylation of mTOR, Akt as well as AS160, compared with mINS alone. These data suggest that certain AA increase glucose uptake in the absence of insulin and augment insulin-stimulated glucose uptake in an additive manner. Furthermore, these effects appear to be mediated via a pathway that is independent from the canonical insulin cascade and therefore may prove effective as an alternative therapeutic treatment for insulin resistance.

An amino acid mixture is essential to optimize insulin-stimulated glucose uptake and GLUT4 translocation in perfused rodent hindlimb muscle

The purpose of this study was to investigate whether an amino acid mixture increases glucose uptake across perfused rodent hindlimb muscle in the presence and absence of a submaximal insulin concentration, and if the increase in glucose uptake is related to an increase in GLUT4 plasma membrane density. Sprague-Dawley rats were separated into one of four treatment groups: basal, amino acid mixture, submaximal insulin, or amino acid mixture with submaximal insulin. Glucose uptake was greater for both insulin-stimulated treatments compared with the non-insulin-stimulated treatment groups but amino acids only increased glucose uptake in the presence of insulin. Phosphatidylinositol 3-kinase (PI 3-kinase) activity was greater for both insulin-stimulated treatments with amino acids having no additional impact. Akt substrate of 160 kDa (AS160) phosphorylation, however, was increased by the amino acids in the presence of insulin, but not in the absence of insulin. AMPK was unaffected by insulin or amino acids. Plasma membrane GLUT4 protein concentration was greater in the rats treated with insulin compared with no insulin in the perfusate. In the presence of insulin, amino acids increased GLUT4 density in the plasma membrane but had no effect in the absence of insulin. AS160 phosphorylation and plasma membrane GLUT4 density accounted for 76% of the variability in muscle glucose uptake. Collectively, these findings suggest that the beneficial effects of an amino acid mixture on skeletal muscle glucose uptake, in the presence of a submaximal insulin concentration, are due to an increase in AS160 phosphorylation and plasma membrane-associated GLUT4, but independent of PI 3-kinase and AMPK activation.

Effect of Mild Intermittent Hypoxia on Glucose Tolerance, Muscle Morphology and AMPK-PGC-1α Signaling

The main goal of this study was to investigate the long-term effect of daily 8-hour mild intermittent hypoxia (14-15% O2) on glucose tolerance and muscle morphology of Sprague-Dawley rats. The involvement of AMPK-PGC-1alpha-VEGF signaling pathways in the skeletal muscle was also determined during the first 8 hours of hypoxia. We found that mRNA levels of VEGF and PGC-1alpha were significantly increased above control after 8-h mild hypoxia without a change in AMPK phosphorylation. After 8 weeks of mild intermittent hypoxia treatment, plasma glucose and insulin levels in oral glucose tolerance test (OGTT), epididymal fat mass, and body weight were significantly lower compared to the control group. While soleus muscle weight was not changed, capillary and fiber densities in the hypoxia group were 33% and 35% above the control suggesting reorganization of muscle fibers. In conclusion, our data provide strong evidence that long-term mild intermittent hypoxia decreases the diffusion distance of glucose and insulin across muscle fibers, and decreases adiposity in rats. These changes may account for the improved glucose tolerance observed following the 8-week hypoxia treatment, and provides grounds for investigating the development of a mild non-pharmacological intervention in the treatment of obesity and type 2 diabetes.

Cereal and nonfat milk support muscle recovery following exercise

BackgroundThis study compared the effects of ingesting cereal and nonfat milk (Cereal) and a carbohydrate-electrolyte sports drink (Drink) immediately following endurance exercise on muscle glycogen synthesis and the phosphorylation state of proteins controlling protein synthesis: Akt, mTOR, rpS6 and eIF4E.MethodsTrained cyclists or triathletes (8 male: 28.0 ± 1.6 yrs, 1.8 ± 0.0 m, 75.4 ± 3.2 kg, 61.0 ± 1.6 ml O2•kg-1•min-1; 4 female: 25.3 ± 1.7 yrs, 1.7 ± 0.0 m, 66.9 ± 4.6 kg, 46.4 ± 1.2 mlO2•kg-1•min-1) completed two randomly-ordered trials serving as their own controls. After 2 hours of cycling at 60–65% VO2MAX, a biopsy from the vastus lateralis was obtained (Post0), then subjects consumed either Drink (78.5 g carbohydrate) or Cereal (77 g carbohydrate, 19.5 g protein and 2.7 g fat). Blood was drawn before and at the end of exercise, and at 15, 30 and 60 minutes after treatment. A second biopsy was taken 60 minutes after supplementation (Post60). Differences within and between treatments were tested using repeated measures ANOVA.ResultsAt Post60, blood glucose was similar between treatments (Drink 6.1 ± 0.3, Cereal 5.6 ± 0.2 mmol/L, p < .05), but after Cereal, plasma insulin was significantly higher (Drink 123.1 ± 11.8, Cereal 191.0 ± 12.3 pmol/L, p < .05), and plasma lactate significantly lower (Drink 1.4 ± 0.1, Cereal 1.00 ± 0.1 mmol/L, p < .05). Except for higher phosphorylation of mTOR after Cereal, glycogen and muscle proteins were not statistically different between treatments. Significant Post0 to Post60 changes occurred in glycogen (Drink 52.4 ± 7.0 to 58.6 ± 6.9, Cereal 58.7 ± 9.6 to 66.0 ± 10.0 μmol/g, p < .05) and rpS6 (Drink 17.9 ± 2.5 to 35.2 ± 4.9, Cereal 18.6 ± 2.2 to 35.4 ± 4.4 %Std, p < .05) for each treatment, but only Cereal significantly affected glycogen synthase (Drink 66.6 ± 6.9 to 64.9 ± 6.9, Cereal 61.1 ± 8.0 to 54.2 ± 7.2%Std, p < .05), Akt (Drink 57.9 ± 3.2 to 55.7 ± 3.1, Cereal 53.2 ± 4.1 to 60.5 ± 3.7 %Std, p < .05) and mTOR (Drink 28.7 ± 4.4 to 35.4 ± 4.5, Cereal 23.0 ± 3.1 to 42.2 ± 2.5 %Std, p < .05). eIF4E was unchanged after both treatments.ConclusionThese results suggest that Cereal is as good as a commercially-available sports drink in initiating post-exercise muscle recovery.

Green tea extract supplementation does not hamper endurance-training adaptation but improves antioxidant capacity in sedentary men

The purpose of this study was to investigate the effect of green tea extract (GTE) supplementation combined with endurance training on endurance capacity and performance in sedentary men. Forty untrained men (age: 20 ± 1 years) participated in this study. Subjects were assigned to 1 of 4 treatments: (i) placebo-control (CTRL), (ii) GTE, (iii) endurance training (Ex), and (iv) endurance training with GTE (ExGTE). During the 4-week intervention, exercise training was prescribed as 75% oxygen uptake reserve for three 20-min sessions per week, and either GTE (250 mg/day) or placebo was provided. Endurance capacity, malondialdehyde (MDA), total antioxidant status (TAS), and creatine kinase (CK) were examined. Ex and ExGTE but not GTE improved exhaustive-run time (Ex: +8.2%, p = 0.031; ExGTE: +14.3%, p < 0.001); in addition, Ex and ExGTE significantly increased maximal oxygen uptake by ∼14% (p = 0.041) and ∼17% (p = 0.017) above the values of the CTRL group, respectively. Both Ex and ExGTE significantly decreased the increase of CK by ∼11%-32% below that of CTRL following an exhaustive run (Ex: p = 0.007; ExGTE: p = 0.001). Moreover, TAS levels increased by ∼11% in ExGTE after training (p = 0.040), and GTE, Ex, and ExGTE markedly attenuated exercise-induced MDA production (p = 0.01, p = 0.005, p = 0.011, respectively). In conclusion, this investigation demonstrated that daily ingestion of GTE during endurance training does not impair improvements in endurance capacity. Moreover, endurance training combined with GTE not only increases antioxidant capacity without attenuating endurance training adaptations, but also further attenuates acute exercise-induced CK release.

Late-onset caloric restriction alters skeletal muscle metabolism by modulating pyruvate metabolism.

Caloric restriction (CR) attenuates age-related muscle loss. However, the underlying mechanism responsible for this attenuation is not fully understood. This study evaluated the role of energy metabolism in the CR-induced attenuation of muscle loss. The aims of this study were twofold: 1) to evaluate the effect of CR on energy metabolism and determine its relationship with muscle mass, and 2) to determine whether the effects of CR are age dependent. Young and middle-aged rats were randomized into either 40% CR or ad libitum (AL) diet groups for 14 wk. Major energy-producing pathways in muscles, i.e., glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), were examined. We found that the effects of CR were age dependent. CR improved muscle metabolism and normalized muscle mass in middle-aged animals but not young animals. CR decreased glycolysis and increased the cellular dependency for OXPHOS vs. glycolysis in muscles of middle-aged rats, which was associated with the improvement of normalized muscle mass. The metabolic reprogramming induced by CR was related to modulation of pyruvate metabolism and increased mitochondrial biogenesis. Compared with animals fed AL, middle-aged animals with CR had lower lactate dehydrogenase A content and greater mitochondrial pyruvate carrier content. Markers of mitochondrial biogenesis, including AMPK activation levels and SIRT1 and COX-IV content, also showed increased levels. In conclusion, 14 wk of CR improved muscle metabolism and preserved muscle mass in middle-aged animals but not in young developing animals. CR-attenuated age-related muscle loss is associated with reprogramming of the metabolic pathway from glycolysis to OXPHOS.

Exercise training increases components of the c-Cbl-associated protein/c-Cbl signaling cascade in muscle of obese Zucker rats

The purpose of this investigation was to determine whether alterations in the c-Cbl-associated protein/c-Cbl pathway and/or p38-mitogen-activated protein kinase (p38 MAP kinase) were associated with improved skeletal muscle insulin responsiveness in exercise-trained obese Zucker rats. Obese Zucker rats ran 5 d/wk on a motorized treadmill for 90 minutes over a 7-week period. Age-matched obese Zucker rats (OB-SED) and their lean littermates (LN-SED) were obtained to serve as nontrained controls. Twenty-four (OB-EX-24 h) or 48 hours (OB-EX-48 h) after the last exercise bout, the trained rats were studied via the hind limb perfusion technique in the presence of insulin. Insulin-stimulated glucose uptake was significantly decreased across the skeletal muscle of OB-SED rats compared with LN-SED, but was normalized in the obese rats by 7 weeks of training. The insulin-stimulated plasma membrane protein concentrations of TC10 and glucose transporter 4 were reduced in the sedentary Zuckers, but both proteins were increased by the training protocol. Training did not increase insulin-stimulated p38 MAP kinase protein concentration, nor did it have an effect on insulin-stimulated p38 MAP kinase phosphorylation at the plasma membrane. These results suggest that skeletal muscle insulin resistance is associated with reduced expression of TC10 and that this deficiency can be corrected with exercise training.

Effect of expiratory muscle strength training intervention on the maximum expiratory pressure and quality of life of patients with Parkinson disease

PURPOSE The purpose of this study was to investigate the effects of 4-weeks expiratory muscle strength training (EMST) on the maximum expiratory pressure (PEmax) and quality of life (QoL) in patients with Parkinson disease (PD). METHODS Thirteen outpatients diagnosed with PD participated in this study, and were assigned into either a 5DE training group (5DE group; n = 4; 75% PEmax for 5-d/wk), 3DE training group (3DE group; n = 5; 75% PEmax for 3-d/wk) and control group (3DC group; n = 4; 0% PEmax for 3-d/wk) by matching their Hoehn and Yahr scale, genders, and age. The PEmax and Parkinson disease questionnaire-39 item (PDQ-39) were evaluated pre- and post-intervention. RESULTS The posttest PEmax of the 5DE was significantly higher than that of the 3DC (P < 0.05). Moreover, 5DE and 3DE but not 3DC significantly increased PEmax after training. There were no differences in the overall quality of life in PD patients measured by PDQ-39 among three groups, but the 5DE group significantly improved the mobility constructs of PDQ-39 compared with 3DC (P < 0.05). CONCLUSION Both 5 d/wk and 3 d/wk of EMST effectively enhance respiratory muscle strength and improve mobility construct measured by PDQ-39 in patients with PD.