Daily protein-polyphenol ingestion increases daily myofibrillar protein synthesis rates and promotes early muscle functional gains during resistance training.

Factors underpinning the time-course of resistance-type exercise training (RET) adaptations are not fully understood. This study hypothesized that consuming a twice-daily protein-polyphenol beverage (PPB; n = 15; age, 24 ± 1 yr; BMI, 22.3 ± 0.7 kg·m-2) previously shown to accelerate recovery from muscle damage and increase daily myofibrillar protein synthesis (MyoPS) rates would accelerate early (10 sessions) improvements in muscle function and potentiate quadriceps volume and muscle fiber cross-sectional area (fCSA) following 30 unilateral RET sessions in healthy, recreationally active, adults. Versus isocaloric placebo (PLA; n = 14; age, 25 ± 2 yr; BMI, 23.9 ± 1.0 kg·m-2), PPB increased 48 h MyoPS rates after the first RET session measured using deuterated water (2.01 ± 0.15 vs. 1.51 ± 0.16%·day-1, respectively; P < 0.05). In addition, PPB increased isokinetic muscle function over 10 sessions of training relative to the untrained control leg (%U) from 99.9 ± 1.8 pretraining to 107.2 ± 2.4%U at session 10 (vs. 102.6 ± 3.9 to 100.8 ± 2.4%U at session 10 in PLA; interaction P < 0.05). Pre to posttraining, PPB increased type II fCSA (PLA: 120.8 ± 8.2 to 109.5 ± 8.6%U; PPB: 92.8 ± 6.2 to 108.4 ± 9.7%U; interaction P < 0.05), but the gain in quadriceps muscle volume was similar between groups. Similarly, PPB did not further increase peak isometric torque, muscle function, or MyoPS measured posttraining. This suggests that although PPB increases MyoPS and early adaptation, it may not influence longer term adaptations to unilateral RET.NEW & NOTEWORTHY Using a unilateral model of resistance training, we show for the first time that a protein-polyphenol beverage increases initial rates of myofibrillar protein synthesis and promotes early functional improvements. Following a prolonged period of training, this strategy also increases type II fiber hypertrophy and causes large individual variation in gains in quadricep muscle cross-sectional area.

Reducing NF-κB Signaling Nutritionally is Associated with Expedited Recovery of Skeletal Muscle Function After Damage.

CONTEXT: The early events regulating the remodeling program following skeletal muscle damage are poorly understood. OBJECTIVE: The objective of this study was to determine the association between myofibrillar protein synthesis (myoPS) and nuclear factor-kappa B (NF-κB) signaling by nutritionally accelerating the recovery of muscle function following damage. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: Healthy males and females consumed daily postexercise and prebed protein-polyphenol (PP; n = 9; 4 females) or isocaloric maltodextrin placebo (PLA; n = 9; 3 females) drinks (parallel design) 6 days before and 3 days after 300 unilateral eccentric contractions of the quadriceps during complete dietary control. MAIN OUTCOME MEASURES: Muscle function was assessed daily, and skeletal muscle biopsies were taken after 24, 27, and 36 hours for measurements of myoPS rates using deuterated water, and gene ontology and NF-κB signaling analysis using a quantitative reverse transcription PCR (RT-qPCR) gene array. RESULTS: Eccentric contractions impaired muscle function for 48 hours in PLA intervention, but just for 24 hours in PP intervention (P = 0.047). Eccentric quadricep contractions increased myoPS compared with the control leg during postexercise (24-27 hours; 0.14 ± 0.01 vs 0.11 ± 0.01%·h-1, respectively; P = 0.075) and overnight periods (27-36 hours; 0.10 ± 0.01 vs 0.07 ± 0.01%·h-1, respectively; P = 0.020), but was not further increased by PP drinks (P > 0.05). Protein-polyphenol drinks decreased postexercise and overnight muscle IL1R1 (PLA = 2.8 ± 0.4, PP = 1.1 ± 0.4 and PLA = 1.9 ± 0.4, PP = 0.3 ± 0.4 log2 fold-change, respectively) and IL1RL1 (PLA = 4.9 ± 0.7, PP = 1.6 ± 0.8 and PLA = 3.7 ± 0.6, PP = 0.7 ± 0.7 log2 fold-change, respectively) messenger RNA expression (P < 0.05) and downstream NF-κB signaling compared with PLA. CONCLUSION: Protein-polyphenol drink ingestion likely accelerates recovery of muscle function by attenuating inflammatory NF-κB transcriptional signaling, possibly to reduce aberrant tissue degradation rather than increase myoPS rates.

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 men and women 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 for 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 5 days after 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 the 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 and 168 h after EE, albeit after function had recovered. Inflammatory and regenerative signaling pathways were dramatically upregulated and clustered after 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.NEW & NOTEWORTHY The present study investigated the contribution of myofibrillar protein synthesis (MyoPS) and associated gene signaling to recovery from 300 muscle-damaging, eccentric contractions. Measured with 2H2O, MyoPS rates were elevated during recovery and observed alongside expression of inflammatory and regenerative signaling pathways. A nutritional intervention accelerated recovery; however, MyoPS and gene signaling were unchanged compared with placebo. These data indicate that MyoPS and associated signaling do not explain accelerated recovery from muscle damage.

A Randomised, Placebo-Controlled, Crossover Study Investigating the Optimal Timing of a Caffeine-Containing Supplement for Exercise Performance.

BACKGROUND: Pre-exercise supplements containing low doses of caffeine improve endurance exercise performance, but the most efficacious time for consumption before intense endurance exercise remains unclear, as does the contribution of caffeine metabolism. METHODS: This study assessed the timing of a commercially available supplement containing 200 mg of caffeine, 1600 mg of ß-alanine and 1000 mg of quercetin [Beachbody Performance Energize, Beachbody LLC, USA] on exercise performance, perception of effort and plasma caffeine metabolites. Thirteen cyclists (V̇O2max 64.5 ± 1.4 ml kg- 1 min- 1 (± SEM)) completed four experimental visits consisting of 30 min of steady-state exercise on a cycle ergometer at 83 ± 1% V̇O2max followed by a 15-min time trial, with perceived exertion measured regularly. On three of the visits, participants consumed caffeine either 35 min before steady-state exercise (PRE), at the onset of steady-state (ONS) or immediately before the time trial (DUR) phases, with a placebo consumed at the other two time points (i.e. three drinks per visit). The other visit (PLA) consisted of consuming the placebo supplement at all three time points. The placebo was taste-, colour- and calorie-matched. RESULTS: Total work performed during the time trial in PRE was 5% greater than PLA (3.53 ± 0.14 vs. 3.36 ± 0.13 kJ kg- 1 body mass; P = 0.0025), but not ONS (3.44 ± 0.13 kJ kg- 1; P = 0.3619) or DUR (3.39 ± 0.13 kJ kg- 1; P = 0.925), which were similar to PLA. Perceived exertion was lowest during steady-state exercise in the PRE condition (P < 0.05), which coincided with elevated plasma paraxanthine in PRE only (P < 0.05). CONCLUSION: In summary, ingestion of a pre-exercise supplement containing 200 mg caffeine 35 min before exercise appeared optimal for improved performance in a subsequent fatiguing time trial, possibly by reducing the perception of effort. Whether this was due to increased circulating paraxanthine requires further investigation. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT02985606 ; 10/26/2016.

Daily physical activity enhances reactivity to insulin in skeletal muscle arterioles of hyperphagic Otsuka Long-Evans Tokushima Fatty rats.

Insulin-mediated glucose disposal is dependent on the vasodilator effects of insulin. In type 2 diabetes, insulin-stimulated vasodilation is impaired as a result of an imbalance in NO and ET-1 production. We tested the hypothesis that chronic voluntary wheel running (RUN) prevents impairments in insulin-stimulated vasodilation associated with obesity and type 2 diabetes independent of the effects of RUN on adiposity by randomizing Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of hyperphagia-induced obesity and type 2 diabetes, to 1) RUN, 2) caloric restriction (CR; diet adjusted to match body weights of RUN group), or 3) sedentary control (SED) groups (n = 8/group) at 4 wk. At 40 wk, NO- and ET-1-mediated vasoreactivity to insulin (1-1,000 µIU/ml) was assessed in the presence of a nonselective ET-1 receptor blocker (tezosentan) or a NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine methyl ester (L-NAME)], respectively, in second-order arterioles isolated from the white portion of the gastrocnemius muscle. Body weight, fasting plasma glucose, and hemoglobin A1c were lower in RUN and CR than SED (P < 0.05); however, the glucose area under the curve (AUC) following the intraperitoneal glucose tolerance test was lower only in the RUN group (P < 0.05). Vasodilator responses to all doses of insulin were greater in RUN than SED or CR in the presence of a tezosentan (P < 0.05), but group differences in vasoreactivity to insulin with coadministration of L-NAME were not observed. We conclude daily wheel running prevents obesity and type 2 diabetes-associated declines in insulin-stimulated vasodilation in skeletal muscle arterioles through mechanisms that appear to be NO mediated and independent of attenuating excess adiposity in hyperphagic rats.

Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model.

BACKGROUND & AIMS: In this study, we sought to determine the temporal relationship between hepatic mitochondrial dysfunction, hepatic steatosis and insulin resistance, and to examine their potential role in the natural progression of non-alcoholic fatty liver disease (NAFLD) utilising a sedentary, hyperphagic, obese, Otsuka Long-Evans Tokushima Fatty (OLETF) rat model. METHODS: OLETF rats and their non-hyperphagic control Long-Evans Tokushima Otsuka (LETO) rats were sacrificed at 5, 8, 13, 20, and 40 weeks of age (n=6-8 per group). RESULTS: At 5 weeks of age, serum insulin and glucose and hepatic triglyceride (TG) concentrations did not differ between animal groups; however, OLETF animals displayed significant (p<0.01) hepatic mitochondrial dysfunction as measured by reduced hepatic carnitine palmitoyl-CoA transferase-1 activity, fatty acid oxidation, and cytochrome c protein content compared with LETO rats. Hepatic TG levels were significantly elevated by 8 weeks of age, and insulin resistance developed by 13 weeks in the OLETF rats. NAFLD progressively worsened to include hepatocyte ballooning, perivenular fibrosis, 2.5-fold increase in serum ALT, hepatic mitochondrial ultrastructural abnormalities, and increased hepatic oxidative stress in the OLETF animals at later ages. Measures of hepatic mitochondrial content and function including beta-hydroxyacyl-CoA dehydrogenase activity, citrate synthase activity, and immunofluorescence staining for mitochondrial carbamoyl phosphate synthetase-1, progressively worsened and were significantly reduced at 40 weeks in OLETF rats compared to LETO animals. CONCLUSIONS: Our study documents that hepatic mitochondrial dysfunction precedes the development of NAFLD and insulin resistance in the OLETF rats. This evidence suggests that progressive mitochondrial dysfunction contributes to the natural history of obesity-associated NAFLD.

Inflammation and exercise (INFLAME): study rationale, design, and methods.

PURPOSE: The INFLAME study is designed to determine the effect of exercise training on elevated high-sensitivity C-Reactive Protein (CRP) concentrations in initially sedentary women and men. METHODS: INFLAME will recruit 170 healthy, sedentary women and men with elevated CRP (>or=2.0 mg/L) to be randomized to either an exercise group or non-exercise control group. Exercising individuals will participate in four months of supervised aerobic exercise with a total energy expenditure of 16 kcal kg(-1) week(-1) (KKW). Exercise intensity will be 60-80% of maximal oxygen consumption (VO(2) max). OUTCOME: The primary outcome will be changed in plasma CRP concentration. Secondary outcomes include visceral adiposity, the cytokines IL-6 and TNF-alpha, and heart rate variability (HRV) in order to examine potential biological mechanisms whereby exercise might affect CRP concentrations. SUMMARY: INFLAME will help us understand the effects of moderate-to-vigorous exercise on CRP concentrations in sedentary individuals. To our knowledge this will be the largest training study specifically designed to examine the effect of exercise on CRP concentrations. This study has the potential to influence therapeutic applications since CRP measurement is becoming an important clinical measurement in Coronary Heart Disease risk assessment. This study will also contribute to the limited body of literature examining the effect of exercise on the variables of visceral adiposity, cytokines, and heart rate variability.