Serum Branched-Chain Amino Acid Metabolites Increase in Males When Aerobic Exercise Is Initiated with Low Muscle Glycogen

This study used global metabolomics to identify metabolic factors that might contribute to muscle anabolic resistance, which develops when aerobic exercise is initiated with low muscle glycogen using global metabolomics. Eleven men completed this randomized, crossover study, completing two cycle ergometry glycogen depletion trials, followed by 24 h of isocaloric refeeding to elicit low (LOW; 1.5 g/kg carbohydrate, 3.0 g/kg fat) or adequate (AD; 6.0 g/kg carbohydrate 1.0 g/kg fat) glycogen. Participants then performed 80 min of cycling (64 ± 3% VO2 peak) while ingesting 146 g carbohydrate. Serum was collected before glycogen depletion under resting and fasted conditions (BASELINE), and before (PRE) and after (POST) exercise. Changes in metabolite profiles were calculated by subtracting BASELINE from PRE and POST within LOW and AD. There were greater increases (p < 0.05, Q < 0.10) in 64% of branched-chain amino acids (BCAA) metabolites and 69% of acyl-carnitine metabolites in LOW compared to AD. Urea and 3-methylhistidine had greater increases (p < 0.05, Q < 0.10) in LOW compared to AD. Changes in metabolomics profiles indicate a greater reliance on BCAA catabolism for substrate oxidation when exercise is initiated with low glycogen stores. These findings provide a mechanistic explanation for anabolic resistance associated with low muscle glycogen, and suggest that exogenous BCAA requirements to optimize muscle recovery are likely greater than current recommendations.

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Muscle glycogen recovery after exercise during glucose and fructose intake monitored by13C-NMR

Journal of Applied Physiology ◽

10.1152/jappl.1996.81.4.1495 ◽

1996 ◽

Vol 81 (4) ◽

pp. 1495-1500 ◽

Cited By ~ 24

Author(s):

Adrianus J. Van Den Bergh ◽

Sibrand Houtman ◽

Arend Heerschap ◽

Nancy J. Rehrer ◽

Hendrikus J. Van Den Boogert ◽

...

Keyword(s):

Nmr Spectroscopy ◽

Muscle Glycogen ◽

Glycogen Content ◽

Vastus Lateralis ◽

Glycogen Depletion ◽

Glycogen Concentration ◽

Fructose Intake ◽

Glycogen Stores ◽

Male Subjects ◽

C Nmr

Van Den Bergh, Adrianus J., Sibrand Houtman, Arend Heerschap, Nancy J. Rehrer, Hendrikus J. Van Den Boogert, Berend Oeseburg, and Maria T. E. Hopman. Muscle glycogen recovery after exercise during glucose and fructose intake monitored by13C-NMR. J. Appl. Physiol. 81(4): 1495–1500, 1996.—The purpose of this study was to examine muscle glycogen recovery with glucose feeding (GF) compared with fructose feeding (FF) during the first 8 h after partial glycogen depletion by using13C-nuclear magnetic resonance (NMR) on a clinical 1.5-T NMR system. After measurement of the glycogen concentration of the vastus lateralis (VL) muscle in seven male subjects, glycogen stores of the VL were depleted by bicycle exercise. During 8 h after completion of exercise, subjects were orally given either GF or FF while the glycogen content of the VL was monitored by13C-NMR spectroscopy every second hour. The muscular glycogen concentration was expressed as a percentage of the glycogen concentration measured before exercise. The glycogen recovery rate during GF (4.2 ± 0.2%/h) was significantly higher ( P < 0.05) compared with values during FF (2.2 ± 0.3%/h). This study shows that 1) muscle glycogen levels are perceptible by 13C-NMR spectroscopy at 1.5 T and 2) the glycogen restoration rate is higher after GF compared with after FF.

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Influence Of Branched-chain Aminoacids (BCAA) Supplementation On Free Fatty Acids Oxidation During Endurance Exercise After Muscle Glycogen Depletion

Medicine & Science in Sports & Exercise ◽

10.1097/00005768-200505001-01836 ◽

2005 ◽

Vol 37 (Supplement) ◽

pp. S349

Author(s):

Thomas B. Adolpho ◽

Patr??cia Lopes Campos ◽

Bruno Gualano ◽

Josilene Carla Gomes ◽

Fernanda Baeza Scagliusi ◽

...

Keyword(s):

Fatty Acids ◽

Free Fatty Acids ◽

Endurance Exercise ◽

Muscle Glycogen ◽

Glycogen Depletion ◽

Branched Chain

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Influence Of Branched-chain Aminoacids (BCAA) Supplementation On Free Fatty Acids Oxidation During Endurance Exercise After Muscle Glycogen Depletion

Medicine & Science in Sports & Exercise ◽

10.1249/00005768-200505001-01836 ◽

2005 ◽

Vol 37 (Supplement) ◽

pp. S349

Author(s):

Thomas B. Adolpho ◽

Patrícia Lopes Campos ◽

Bruno Gualano ◽

Josilene Carla Gomes ◽

Fernanda Baeza Scagliusi ◽

...

Keyword(s):

Fatty Acids ◽

Free Fatty Acids ◽

Endurance Exercise ◽

Muscle Glycogen ◽

Glycogen Depletion ◽

Branched Chain

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Effects of 24-hour fast on cycling endurance time at two different intensities

Journal of Applied Physiology ◽

10.1152/jappl.1986.61.2.654 ◽

1986 ◽

Vol 61 (2) ◽

pp. 654-659 ◽

Cited By ~ 35

Author(s):

S. F. Loy ◽

R. K. Conlee ◽

W. W. Winder ◽

A. G. Nelson ◽

D. A. Arnall ◽

...

Keyword(s):

Muscle Glycogen ◽

Plasma Free Fatty Acid ◽

Normal Diet ◽

Glycogen Depletion ◽

Endurance Time ◽

Competitive Cyclists ◽

Pedal Frequency ◽

Glycogen Stores ◽

Resting Muscle ◽

Initial Intensity

Ten competitive cyclists were exercised to exhaustion to test the potential of a 24-h fast for increasing endurance. One group (n = 4) was tested at an initial intensity of 86% maximum O2 uptake (VO2max) (HI) and a second group (n = 6) at 79% VO2max (MI). Both groups repeated test rides in fasted and normal-diet conditions. Time to fatigue was designated at two points: fatigue 1 occurred when pedal frequency could not be maintained at the initial percent VO2max; fatigue 2 occurred when pedal frequency could not be maintained at a workload of approximately 65% VO2max. In both HI and MI the 24-h fast had no effect on resting muscle glycogen stores but significantly increased plasma free fatty acid (FFA) levels. Despite the increased FFA availability, time to fatigue was reduced in the fasted groups. Fatigue 1 and 2 times (mean +/- SE) for HI-fasted were 42.0 +/- 6.2 and 170.0 +/- 20.4 min, respectively, compared with those of the HI-normal diet of 115.3 +/- 25.6 and 201.0 +/- 14.8 min. Fatigue 1 and 2 times for MI-fasted were 142.0 +/- 19.6 and 167.5 +/- 10.5 min compared with those of the MI-normal diet of 191.3 +/- 25.0 and 214.3 +/- 18.9 min. The cause of fatigue at fatigue 1 was not readily apparent. Fatigue 2 in all groups seemed to be related to hypoglycemia as well as muscle glycogen depletion.

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Role of glycogen in control of glycolysis and IMP formation in human muscle during exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.260.6.e859 ◽

1991 ◽

Vol 260 (6) ◽

pp. E859-E864 ◽

Cited By ~ 7

Author(s):

M. K. Spencer ◽

A. Katz

Keyword(s):

Muscle Glycogen ◽

Work Load ◽

Amp Deaminase ◽

Glycogen Depletion ◽

Intense Exercise ◽

O2 Uptake ◽

Contraction Phase ◽

Muscle Ph ◽

Glycogen Stores

The effect of prior glycogen depletion on glycolysis [flux through phosphofructokinase (PFK)] and inosine monophosphate (IMP) formation in human skeletal muscle has been investigated. Eight subjects cycled at a work load calculated to elicit 95% of maximal O2 uptake on two occasions, the first to fatigue [5.5 +/- 0.3 (SE) min] and the second at the same workload and for the same duration as the first. Before the first experiment, muscle glycogen stores were lowered by a combination of exercise and diet. Before the second experiment, muscle glycogen stores were supercompensated. In the low-glycogen (LG) state muscle glycogen decreased from 201 +/- 31 mmol glucosyl units/kg dry wt at rest to 105 +/- 28 after exercise, and in the high-glycogen (HG) state from 583 +/- 40 to 460 +/- 49. The accumulation of fructose 6-phosphate (F-6-P; activator of PFK) during exercise was markedly attenuated in the LG state (P less than 0.01), whereas lactate accumulation in muscle was similar between treatments, suggesting that muscle pH was also similar. Glycolysis (estimated from glycogenolysis minus accumulation of hexose monophosphates) was not measurably different between treatments (LG = 88 +/- 17, HG = 106 +/- 43 mmol/kg dry wt; P greater than 0.05). IMP was significantly greater in the LG state after exercise (3.63 +/- 0.85 vs. 1.97 +/- 0.44 mmol/kg dry wt; P less than 0.05). It is concluded that decreased glycogen availability does not measurably alter the rate of muscle glycolysis during intense exercise. It is hypothesized that the attenuated increase in F-6-P in the LG state, which should theoretically decrease glycolysis, is compensated for by increases in free ADP and AMP (activators of PFK) at the enzymatic site during the contraction phase. The greater increase in IMP in the LG state is consistent with this hypothesis, since ADP and AMP are also activators of AMP deaminase.

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Carbohydrate, Fluids and Electrolyte Requirements of the Soccer Player: A Stewiew

International Journal of Sport Nutrition ◽

10.1123/ijsn.4.3.221 ◽

1994 ◽

Vol 4 (3) ◽

pp. 221-236 ◽

Cited By ~ 19

Author(s):

John A. Hawley ◽

Steven C. Dennis ◽

Timothy D. Noakes

Keyword(s):

Body Weight ◽

Muscle Glycogen ◽

Soccer Player ◽

Liver Glycogen ◽

Soccer Players ◽

Insufficient Evidence ◽

Glycogen Depletion ◽

Low Concentrations ◽

Glycogen Stores ◽

Glycogen Sparing

Soccer requires field players to exercise repetitively at high intensities for the duration of a game, which can result in marked muscle glycogen depletion and hypoglycemia. A soccer match places heavy demands on endogenous muscle and liver glycogen stores and fluid reserves, which must be rapidly replenished when players complete several matches within a brief period of time. Low concentrations of muscle glycogen have been reported in soccer players before a game, and daily carbohydrate (CHO) intakes are often insufficient to replenish muscle glycogen stores, CHO supplementation during soccer matches has been found to result in muscle glycogen sparing (39%), greater second-half running distances, and more goals being scored with less conceded, when compared to consumption of water. Thus, CHO supplementation has been recommended prior to, during, and after matches. In contrast, there is currently insufficient evidence to recommend without reservation the addition of electrolytes to a beverage for ingestion by players during a game resulting in sweat losses of < 4% of body weight.

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Initiating aerobic exercise with low glycogen content reduces markers of myogenesis but not mTORC1 signaling

Journal of the International Society of Sports Nutrition ◽

10.1186/s12970-021-00455-z ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Lee M. Margolis ◽

Marques A. Wilson ◽

Claire C. Whitney ◽

Christopher T. Carrigan ◽

Nancy E. Murphy ◽

...

Keyword(s):

Aerobic Exercise ◽

Muscle Glycogen ◽

Glycogen Content ◽

Vastus Lateralis ◽

Cycle Ergometry ◽

Glycogen Depletion ◽

Muscle Recovery ◽

Carbohydrate Ingestion ◽

Post Exercise ◽

Mtorc1 Signaling

Abstract Background The effects of low muscle glycogen on molecular markers of protein synthesis and myogenesis before and during aerobic exercise with carbohydrate ingestion is unclear. The purpose of this study was to determine the effects of initiating aerobic exercise with low muscle glycogen on mTORC1 signaling and markers of myogenesis. Methods Eleven men completed two cycle ergometry glycogen depletion trials separated by 7-d, followed by randomized isocaloric refeeding for 24-h to elicit low (LOW; 1.5 g/kg carbohydrate, 3.0 g/kg fat) or adequate (AD; 6.0 g/kg carbohydrate, 1.0 g/kg fat) glycogen. Participants then performed 80-min of cycle ergometry (64 ± 3% VO2peak) while ingesting 146 g carbohydrate. mTORC1 signaling (Western blotting) and gene transcription (RT-qPCR) were determined from vastus lateralis biopsies before glycogen depletion (baseline, BASE), and before (PRE) and after (POST) exercise. Results Regardless of treatment, p-mTORC1Ser2448, p-p70S6KSer424/421, and p-rpS6Ser235/236 were higher (P < 0.05) POST compared to PRE and BASE. PAX7 and MYOGENIN were lower (P < 0.05) in LOW compared to AD, regardless of time, while MYOD was lower (P < 0.05) in LOW compared to AD at PRE, but not different at POST. Conclusion Initiating aerobic exercise with low muscle glycogen does not affect mTORC1 signaling, yet reductions in gene expression of myogenic regulatory factors suggest that muscle recovery from exercise may be reduced.

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Muscle Regenerative Capacity May Be Reduced When Aerobic Exercise Is Initiated with Low Glycogen Content

Current Developments in Nutrition ◽

10.1093/cdn/nzaa049_037 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 644-644

Author(s):

Lee Margolis ◽

Marques Wilson ◽

Claire Whitney ◽

Christopher Carrigan ◽

Nancy Murphy ◽

...

Keyword(s):

Aerobic Exercise ◽

Muscle Glycogen ◽

Glycogen Content ◽

Cycle Ergometry ◽

Glycogen Depletion ◽

High Fat ◽

Carbohydrate Ingestion ◽

Muscle Glycogen Content ◽

High Carbohydrate ◽

Insulin Dependent

Abstract Objectives Maintaining low muscle glycogen content during recovery from aerobic exercise with low carbohydrate, high fat feeding has been shown to reduce insulin-mediated anabolic signaling compared to high carbohydrate feeding. The effects of low muscle glycogen content on intracellular regulators of muscle mass before and after aerobic exercise with carbohydrate ingestion is unclear. This study examined the effect of initiating aerobic exercise with low muscle glycogen content on postprandial insulin-dependent muscle anabolic signaling and myogenesis. Methods Twelve men (mean ± SD, age: 21 ± 4 y; body mass: 83 ± 11 kg; VO2peak: 44 ± 3 mL/kg/min) completed 2 cycle ergometry glycogen depletion trials separated by 7 d, followed by a 24-h period of isocaloric high fat (1.5 g/kg carbohydrate, 3.0 g/kg fat) or high carbohydrate (6.0 g/kg carbohydrate, 1.0 g/kg fat) refeeding to elicit low (LOW; 217 ± 103 mmol/kg dry wt) or adequate (AD; 396 ± 70 mmol/kg dry wt) glycogen content in randomized order. Participants then performed 80 min of cycle ergometry (64 ± 3% VO2peak) while ingesting 146 g of carbohydrate. Protein signaling (Western blotting) and gene transcription (RT-qPCR) were determined from vastus lateralis biopsies obtained before glycogen depletion (baseline, BASE), and before (PRE) and after (POST) exercise. Data presented as fold change relative to BASE for LOW and AD. Results Independent of time, carbohydrate sensing p-AMPKThr172 was higher (P < 0.05) in LOW compared to AD, while p-p38MAPKThr180/Tyr182 was higher (P < 0.05) in LOW at POST, but not different PRE. Insulin sensitive p-AKTThr473 was higher (P < 0.05) in AD compared to LOW, regardless of time. Anabolic regulators, p-mTORC1Ser2448, p-p70S6KSer424/421, and p-rpS6Ser235/236 were higher (P < 0.05) POST compared to PRE and BASE, independent of group. Regulators of myogenesis, MYOD and MYOGENIN were lower (P < 0.05) in LOW compared to AD, regardless of time, while PAX7 was lower (P < 0.05) in LOW compared to AD at PRE, but not different POST. Conclusions Initiating aerobic exercise with low muscle glycogen content does not appear to affect downstream insulin-dependent anabolic signaling, yet reductions in myogenic regulator factors suggest muscle repair and remodeling in recovery from exercise may be impaired. Funding Sources Work supported by DHP JPC-5/MOMRP; authors’ views not official U.S. Army or DoD policy.

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Effects of Nutrient Intake Timing on Post-Exercise Glycogen Accumulation and its Related Signaling Pathways in Mouse Skeletal Muscle

Nutrients ◽

10.3390/nu11112555 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2555 ◽

Cited By ~ 1

Author(s):

Takahashi ◽

Matsunaga ◽

Banjo ◽

Takahashi ◽

Sato ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Glycogen ◽

Nutrient Intake ◽

Matched Control ◽

Control Group ◽

Glycogen Depletion ◽

Post Exercise ◽

Glycogen Accumulation ◽

Matched Control Group ◽

Significant Difference

We investigated the effects of nutrient intake timing on glycogen accumulation and its related signals in skeletal muscle after an exercise that did not induce large glycogen depletion. Male ICR mice ran on a treadmill at 25 m/min for 60 min under a fed condition. Mice were orally administered a solution containing 1.2 mg/g carbohydrate and 0.4 mg/g protein or water either immediately (early nutrient, EN) or 180 min (late nutrient, LN) after the exercise. Tissues were harvested at 30 min after the oral administration. No significant difference in blood glucose or plasma insulin concentrations was found between the EN and LN groups. The plantaris muscle glycogen concentration was significantly (p < 0.05) higher in the EN group—but not in the LN group—compared to the respective time-matched control group. Akt Ser473 phosphorylation was significantly higher in the EN group than in the time-matched control group (p < 0.01), while LN had no effect. Positive main effects of time were found for the phosphorylations in Akt substrate of 160 kDa (AS160) Thr642 (p < 0.05), 5'-AMP-activated protein kinase (AMPK) Thr172 (p < 0.01), and acetyl-CoA carboxylase Ser79 (p < 0.01); however, no effect of nutrient intake was found for these. We showed that delayed nutrient intake could not increase muscle glycogen after endurance exercise which did not induce large glycogen depletion. The results also suggest that post-exercise muscle glycogen accumulation after nutrient intake might be partly influenced by Akt activation. Meanwhile, increased AS160 and AMPK activation by post-exercise fasting might not lead to glycogen accumulation.

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