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

Author(s):  
Lee M. Margolis ◽  
Marques A. Wilson ◽  
Claire C. Whitney ◽  
Christopher T. Carrigan ◽  
Nancy E. Murphy ◽  
...  

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.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 644-644
Author(s):  
Lee Margolis ◽  
Marques Wilson ◽  
Claire Whitney ◽  
Christopher Carrigan ◽  
Nancy Murphy ◽  
...  

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 &lt; 0.05) in LOW compared to AD, while p-p38MAPKThr180/Tyr182 was higher (P &lt; 0.05) in LOW at POST, but not different PRE. Insulin sensitive p-AKTThr473 was higher (P &lt; 0.05) in AD compared to LOW, regardless of time. Anabolic regulators, p-mTORC1Ser2448, p-p70S6KSer424/421, and p-rpS6Ser235/236 were higher (P &lt; 0.05) POST compared to PRE and BASE, independent of group. Regulators of myogenesis, MYOD and MYOGENIN were lower (P &lt; 0.05) in LOW compared to AD, regardless of time, while PAX7 was lower (P &lt; 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.


1996 ◽  
Vol 81 (4) ◽  
pp. 1495-1500 ◽  
Author(s):  
Adrianus J. Van Den Bergh ◽  
Sibrand Houtman ◽  
Arend Heerschap ◽  
Nancy J. Rehrer ◽  
Hendrikus J. Van Den Boogert ◽  
...  

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.


2003 ◽  
Vol 94 (5) ◽  
pp. 1917-1925 ◽  
Author(s):  
D. C. Nieman ◽  
J. M. Davis ◽  
D. A. Henson ◽  
J. Walberg-Rankin ◽  
M. Shute ◽  
...  

Sixteen experienced marathoners ran on treadmills for 3 h at ∼70% maximal oxygen consumption (V˙o 2 max) on two occasions while receiving 1 l/h carbohydrate (CHO) or placebo (Pla) beverages. Blood and vastus lateralis muscle biopsy samples were collected before and after exercise. Plasma was analyzed for IL-6, IL-10, IL-1 receptor agonist (IL-1ra), IL-8, cortisol, glucose, and insulin. Muscle was analyzed for glycogen content and relative gene expression of 13 cytokines by using real-time quantitative RT-PCR. Plasma glucose and insulin were higher, and cortisol, IL-6, IL-10, and IL-1ra, but not IL-8, were significantly lower postexercise in CHO vs. Pla. Change in muscle glycogen content did not differ between CHO and Pla ( P = 0.246). Muscle cytokine mRNA content was detected preexercise for seven cytokines in this order (highest to lowest): IL-15, TNF-α, IL-8, IL-1β, IL-12p35, IL-6, and IFN-γ. After subjects ran for 3 h, gene expression above prerun levels was measured for five of these cytokines: IL-1β, IL-6, and IL-8 (large increases), and IL-10 and TNF-α (small increases). The increase in mRNA (fold difference from preexercise) was attenuated in CHO (15.9-fold) compared with Pla (35.2-fold) for IL-6 ( P = 0.071) and IL-8 (CHO, 7.8-fold; Pla, 23.3-fold; P = 0.063). CHO compared with Pla beverage ingestion attenuates the increase in plasma IL-6, IL-10, and IL-1ra and gene expression for IL-6 and IL-8 in athletes running 3 h at 70%V˙o 2 max despite no differences in muscle glycogen content.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2555 ◽  
Author(s):  
Takahashi ◽  
Matsunaga ◽  
Banjo ◽  
Takahashi ◽  
Sato ◽  
...  

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.


1998 ◽  
Vol 275 (2) ◽  
pp. R596-R603 ◽  
Author(s):  
Alan Chesley ◽  
Richard A. Howlett ◽  
George J. F. Heigenhauser ◽  
Eric Hultman ◽  
Lawrence L. Spriet

This study examined the effects of caffeine (Caf) ingestion on muscle glycogen use and the regulation of muscle glycogen phosphorylase (Phos) activity during intense aerobic exercise. In two separate trials, 12 untrained males ingested either placebo (Pl) or Caf (9 mg/kg body wt) 1 h before cycling at 80% maximum O2 consumption (V˙o 2 max) for 15 min. Muscle biopsies were obtained from the vastus lateralis at 0, 3, and 15 min of exercise. In this study, glycogen “sparing” was defined as a 10% or greater reduction in muscle glycogen use during exercise after Caf ingestion compared with Pl. Muscle glycogen use decreased by 28% (Pl 255 ± 38 vs. Caf 184 ± 24 mmol/kg dry muscle) after Caf in six subjects [glycogen sparers (Sp)] but was unaffected by Caf in six other subjects [nonsparers (NSp), Pl 210 ± 35 vs. Caf 214 ± 37 mmol/kg dry muscle]. In both groups, Caf significantly increased resting free fatty acid concentration, significantly increased epinephrine concentration by twofold during exercise, and increased the Phos a mole fraction at 3 min of exercise compared with Pl, although not significantly. Caf improved the energy status of the muscle during exercise in the Sp group: muscle phosphocreatine (PCr) degradation was significantly reduced (Pl 47.9 ± 3.6 vs. Caf 40.4 ± 6.7 mmol/kg dry muscle at 3 min) and the accumulations of free ADP and free AMP (Pl 6.8 ± 1.3 vs. Caf 3.1 ± 1.4 μmol/kg dry muscle at 3 min; Pl 8.7 ± 0.8 vs. Caf 4.7 ± 1.1 μmol/kg dry muscle at 15 min) were significantly reduced. Caf had no effect on these measurements in the NSp group. It is concluded that the Caf-induced decrease in flux through Phos (glycogen-sparing effect) is mediated via an improved energy status of the muscle in the early stages of intense aerobic exercise. This may be related to an increased availability of fat and/or ability of mitochondria to oxidize fat during exercise preceded by Caf ingestion. It is presently unknown why the glycogen-sparing effect of Caf does not occur in all untrained individuals during intense aerobic exercise.


1988 ◽  
Vol 254 (4) ◽  
pp. R572-R577 ◽  
Author(s):  
H. T. Yang ◽  
R. L. Hammer ◽  
T. L. Sellers ◽  
J. Arogyasami ◽  
D. T. Carrell ◽  
...  

Sham-operated (SHAM) and saline (ADM-S)- or epinephrine (ADM-E)-infused adrenodemedullated rats were run on a treadmill (21 m/min, 15% grade) for 80 min or until exhaustion. ADM-S rats had significantly lower endurance run times (116 +/- 6 min) than ADM-E rats (136 +/- 8 min) and SHAM rats (150 +/- 6 min). Liver glycogen content dropped from 56 +/- 4 to 10 +/- 2 mg/g in SHAM and from 54 +/- 4 to 18 +/- 5 mg/g in ADM-S and to 20 +/- 8 mg/g in ADM-E rats at 80 min. Liver glycogen was depleted in all rats at exhaustion. Liver fructose 2,6-bisphosphate was decreased markedly in exercising rats, and the extent of decrease was not influenced by adrenodemedullation or by epinephrine infusion. ADM-S rats showed impaired glycogen depletion in the white vastus lateralis and soleus muscles, hypoglycemia, and low blood lactate at 80 min and at exhaustion. Infusion of epinephrine into ADM rats reversed these deficiencies. These data indicate that the adrenal medulla is unessential for normal endurance exercise as long as liver glycogen is available. After liver glycogen is depleted, epinephrine from the adrenal medulla prevents hypoglycemia and is essential for allowing continuation of exercise.


2002 ◽  
Vol 282 (3) ◽  
pp. E688-E694 ◽  
Author(s):  
T. J. Stephens ◽  
Z.-P. Chen ◽  
B. J. Canny ◽  
B. J. Michell ◽  
B. E. Kemp ◽  
...  

The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protein kinase (AMPK)α1 and -α2 activity and acetyl-CoA carboxylase (ACCβ) and neuronal nitric oxide synthase (nNOSμ) phosphorylation was investigated. Seven active healthy individuals cycled for 30 min at a workload requiring 62.8 ± 1.3% of peak O2consumption (V˙o 2 peak) with muscle biopsies obtained from the vastus lateralis at rest and at 5 and 30 min of exercise. AMPKα1 activity was not altered by exercise; however, AMPKα2 activity was significantly ( P < 0.05) elevated after 5 min (∼2-fold), and further elevated ( P < 0.05) after 30 min (∼3-fold) of exercise. ACCβ phosphorylation was increased ( P < 0.05) after 5 min (∼18-fold compared with rest) and increased ( P< 0.05) further after 30 min of exercise (∼36-fold compared with rest). Increases in AMPKα2 activity were significantly correlated with both increases in ACCβ phosphorylation and reductions in muscle glycogen content. Fat oxidation tended ( P = 0.058) to increase progressively during exercise. Muscle creatine phosphate was lower ( P < 0.05), and muscle creatine, calculated free AMP, and free AMP-to-ATP ratio were higher ( P < 0.05) at both 5 and 30 min of exercise compared with those at rest. At 30 min of exercise, the values of these metabolites were not significantly different from those at 5 min of exercise. Phosphorylation of nNOSμ was variable, and despite the mean doubling with exercise, statistically significance was not achieved ( P = 0.304). Western blots indicated that AMPKα2 was associated with both nNOSμ and ACCβ consistent with them both being substrates of AMPKα2 in vivo. In conclusion, AMPKα2 activity and ACCβ phosphorylation increase progressively during moderate exercise at ∼60% of V˙o 2 peak in humans, with these responses more closely coupled to muscle glycogen content than muscle AMP/ATP ratio.


1991 ◽  
Vol 70 (3) ◽  
pp. 1323-1327 ◽  
Author(s):  
R. K. Conlee ◽  
D. W. Barnett ◽  
K. P. Kelly ◽  
D. H. Han

This study was designed to test the hypothesis that cocaine (C) alters the normal physiological responses to exercise. Male rats were injected with saline (S) or C (12.5 mg/kg) either intravenously (iv) or intraperitoneally (ip). After injection the animals were allowed to rest for 30 min or were run on the treadmill (26 m/min, 10% grade). At rest plasma epinephrine values were 245 +/- 24 pg/ml in the S group and 411 +/- 43 (ip) and 612 +/- 41 (iv) pg/ml in the C groups (P less than 0.05 between S and C). During exercise plasma epinephrine levels were 615 +/- 32 pg/ml in S and 1,316 +/- 58 (ip) and 1,208 +/- 37 (iv) pg/ml in the C groups (P less than 0.05 between S and C). Similar results were obtained for norepinephrine. Glycogen content in the white vastus lateralis muscle was reduced to 31 +/- 2 mumol/g in S after exercise, but after C and exercise the values were 12 +/- 4 (ip) and 16 +/- 3 (iv) mumol/g (P less than 0.05 between S and C). There was no effect of the drug on this parameter at rest. Blood lactate rose to 4.8 +/- 1.0 (ip) and 5.8 +/- 1.3 (iv) mM in the C groups but to only 3.0 +/- 0.2 in the S group after exercise (P less than 0.05 between S and C). These results show that C and exercise combined exert a more dramatic effect on plasma catecholamine, muscle glycogen, and blood lactate concentrations than do C and exercise alone. They provide further insight into explaining the adverse effects of C on exercise endurance observed previously (Bracken et al., J. Appl. Physiol. 66: 377-383, 1989).


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3145 ◽  
Author(s):  
Dylan T. Wilburn ◽  
Steven B. Machek ◽  
Thomas D. Cardaci ◽  
Darryn S. Willoughby

Research has suggested that nutrient, exercise, and metabolism-related proteins interact to regulate mammalian target of rapamycin complex one (mTOR) post-exercise and their interactions needs clarification. In a double-blind, cross-over, repeated measures design, ten participants completed four sets to failure at 70% of 1-repitition maximum (1-RM) with 45 s rest on angled leg press with or without pre-exercise maltodextrin (2 g/kg) after a 3 h fast. Vastus lateralis biopsies were collected at baseline before supplementation and 1 h post-exercise to analyze Focal Adhesion Kinase (FAK), ribosomal protein S6 kinase beta-1 (p70S6K), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and 5′ AMP-activated protein kinase (AMPK) activation. FAK and IRS-1 activity were only elevated 1 h post-exercise with carbohydrate ingestion (p < 0.05). PI3K and p70S6K activation were both elevated after exercise in both conditions (p < 0.05). However, AMPK activity did not change from baseline in both conditions (p > 0.05). We conclude that FAK does not induce mTOR activation through PI3K crosstalk in response to exercise alone. In addition, FAK may not be regulated by AMPK catalytic activity, but this needs further research. Interestingly, carbohydrate-induced insulin signaling appears to activate FAK at the level of IRS-1 but did not enhance mTOR activity 1 h post-exercise greater than the placebo condition. Future research should investigate these interactions under different conditions and within different time frames to clearly understand the interactions between these signaling molecules.


1994 ◽  
Vol 76 (5) ◽  
pp. 1876-1881 ◽  
Author(s):  
K. D. Sumida ◽  
C. M. Donovan

The effects of endurance training (running 30 m/min, 10% grade for 90 min, 5 days/wk for 12 wk) on skeletal muscle glucose uptake during steady-state exercise (running 20 m/min) were studied in fed rats. A bolus injection of 2-[1,2–3H]deoxyglucose was administered to assess the glucose metabolic index (R′g), an indicator of glucose uptake, in individual tissues of the animal. After 55 min of rest or moderate exercise, various tissues were analyzed for accumulation of phosphorylated 2-[1,2–3H]-deoxyglucose and/or glycogen content. No differences were observed between groups in the resting glycogen content for any of the muscle samples examined. Resting plasma glucose concentrations were not significantly different between groups. Furthermore, no significant differences were observed in R′g between groups for any of the muscle examined (tibialis anterior, extensor digitorum longus, soleus, white gastrocnemius, red gastrocnemius). During exercise, plasma glucose concentrations were not significantly different between groups. Exercise significantly elevated R′g above resting values in the tibialis anterior (5-fold), soleus (3-fold), and red gastrocnemius (7.5-fold). Despite an elevated R′g for specific muscles during exercise, no significant differences were observed in glucose uptake between groups for any tissue examined. Concomitantly, trained animals exhibited significantly less muscle glycogen depletion during exercise compared with control animals. Liver glycogen levels were also significantly higher post-exercise in trained vs. control animals.(ABSTRACT TRUNCATED AT 250 WORDS)


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