| 1. |
- Apró, William, et al.
(författare)
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Resistance exercise induced mTORC1 signaling is not impaired by subsequent endurance exercise in human skeletal muscle.
- 2013
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 305:1, s. E22-32
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Tidskriftsartikel (refereegranskat)abstract
- The current dogma is that the muscle adaptation to resistance exercise is blunted when combined with endurance exercise. The suggested mechanism (based on rodent experiments) is that activation of adenosine monophosphate-activated protein kinase (AMPK) during endurance exercise impairs muscle growth through inhibition of the mechanistic target of rapamycin complex 1 (mTORC1). The purpose of this study was to investigate potential interference of endurance training on the signaling pathway of resistance training [mTORC1 phosphorylation of ribosomal protein S6 kinase 1 (S6K1)] in human muscle. Ten healthy and moderately trained male subjects performed on two separate occasions either acute high-intensity and high-volume resistance exercise (leg press, R) or R followed by 30 min of cycling (RE). Muscle biopsies were collected before and 1 and 3 h post resistance exercise. Phosphorylation of mTOR (Ser(2448)) increased 2-fold (P < 0.05) and that of S6K1 (Thr(389)) 14-fold (P < 0.05), with no difference between R and RE. Phosphorylation of eukaryotic elongation factor 2 (eEF2, Thr(56)) was reduced ∼70% during recovery in both trials (P < 0.05). An interesting finding was that phosphorylation of AMPK (Thr(172)) and acetyl-CoA carboxylase (ACC, Ser(79)) decreased ∼30% and ∼50%, respectively, 3 h postexercise (P < 0.05). Proliferator-activated receptor-γ coactivator-1 (PGC-1α) mRNA increased more after RE (6.5-fold) than after R (4-fold) (RE vs. R: P < 0.01) and was the only gene expressed differently between trials. These data show that the signaling of muscle growth through the mTORC1-S6K1 axis after heavy resistance exercise is not inhibited by subsequent endurance exercise. It is also suggested that prior activation of mTORC1 signaling may repress subsequent phosphorylation of AMPK.
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| 2. |
- Apró, William, et al.
(författare)
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Resistance exercise induced S6K1 kinase activity is not inhibited in human skeletal muscle despite prior activation of AMPK by high intensity interval cycling.
- 2015
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 308:6, s. E470-E481
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Tidskriftsartikel (refereegranskat)abstract
- Combining endurance and strength training in the same session has been reported to reduce the anabolic response to the latter form of exercise. The underlying mechanism, based primarily on results from rodent muscle, is proposed to involve AMPK-dependent inhibition of mTORC1 signaling. This hypothesis was tested in eight trained male subjects who in a randomized order performed either resistance exercise only (R) or interval cycling followed by resistance exercise (ER). Biopsies taken from the vastus lateralis before and after endurance exercise and repeatedly after resistance exercise were assessed for glycogen content, kinase activity, protein phosphorylation and gene expression. Mixed muscle fractional synthetic rate was measured at rest and during 3h of recovery using the stable isotope technique. In ER, AMPK activity was elevated immediately after both endurance and resistance exercise (~90%, P<0.05) but was unchanged in R. Thr389 phosphorylation of S6K1 was increased several-fold immediately after exercise (P<0.05) in both trials and increased further throughout recovery. After 90 and 180 min recovery, S6K1 activity was elevated (~55% and ~110%, respectively, P<0.05) and eEF2 phosphorylation was reduced (~55%, P<0.05) with no difference between trials. In contrast, markers for protein catabolism were differently influenced by the two modes of exercise; ER induced a significant increase in gene and protein expression of MuRF1 (P<0.05), which was not observed following R exercise only. In conclusion, cycling-induced elevation in AMPK activity does not inhibit mTORC1 signaling after subsequent resistance exercise, but may instead interfere with the hypertrophic response by influencing key components in protein breakdown.
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| 3. |
- Bishop, David J, et al.
(författare)
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Sodium bicarbonate ingestion prior to training improves mitochondrial adaptations in rats.
- 2010
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 299:2, s. E225-33
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Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis that reducing hydrogen ion accumulation during training would result in greater improvements in muscle oxidative capacity and time to exhaustion (TTE). Male Wistar rats were randomly assigned to one of three groups (CON, PLA, and BIC). CON served as a sedentary control, whereas PLA ingested water and BIC ingested sodium bicarbonate 30 min prior to every training session. Training consisted of seven to twelve 2-min intervals performed five times/wk for 5 wk. Following training, TTE was significantly greater in BIC (81.2 +/- 24.7 min) compared with PLA (53.5 +/- 30.4 min), and TTE for both groups was greater than CON (6.5 +/- 2.5 min). Fiber respiration was determined in the soleus (SOL) and extensor digitorum longus (EDL), with either pyruvate (Pyr) or palmitoyl carnitine (PC) as substrates. Compared with CON (14.3 +/- 2.6 nmol O(2).min(-1).mg dry wt(-1)), there was a significantly greater SOL-Pyr state 3 respiration in both PLA (19.6 +/- 3.0 nmol O(2).min(-1).mg dry wt(-1)) and BIC (24.4 +/- 2.8 nmol O(2).min(-1).mg dry wt(-1)), with a significantly greater value in BIC. However, state 3 respiration was significantly lower in the EDL from both trained groups compared with CON. These differences remained significant in the SOL, but not the EDL, when respiration was corrected for citrate synthase activity (an indicator of mitochondrial mass). These novel findings suggest that reducing muscle hydrogen ion accumulation during running training is associated with greater improvements in both mitochondrial mass and mitochondrial respiration in the soleus.
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| 4. |
- Blackwood, Sarah J, et al.
(författare)
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Insulin resistance after a 3-day fast is associated with an increased capacity of skeletal muscle to oxidize lipids.
- 2023
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 324:5, s. E390-E401
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Tidskriftsartikel (refereegranskat)abstract
- There is a debate on whether lipid-mediated insulin resistance derives from an increased or decreased capacity of muscle to oxidize fats. Here we examine the involvement of muscle fiber composition in the metabolic responses to a 3-day fast (starvation, which results in increases in plasma lipids and insulin resistance) in two groups of healthy young subjects: 1, area occupied by type I fibers = 61.0 ± 11.8%; 2, type I area = 36.0 ± 4.9% (P<0.001). Muscle biopsies and intravenous glucose tolerance tests were performed after an overnight fast and after starvation. Biopsies were analyzed for muscle fiber composition and mitochondrial respiration. Indices of glucose tolerance and insulin sensitivity were determined. Glucose tolerance was similar in both groups after an overnight fast and deteriorated to a similar degree in both groups after starvation. In contrast, whole-body insulin sensitivity decreased markedly after starvation in group 1 (P<0.01), whereas the decrease in group 2 was substantially smaller (P=0.06). Non-esterified fatty acids and β-hydroxybutyrate levels in plasma after an overnight fast were similar between groups and increased markedly and comparably in both groups after starvation, demonstrating similar degrees of lipid load. The capacity of permeabilized muscle fibers to oxidize lipids was significantly higher in group 1 vs. 2, whereas there was no significant difference in pyruvate oxidation between groups. The data demonstrate that loss of whole-body insulin sensitivity after short-term starvation is a function of muscle fiber composition and is associated with an elevated rather than a diminished capacity of muscle to oxidize lipids.
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| 5. |
- Blackwood, Sarah J, et al.
(författare)
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Role of nitration in control of phosphorylase and glycogenolysis in mouse skeletal muscle.
- 2021
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 320:4, s. E691-E701
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylase is one of the most carefully studied proteins in history, but knowledge of its regulation during intense muscle contraction is incomplete. Tyrosine nitration of purified preparations of skeletal muscle phosphorylase results in inactivation of the enzyme and this is prevented by antioxidants. Whether an altered redox state affects phosphorylase activity and glycogenolysis in contracting muscle is not known. Here, we investigate the role of redox state in control of phosphorylase and glycogenolysis in isolated mouse fast-twitch (extensor digitorum longus, EDL) and slow-twitch (soleus) muscle preparations during repeated contractions. Exposure of crude muscle extracts to H2O2 had little effect on phosphorylase activity. However, exposure of extracts to peroxynitrite (ONOO-), a nitrating/oxidizing agent, resulted in complete inactivation of phosphorylase (half maximal inhibition at ~200 µM ONOO-), which was fully reversed by the presence of an ONOO-scavanger, dithiothreitol (DTT). Incubation of isolated muscles with ONOO- resulted in nitration of phosphorylase and marked inhibition of glycogenolysis during repeated contractions. ONOO- also resulted in large decreases in high-energy phosphates (ATP and phosphocreatine) in the rested state and following repeated contractions. These metabolic changes were associated with decreased force production during repeated contractions (to ~60% of control). In contrast, repeated contractions did not result in nitration of phosphorylase, nor did DTT or the general antioxidant N-acetylcysteine alter glycogenolysis during repeated contractions. These findings demonstrate that ONOO- inhibits phosphorylase and glycogenolysis in living muscle under extreme conditions. However, nitration does not play a significant role in control of phosphorylase and glycogenolysis during repeated contractions.
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| 6. |
- Blomstrand, Eva, et al.
(författare)
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BCAA intake affects protein metabolism in muscle after but not during exercise in humans.
- 2001
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - 0193-1849 .- 1522-1555. ; 281:2, s. E365-74
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Tidskriftsartikel (refereegranskat)abstract
- Branched-chain amino acids (BCAA) or a placebo was given to seven subjects during 1 h of ergometer cycle exercise and a 2-h recovery period. Intake of BCAA did not influence the rate of exchange of the aromatic amino acids, tyrosine and phenylalanine, in the legs during exercise or the increase in their concentration in muscle. The increase was approximately 30% in both conditions. On the other hand, in the recovery period after exercise, a faster decrease in the muscle concentration of aromatic amino acids was found in the BCAA experiment (46% compared with 25% in the placebo condition). There was also a tendency to a smaller release (an average of 32%) of these amino acids from the legs during the 2-h recovery. The results suggest that BCAA have a protein-sparing effect during the recovery after exercise, either that protein synthesis has been stimulated and/or protein degradation has decreased, but the data during exercise are too variable to make any conclusions about the effects during exercise. The effect in the recovery period does not seem to be mediated by insulin.
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| 7. |
- Borgenvik, Marcus, et al.
(författare)
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Intake of branched-chain amino acids influences the levels of MAFbx mRNA and MuRF-1 total protein in resting and exercising human muscle.
- 2012
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 302:5, s. E510-21
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Tidskriftsartikel (refereegranskat)abstract
- Resistance exercise and amino acids are two major factors that influence muscle protein turnover. Here, we examined the effects of resistance exercise and branched-chain amino acids (BCAA), individually and in combination, on the expression of anabolic and catabolic genes in human skeletal muscle. Seven subjects performed two sessions of unilateral leg press exercise with randomized supplementation with BCAA or flavored water. Biopsies were collected from the vastus lateralis muscle of both the resting and exercising legs before and repeatedly after exercise to determine levels of mRNA, protein phosphorylation, and amino acid concentrations. Intake of BCAA reduced (P < 0.05) MAFbx mRNA by 30 and 50% in the resting and exercising legs, respectively. The level of MuRF-1 mRNA was elevated (P < 0.05) in the exercising leg two- and threefold under the placebo and BCAA conditions, respectively, whereas MuRF-1 total protein increased by 20% (P < 0.05) only in the placebo condition. Phosphorylation of p70(S6k) increased to a larger extent (∼2-fold; P < 0.05) in the early recovery period with BCAA supplementation, whereas the expression of genes regulating mTOR activity was not influenced by BCAA. Muscle levels of phenylalanine and tyrosine were reduced (13-17%) throughout recovery (P < 0.05) in the placebo condition and to a greater extent (32-43%; P < 0.05) following BCAA supplementation in both resting and exercising muscle. In conclusion, BCAA ingestion reduced MAFbx mRNA and prevented the exercise-induced increase in MuRF-1 total protein in both resting and exercising leg. Further-more, resistance exercise differently influenced MAFbx and MuRF-1 mRNA expression, suggesting both common and divergent regulation of these two ubiquitin ligases.
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| 8. |
- Eliasson, Jörgen, et al.
(författare)
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Maximal lengthening contractions increase p70 S6 kinase phosphorylation in human skeletal muscle in the absence of nutritional supply.
- 2006
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 291:6, s. 1197-1205
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the training stimuli of eccentric (lengthening) and concentric (shortening) contractions regarding the effect on signaling enzymes involved in protein synthesis. Ten male subjects performed 4 x 6 maximal eccentric contractions on one leg followed by 4 x 6 maximal concentric contractions on the other. Six additional subjects performed the same protocol, but with maximal concentric and submaximal eccentric exercise of equal force to that of the maximal concentric contractions. Muscle biopsy samples were taken from the vastus lateralis before, immediately after, and 1 and 2 h after exercise in both legs. The average peak force produced during the maximal eccentric exercise was 31% higher than during the maximal concentric exercise, 2,490 (+/-100) vs. 1,894 (+/-108) N (P < 0.05). The maximal eccentric contractions led to two- to eightfold increases in the phosphorylation of p70 S6 kinase (p70(S6k)) and the ribosomal protein S6 that persisted for 2 h into recovery but no significant changes in phosphorylation of Akt or mammalian target of rapamycin (mTOR). Maximal concentric and submaximal eccentric contractions did not induce any significant changes in Akt, mTOR, p70(S6k), or S6 phosphorylation up to 2 h after the exercise. The results indicate that one session of maximal eccentric contractions activates p70(S6k) in human muscle via an Akt-independent pathway and suggest that maximal eccentric contractions are more effective than maximal concentric contractions in stimulating protein synthesis in the absence of a nutritional intake, an effect that may be mediated through a combination of greater tension and stretching of the muscle.
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| 9. |
- Fernström, Maria, et al.
(författare)
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The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise
- 2007
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 292:1, s. E223-30
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate fatty acid (FA) oxidation in isolated mitochondrial vesicles (mit) and its relation to training status, fiber type composition, and whole body FA oxidation. Trained (Vo(2 peak) 60.7 +/- 1.6, n = 8) and untrained subjects (39.5 +/- 2.0 ml.min(-1).kg(-1), n = 5) cycled at 40, 80, and 120 W, and whole body relative FA oxidation was assessed from respiratory exchange ratio (RER). Mit were isolated from muscle biopsies, and maximal ADP stimulated respiration was measured with carbohydrate-derived substrate [pyruvate + malate (Pyr)] and FA-derived substrate [palmitoyl-l-carnitine + malate (PC)]. Fiber type composition was determined from analysis of myosin heavy-chain (MHC) composition. The rate of mit oxidation was lower with PC than with Pyr, and the ratio between PC and Pyr oxidation (MFO) varied greatly between subjects (49-93%). MFO was significantly correlated to muscle fiber type distribution, i.e., %MHC I (r = 0.62, P = 0.03), but was not different between trained (62 +/- 5%) and untrained subjects (72 +/- 2%). MFO was correlated to RER during submaximal exercise at 80 (r = -0.62, P = 0.02) and 120 W (r = -0.71, P = 0.007) and interpolated 35% Vo(2 peak) (r = -0.74, P = 0.004). ADP sensitivity of mit respiration was significantly higher with PC than with Pyr. It is concluded that MFO is influenced by fiber type composition but not by training status. The inverse correlation between RER and MFO implies that intrinsic mit characteristics are of importance for whole body FA oxidation during low-intensity exercise. The higher ADP sensitivity with PC than that with Pyr may influence fuel utilization at low rate of respiration.
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| 10. |
- Frank, Per, et al.
(författare)
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Acute exercise reverses starvation-mediated insulin resistance in humans.
- 2013
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 304:4, s. E436-43
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Tidskriftsartikel (refereegranskat)abstract
- Within 2-3 days of starvation, pronounced insulin resistance develops, possibly mediated by increased lipid load. Here, we show that one exercise bout increases mitochondrial fatty acid (FA) oxidation and reverses starvation-induced insulin resistance. Nine healthy subjects underwent 75-h starvation on two occasions: with no exercise (NE) or with one exercise session at the end of the starvation period (EX). Muscle biopsies were analyzed for mitochondrial function, contents of glycogen, and phosphorylation of regulatory proteins. Glucose tolerance and insulin sensitivity, measured with an intravenous glucose tolerance test (IVGTT), were impaired after starvation, but in EX the response was attenuated or abolished. Glycogen stores were reduced, and plasma FA was increased in both conditions, with a more pronounced effect in EX. After starvation, mitochondrial respiration decreased with complex I substrate (NE and EX), but in EX there was an increased respiration with complex I + II substrate. EX altered regulatory proteins associated with increases in glucose disposal (decreased phosphorylation of glycogen synthase), glucose transport (increased phosphorylation of Akt substrate of 160 kDa), and FA oxidation (increased phosphorylation of acetyl-CoA carboxylase). In conclusion, exercise reversed starvation-induced insulin resistance and was accompanied by reduced glycogen stores, increased lipid oxidation capacity, and activation of signaling proteins involved in glucose transport and FA metabolism.
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