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Jonsson, W. O., Ponette, J., Horwath, O., Rydenstam, T., Söderlund, K., Ekblom, B., . . . Blomstrand, E. (2022). Changes in plasma concentration of kynurenine following intake of branched-chain amino acids are not caused by alterations in muscle kynurenine metabolism.. American Journal of Physiology - Cell Physiology, 322, C49-C62
Öppna denna publikation i ny flik eller fönster >>Changes in plasma concentration of kynurenine following intake of branched-chain amino acids are not caused by alterations in muscle kynurenine metabolism.
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2022 (Engelska)Ingår i: American Journal of Physiology - Cell Physiology, ISSN 0363-6143, E-ISSN 1522-1563, Vol. 322, s. C49-C62Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Administration of branched-chain amino acids (BCAA) has been suggested to enhance mitochondrial biogenesis, including levels of PGC-1α, which may, in turn, alter kynurenine metabolism. Ten healthy subjects performed 60 min of dynamic one-leg exercise at ~70% of Wmax on two occasions. They were in random order supplied either a mixture of BCAA or flavored water (placebo) during the experiment. Blood samples were collected during exercise and recovery, and muscle biopsies were taken from both legs before, after and 90 and 180 min following exercise. Ingestion of BCAA doubled their concentration in both plasma and muscle while causing a 30-40% reduction (P<0.05 vs. placebo) in levels of aromatic amino acids in both resting and exercising muscle during 3-h recovery. The muscle concentration of kynurenine decreased by 25% (P<0.05) during recovery, similar in both resting and exercising leg and with both supplements, although plasma concentration of kynurenine during recovery was 10% lower (P<0.05) when BCAA were ingested. Ingestion of BCAA reduced the plasma concentration of kynurenic acid by 60% (P<0.01) during exercise and recovery, while the level remained unchanged with placebo. Exercise induced a 3-4-fold increase (P<0.05) in muscle content of PGC-1a1 mRNA after 90 min of recovery under both conditions, whereas levels of KAT4 mRNA and protein were unaffected by exercise or supplement. In conclusion, the reduction of plasma levels of kynurenine and kynurenic acid caused by BCAA were not associated with any changes in the level of muscle kynurenine, suggesting that kynurenine metabolism was altered in tissues other than muscle.

Ort, förlag, år, upplaga, sidor
American Physiological Society, 2022
Nyckelord
PGC-1α, kynurenic acid, muscle, tryptophan
Nationell ämneskategori
Fysiologi
Forskningsämne
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-6862 (URN)10.1152/ajpcell.00285.2021 (DOI)000744029900005 ()34817270 (PubMedID)
Forskningsfinansiär
Centrum för IdrottsforskningNovo Nordisk
Tillgänglig från: 2021-12-02 Skapad: 2021-12-02 Senast uppdaterad: 2022-02-23Bibliografiskt granskad
Valente-Silva, P., Cervenka, I., Ferreira, D. M., Correia, J. C., Edman, S., Horwath, O., . . . Ruas, J. L. (2021). Effects of Tryptophan Supplementation and Exercise on the Fate of Kynurenine Metabolites in Mice and Humans.. Metabolites, 11(8), Article ID 508.
Öppna denna publikation i ny flik eller fönster >>Effects of Tryptophan Supplementation and Exercise on the Fate of Kynurenine Metabolites in Mice and Humans.
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2021 (Engelska)Ingår i: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 11, nr 8, artikel-id 508Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The kynurenine pathway of tryptophan (TRP) degradation (KP) generates metabolites with effects on metabolism, immunity, and mental health. Endurance exercise training can change KP metabolites by changing the levels of KP enzymes in skeletal muscle. This leads to a metabolite pattern that favors energy expenditure and an anti-inflammatory immune cell profile and reduces neurotoxic metabolites. Here, we aimed to understand if TRP supplementation in untrained vs. trained subjects affects KP metabolite levels and biological effects. Our data show that chronic TRP supplementation in mice increases all KP metabolites in circulation, and that exercise reduces the neurotoxic branch of the pathway. However, in addition to increasing wheel running, we did not observe other effects of TRP supplementation on training adaptations, energy metabolism or behavior in mice. A similar increase in KP metabolites was seen in trained vs. untrained human volunteers that took a TRP drink while performing a bout of aerobic exercise. With this acute TRP administration, TRP and KYN were higher in the trained vs. the untrained group. Considering the many biological effects of the KP, which can lead to beneficial or deleterious effects to health, our data encourage future studies of the crosstalk between TRP supplementation and physical exercise.

Nyckelord
behavior, dietary supplements, energy metabolism, exercise, kynurenine metabolites, skeletal muscle, tryptophan
Nationell ämneskategori
Idrottsvetenskap
Forskningsämne
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-6782 (URN)10.3390/metabo11080508 (DOI)000690525000001 ()34436450 (PubMedID)
Tillgänglig från: 2021-08-30 Skapad: 2021-08-30 Senast uppdaterad: 2021-10-06
Moberg, M., Apro, W., Cervenka, I., Ekblom, B., van Hall, G., Holmberg, H.-C., . . . Blomstrand, E. (2021). High-intensity leg cycling alters the molecular response to resistance exercise in the arm muscles.. Scientific Reports, 11(1), Article ID 6453.
Öppna denna publikation i ny flik eller fönster >>High-intensity leg cycling alters the molecular response to resistance exercise in the arm muscles.
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2021 (Engelska)Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 6453Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

This study examined acute molecular responses to concurrent exercise involving different muscles. Eight men participated in a randomized crossover-trial with two sessions, one where they performed interval cycling followed by upper body resistance exercise (ER-Arm), and one with upper body resistance exercise only (R-Arm). Biopsies were taken from the triceps prior to and immediately, 90- and 180-min following exercise. Immediately after resistance exercise, the elevation in S6K1 activity was smaller and the 4E-BP1:eIF4E interaction greater in ER-Arm, but this acute attenuation disappeared during recovery. The protein synthetic rate in triceps was greater following exercise than at rest, with no difference between trials. The level of PGC-1α1 mRNA increased to greater extent in ER-Arm than R-Arm after 90 min of recovery, as was PGC-1α4 mRNA after both 90 and 180 min. Levels of MuRF-1 mRNA was unchanged in R-Arm, but elevated during recovery in ER-Arm, whereas MAFbx mRNA levels increased slightly in both trials. RNA sequencing in a subgroup of subjects revealed 862 differently expressed genes with ER-Arm versus R-Arm during recovery. These findings suggest that leg cycling prior to arm resistance exercise causes systemic changes that potentiate induction of specific genes in the triceps, without compromising the anabolic response.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2021
Nyckelord
Metabolism, Proteins
Nationell ämneskategori
Idrottsvetenskap
Forskningsämne
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-6624 (URN)10.1038/s41598-021-85733-1 (DOI)000632047400024 ()33742064 (PubMedID)
Tillgänglig från: 2021-03-31 Skapad: 2021-03-31 Senast uppdaterad: 2022-09-15
Hammarström, D., Øfsteng, S., Koll, L., Hanestadhaugen, M., Hollan, I., Apro, W., . . . Ellefsen, S. (2020). Benefits of higher resistance-training volume are related to ribosome biogenesis.. Journal of Physiology, 598(3), 543-565
Öppna denna publikation i ny flik eller fönster >>Benefits of higher resistance-training volume are related to ribosome biogenesis.
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2020 (Engelska)Ingår i: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 598, nr 3, s. 543-565Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

KEY POINTS: For individuals showing suboptimal adaptations to resistance training, manipulation of training volume is a potential measure to facilitate responses. This remains unexplored. Here, 34 untrained individuals performed contralateral resistance training with moderate and low volume for 12 weeks. Moderate volume led to larger increases in muscle cross-sectional area, strength and type II fibre-type transitions. These changes coincided with greater activation of signalling pathways controlling muscle growth and greater induction of ribosome synthesis. Thirteen and sixteen participants, respectively, displayed clear benefits of moderate-volume training on muscle hypertrophy and strength. This coincided with greater total RNA accumulation in the early-phase of the training period, suggesting that ribosomal biogenesis regulates the dose-response relationship between training volume and muscle hypertrophy. These results demonstrate that there is a dose-dependent relationship between training volume and outcomes. On the individual level, benefits of higher training volume were associated with increased ribosomal biogenesis.

ABSTRACT: Resistance-exercise volume is a determinant of training outcomes. However not all individuals respond in a dose-dependent fashion. In this study, 34 healthy individuals (males n = 16, 23.6 (4.1) years; females n = 18, 22.0 (1.3)) performed moderate- (3 sets per exercise, MOD) and low-volume (1 set, LOW) resistance training in a contralateral fashion for 12 weeks (2-3 sessions × week-1 ). Muscle cross-sectional area (CSA) and strength were assessed at weeks 0 and 12, along with biopsy sampling (m. Vastus lateralis). Muscle biopsies were also sampled before and one hour after the fifth session (Week 2). MOD resulted in larger increases in muscle CSA (5.2 (3.8)% versus 3.7 (3.7)%, P < 0.001) and strength (3.4-7.7% difference, all P < 0.05. This coincided with greater reductions in type IIX fibres from week 0 to 12 (MOD, -4.6; LOW -3.2%-point), greater phosphorylation of S6-kinase 1 (p85 S6K1Thr412 , 19%; p70 S6K1Thr389 , 58%) and ribosomal protein S6Ser235/236 (37%), greater rested-state total RNA (8.8%) and greater exercise-induced c-Myc mRNA expression (25%; Week 2, all P < 0.05). Thirteen and sixteen participants, respectively, displayed clear benefits in response to MOD on muscle hypertrophy and strength. Benefits were associated with greater accumulation of total RNA at Week 2 in the MOD leg, with every 1% difference increasing the odds of MOD benefit by 7.0% (P = 0.005) and 9.8% (P = 0.002). In conclusion, MOD led to greater functional and biological adaptations than LOW. Associations between dose-dependent total RNA accumulation and increases in muscle mass and strength points to ribosome biogenesis as a determinant of dose-dependent training responses. This article is protected by copyright. All rights reserved.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2020
Nationell ämneskategori
Fysiologi
Forskningsämne
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-5958 (URN)10.1113/JP278455 (DOI)31813190 (PubMedID)
Tillgänglig från: 2019-12-18 Skapad: 2019-12-18 Senast uppdaterad: 2021-05-17Bibliografiskt granskad
Holm, L., Dideriksen, K., Nielsen, R. H., Doessing, S., Bechshoeft, R. L., Højfeldt, G., . . . van Hall, G. (2019). An exploration of the methods to determine the protein-specific synthesis and breakdown rates in vivo in humans.. Physiological Reports, 7(17), Article ID e14143.
Öppna denna publikation i ny flik eller fönster >>An exploration of the methods to determine the protein-specific synthesis and breakdown rates in vivo in humans.
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2019 (Engelska)Ingår i: Physiological Reports, E-ISSN 2051-817X, Vol. 7, nr 17, artikel-id e14143Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The present study explores the methods to determine human in vivo protein-specific myofibrillar and collagenous connective tissue protein fractional synthesis and breakdown rates. We found that in human myofibrillar proteins, the protein-bound tracer disappearance method to determine the protein fractional breakdown rate (FBR) (via 2 H2 O ingestion, endogenous labeling of 2 H-alanine that is incorporated into proteins, and FBR quantified by its disappearance from these proteins) has a comparable intrasubject reproducibility (range: 0.09-53.5%) as the established direct-essential amino acid, here L-ring-13 C6 -phenylalanine, incorporation method to determine the muscle protein fractional synthesis rate (FSR) (range: 2.8-56.2%). Further, the determination of the protein breakdown in a protein structure with complex post-translational processing and maturation, exemplified by human tendon tissue, was not achieved in this experimentation, but more investigation is encouraged to reveal the possibility. Finally, we found that muscle protein FBR measured with an essential amino acid tracer prelabeling is inappropriate presumably because of significant and prolonged intracellular recycling, which also may become a significant limitation for determination of the myofibrillar FSR when repeated infusion trials are completed in the same participants.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2019
Nyckelord
Amino acid recycling, deuterated alanine, deuterated water, fractional breakdown rate, fractional synthesis rate, protein turnover, stable isotope
Nationell ämneskategori
Fysiologi
Forskningsämne
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-5840 (URN)10.14814/phy2.14143 (DOI)000485983500012 ()31496135 (PubMedID)
Tillgänglig från: 2019-09-17 Skapad: 2019-09-17 Senast uppdaterad: 2019-10-11
Blomstrand, E. & Schantz, P. (2019). Berit Sjöberg: 1939-2018. Stockholm
Öppna denna publikation i ny flik eller fönster >>Berit Sjöberg: 1939-2018
2019 (Svenska)Övrigt (Övrig (populärvetenskap, debatt, mm))
Ort, förlag, år, sidor
Stockholm: , 2019. s. 1
Nyckelord
muskelfysiologi, muskelbiokemi, muskelfibrer, träning, Fysiologiska institutionen, Kungl. Gymnastiska Centralinstitutet, Gymnastik- och idrottshögskolan, Karolinska Institutet, Bengt Saltin, Stig Strand, Ingemar Stenmark
Nationell ämneskategori
Medicin och hälsovetenskap
Forskningsämne
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-5681 (URN)
Tillgänglig från: 2019-03-27 Skapad: 2019-03-27 Senast uppdaterad: 2020-01-13Bibliografiskt granskad
Edman, S., Horwath, O. & Blomstrand, E. (2019). Intake of branched-chain amino acids in combination with endurance exercise – no effect on mRNA expression of proteins regulating mitochondrial biogenesis. In: : . Paper presented at European College of Sport Science ECSS 2019, Prague 3-6 July.
Öppna denna publikation i ny flik eller fönster >>Intake of branched-chain amino acids in combination with endurance exercise – no effect on mRNA expression of proteins regulating mitochondrial biogenesis
2019 (Engelska)Konferensbidrag, Poster (med eller utan abstract) (Övrigt vetenskapligt)
Nationell ämneskategori
Fysiologi
Forskningsämne
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-5944 (URN)
Konferens
European College of Sport Science ECSS 2019, Prague 3-6 July
Forskningsfinansiär
Centrum för Idrottsforskning
Tillgänglig från: 2019-12-04 Skapad: 2019-12-04 Senast uppdaterad: 2021-10-06Bibliografiskt granskad
Edman, S., Söderlund, K., Moberg, M., Apro, W. & Blomstrand, E. (2019). mTORC1 Signaling in Individual Human Muscle Fibers Following Resistance Exercise in Combination With Intake of Essential Amino Acids. Frontiers in Nutrition, 6, Article ID 96.
Öppna denna publikation i ny flik eller fönster >>mTORC1 Signaling in Individual Human Muscle Fibers Following Resistance Exercise in Combination With Intake of Essential Amino Acids
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2019 (Engelska)Ingår i: Frontiers in Nutrition, E-ISSN 2296-861X, Vol. 6, artikel-id 96Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Human muscles contain a mixture of type I and type II fibers with different contractile and metabolic properties. Little is presently known about the effect of anabolic stimuli, in particular nutrition, on the molecular responses of these different fiber types. Here, we examine the effect of resistance exercise in combination with intake of essential amino acids (EAA) on mTORC1 signaling in individual type I and type II human muscle fibers. Five strength-trained men performed two sessions of heavy leg press exercise. During exercise and recovery, the subjects ingested an aqueous solution of EAA (290 mg/kg) or flavored water (placebo). Muscle biopsies were taken from the vastus lateralis before and 90 min after exercise. The biopsies were freeze-dried and single fibers dissected out and weighed (range 0.95-8.1 mu g). The fibers were homogenized individually and identified as type I or II by incubation with antibodies against the different isoforms of myosin. They were also analyzed for both the levels of protein as well as phosphorylation of proteins in the mTORC1 pathway using Western blotting. The levels of the S6K1 and eEF2 proteins were similar to 50% higher in type II than in type I fibers (P < 0.05), but no difference was found between fiber types with respect to the level of mTOR protein. Resistance exercise led to non-significant increases (2-3-fold) in mTOR and S6K1 phosphorylation as well as a 50% decrease (P < 0.05) in eEF2 phosphorylation in both fiber types. Intake of EAA caused a 2 and 6-fold higher (P < 0.05) elevation of mTOR and S6K1 phosphorylation, respectively, in both type I and type II fibers compared to placebo, with no effect on phosphorylation of eEF2. In conclusion, protein levels of S6K1 and eEF2 were significantly higher in type II than type I fibers suggesting higher capacity of the mTOR pathway in type II fibers. Ingestion of EAA enhanced the effect of resistance exercise on phosphorylation of mTOR and S6K1 in both fiber types, but with considerable variation between single fibers of both types.

Ort, förlag, år, upplaga, sidor
Frontiers Media S.A., 2019
Nyckelord
muscle fiber type, protein expression, S6K1, single muscle fiber, EAA
Nationell ämneskategori
Fysiologi
Forskningsämne
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-5807 (URN)10.3389/fnut.2019.00096 (DOI)000472610200002 ()31294029 (PubMedID)
Tillgänglig från: 2019-08-14 Skapad: 2019-08-14 Senast uppdaterad: 2022-11-18
Edman, S., Söderlund, K. & Blomstrand, E. (2018). Anabolic signalling in individual muscle fibres following resistance exercise in combination with amino acid intake: PO-260. In: Exercise Biochemistry Review: Vol 1 No 5 (2018): Proceedings of IBEC 2018, Beijing, China (PO-201 -> PO-308). Paper presented at 17th International Biochemistry of Exercise Conference (IBEC), October 23-25 2018, Beijing, China.
Öppna denna publikation i ny flik eller fönster >>Anabolic signalling in individual muscle fibres following resistance exercise in combination with amino acid intake: PO-260
2018 (Engelska)Ingår i: Exercise Biochemistry Review: Vol 1 No 5 (2018): Proceedings of IBEC 2018, Beijing, China (PO-201 -> PO-308), 2018Konferensbidrag (Övrigt vetenskapligt)
Abstract [en]

Objective Human muscle consists of a mixture of fibres with different contractile and metabolic properties, type I (slow-twitch) and type II (fast-twitch) fibres. Little is known about the effect of anabolic stimuli, in particular nutrition, on the molecular response in the different fibre types. Here, we examine the effect of resistance exercise and essential amino acid (EAA) supplementation on mTOR signalling in individual type I and type II human muscle fibres.

Methods Five strength-trained male subjects performed two sessions of leg press exercise (10 x 10 repetition at 62-85 % of 1RM). During exercise and recovery, the subjects ingested an aqueous solution with EAA (290 mg/kg) or flavoured water (placebo). Muscle biopsies were taken from the vastus lateralis before and 90 min after exercise. The biopsies were freeze-dried and single fibres dissected out and weighed (range 0.9 – 8 ug). The fibres were individually homogenized and analysed for proteins in the mTOR pathway using Western blot. Membranes were repeatedly stripped and fibres were identified as type I or type II following incubation with antibodies against the different myosin isoforms.

Results Exercise led to a significant increase in mTOR and p70S6k1 phosphorylation and a fall in eEF2 phosphorylation, similar in both fibre types. There was a large variation between individual fibres; some fibres were highly activated whereas others were not activated at all despite the heavy exercise performed. Intake of EAA caused a 2- to 6-fold higher increase in mTOR and p70S6k1 phosphorylation in both type I and type II fibres as compared to intake of placebo, with no difference between the fibre types. The phosphorylation of eEF2 was not affected by intake of EAA. The total expression of p70S6k1 and eEF2 was 145% and 155% higher in type II than in type I fibres (P<0.05), respectively, whereas no difference between the fibre types was observed for mTOR protein.

Conclusions The response to heavy resistance exercise regarding mTOR signalling was similar in type I and type II fibres in trained subjects, but with a large variation between single fibres of both types. Furthermore, ingestion of EAA enhanced the effect of resistance exercise on phosphorylation of mTOR and p70S6k1 in both fibre types.

Nationell ämneskategori
Idrottsvetenskap
Forskningsämne
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-5476 (URN)10.14428/ebr.v1i5.11083 (DOI)
Konferens
17th International Biochemistry of Exercise Conference (IBEC), October 23-25 2018, Beijing, China
Tillgänglig från: 2018-11-19 Skapad: 2018-11-19 Senast uppdaterad: 2018-11-27Bibliografiskt granskad
Blomstrand, E. & Apro, W. (2018). Det viktigaste du behöver veta om protein och träning. Idrottsforskning.se, Article ID 30 maj.
Öppna denna publikation i ny flik eller fönster >>Det viktigaste du behöver veta om protein och träning
2018 (Svenska)Ingår i: Idrottsforskning.se, ISSN 2002-3944, artikel-id 30 majArtikel i tidskrift (Övrig (populärvetenskap, debatt, mm)) Published
Ort, förlag, år, upplaga, sidor
Stockholm: Centrum för idrottsforskning, CIF, 2018
Nationell ämneskategori
Idrottsvetenskap
Forskningsämne
Medicin/Teknik
Identifikatorer
urn:nbn:se:gih:diva-5443 (URN)
Tillgänglig från: 2018-10-16 Skapad: 2018-10-16 Senast uppdaterad: 2018-10-17Bibliografiskt granskad
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0002-6537-042X

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