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The effect of different exercise regimens on mitochondrial biogenesis and performance
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Research group for Mitokondriell funktion och metabolisk kontroll. Karolinska institutet, Inst för fysiologi och farmakologi / Dept of Physiology and Pharmacology .ORCID iD: 0000-0003-1848-5491
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Endurance training is a powerful tool to improve both health and performance. Physical activity is now recognized as an effective treatment and prevention therapy for a wide range of diseases. One of the most profound adaptations to endurance training is increased mitochondrial function and content within the exercising muscles. Mitochondrial quality and quantity are closely related to several of the positive health effects reported after training. High mitochondrial content strongly correlates with muscle oxidative capacity and endurance performance. Even though it is well known that endurance training increases mitochondrial content, it is unclear which type of training is the most efficient to promote mitochondrial biogenesis. Therefore, the basis for current exercise recommendations relative to mitochondrial biogenesis is poor or absent. Thus, the main objective of this thesis was to evaluate the effect of different training strategies on mitochondrial biogenesis.

Recent developments in molecular methods have made it possible to study the initial adaptations to training through measurement of mRNA gene expression of exercise induced genes. One such gene is transcriptional coactivator peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α). PGC-1α is a key regulator of mitochondrial biogenesis and the expression of PGC-1α can therefore be used as a marker of this process.

The first four studies presented in this thesis are acute exercise studies where two different exercise models were compared using a cross-over design. Muscle biopsies were obtained pre and post exercise and analysed for gene expression and glycogen, apart from study II. The final study was a long-term training study where muscle biopsies were obtained before and after the training period and analysed for mitochondrial enzyme activities and protein content.

Study I: The expression of PGC-1α and related genes were examined after 90 min of continuous and interval exercise in untrained subjects. The exercise protocols influenced the expression of genes involved in mitochondrial biogenesis and oxidative metabolism in a similar manner. Both interval and continuous exercise were potent training strategies for relatively sedentary individuals.

Study II: The expression of PGC-1α and related genes were examined after low-volume sprint interval (SIT) and high-volume interval (IE) exercise in highly trained cyclists. SIT induced a similar increase in PGC-1α expression as IE despite a much lower time commitment and work completed. Sprint interval exercise might, therefore, be a time efficient training strategy for highly trained individuals.

Study III: The expression of PGC-1α and related genes, as well as the activity of upstream proteins, were examined after concurrent (ER: cycling + leg press) and single-mode (E: cycling only) exercise in untrained subjects. PGC-1α expression doubled after ER compared with E. It was concluded that concurrent training might be beneficial for mitochondrial biogenesis in untrained individuals.

Study IV: The expression of PGC-1α and related genes were examined after exercise performed with low (LG) and normal (NG) muscle glycogen in well-trained cyclists. PGC-1α expression increased approximately three times more after LG compared with NG. This finding suggested that low glycogen exercise is a potent inducer of mitochondrial biogenesis in well-trained individuals.

Study V: Mitochondrial enzyme activity, protein content and endurance performance were examined after eight weeks of concurrent (ES: cycling + leg press) or single-mode (E: cycling only) training in cyclists. ES did not affect enzyme activity, protein content or endurance performance differently than E. The beneficial effect previously observed in untrained subjects did not translate to higher numbers of mitochondria in trained individuals.

In three of the studies, I, III, and IV, both glycogen and PGC-1α expression were measured after exercise. These data were then pooled and examined. The highest PGC-1α mRNA expression levels were identified when glycogen levels were low, and vice versa. This suggests that low glycogen might play an important role in the regulation of mitochondrial biogenesis also during interval and concurrent strength and endurance exercise.

In conclusion, key markers of mitochondrial biogenesis can be effectively up-regulated by interval, concurrent and low glycogen exercise. A possible explanation for this might be that though the exercise protocols are quite divergent in nature, they all have a pronounced effect on muscle glycogen and/or perturbation in energetic stress.

Place, publisher, year, edition, pages
Karolinska insitutet , 2014.
National Category
Physiology
Research subject
Medicine/Technology
Identifiers
URN: urn:nbn:se:gih:diva-3579ISBN: 978-91-7549-774-7 (print)OAI: oai:DiVA.org:gih-3579DiVA: diva2:766681
Public defence
2014-12-19, Aulan, GIH, Lidingövägen 1, Stockholm, 09:00 (English)
Opponent
Supervisors
Available from: 2014-11-28 Created: 2014-11-28 Last updated: 2016-12-05Bibliographically approved
List of papers
1. Similar expression of oxidative genes after interval and continuous exercise.
Open this publication in new window or tab >>Similar expression of oxidative genes after interval and continuous exercise.
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2009 (English)In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 41, no 12, 2136-44 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: There is a debate whether interval or traditional endurance training is the most effective stimulus of mitochondrial biogenesis. Here, we compared the effects of acute interval exercise (IE) or continuous exercise (CE) on the muscle messenger RNA (mRNA) content for several genes involved in mitochondrial biogenesis and lipid metabolism. METHODS: Nine sedentary subjects cycled for 90 min with two protocols: CE (at 67% VO2max) and IE (12 s at 120% and 18 s at 20% of VO2max). The duration of exercise and work performed with CE and IE was identical. Muscle biopsies were taken before and 3 h after exercise. RESULTS: There were no significant differences between the two exercise protocols in the increases in VO2 and HR, the reduction in muscle glycogen (35%-40% with both protocols) or the changes in blood metabolites (lactate, glucose, and fatty acids). The mRNA content for major regulators of mitochondrial biogenesis [peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha (PGC-1alpha), PGC-1-related coactivator, PPARbeta/delta] and of lipid metabolism [pyruvate dehydrogenase kinase isozyme 4 (PDK4)] increased after exercise, but there was no significant difference between IE and CE. However, the mRNA content for several downstream targets of PGC-1alpha increased significantly only after CE, and mRNA content for nuclear respiratory factor 2 was significantly higher after CE (P < 0.025 vs IE). CONCLUSIONS: The present findings demonstrate that, when the duration of exercise and work performed is the same, IE and CE influence the transcription of genes involved in oxidative metabolism in a similar manner.

National Category
Physiology
Identifiers
urn:nbn:se:gih:diva-1583 (URN)10.1249/MSS.0b013e3181abc1ec (DOI)19915506 (PubMedID)
Available from: 2010-12-06 Created: 2010-12-06 Last updated: 2016-12-05Bibliographically approved
2. Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise.
Open this publication in new window or tab >>Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise.
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2010 (English)In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 110, no 3, 597-606 p.Article in journal (Refereed) Published
Abstract [en]

Little is known about the effect of training on genetic markers for mitochondrial biogenesis in elite athletes. We tested the hypothesis that low-volume sprint interval exercise (SIE) would be as effective as high-volume interval exercise (IE). Ten male cyclists competing on national elite level (W (max) 403 ± 13 W, VO(2peak) 68 ± 1 mL kg(-1) min(-1)) performed two interval exercise protocols: 7 × 30-s "all-out" bouts (SIE) and 3 × 20-min bouts at ~87% of VO(2peak) (IE). During IE, the work was eightfold larger (1,095 ± 43 vs. 135 ± 5 kJ) and the exercise duration 17 times longer (60 vs. 3.5 min) than during SIE. Muscle samples were taken before and 3 h after exercise. The mRNA of upstream markers of mitochondrial biogenesis [peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1α), PGC-1α-related coactivator (PRC) and peroxisome proliferator-activated receptor δ (PPARδ)] increased to the same extent after SIE and IE (6-, 1.5- and 1.5-fold increase, respectively). Of the downstream targets of PGC-1α, mitochondrial transcription factor A (Tfam) increased only after SIE and was significantly different from that after IE (P < 0.05), whereas others increased to the same extent (pyruvate dehydrogenase kinase, PDK4) or was unchanged (nuclear respiratory factor 2, NRF2). We conclude that upstream genetic markers of mitochondrial biogenesis increase in a similar way in elite athletes after one exercise session of SIE and IE. However, since the volume and duration of work was considerably lower during SIE and since Tfam, the downstream target of PGC-1α, increased only after SIE, we conclude that SIE might be a time-efficient training strategy for highly trained individuals.

National Category
Physiology
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-1590 (URN)10.1007/s00421-010-1544-1 (DOI)20571821 (PubMedID)
Available from: 2010-12-06 Created: 2010-12-06 Last updated: 2016-12-05Bibliographically approved
3. Resistance exercise enhances the molecular signaling of mitochondrial biogenesis induced by endurance exercise in human skeletal muscle.
Open this publication in new window or tab >>Resistance exercise enhances the molecular signaling of mitochondrial biogenesis induced by endurance exercise in human skeletal muscle.
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2011 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 111, no 5, 1335-1344 p.Article in journal (Refereed) Published
Abstract [en]

Combining endurance and strength training (concurrent training) may change the adaptation compared with single mode training. However, the site of interaction and the mechanisms are unclear. We have investigated the hypothesis that molecular signaling of mitochondrial biogenesis after endurance exercise is impaired by resistance exercise. Ten healthy subjects performed either only endurance exercise (E: 1h cycling at ~65% of VO(2max)) or endurance exercise followed by resistance exercise (ER: 1h cycling + 6 sets of leg press at 70-80% of 1 repetition maximum) in a randomized cross-over design. Muscle biopsies were obtained before and after exercise (1 and 3h Post cycling). The mRNA of genes related to mitochondrial biogenesis (PGC-1α, PRC) and substrate regulation (PDK4) increased after both E and ER, but the mRNA levels were about 2-fold higher after ER (P<0.01). Phosphorylation of proteins involved in the signaling cascade of protein synthesis (mTOR, S6K1 and eEF2) was altered after ER but not after E. Moreover, ER induced a larger increase in mRNA of genes associated with positive mTOR signaling (cMyc and Rheb). Phosphorylation of AMPK, ACC and Akt increased similarly at 1h Post (P<0.01) after both types of exercise. Contrary to our hypothesis, the results demonstrate that resistance exercise, performed after endurance exercise, amplifies the adaptive signaling response of mitochondrial biogenesis compared with single-mode endurance exercise. The mechanism may relate to a crosstalk between signaling pathways mediated by mTOR. The results suggest that concurrent training may be beneficial for the adaptation of muscle oxidative capacity.

Keyword
PGC, AMPK, endurance, exercise, resistance, mTOR
National Category
Medical and Health Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-1930 (URN)10.1152/japplphysiol.00086.2011 (DOI)21836044 (PubMedID)
Available from: 2011-10-19 Created: 2011-10-19 Last updated: 2016-12-05Bibliographically approved
4. Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle.
Open this publication in new window or tab >>Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle.
2013 (English)In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 113, no 4, 951-963 p.Article in journal (Refereed) Published
Abstract [en]

Recent studies suggest that carbohydrate restriction can improve the training-induced adaptation of muscle oxidative capacity. However, the importance of low muscle glycogen on the molecular signaling of mitochondrial biogenesis remains unclear. Here, we compare the effects of exercise with low (LG) and normal (NG) glycogen on different molecular factors involved in the regulation of mitochondrial biogenesis. Ten highly trained cyclists (VO(2max) 65 ± 1 ml/kg/min, W (max) 387 ± 8 W) exercised for 60 min at approximately 64 % VO(2max) with either low [166 ± 21 mmol/kg dry weight (dw)] or normal (478 ± 33 mmol/kg dw) muscle glycogen levels achieved by prior exercise/diet intervention. Muscle biopsies were taken before, and 3 h after, exercise. The mRNA of peroxisome proliferator-activated receptor-γ coactivator-1 was enhanced to a greater extent when exercise was performed with low compared with normal glycogen levels (8.1-fold vs. 2.5-fold increase). Cytochrome c oxidase subunit I and pyruvate dehydrogenase kinase isozyme 4 mRNA were increased after LG (1.3- and 114-fold increase, respectively), but not after NG. Phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases and acetyl-CoA carboxylase was not changed 3 h post-exercise. Mitochondrial reactive oxygen species production and glutathione oxidative status tended to be reduced 3 h post-exercise. We conclude that exercise with low glycogen levels amplifies the expression of the major genetic marker for mitochondrial biogenesis in highly trained cyclists. The results suggest that low glycogen exercise may be beneficial for improving muscle oxidative capacity.

National Category
Medical and Health Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-2481 (URN)10.1007/s00421-012-2504-8 (DOI)23053125 (PubMedID)
Available from: 2012-11-19 Created: 2012-11-19 Last updated: 2016-12-05Bibliographically approved
5. Adding strength to endurance training does not enhance aerobic capacity in cyclists
Open this publication in new window or tab >>Adding strength to endurance training does not enhance aerobic capacity in cyclists
2015 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 25, no 4, e353-e359 p.Article in journal (Refereed) Published
Abstract [en]

The molecular signaling of mitochondrial biogenesis is enhanced when resistance exercise is added to a bout of endurance exercise. The purpose of the present study was to examine if this mode of concurrent training translates into increased mitochondrial content and improved endurance performance. Moderately trained cyclists performed 8 weeks (two sessions per week) of endurance training only (E, n = 10; 60-min cycling) or endurance training followed by strength training (ES, n = 9; 60-min cycling + leg press). Muscle biopsies were obtained before and after the training period and analyzed for enzyme activities and protein content. Only the ES group increased in leg strength (+19%, P < 0.01), sprint peak power (+5%, P < 0.05), and short-term endurance (+9%, P < 0.01). In contrast, only the E group increased in muscle citrate synthase activity (+11%, P = 0.06), lactate threshold intensity (+3%, P < 0.05), and long-term endurance performance (+4%, P < 0.05). Content of mitochondrial proteins and cycling economy was not affected by training. Contrary to our hypothesis, the results demonstrate that concurrent training does not enhance muscle aerobic capacity and endurance performance in cyclists.

National Category
Physiology
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-3500 (URN)10.1111/sms.12338 (DOI)25438613 (PubMedID)
Note

At the time of Per Frank's and Niklas Psilander's dissertations the article was accepted for publication.

Available from: 2014-10-16 Created: 2014-10-16 Last updated: 2016-12-05Bibliographically approved

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