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Effects of endurance exercise on mitochondrial efficiency, uncoupling and lipid oxidation in human skeletal muscle
Swedish School of Sport and Health Sciences, GIH.
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During the last years the importance of muscle mitochondria, and mitochondrial function, not only for performance but also for health has been highlighted. The main function of the mitochondria is to produce ATP by oxidative phosphorylation (coupled respiration). In skeletal muscle a substantial part of the energy is lost in non-coupled reactions, it has been estimated that non-coupled respiration accounts for as much as 20-25% of the total energy expenditure. It is now almost 10 years since the discovery of uncoupling protein 3 (UCP3), but the functional role of UCP3 in non-coupled respiration is not completely understood. The aim of this thesis was to investigate mitochondrial efficiency (P/O ratio), mitochondrial fat oxidation, non-coupled respiration (state 4) and protein expression of UCP3 in response to exercise and training in human skeletal muscle.

In study I eight healthy subjects endurance trained for 6 weeks and 9 subjects performed one exercise session (75 min). In the cycling efficiency study II, and in the study on mitochondrial lipid oxidation III, 9 healthy trained and 9 healthy untrained men participated. In study IV mitochondrial function and reactive oxygen species (ROS) production was studied in 9 elite athletes after extreme exercise, 24 hours of cycling, running and paddling.

Endurance training increased whole body oxygen uptake (VO2 peak) by 24% and muscle citrate synthase (CS) activity (marker of mitochondrial volume) by 47% (P< 0.05), but non-coupled respiration and UCP3 adjusted for mitochondrial volume were reduced (P< 0.05). One session of exercise did not affect non-coupled respiration or UCP3.

Cycling efficiency (expressed as work efficiency) was inversely related to protein expression of UCP3 (r= 0.57) and correlated to type 1 fibers (r= 0.58). Work efficiency was not influenced by training status or correlated to mitochondrial efficiency. UCP3 was 52% higher in the untrained men (P< 0.05). Mitochondrial capacity for fat oxidation was not influenced by training status, but related to fiber type composition. The hypothesis that mitochondrial fat oxidation is related to whole body lipid oxidation during low-intensity exercise was confirmed (r= 0.62).

Mitochondrial capacity for fat oxidation increased after 24 hours of exercise, whereas mitochondrial efficiency (P/O ratio) decreased. P/O ratio remained reduced also after 28 hours of recovery. Formation of ROS by isolated mitochondria increased after exercise. Non-coupled respiration (state 4), however, decreased and UCP3 tended to be reduced after recovery from ultra-endurance exercise (P= 0.07).

In conclusion: UCP3 does not follow exercise induced mitochondrial biogenesis. UCP3 is reduced by endurance training and lower in trained men compared with untrained men. Non-coupled respiration, measured in isolated mitochondria was reduced by endurance training and reduced after recovery from ultra-endurance exercise, but similar in trained and untrained men. In these studies UCP3 and non-coupled respiration follow the same pattern but are not correlated. Further studies are needed to understand the complex role of UCP3 in skeletal muscle metabolism.

Place, publisher, year, edition, pages
Department of Physiology and Pharmacology, Karolinska Institutet , 2006.
Identifiers
URN: urn:nbn:se:gih:diva-13ISBN: 91-7357-059-1 (print)OAI: oai:DiVA.org:gih-13DiVA: diva2:1824
Public defence
2007-01-19, Aulan, GIH, 09:00 (English)
Opponent
Supervisors
Available from: 2007-01-25 Created: 2007-01-25 Last updated: 2011-05-05
List of papers
1. The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise
Open this publication in new window or tab >>The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise
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2007 (English)In: American journal of physiology. Endocrinology and metabolism, ISSN 0193-1849, Vol. 292, no 1, E223-30 p.Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:gih:diva-456 (URN)10.1152/ajpendo.00266.2006 (DOI)16926382 (PubMedID)
Available from: 2007-01-25 Created: 2009-03-03 Last updated: 2011-05-06Bibliographically approved
2. Reduced efficiency, but increased fat oxidation, in mitochondria from human skeletal muscle after 24-h ultraendurance exercise.
Open this publication in new window or tab >>Reduced efficiency, but increased fat oxidation, in mitochondria from human skeletal muscle after 24-h ultraendurance exercise.
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2007 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 102, no 5, 1844-1849 p.Article in journal (Refereed) Published
Abstract [en]

The hypothesis that ultraendurance exercise influences muscle mitochondrial function has been investigated. Athletes in ultraendurance performance performed running, kayaking, and cycling at 60% of their peak O(2) consumption for 24 h. Muscle biopsies were taken preexercise (Pre-Ex), postexercise (Post-Ex), and after 28 h of recovery (Rec). Respiration was analyzed in isolated mitochondria during state 3 (coupled to ATP synthesis) and state 4 (noncoupled respiration), with fatty acids alone [palmitoyl carnitine (PC)] or together with pyruvate (Pyr). Electron transport chain activity was measured with NADH in permeabilized mitochondria. State 3 respiration with PC increased Post-Ex by 39 and 41% (P < 0.05) when related to mitochondrial protein and to electron transport chain activity, respectively. State 3 respiration with Pyr was not changed (P > 0.05). State 4 respiration with PC increased Post-Ex but was lower than Pre-Ex at Rec (P < 0.05 vs. Pre-Ex). Mitochondrial efficiency [amount of added ADP divided by oxygen consumed during state 3 (P/O ratio)] decreased Post-Ex by 9 and 6% (P < 0.05) with PC and PC + Pyr, respectively. P/O ratio remained reduced at Rec. Muscle uncoupling protein 3, measured with Western blotting, was not changed Post-Ex but tended to decrease at Rec (P = 0.07 vs. Pre-Ex). In conclusion, extreme endurance exercise decreases mitochondrial efficiency. This will increase oxygen demand and may partly explain the observed elevation in whole body oxygen consumption during standardized exercise (+13%). The increased mitochondrial capacity for PC oxidation indicates plasticity in substrate oxidation at the mitochondrial level, which may be of advantage during prolonged exercise.

National Category
Physiology
Identifiers
urn:nbn:se:gih:diva-838 (URN)10.1152/japplphysiol.01173.2006 (DOI)17234801 (PubMedID)
Projects
Physiology of Adventure Racing
Available from: 2010-06-17 Created: 2009-02-25 Last updated: 2017-08-18Bibliographically approved
3. Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle.
Open this publication in new window or tab >>Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle.
2004 (English)In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 554, 755-763 p.Article in journal (Refereed) Published
Abstract [en]

Mitochondrial proteins such as uncoupling protein 3 (UCP3) and adenine nucleotide translocase (ANT) may mediate back-leakage of protons and serve as uncouplers of oxidative phosphorylation. We hypothesized that UCP3 and ANT increase after prolonged exercise and/or endurance training, resulting in increased uncoupled respiration (UCR). Subjects were investigated with muscle biopsies before and after acute exercise (75 min of cycling at 70% of .VO2peak) or 6 weeks endurance training. Mitochondria were isolated and respiration measured in the absence (UCR or state 4) and presence of ADP (coupled respiration or state 3). Protein expression of UCP3 and ANT was measured with Western blotting. After endurance training, .VO2peak, citrate synthase activity (CS), state 3 respiration and ANT increased by 24, 47, 40 and 95%, respectively (all P < 0.05), whereas UCP3 remained unchanged. When expressed per unit of CS (a marker of mitochondrial volume) UCP3 and UCR decreased by 54% and 18%(P < 0.05). CS increased by 43% after acute exercise and remained elevated after 3 h of recovery (P < 0.05), whereas the other muscle parameters remained unchanged. An intriguing finding was that acute exercise reversibly enhanced the capacity of mitochondria to accumulate Ca2+(P < 0.05) before opening of permeability transition pores. In conclusion, UCP3 protein and UCR decrease after endurance training when related to mitochondrial volume. These changes may prevent excessive basal thermogenesis. Acute exercise enhances mitochondrial resistance to Ca2+ overload but does not influence UCR or protein expression of UCP3 and ANT. The increased Ca2+ resistance may prevent mitochondrial degradation and the mechanism needs to be further explored.

National Category
Physiology
Identifiers
urn:nbn:se:gih:diva-196 (URN)
Note
The definitive version is available at www.blackwell-synergy.comAvailable from: 2007-05-08 Created: 2007-05-08 Last updated: 2011-05-06
4. Cycling efficiency in humans is related to low UCP3 content and to type I fibres but not to mitochondrial efficiency
Open this publication in new window or tab >>Cycling efficiency in humans is related to low UCP3 content and to type I fibres but not to mitochondrial efficiency
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2006 (English)In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 571, no 3, 669-681 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to investigate the hypothesis that cycling efficiency in vivo is related to mitochondrial efficiency measured in vitro and to investigate the effect of training status on these parameters. Nine endurance trained and nine untrained male subjects ( , respectively) completed an incremental submaximal efficiency test for determination of cycling efficiency (gross efficiency, work efficiency (WE) and delta efficiency). Muscle biopsies were taken from m. vastus lateralis and analysed for mitochondrial respiration, mitochondrial efficiency (MEff; i.e. P/O ratio), UCP3 protein content and fibre type composition (% MHC I). MEff was determined in isolated mitochondria during maximal (state 3) and submaximal (constant rate of ADP infusion) rates of respiration with pyruvate. The rates of mitochondrial respiration and oxidative phosphorylation per muscle mass were about 40% higher in trained subjects but were not different when expressed per unit citrate synthase (CS) activity (a marker of mitochondrial density). Training status had no influence on WE (trained 28.0 +/- 0.5, untrained 27.7 +/- 0.8%, N.S.). Muscle UCP3 was 52% higher in untrained subjects, when expressed per muscle mass (P < 0.05 versus trained). WE was inversely correlated to UCP3 (r=-0.57, P < 0.05) and positively correlated to percentage MHC I (r= 0.58, P < 0.05). MEff was lower (P < 0.05) at submaximal respiration rates (2.39 +/- 0.01 at 50% ) than at state 3 (2.48 +/- 0.01) but was neither influenced by training status nor correlated to cycling efficiency. In conclusion cycling efficiency was not influenced by training status and not correlated to MEff, but was related to type I fibres and inversely related to UCP3. The inverse correlation between WE and UCP3 indicates that extrinsic factors may influence UCP3 activity and thus MEff in vivo.

National Category
Dentistry
Identifiers
urn:nbn:se:gih:diva-197 (URN)
Note
The definitive version is available at www.blackwell-synergy.comAvailable from: 2007-05-08 Created: 2007-05-08 Last updated: 2011-05-06

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