Effects of endurance exercise on mitochondrial efficiency, uncoupling and lipid oxidation in human skeletal muscle

During the lest years the importance of muscle mitochondria, and mitochondrial function, not only for performance but else 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/0 ratio), mitochondrial fat oxidation, noncoupled 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, end in the study on mitochondrial lipid oxidation III, 9 healthy trained and 9 healthy untrained men participated. In study IV mitochondrial function end reactive oxygen species (ROS) production was studied in 9 elite athletes after extreme exercise, 24 hours of cycling, running end peddling.

Endurance training increased whole body oxygen uptake (V02 peck) by 24% and muscle citrate synthase (CS) activity (marker of mitochondrial volume) by 47% (P< 0.05), but non-coupled respiration end UCP3 adjusted for mitochondrial volume were reduced (P< 0.05). One session of exercise did not cif f ect noncoupled 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/0 ratio) decreased. P/0 ratio remained reduced else 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 ultraendurance 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 compered 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 end untrained men. In these studies UCP3 end non-coupled respiration follow the same pattern but are not correlated. Further studies ore needed to understand the complex role of UCP3 in skeletal muscle metabolism.

List of scientific papers

I. Fernstrom M, Tonkonogi M, Sahlin K. (2004). Effects of acute and chronic endurance exercise on mitochondrial uncoupling in human skeletal muscle. J Physiol. 554(Pt 3): 755-63.
https://pubmed.ncbi.nlm.nih.gov/14634202

II. Mogensen M, Bagger M, Pedersen PK, Fernstrom M, Sahlin K. (2006). Cycling efficiency in humans is related to low UCP3 content and to type I fibres but not to mitochondrial efficiency. J Physiol. 571(Pt 3): 669-81.
https://pubmed.ncbi.nlm.nih.gov/16423857

III. Sahlin K, Mogensen M, Bagger M, Fernstrom M, Pedersen PK. (2006). The potential for mitochondrial fat oxidation in human skeletal muscle influences whole body fat oxidation during low-intensity exercise. Am J Physiol Endocrinol Metab. [Accepted]
https://pubmed.ncbi.nlm.nih.gov/16926382

IV. Fernström M, Bakkman L, Tonkonogi M, Shabalina IG, Rozhdestvenskaya Z, Mattsson CM, Enqvist JK, Ekblom B, Sahlin K. (2006). Reduced efficiency, but increased fat oxidation in mitochondria from human skeletal muscle after 24 hours ultra-endurance exercise. [Manuscript]