Abstract
The aim of the present PhD thesis was to examine the role of exercise intensity and β-adrenergic signalling in PGC-1α mediated exercise training-induced adaptations in skeletal muscle. To investigate this, the following three hypotheses were addressed: 1) Exercise-induced PGC-1α mRNA responses and intracellular signalling in human skeletal muscle depend on adrenaline levels or metabolic stress. 2) PGC-1α mediated exercise and exercise training-induced adaptive metabolic responses in mouse skeletal muscle depend on exercise intensity. 3) β-adrenergic signalling contributes to exercise training-induced metabolic adaptations in mouse skeletal muscle through PGC-1α .
Paper I demonstrated that di erences in plasma adrenaline and muscle metabolic stress during exercise do not reinforce exercise-induced PGC-1 α mRNA response in human skeletal muscle. In addition, di erences in exercise-induced AMPK and p38 signaling were not associated with di erences in the PGC-1α mRNA responses in human muscle.
Paper II demonstrated intensity dependent increases in LC3I and LC3II protein in mouse skeletal muscle late in recovery from acute exercise and increased LC3II protein with exercise training independent of exercise intensity and volume in WT mice, and this ocurred without changes in OXPHOS and Cyt c protein content. Furthermore, acute exercise and exercise training did not increase LC3I and LC3II protein in PGC-1 α KO. In addition, exercise-induced mRNA responses of PGC-1α isoforms were intensity dependent.
Paper III demonstrated that -adrenergic signaling is required but not sucient for exercise training-induced adaptations in skeletal muscle AKT2 protein, and not involved in exercise training adaptations in oxidative and autophagy markers, although acute β2-adrenergic stimulation may induce responses.
In conclusion, β2-adrenergic signaling mediates exercise-induced PGC-1α mRNA responses with most potent stimulation of the alternative promoter of the PGC-1α gene in mouse skeletal muscle but, neither elevated plasma adrenaline nor metabolic stress augment exercise-induced PGC-1α mRNA response in human skeletal muscle. While β2-adrenergic signaling increases mRNAs of metabolic related proteins in a PGC-1α dependent manner, prolonged 2-adrenergic stimulation may reduce skeletal muscle metabolic capacity when PGC-1α is lacking in skeletal muscles. Whereas β2-adrenergic signaling is not required for exercise training-induced improvements in skeletal muscle metabolic capacity, but may contribute to the exercise training-induced maintenance of skeletal muscle mass. In addition, the results indicate an exercise intensity dependent regulation of autophagy in skeletal muscle and suggest that PGC-1 α regulates both acute and exercise training-induced autophagy in skeletal muscle potentially in a PGC-1 α isoform speci c manner.
Paper I demonstrated that di erences in plasma adrenaline and muscle metabolic stress during exercise do not reinforce exercise-induced PGC-1 α mRNA response in human skeletal muscle. In addition, di erences in exercise-induced AMPK and p38 signaling were not associated with di erences in the PGC-1α mRNA responses in human muscle.
Paper II demonstrated intensity dependent increases in LC3I and LC3II protein in mouse skeletal muscle late in recovery from acute exercise and increased LC3II protein with exercise training independent of exercise intensity and volume in WT mice, and this ocurred without changes in OXPHOS and Cyt c protein content. Furthermore, acute exercise and exercise training did not increase LC3I and LC3II protein in PGC-1 α KO. In addition, exercise-induced mRNA responses of PGC-1α isoforms were intensity dependent.
Paper III demonstrated that -adrenergic signaling is required but not sucient for exercise training-induced adaptations in skeletal muscle AKT2 protein, and not involved in exercise training adaptations in oxidative and autophagy markers, although acute β2-adrenergic stimulation may induce responses.
In conclusion, β2-adrenergic signaling mediates exercise-induced PGC-1α mRNA responses with most potent stimulation of the alternative promoter of the PGC-1α gene in mouse skeletal muscle but, neither elevated plasma adrenaline nor metabolic stress augment exercise-induced PGC-1α mRNA response in human skeletal muscle. While β2-adrenergic signaling increases mRNAs of metabolic related proteins in a PGC-1α dependent manner, prolonged 2-adrenergic stimulation may reduce skeletal muscle metabolic capacity when PGC-1α is lacking in skeletal muscles. Whereas β2-adrenergic signaling is not required for exercise training-induced improvements in skeletal muscle metabolic capacity, but may contribute to the exercise training-induced maintenance of skeletal muscle mass. In addition, the results indicate an exercise intensity dependent regulation of autophagy in skeletal muscle and suggest that PGC-1 α regulates both acute and exercise training-induced autophagy in skeletal muscle potentially in a PGC-1 α isoform speci c manner.
| Originalsprog | Engelsk |
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| Forlag | Department of Biology, Faculty of Science, University of Copenhagen |
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| Status | Udgivet - 2017 |