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Impact of β-adrenergic signaling in PGC-1α-mediated adaptations in mouse skeletal muscle

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PGC-1α has been suggested to regulate exercise training-induced metabolic adaptations and autophagy in skeletal muscle. The factors regulating PGC-1α are however not fully resolved. The aim was to investigate the impact of β-adrenergic signaling in PGC-1α mediated metabolic adaptations in skeletal muscle with exercise training. Muscle was obtained from muscle specific PGC-1α knockout (MKO) mice and LOX/LOX 1) 3h after a single exercise bout with or without prior injection of propranolol or 3h after a single injection of clenbuterol and 2) after 5 weeks of wheel running exercise training with or without propranolol treatment or after 5 weeks of clenbuterol treatment. A single clenbuterol injection and an acute exercise bout increased similarly the mRNA content of both N-Terminal and full-length PGC-1α isoforms and prior propranolol treatment reduced the exercise-induced increase of all isoforms. Furthermore, a single clenbuterol injection elicited a PGC-1α-dependent increase in Cyt c and VEGF mRNA, whereas prolonged clenbuterol treatment increased fiber size but reduced capillary density. Exercise training increased the protein content of OXPHOS, LC3I, and Parkin in a PGC-1α-dependent manner without effect of propranolol, while an exercise training-induced increase in Akt2 and p62 protein required PGC-1α and was blunted by prolonged propranolol treatment. This suggests that β-adrenergic signaling is not required for PGC-1α mediated exercise training-induced adaptations in mitochondrial proteins, but contributes to exercise training mediated adaptations in insulin signaling and autophagy regulation through PGC-1α. Furthermore, changes observed with acute stimulation of compounds like clenbuterol and propranolol may not lead to corresponding adaptations with prolonged treatment.

Original languageEnglish
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume314
Issue number1
Pages (from-to)E1-E20
Number of pages20
ISSN0193-1849
DOIs
Publication statusPublished - 1 Jan 2018

Bibliographical note

CURIS 2018 NEXS 083

    Research areas

  • Skeletal muscle, PGC-1α, PGC-1α isoforms, Exercise, Training, Autophagy, β-adrenergic signaling, Clenbuterol, Propranolol

ID: 183009609