TY - JOUR

T1 - Impact of β-adrenergic signaling in PGC-1α-mediated adaptations in mouse skeletal muscle

AU - Brandt, Nina

AU - Nielsen, Lene

AU - Buch, Bjørg Thiellesen

AU - Gudiksen, Anders

AU - Ringholm Jørgensen, Stine

AU - Hellsten, Ylva

AU - Bangsbo, Jens

AU - Pilegaard, Henriette

N1 - CURIS 2018 NEXS 083

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Skeletal muscle

KW - PGC-1α

KW - PGC-1α isoforms

KW - Exercise

KW - Training

KW - Autophagy

KW - β-adrenergic signaling

KW - Clenbuterol

KW - Propranolol

U2 - 10.1152/ajpendo.00082.2017

DO - 10.1152/ajpendo.00082.2017

M3 - Journal article

C2 - 28874356

VL - 314

SP - E1-E20

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 1

ER -