PGC-1alpha mediates exercise-induced skeletal muscle VEGF expression in mice

Area of Science:

• Exercise physiology
• Molecular biology
• Skeletal muscle biology

Background:

• Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and muscle adaptation to exercise.
• The role of PGC-1alpha and AMPK in exercise-induced VEGF expression, particularly in aging muscle, remains incompletely understood.

Purpose of the Study:

• To investigate the necessity of PGC-1alpha for exercise-induced VEGF expression in young and old mice.
• To determine if AMPK activation enhances VEGF expression through a PGC-1alpha-dependent pathway.

Main Methods:

• Utilized whole-body PGC-1alpha knockout (KO) and wild-type (WT) mice.
• Administered exercise training (5 weeks or lifelong), single exercise bouts, and AICAR injections.
• Measured VEGF protein and mRNA expression, and capillary-to-fiber ratio in skeletal muscle.

Main Results:

• PGC-1alpha KO mice exhibited significantly lower basal VEGF protein and capillary-to-fiber ratio compared to WT mice.
• Acute exercise and AICAR treatment increased VEGF mRNA in WT but not in KO mice.
• Exercise training increased VEGF protein in WT mice, an effect absent in KO mice, and prevented age-related decline in WT but not KO mice.
• Repeated AICAR treatment increased VEGF protein in WT but not KO mice.

Conclusions:

• PGC-1alpha is indispensable for exercise-induced upregulation of skeletal muscle VEGF expression.
• PGC-1alpha mediates the prevention of age-associated decline in VEGF protein content due to training.
• Findings suggest an AMPK-mediated regulation of VEGF expression that is dependent on PGC-1alpha.