Objective: 

Exercise increases the metabolic capacity of skeletal muscle. At the level of transcription, many genes are regulated by peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC-1) of transcriptional activator, through their interaction with myocyte enhancer factor 2 (MEF2). However, the molecular mechanisms involved remain elusive. The role of AMPKa2 in regulating the endurance exercise induced nuclear PGC-1a protein expression and nuclear PGC-1a association with MEF2 was investigated.

Methods: 

This was investigated in muscles from AMPKa2 over-expression (OE;n=20), AMPKa2 knockout (KO; n=20) and corresponding wild-type (WT;n=20)) mice that had undertaken a program of treadmill training at the speed of 12m/min with a slope of 0 at the speed of 12m/min with a slope of 0, 60min/day for 28 days. The nuclear PGC-1a protein expression was measured by western blot and nuclear PGC-1a association with MEF2 by CoIP.

Results: 

After four weeks of endurance training, the nuclear PGC-1a content and PGC-1a associated with MEF2 in OE, KO and WT mice were significantly higher than their control groups respectively, however, OE AMPKa2 isoform heightened the training-induced increase in nuclear PGC-1a content and PGC-1a associated with MEF2 compared with WT mice, while the training-induced increases of nuclear PGC-1a content and PGC-1a associated with MEF2 were normal in a2-KO muscles compared with WT mice despite the reduced AMPK signaling.

Conclusion: Exercise training can activate nuclear PGC-1a protein expression and increase PGC-1a/MEF2 association. And then AMPK activity during exercise is required, though not indispensable, for expression of PGC-1a protein and PGC-1a/MEF2 association.