Exercise Training-Induced PPARβ Increases PGC-1α Protein Stability and Improves Insulin-Induced Glucose Uptake in Rodent Muscles

This study aimed to investigate the long-term effects of training intervention and resting on protein expression and stability of peroxisome proliferator-activated receptor beta/delta (PPAR beta), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha), glucose transporter type 4 (GLUT4), and mitochondrial proteins, and determine whether glucose homeostasis can be regulated through stable expression of these proteins after training. Rats swam daily for 3, 6, 9, 14, or 28 days, and then allowed to rest for 5 days post-training. Protein and mRNA levels were measured in the skeletal muscles of these rats. PPAR beta was overexpressed and knocked down in myotubes in the skeletal muscle to investigate the effects of swimming training on various signaling cascades of PGC-1 alpha transcription, insulin signaling, and glucose uptake. Exercise training (Ext) upregulated PPAR beta, PGC-1 alpha, GLUT4, and mitochondrial enzymes, including NADH-ubiquinone oxidoreductase (NUO), cytochrome c oxidase subunit I (COX1), citrate synthase (CS), and cytochrome c (Cyto C) in a time-dependent manner and promoted the protein stability of PPAR beta, PGC-1 alpha, GLUT4, NUO, CS, and Cyto C, such that they were significantly upregulated 5 days after training cessation. PPAR beta overexpression increased the PGC-1 alpha protein levels post-translation and improved insulin-induced signaling responsiveness and glucose uptake. The present results indicate that Ext promotes the protein stability of key mitochondria enzymes GLUT4, PGC-1 alpha, and PPAR beta even after Ext cessation.