Fig. 4.

The PPAR, PGC1α, AMPK signaling network in exercise-induced metabolic changes and exercise-induced cardioprotection. Exercise triggers an increase in NO production, Ca²⁺-Calmodulin kinase interaction, and AMPK activation, leading to PGC1α upregulation and activation in cardiac muscle cells. The PGC1α may form transcriptional regulatory complex with PPARα and RXR, or coactivate other transcriptional partners such as NRF-1/2 and ERR, to promote downstream transcription of genes involved in fatty acid oxidation and mitochondrial biogenesis/energy metabolism, respectively. Exercise-induced AMPK may modulate glucose uptake, glycolysis and glucose oxidation, and may modulate fatty acid utilization including fatty acid uptake, translocation to mitochondrial, and fatty acid oxidation as well. PPARα peroxisome proliferator-activated receptor α, PGC1α peroxisome proliferator-activated receptor-alpha coactivator 1α, AMPK adenosine monophosphate-activated protein kinase, CAM calmodulin, NO nitric oxide, RXR retinoid X receptor, NRF1/2 nuclear respiratory factor-1 and 2, ERRα estrogen-related receptor α, FAO fatty acid oxidation, FATP1 fatty acid transport protein 1, CPTI carnitine palmitoyltransferase I, MCAD medium-chain acyl-CoA dehydrogenase, Tfam nuclear-encoded mitochondrial transcription factor A, PFK2 6-phosphofructo-2-kinase