The objective of this study was to evaluate the specific mechanism(s) by which PPARβ regulates mitochondrial content in skeletal muscle. We discovered that PPARβ increases PGC-1α by protecting it from degradation by binding to PGC-1α and limiting ubiquitination. PPARβ also induces an increase in nuclear respiratory factor 1 (NRF-1) expression, resulting in increases in mitochondrial respiratory chain proteins and MEF2A, for which NRF-1 is a transcription factor. There was also an increase in AMP kinase phosphorylation mediated by an NRF-1-induced increase in CAM kinase kinase-β (CaMKKβ). Knockdown of PPARβ resulted in large decreases in the levels of PGC-1α and mitochondrial proteins and a marked attenuation of the exercise-induced increase in mitochondrial biogenesis. In conclusion, PPARβ induces an increase in PGC-1α protein, and PPARβ is a transcription factor for NRF-1. Thus, PPARβ plays essential roles in the maintenance and adaptive increase in mitochondrial enzymes in skeletal muscle by exercise.
Pubmed ID: 28467933 RIS Download
Mesh terms: AMP-Activated Protein Kinases | Animals | Calcium-Calmodulin-Dependent Protein Kinase Kinase | Cell Line | Enzyme Activation | Gene Knockdown Techniques | HEK293 Cells | Humans | Male | Mice, Inbred C57BL | Mitochondria, Muscle | Nuclear Respiratory Factor 1 | PPAR-beta | Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha | Physical Conditioning, Animal | Proteolysis | Rats, Wistar | Transcriptional Activation | Ubiquitination | Up-Regulation
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