Essential role of the PGC-1α/PPARβ axis in Ucp3 gene induction.
Tanes Iamamura de LimaDimitrius Santiago Passos Simões Fróes GuimarãesCarlos H SpontonMarcio Chaim BajgelmanSoledad PalametaJessica M ToscaroOsvaldo ReisLeonardo Reis SilveiraPublished in: The Journal of physiology (2019)
Uncoupling protein 3 (UCP3) has an essential role in fatty acid metabolism and mitochondrial redox regulation in skeletal muscle. However, the molecular mechanisms involved in the expression of Ucp3 are poorly known. In the present study, we show that the peroxisome proliferator-activated receptor (PPAR)γ coactivator 1-α (PGC-1α)/PPARβ axis is a crucial mediator of Ucp3 expression in skeletal muscle cells. In silico analysis of the UCP3 promoter and quantitative chromatin immunoprecipitation experiments revealed that the induction of the UCP3 transcript is mediated by the transactivation of a distal PPAR response element at the Ucp3 gene promoter by the coactivator PGC-1α. This mechanism is activated during myogenesis and during metabolic stress induced by fatty acids independent of PGC-1α protein levels. We also provide evidence that Ucp3 is essential for PGC-1α-induced oxidative capacity. Taken together, our results highlight PGC-1ɑ/PPARβ as an essential component of the molecular regulation of Ucp3 gene in skeletal muscle cells.
Keyphrases
- skeletal muscle
- insulin resistance
- fatty acid
- induced apoptosis
- genome wide
- dna methylation
- poor prognosis
- transcription factor
- binding protein
- gene expression
- copy number
- cell cycle arrest
- oxidative stress
- genome wide identification
- dna damage
- high resolution
- signaling pathway
- type diabetes
- endoplasmic reticulum stress
- cell death
- small molecule
- endothelial cells
- high glucose