PGC1α is a key transcriptional coregulator of oxidative metabolism and thermogenesis. Through a high-throughput chemical screen, we found that molecules antagonizing the TRPVs (transient receptor potential vanilloid), a family of ion channels, induced PGC1α expression in adipocytes. In particular, TRPV4 negatively regulated the expression of PGC1α, UCP1, and cellular respiration. Additionally, ...

Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a transcriptional coactivator able to up-regulate mitochondrial biogenesis, respiratory capacity, oxidative phosphorylation, and fatty acid β-oxidation with the final aim of providing a more efficient pathway for aerobic energy production. In the continuously renewed intestinal epithelium, proliferative cells in the crypts ...

Expression of the brown adipocyte-specific gene, uncoupling protein 1 (UCP1), is increased by both PPARγ stimulation and cAMP activation through their ability to stimulate the expression of the PPAR coactivator PGC1α. In HIB1B brown preadipocytes, combination of the PPARγ agonist, rosiglitazone, and the cAMP stimulator forskolin synergistically increased UCP1 mRNA expression, but PGC1α expressi...

Skeletal muscle function largely depend on intact energy metabolism, stress response, and antioxidant defense mechanisms. In this study, we tested the effect of a combined supplementation of α-lipoic acid (LA) plus coenzyme Q10 (Q10) on PPARγ-coactivator α (PGC1α) activity, expression of glutathione-related phase II enzymes and glutathione (GSH) levels in cultured C2C12 myotubes. Supplementatio...

Fibronectin type III domain-containing protein 5 (FNDC5) expression is controlled by the transcriptional co-activator, peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α). FNDC5 expression has been shown to be increased in muscle in response to endurance exercise in some but not all studies, therefore a greater understanding of the mechanisms controlling this process a...

Pregnane X receptor (PXR) mRNA was detected in HepG2 cells by RT-PCR, but not in human fetal liver (HFL) cells. CYP3A4 was induced by rifampicin (RIF), mifepristone (RU486), clotrimazole (CTZ), and dexamethasone (DEX) in HepG2 cells, while these PXR ligands with the exception of DEX did not induce CYP3A4 mRNA expression in HFL cells. Ad-PXR infection increased mRNA levels of PXR and CYP3A4 in b...

Epithelial ovarian carcinoma (EOC), the major cause of gynaecological cancer death, is a heterogeneous disease classified into five subtypes. Each subtype has distinct clinical characteristics and is associated with different genetic risk factors and molecular events, but all are treated with surgery and platinum/taxane regimes. Tumour progression and chemoresistance is generally associated wit...

Metabolic heterogeneity is a key factor in cancer pathogenesis. We found that a subset of BRAF- and NRAS-mutant human melanomas resistant to the MEK inhibitor selumetinib displayed increased oxidative phosphorylation (OxPhos) mediated by the transcriptional coactivator PGC1α. Notably, all selumetinib-resistant cells with elevated OxPhos could be resensitized by cotreatment with the mTORC1/2 inh...