| First Author | Wei W | Year | 2016 |
| Journal | Cell Metab | Volume | 23 |
| Issue | 3 | Pages | 479-91 |
| PubMed ID | 26777690 | Mgi Jnum | J:232856 |
| Mgi Id | MGI:5780350 | Doi | 10.1016/j.cmet.2015.12.010 |
| Citation | Wei W, et al. (2016) Ligand Activation of ERRalpha by Cholesterol Mediates Statin and Bisphosphonate Effects. Cell Metab 23(3):479-91 |
| abstractText | Nuclear receptors (NRs) are key regulators of gene expression and physiology. Nearly half of all human NRs lack endogenous ligands including estrogen-related receptor alpha (ERRalpha). ERRalpha has important roles in cancer, metabolism, and skeletal homeostasis. Affinity chromatography of tissue lipidomes with the ERRalpha ligand-binding domain (LBD) and subsequent transcriptional assays identified cholesterol as an endogenous ERRalpha agonist. Perturbation of cholesterol biosynthesis or inhibition of ERRalpha revealed the interdependence of cholesterol and ERRalpha. In bone, the effects of cholesterol, statin, and bisphosphonate on osteoclastogenesis require ERRalpha; and consequently, cholesterol-induced bone loss or bisphosphonate osteoprotection is lost in ERRalpha knockout mice. Furthermore, statin induction of muscle toxicity and cholesterol suppression of macrophage cytokine secretion are impaired by loss or inhibition of ERRalpha. These findings reveal a key step in ERRalpha regulation and explain the actions of two highly prescribed drugs, statins and bisphosphonates. |
