Abstract：
:Nuclear receptors (NRs) are key regulators of gene expression and physiology. Nearly half of all human NRs lack endogenous ligands including estrogen-related receptor α (ERRα). ERRα has important roles in cancer, metabolism, and skeletal homeostasis. Affinity chromatography of tissue lipidomes with the ERRα ligand-binding domain (LBD) and subsequent transcriptional assays identified cholesterol as an endogenous ERRα agonist. Perturbation of cholesterol biosynthesis or inhibition of ERRα revealed the interdependence of cholesterol and ERRα. In bone, the effects of cholesterol, statin, and bisphosphonate on osteoclastogenesis require ERRα; and consequently, cholesterol-induced bone loss or bisphosphonate osteoprotection is lost in ERRα knockout mice. Furthermore, statin induction of muscle toxicity and cholesterol suppression of macrophage cytokine secretion are impaired by loss or inhibition of ERRα. These findings reveal a key step in ERRα regulation and explain the actions of two highly prescribed drugs, statins and bisphosphonates.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Wei W,Schwaid AG,Wang X,Wang X,Chen S,Chu Q,Saghatelian A,Wan Ydoi
10.1016/j.cmet.2015.12.010subject
Has Abstractpub_date
2016-03-08 00:00:00pages
479-91issue
3eissn
1550-4131issn
1932-7420pii
S1550-4131(15)00625-7journal_volume
23pub_type
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