First Author | Izawa T | Year | 2015 |
Journal | Cell Rep | Volume | 11 |
Issue | 10 | Pages | 1625-37 |
PubMed ID | 26051940 | Mgi Jnum | J:228702 |
Mgi Id | MGI:5708478 | Doi | 10.1016/j.celrep.2015.05.019 |
Citation | Izawa T, et al. (2015) ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis. Cell Rep 11(10):1625-37 |
abstractText | ASXL2 is an ETP family protein that interacts with PPARgamma. We find that ASXL2-/- mice are insulin resistant, lipodystrophic, and fail to respond to a high-fat diet. Consistent with genetic variation at the ASXL2 locus and human bone mineral density, ASXL2-/- mice are also severely osteopetrotic because of failed osteoclast differentiation attended by normal bone formation. ASXL2 regulates the osteoclast via two distinct signaling pathways. It induces osteoclast formation in a PPARgamma/c-Fos-dependent manner and is required for RANK ligand- and thiazolidinedione-induced bone resorption independent of PGC-1beta. ASXL2 also promotes osteoclast mitochondrial biogenesis in a process mediated by PGC-1beta but independent of c-Fos. Thus, ASXL2 is a master regulator of skeletal, lipid, and glucose homeostasis. |