ASXL2 Regulates Glucose.pdf (3.91 MB)
Download fileASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis
journal contribution
posted on 17.02.2016, 00:00 by T. Izawa, N. Rohatgi, T. Fukunaga, QT Wang, MJ Silva, MJ Gardner, ML McDaniel, NA Abumrad, CF Semenkovich, SL Teitelbaum, W. ZouASXL2 is an ETP family protein that interacts with PPARγ. 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 PPARγ/c-Fos-dependent manner and is required for RANK ligand- and thiazolidinedione-induced bone resorption independent of PGC-1β. ASXL2 also promotes osteoclast mitochondrial biogenesis in a process mediated by PGC-1β but independent of c-Fos. Thus, ASXL2 is a master regulator of skeletal, lipid, and glucose homeostasis.