Jun, 2015
ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis
CELL REPORTS
- Volume
- 11
- Number
- 10
- First page
- 1625
- Last page
- 1637
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1016/j.celrep.2015.05.019
- Publisher
- CELL PRESS
ASXL2 is an ETP family protein that interacts with PPAR gamma. 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 PPAR gamma/c-Fos-dependent manner and is required for RANK ligand-and thiazolidinedione-induced bone resorption independent of PGC-1 beta. ASXL2 also promotes osteoclast mitochondrial biogenesis in a process mediated by PGC-1 beta but independent of c-Fos. Thus, ASXL2 is a master regulator of skeletal, lipid, and glucose homeostasis.
- Link information
- ID information
-
- DOI : 10.1016/j.celrep.2015.05.019
- ISSN : 2211-1247
- Pubmed ID : 26051940
- Web of Science ID : WOS:000356372100013