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ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis.


ABSTRACT: ASXL2 is an ETP family protein that interacts with PPAR?. 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?/c-Fos-dependent manner and is required for RANK ligand- and thiazolidinedione-induced bone resorption independent of PGC-1?. ASXL2 also promotes osteoclast mitochondrial biogenesis in a process mediated by PGC-1? but independent of c-Fos. Thus, ASXL2 is a master regulator of skeletal, lipid, and glucose homeostasis.

SUBMITTER: Izawa T 

PROVIDER: S-EPMC4472564 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

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