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ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis.

Abstract：

:ASXL2 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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Izawa T,Rohatgi N,Fukunaga T,Wang QT,Silva MJ,Gardner MJ,McDaniel ML,Abumrad NA,Semenkovich CF,Teitelbaum SL,Zou W

doi

10.1016/j.celrep.2015.05.019

subject

Has Abstract

pub_date

2015-06-16 00:00:00

pages

1625-37

issue

10

issn

2211-1247

pii

S2211-1247(15)00545-8

journal_volume

11

pub_type

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