ASXL2 Regulates Glucose.pdf (3.91 MB)
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ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis

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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. Zou
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.


This work was supported by NIH grants DK076729, DK56341, and DK20579 (to C.F.S.); 5R01AR050211 (to M.J.S.); 5R01AR03278828, 5R01AR05703705, and 5R37AR04652315 (to S.L.T.); P30AR057235 and P30DK056341 and Shriners Hospitals for Children grant 85400-STL (to S.L.T.).


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This is the copy of an article published in Cell Reports © 2015 Elsevier Publications.


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