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ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis

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Title: ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis
Author(s): Izawa, T.; Rohatgi, N.; Fukunaga, T.; Wang, QT; Silva, MJ; Gardner, MJ; McDaniel, ML; Abumrad, NA; Semenkovich, CF; Teitelbaum, SL; Zou, W.
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.
Issue Date: 2015-06-16
Publisher: Elsevier Inc.
Citation Info: Izawa, T., Rohatgi, N., Fukunaga, T., Wang, Q. T., Silva, M. J., Gardner, M. J., McDaniel, M. L., Abumrad, N. A., Semenkovich, C. F., Teitelbaum, S. L. and Zou, W. ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis. Cell Reports. 2015. 11(10): 1625-1637. DOI: 10.1016/j.celrep.2015.05.019.
Type: Article
Description: This is the copy of an article published in Cell Reports © 2015 Elsevier Publications.
ISSN: 2211-1247
Sponsor: 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.).
Date Available in INDIGO: 2016-02-17

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