ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis

Takashi Izawa, Nidhi Rohatgi, Tomohiro Fukunaga, Qun Tian Wang, Matthew J. Silva, Michael J. Gardner, Michael L. McDaniel, Nada A. Abumrad, Clay F. Semenkovich, Steven L. Teitelbaum, Wei Zou

Research output: Contribution to journalArticle

19 Citations (Scopus)

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. ASXL2 regulates glucose homeostasis, adipogenesis, and osteoclast differentiation by activating PPARγ. Izawa et al. find that ASXL2-deficient mice are insulin resistant, lipodystrophic, and osteopetrotic. ASXL2 promotes osteoclast formation in a Fos-dependent manner independent of PGC-1β. ASXL2 enhances osteoclast mitochondrial biogenesis in a process mediated by PGC-1β but independent of c-Fos.

Original languageEnglish
Pages (from-to)1625-1637
Number of pages13
JournalCell Reports
Volume11
Issue number10
DOIs
Publication statusPublished - Jun 16 2015
Externally publishedYes

Fingerprint

Osteoclasts
Homeostasis
Lipids
Glucose
Peroxisome Proliferator-Activated Receptors
Bone
Organelle Biogenesis
Insulin
RANK Ligand
Adipogenesis
High Fat Diet
Bone Resorption
Nutrition
Osteogenesis
Bone Density
Minerals
Fats
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Izawa, T., Rohatgi, N., Fukunaga, T., Wang, Q. T., Silva, M. J., Gardner, M. J., ... Zou, W. (2015). ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis. Cell Reports, 11(10), 1625-1637. https://doi.org/10.1016/j.celrep.2015.05.019

ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis. / Izawa, Takashi; Rohatgi, Nidhi; Fukunaga, Tomohiro; Wang, Qun Tian; Silva, Matthew J.; Gardner, Michael J.; McDaniel, Michael L.; Abumrad, Nada A.; Semenkovich, Clay F.; Teitelbaum, Steven L.; Zou, Wei.

In: Cell Reports, Vol. 11, No. 10, 16.06.2015, p. 1625-1637.

Research output: Contribution to journalArticle

Izawa, T, Rohatgi, N, Fukunaga, T, Wang, QT, Silva, MJ, Gardner, MJ, McDaniel, ML, Abumrad, NA, Semenkovich, CF, Teitelbaum, SL & Zou, W 2015, 'ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis', Cell Reports, vol. 11, no. 10, pp. 1625-1637. https://doi.org/10.1016/j.celrep.2015.05.019
Izawa T, Rohatgi N, Fukunaga T, Wang QT, Silva MJ, Gardner MJ et al. ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis. Cell Reports. 2015 Jun 16;11(10):1625-1637. https://doi.org/10.1016/j.celrep.2015.05.019
Izawa, Takashi ; Rohatgi, Nidhi ; Fukunaga, Tomohiro ; Wang, Qun Tian ; Silva, Matthew J. ; Gardner, Michael J. ; McDaniel, Michael L. ; Abumrad, Nada A. ; Semenkovich, Clay F. ; Teitelbaum, Steven L. ; Zou, Wei. / ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis. In: Cell Reports. 2015 ; Vol. 11, No. 10. pp. 1625-1637.
@article{31ee5f3306f04fcb8afc28b5b41c7719,
title = "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. ASXL2 regulates glucose homeostasis, adipogenesis, and osteoclast differentiation by activating PPARγ. Izawa et al. find that ASXL2-deficient mice are insulin resistant, lipodystrophic, and osteopetrotic. ASXL2 promotes osteoclast formation in a Fos-dependent manner independent of PGC-1β. ASXL2 enhances osteoclast mitochondrial biogenesis in a process mediated by PGC-1β but independent of c-Fos.",
author = "Takashi Izawa and Nidhi Rohatgi and Tomohiro Fukunaga and Wang, {Qun Tian} and Silva, {Matthew J.} and Gardner, {Michael J.} and McDaniel, {Michael L.} and Abumrad, {Nada A.} and Semenkovich, {Clay F.} and Teitelbaum, {Steven L.} and Wei Zou",
year = "2015",
month = "6",
day = "16",
doi = "10.1016/j.celrep.2015.05.019",
language = "English",
volume = "11",
pages = "1625--1637",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",

}

TY - JOUR

T1 - ASXL2 Regulates Glucose, Lipid, and Skeletal Homeostasis

AU - Izawa, Takashi

AU - Rohatgi, Nidhi

AU - Fukunaga, Tomohiro

AU - Wang, Qun Tian

AU - Silva, Matthew J.

AU - Gardner, Michael J.

AU - McDaniel, Michael L.

AU - Abumrad, Nada A.

AU - Semenkovich, Clay F.

AU - Teitelbaum, Steven L.

AU - Zou, Wei

PY - 2015/6/16

Y1 - 2015/6/16

N2 - 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. ASXL2 regulates glucose homeostasis, adipogenesis, and osteoclast differentiation by activating PPARγ. Izawa et al. find that ASXL2-deficient mice are insulin resistant, lipodystrophic, and osteopetrotic. ASXL2 promotes osteoclast formation in a Fos-dependent manner independent of PGC-1β. ASXL2 enhances osteoclast mitochondrial biogenesis in a process mediated by PGC-1β but independent of c-Fos.

AB - 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. ASXL2 regulates glucose homeostasis, adipogenesis, and osteoclast differentiation by activating PPARγ. Izawa et al. find that ASXL2-deficient mice are insulin resistant, lipodystrophic, and osteopetrotic. ASXL2 promotes osteoclast formation in a Fos-dependent manner independent of PGC-1β. ASXL2 enhances osteoclast mitochondrial biogenesis in a process mediated by PGC-1β but independent of c-Fos.

UR - http://www.scopus.com/inward/record.url?scp=84937632908&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937632908&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2015.05.019

DO - 10.1016/j.celrep.2015.05.019

M3 - Article

C2 - 26051940

AN - SCOPUS:84937632908

VL - 11

SP - 1625

EP - 1637

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 10

ER -