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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Izawa
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Rohatgi
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fukunaga
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Qun-Tian
authors.initials: QT
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Silva
authors.affiliation: Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gardner
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: McDaniel
authors.affiliation: Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Nada A
authors.initials: NA
authors.lastname: Abumrad
authors.affiliation: Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Clay F
authors.initials: CF
authors.lastname: Semenkovich
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: teitelbs@wustl.edu.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Teitelbaum
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: weizou@wustl.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D044127:Epigenesis, Genetic; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D008050:Lipid A / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C484296:ASXL2 protein, mouse; D008050:Lipid A; D012097:Repressor Proteins; D005947:Glucose