title: Adiponectin regulates bone mass via opposite central and peripheral mechanisms through FoxO1.
abstract: The synthesis of adiponectin, an adipokine with ill-defined functions in animals fed a normal diet, is enhanced by the osteoblast-derived hormone osteocalcin. Here we show that adiponectin signals back in osteoblasts to hamper their proliferation and favor their apoptosis, altogether decreasing bone mass and circulating osteocalcin levels. Adiponectin fulfills these functions, independently of its known receptors and signaling pathways, by decreasing FoxO1 activity in a PI3-kinase-dependent manner. Over time, however, these local effects are masked because adiponectin signals in neurons of the locus coeruleus, also through FoxO1, to decrease the sympathetic tone, thereby increasing bone mass and decreasing energy expenditure. This study reveals that adiponectin has the unusual ability to regulate the same function in two opposite manners depending on where it acts and that it opposes, partially, leptin's influence on the sympathetic nervous system. It also proposes that adiponectin regulation of bone mass occurs through a PI3-kinase-FoxO1 pathway.
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kajimura
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Ha Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Riley
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Emilio
authors.initials: E
authors.lastname: Arteaga-Solis
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ferron
authors.affiliation: Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Stony Brook University Cancer Center, Stony Brook, NY 11794, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Clarke
authors.affiliation: Stony Brook University Cancer Center, Stony Brook, NY 11794, USA.
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Hannun
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: DePinho
authors.affiliation: Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
authors.forename: X Edward
authors.initials: XE
authors.lastname: Guo
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: gk2172@columbia.edu.
authors.forename: Gerard
authors.initials: G
authors.lastname: Karsenty
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015519:Bone Density / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism; D049109:Cell Proliferation; D004734:Energy Metabolism; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D020738:Leptin; D015675:Osteocalcin; D019869:Phosphatidylinositol 3-Kinases