title: Leptin regulates bone formation via the sympathetic nervous system.
abstract: We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.
authors.affiliation: Department of Molecular and Human Genetics, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Takeda
authors.forename: Florent
authors.initials: F
authors.lastname: Elefteriou
authors.forename: Regis
authors.initials: R
authors.lastname: Levasseur
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Liu
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.forename: Keith L
authors.initials: KL
authors.lastname: Parker
authors.forename: Dawna
authors.initials: D
authors.lastname: Armstrong
authors.forename: Patricia
authors.initials: P
authors.lastname: Ducy
authors.forename: Gerard
authors.initials: G
authors.lastname: Karsenty
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000378:metabolism; D009765:Obesity; D009842:Oligopeptides / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D044105:Receptor, Melanocortin, Type 4; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000378:metabolism; D054411:Receptors, Leptin; D013564:Sympathetic Nervous System / Q000378:metabolism* / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D020738:Leptin; D009479:Neuropeptides; D009842:Oligopeptides; D044105:Receptor, Melanocortin, Type 4; D011943:Receptors, Adrenergic, beta; D018043:Receptors, Corticotropin; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; C023866:pyroglutamyl-histidyl-glycine; D011761:Pyrrolidonecarboxylic Acid