Leptin regulates bone formation via the sympathetic nervous system.
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.
Takeda
Shu
S
Department of Molecular and Human Genetics, One Baylor Plaza, Houston, TX 77030, USA.
Elefteriou
Florent
F
Levasseur
Regis
R
Liu
Xiuyun
X
Zhao
Liping
L
Parker
Keith L
KL
Armstrong
Dawna
D
Ducy
Patricia
P
Karsenty
Gerard
G
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
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