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NASA NTRS · 20040088007

Leptin regulates bone formation via the sympathetic nervous system

Takeda, Shu·Elefteriou, Florent·Levasseur, Regis·Liu, Xiuyun·Zhao, Liping·Parker, Keith L.·Armstrong, Dawna·Ducy, Patricia·Karsenty, Gerard
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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.

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NASA Discipline Regulatory PhysiologyNon-NASA CenterOsteogenesis/physiologySympathetic Nervous System/metabolism/physiologyLeptin/metabolismMiceReceptor, Melanocortin, Type 4Cells, CulturedAdrenergic beta-Antagonists/pharmacologyMice, Inbred C57BLObesityAnimalsSupport, U.S. Gov't, Non-P.H.SReceptors, Adrenergic, beta/metabolismNeuropeptides/metabolismSupport, Non-U.S. Gov'tSupport, U.S. Gov't, P.H.SOligopeptides/metabolismOsteoblasts/cytology/metabolismReceptors, Corticotropin/metabolismHypothalamus/metabolism/physiology

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Takeda, Shu, Elefteriou, Florent, Levasseur, Regis, Liu, Xiuyun, Zhao, Liping, Parker, Keith L., Armstrong, Dawna, Ducy, Patricia, Karsenty, Gerard. 2002-11-01. Leptin regulates bone formation via the sympathetic nervous system. https://ntrs.nasa.gov/citations/20040088007

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