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

Affiliations

¹Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030

²Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390

³Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030

⁴Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030

⁵Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030

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. β-adrenergic receptors on osteoblasts regulate their proliferation, and a β-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a β-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.

Links

DOI: 10.1016/S0092-8674(02)01049-8

PubMed: 12419242

WoS: 000179010100004

History

Received: 2002-04-30

Revised: 2002-11-1

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