Cited by 1,735Bone Metabolism and DiseasesBone health and osteoporosis researchRegulation of Appetite and Obesity

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Leptin Regulates Bone Formation via the Sympathetic Nervous System

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Takeda, Shu, Elefteriou, Florent, Levasseur, Regis, Liu, Xiuyun, Zhao, Liping, Parker, Keith L., Armstrong, Dawna, Ducy, Patricia, Karsenty, Gerard·2002·Cell

DOI 10.1016/s0092-8674(02)01049-8

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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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Authors: Takeda, S., Elefteriou, F., Levasseur, R., Liu, X., Zhao, L., Parker, K. L., Armstrong, D., Ducy, P., & Karsenty, G.
Affiliations: The University of Texas Southwestern Medical Center (US)
Baylor College of Medicine (US)
ORCID: Elefteriou, Florent
Liu, Xiuyun
Zhao, Liping
Ducy, Patricia
Venue: Cell
Publisher: Elsevier BV
Published: 2002-11
Volume: 111
Issue: 3
Pages: 305-317
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(02)01049-8
OpenAlex: W2147510409
Cited by: 1,735
References: 54
Citations by year: 2026: 50 · 2025: 58 · 2024: 61 · 2023: 49 · 2022: 55 · 2021: 57 · 2020: 69 · 2019: 70 · 2018: 66 · 2017: 68 · 2016: 66 · 2015: 81 · 2014: 86 · 2013: 71 · 2012: 105
FWCI: 23.47
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3911 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK-54480, R01DK058883, R01DK054480, DK58883)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD24054)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: leptin, bone formation, sympathetic nervous system, beta-adrenergic receptors, osteoblast proliferation, leptin resistance, leptin deficiency, hypothalamic neurons, osteoporosis, bone mass, ovariectomy
MeSH terms: Adrenergic beta-Antagonists, Animals, Cells, Cultured, Hypothalamus, Mice, Inbred C57BL, Neuropeptides, Obesity, Oligopeptides, Osteoblasts, Osteogenesis, Pyrrolidonecarboxylic Acid, Receptors, Adrenergic, beta, Sympathetic Nervous System, Receptors, Corticotropin, Leptin, Receptor, Melanocortin, Type 4, Mice, Receptors, Leptin

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Leptin Regulates Bone Formation via the Sympathetic Nervous System

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