Leptin Inhibits Bone Formation through a Hypothalamic Relay A Central Control of Bone Mass

  title={Leptin Inhibits Bone Formation through a Hypothalamic Relay A Central Control of Bone Mass},
  author={Patricia Ducy and Michael Amling and Shu Takeda and Matthias H. Priemel and Arndt Friedrich Schilling and Frank Timo Beil and Jianhe Shen and Charles R. Vinson and Johannes Maria Rueger and G{\'e}rard Karsenty},

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Leptin Regulates Bone Formation via the Sympathetic Nervous System
Serum leptin level is a regulator of bone mass.
It is indicated that adipocyte-derived circulating leptin is a determinant of bone formation and suggests that leptin antiosteogenic function is conserved in vertebrates.
Leptin and bone: does the brain control bone biology?
The study of bone biology in two mouse models of obesity, leptin-deficient (ob/ob) and leptin receptor- deficient (db/db) mice, points to a role for leptin in the control of bone density.
[Bone mass regulation by leptin: a hypothalamic control of bone formation].
The peripheral mediator of leptin's antiosteogenic function has been identified as being the sympathetic nervous system, and it has been shown that those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism.
Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo.
It is concluded that the direct bone effects of leptin tend to reduce bone fragility and could contribute to the high bone mass and low fracture rates of obesity.
Leptin, Bone Mass, and the Thrifty Phenotype
  • M. Hamrick
  • Biology
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 2004
THE CYTOKINE-LIKE HORMONE leptin has emerged as a significant factor in the regulation of bone metabolism. Leptin is produced by fat cells (adipocytes) and is thought to regulate bone mass through
Common endocrine control of body weight, reproduction, and bone mass.
Intacerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay, and the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system.
Central control of bone remodeling by neuromedin U
Physiological and cell-based assays indicate that NMU acts in the central nervous system, rather than directly on bone cells, to regulate bone remodeling, and suggest that it may be the first central mediator of leptin-dependent regulation of bone mass identified to date.
The complex effects of leptin on bone metabolism through multiple pathways.
  • T. Thomas
  • Biology, Medicine
    Current opinion in pharmacology
  • 2004
Hypothalamic Y2 receptors regulate bone formation.
The lack of any changes in plasma total calcium, leptinemia, or hypothalamo-pituitary-corticotropic, -thyrotropic, -somatotropic, or -gonadotropic output suggests that Y2 receptors do not modulate bone formation by humoral mechanisms, and that alteration of autonomic function through hypothalamic Y1 receptors may play a key role in a major central regulatory circuit of bone formation.


Leptin accelerates the onset of puberty in normal female mice.
It is proposed that leptin is the signal that informs the brain that energy stores are sufficient to support the high energy demands of reproduction, and may be a major determinant of the timing of puberty.
Role of leptin in the neuroendocrine response to fasting
It is proposed that regulation of the neuroendocrine system during starvation could be the main physiological role of leptin, and preventing the starvation-induced fall in leptin with exogenous leptin substantially blunts the changes in gonadal, adrenal and thyroid axes in male mice, and prevents the starve-induced delay in ovulation in female mice.
Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density
Physiological response to long-term peripheral and central leptin infusion in lean and obese mice.
The decreased response to leptin in diet-induced obese, NZO, and Ay mice suggests that obesity in these strains is the result of leptin resistance, which probably results from defects downstream of the leptin receptor in the hypothalamus.
Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes.
The hypothesis that leptin is a previously unrecognized, physiological regulator of these two differentiation pathways, acting primarily on maturation of stromal cells into both lineages is supported.
Attenuation of the Obesity Syndrome of ob/ob Mice by the Loss of Neuropeptide Y
Results suggest that NPY is a central effector of leptin deficiency, and ob/ob mice deficient for NPY are less obese because of reduced food intake and increased energy expenditure, and are less severely affected by diabetes, sterility, and somatotropic defects.
Feeding and body-weight regulation by hypothalamic neuropeptides—mediation of the actions of leptin
  • A. Inui
  • Biology
    Trends in Neurosciences
  • 1999
A Unitary Model for Involutional Osteoporosis: Estrogen Deficiency Causes Both Type I and Type II Osteoporosis in Postmenopausal Women and Contributes to Bone Loss in Aging Men
  • B. L. Riggs, S. Khosla, L. Melton
  • Medicine, Biology
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 1998
We propose here a new unitary model for the pathophysiology of involutional osteoporosis that identifies estrogen (E) deficiency as the cause of both the early, accelerated and the late, slow phases