Effects of Leptin on the Skeleton
- 31 August 2018
- journal article
- review article
- Published by The Endocrine Society in Endocrine Reviews
- Vol. 39 (6), 938-959
- https://doi.org/10.1210/er.2017-00226
Abstract
Leptin originates in adipocytes, including those in bone marrow and circulates in concentrations 20- 90-fold higher than those in the cerebrospinal fluid. It has direct anabolic effects on osteoblasts and chondrocytes, but also influences bone indirectly: via the hypothalamus and sympathetic nervous system, via changes in body weight, and via effects on the production of other hormones (e.g. pituitary). Leptin’s role in bone physiology is determined by the balance of these conflicting effects. Reflecting this inconsistency, the leptin-deficient mouse has reduced length and bone mineral content of long bones, but increased vertebral trabecular bone. A consistent bone phenotype in human leptin deficiency has not been established. Systemic leptin administration in animals and humans usually exerts a positive effect on bone mass, and leptin administration into the cerebral ventricles usually normalizes the bone phenotype in leptin-deficient mice. Reflecting the role of the sympathetic nervous system in mediating the central catabolic effects of leptin on the skeleton, β-adrenergic agonists and antagonists have major effects on bone in mice, but this is not consistently seen in humans. The balance of the central and peripheral effects of leptin on bone remains an area of substantial controversy, and might vary between species and according to other factors such as body weight, baseline circulating leptin levels, and the presence of specific pathologies. In humans, leptin is likely to contribute to the positive relationship observed between adiposity and bone density, which allows the skeleton to respond appropriately to changes in soft tissue mass.Keywords
Funding Information
- Health Research Council of New Zealand
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