Leptin deficiency produces contrasting phenotypes in bones of the limb and spine

M. W. Hamrick, C. Pennington, D. Newton, D. Xie, C. Isales

Research output: Contribution to journalArticle

279 Scopus citations

Abstract

Leptin is a hormone secreted by adipocytes that can regulate bone mass through a central, neuroendocrine signaling pathway. We tested the hypothesis that the response of bone tissue to altered leptin signaling is not uniform throughout the skeleton, but may vary between different skeletal regions and between cortical and trabecular moieties. We investigated the effects of leptin deficiency on muscle mass and bone architecture in obese, leptin-deficient (ob/ob) mice, and in lean controls. Results indicate that the obese mice weigh approximately twice as much as the lean mice, but the quadriceps muscles of the ob/ob mice are 40% smaller than those of controls. Leptin-deficient mice have significantly shorter femora, lower femoral bone mineral content (BMC), bone mineral density (BMD), cortical thickness, and trabecular bone volume compared to lean mice. Marrow tissue from the femora of ob/ob mice also shows a marked increase in adipocyte number compared to that of normal mice. In contrast to the pattern observed in the femur, ob/ob mice have significantly increased vertebral length, lumbar BMC, lumbar BMD, and trabecular bone volume compared to lean controls. Few adipocytes are observed in bone marrow from lumbar vertebrae of ob/ob mice, despite being numerous in marrow of the femur. However, like the femur, significant cortical thinning is also observed in the spine. These results indicate that the effects of altered leptin signaling on bone differ significantly between axial and appendicular regions, and may be mediated in part by muscle mass. The muscle hypoplasia, increased marrow adipogenesis, and decreased bone mass observed in the hindlimbs of ob/ob mice are also observed with aging in humans, suggesting that the ob/ob mouse may be a new and useful animal model for studying the relationship between bone marrow adipogenesis and osteopenia.

Original languageEnglish (US)
Pages (from-to)376-383
Number of pages8
JournalBone
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2004

Keywords

  • Adipocyte
  • Bone density
  • Bone mass
  • Cortical bone
  • Trabecular bone

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Fingerprint Dive into the research topics of 'Leptin deficiency produces contrasting phenotypes in bones of the limb and spine'. Together they form a unique fingerprint.

  • Cite this