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Yue et al. The leptin receptor regulates adipogenesis/osteogenesis balance


Yue et al. investigated the role of the leptin receptor (LepR) in osteogenesis and adipogenesis by deleting LepR in mice; the deletion was specific for bone marrow stromal cells originating in the limbs but not from the hypothalamic neurons or the axial skeleton.

Body mass in LepR− mice was normal, as was hematopoiesis but the limb bones were able to heal fractures more quickly, adipogenesis was reduced and osteogenesis was enhanced. The effect on the two latter processes appears to be mediated through Jak2/Stat3 signaling in stromal cells in the bone marrow.

Interestingly, mice with the specific LepR deletion showed a much smaller increase in adipogenesis and fall in osteogenesis than wild type mice when they were fed a high-fat diet. The authors conclude that mesenchymal stromal cells in the bone marrow of adult mice respond to the change in diet because of alterations in leptin/LepR interactions at the local bone level. They further suggest possible therapeutic implications for patients with osteoporosis.

Editor’s comment: The effect of leptin on osteoblasts has been controversial but this study demonstrates that LepR+ skeletal stem cells in the bone marrow respond to systemic leptin by enhancing adipogenesis and suppressing osteogenesis. This explains why increased adiposity negatively regulates bone mass and suggests that blocking the action of leptin locally might protect bone.

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