Serum leptin level is a regulator of bone mass

F. Elefteriou, S. Takeda, K. Ebihara, J. Magre, N. Patano, C. Ae Kim, Y. Ogawa, X. Liu, S. M. Ware, W. J. Craigen, J. J. Robert, C. Vinson, K. Nakao, J. Capeau, G. Karsenty

研究成果: Contribution to journalArticle査読

275 被引用数 (Scopus)

抄録

Leptin is a powerful inhibitor of bone formation in vivo. This antiosteogenic function involves leptin binding to its receptors on ventromedial hypothalamic neurons, the autonomous nervous system and β-adrenergic receptors on osteoblasts. However, the mechanisms whereby leptin controls the function of ventromedial hypothalamic antiosteogenic neurons remain unclear. In this study, we compared the ability of leptin to regulate body weight and bone mass and show that leptin antiosteogenic and anorexigenic functions are affected by similar amounts of leptin. Using a knock-in of LacZ in the leptin locus, we failed to detect any leptin synthesis in the central nervous system. However, increasing serum leptin level, even dramatically, reduced bone mass. Conversely, reducing serum-free leptin level by overexpressing a soluble receptor for leptin increased bone mass. Congruent with these results, the high bone mass of lipodystrophic mice could be corrected by restoring serum leptin level, suggesting that leptin is an adipocyte product both necessary and sufficient to control bone mass. Consistent with the high bone mass phenotype of lipodystrophic mice, we observed an advanced bone age, an indirect reflection of premature bone formation, in lipodystrophic patients. Taken together, these results indicate that adipocyte-derived circulating leptin is a determinant of bone formation and suggests that leptin antiosteogenic function is conserved in vertebrates.

本文言語英語
ページ(範囲)3258-3263
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
101
9
DOI
出版ステータス出版済み - 3 2 2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 一般

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