{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:25:43Z","timestamp":1791300343170,"version":"4.1.0"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,3,2]]},"abstract":"<jats:p>\n                    Leptin is a powerful inhibitor of bone formation\n                    <jats:italic>in vivo<\/jats:italic>\n                    . This antiosteogenic function involves leptin binding to its receptors on ventromedial hypothalamic neurons, the autonomous nervous system and \u03b2-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\n                    <jats:italic>LacZ<\/jats:italic>\n                    in the\n                    <jats:italic>leptin<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0308744101","type":"journal-article","created":{"date-parts":[[2004,3,2]],"date-time":"2004-03-02T21:33:11Z","timestamp":1078263191000},"page":"3258-3263","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":284,"title":["Serum leptin level is a regulator of bone mass"],"prefix":"10.1073","volume":"101","author":[{"given":"F.","family":"Elefteriou","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030; Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U.402, Facult\u00e9 de M\u00e9decine St-Antoine, 75012 Paris, France; Genetica Instituto da Crian\u00e7a, CEP 05403-900, S\u00e3o Paulo, Brazil; Center of Excellence Program for Frontier Research on Molecular Destruction and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030; Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U.402, Facult\u00e9 de M\u00e9decine St-Antoine, 75012 Paris, France; Genetica Instituto da Crian\u00e7a, CEP 05403-900, S\u00e3o Paulo, Brazil; Center of Excellence Program for Frontier Research on Molecular Destruction and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Ebihara","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030; Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U.402, Facult\u00e9 de M\u00e9decine St-Antoine, 75012 Paris, France; Genetica Instituto da Crian\u00e7a, CEP 05403-900, S\u00e3o Paulo, Brazil; Center of Excellence Program for Frontier Research on Molecular Destruction and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Magre","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030; Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U.402, Facult\u00e9 de M\u00e9decine St-Antoine, 75012 Paris, France; Genetica Instituto da Crian\u00e7a, CEP 05403-900, S\u00e3o Paulo, Brazil; Center of Excellence Program for Frontier Research on Molecular Destruction and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Patano","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030; Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U.402, Facult\u00e9 de M\u00e9decine St-Antoine, 75012 Paris, France; Genetica Instituto da Crian\u00e7a, CEP 05403-900, S\u00e3o Paulo, Brazil; Center of Excellence Program for Frontier Research on Molecular Destruction and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ae Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030; Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U.402, Facult\u00e9 de M\u00e9decine St-Antoine, 75012 Paris, France; Genetica Instituto da Crian\u00e7a, CEP 05403-900, S\u00e3o Paulo, Brazil; Center of Excellence Program for Frontier Research on Molecular Destruction and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030; Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U.402, Facult\u00e9 de M\u00e9decine St-Antoine, 75012 Paris, France; Genetica Instituto da Crian\u00e7a, CEP 05403-900, S\u00e3o Paulo, Brazil; Center of Excellence Program for Frontier Research on Molecular Destruction and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030; Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U.402, Facult\u00e9 de M\u00e9decine St-Antoine, 75012 Paris, France; Genetica Instituto da Crian\u00e7a, CEP 05403-900, S\u00e3o Paulo, Brazil; Center of Excellence Program for Frontier Research on Molecular Destruction and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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