Endocrine regulation of energy metabolism by the skeleton.
The regulation of bone remodeling by an adipocyte-derived hormone implies that bone may exert a feedback control of energy homeostasis. To test this hypothesis we looked for genes expressed in osteoblasts, encoding signaling molecules and affecting energy metabolism. We show here that mice lacking the protein tyrosine phosphatase OST-PTP are hypoglycemic and are protected from obesity and glucose intolerance because of an increase in beta-cell proliferation, insulin secretion, and insulin sensitivity. In contrast, mice lacking the osteoblast-secreted molecule osteocalcin display decreased beta-cell proliferation, glucose intolerance, and insulin resistance. Removing one Osteocalcin allele from OST-PTP-deficient mice corrects their metabolic phenotype. Ex vivo, osteocalcin can stimulate CyclinD1 and Insulin expression in beta-cells and Adiponectin, an insulin-sensitizing adipokine, in adipocytes; in vivo osteocalcin can improve glucose tolerance. By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism.
Lee
Na Kyung
NK
Department of Genetics & Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Sowa
Hideaki
H
Hinoi
Eiichi
E
Ferron
Mathieu
M
Ahn
Jong Deok
JD
Confavreux
Cyrille
C
Dacquin
Romain
R
Mee
Patrick J
PJ
McKee
Marc D
MD
Jung
Dae Young
DY
Zhang
Zhiyou
Z
Kim
Jason K
JK
Mauvais-Jarvis
Franck
F
Ducy
Patricia
P
Karsenty
Gerard
G
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004734:Energy Metabolism / Q000502:physiology*; D005804:Genes, Lethal; D005947:Glucose / Q000502:physiology*; D018149:Glucose Intolerance / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D007003:Hypoglycemia / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
D007328:Insulin; D017027:Protein Tyrosine Phosphatases; C474713:Ptprv protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D005947:Glucose
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