title: Increased Gs Signaling in Osteoblasts Reduces Bone Marrow and Whole-Body Adiposity in Male Mice.
abstract: Bone is increasingly recognized as an endocrine organ that can regulate systemic hormones and metabolism through secreted factors. Although bone loss and increased adiposity appear to be linked clinically, whether conditions of increased bone formation can also change systemic metabolism remains unclear. In this study, we examined how increased osteogenesis affects metabolism by using an engineered G protein-coupled receptor, Rs1, to activate Gs signaling in osteoblastic cells in ColI(2.3)(+)/Rs1(+) transgenic mice. We previously showed that these mice have dramatically increased bone formation resembling fibrous dysplasia of the bone. We found that total body fat was significantly reduced starting at 3 weeks of age. Furthermore, ColI(2.3)(+)/Rs1(+) mice showed reduced O2 consumption and respiratory quotient measures without effects on food intake and energy expenditure. The mice had significantly decreased serum triacylglycerides, leptin, and adiponectin. Resting glucose and insulin levels were unchanged; however, glucose and insulin tolerance tests revealed increased sensitivity to insulin. The mice showed resistance to fat accumulation from a high-fat diet. Furthermore, ColI(2.3)(+)/Rs1(+) mouse bones had dramatically reduced mature adipocyte differentiation, increased Wingless/Int-1 (Wnt) signaling, and higher osteoblastic glucose utilization than controls. These findings suggest that osteoblasts can influence both local and peripheral adiposity in conditions of increased bone formation and suggest a role for osteoblasts in the regulation of whole-body adiposity and metabolic homeostasis.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism; Institute for Human Genetics; and Program in Craniofacial Biology (C.J.C., S.H., K.J., A.M., B.M.M., and E.C.H.); and the Biomedical Sciences Graduate Program (J.T.V. and E.C.H.); University of California, San Francisco, San Francisco, California 94143-0794.
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Cain
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism; Institute for Human Genetics; and Program in Craniofacial Biology (C.J.C., S.H., K.J., A.M., B.M.M., and E.C.H.); and the Biomedical Sciences Graduate Program (J.T.V. and E.C.H.); University of California, San Francisco, San Francisco, California 94143-0794.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Valencia
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism; Institute for Human Genetics; and Program in Craniofacial Biology (C.J.C., S.H., K.J., A.M., B.M.M., and E.C.H.); and the Biomedical Sciences Graduate Program (J.T.V. and E.C.H.); University of California, San Francisco, San Francisco, California 94143-0794.
authors.forename: Samantha
authors.initials: S
authors.lastname: Ho
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism; Institute for Human Genetics; and Program in Craniofacial Biology (C.J.C., S.H., K.J., A.M., B.M.M., and E.C.H.); and the Biomedical Sciences Graduate Program (J.T.V. and E.C.H.); University of California, San Francisco, San Francisco, California 94143-0794.
authors.forename: Kate
authors.initials: K
authors.lastname: Jordan
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism; Institute for Human Genetics; and Program in Craniofacial Biology (C.J.C., S.H., K.J., A.M., B.M.M., and E.C.H.); and the Biomedical Sciences Graduate Program (J.T.V. and E.C.H.); University of California, San Francisco, San Francisco, California 94143-0794.
authors.forename: Aaron
authors.initials: A
authors.lastname: Mattingly
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism; Institute for Human Genetics; and Program in Craniofacial Biology (C.J.C., S.H., K.J., A.M., B.M.M., and E.C.H.); and the Biomedical Sciences Graduate Program (J.T.V. and E.C.H.); University of California, San Francisco, San Francisco, California 94143-0794.
authors.forename: Blanca M
authors.initials: BM
authors.lastname: Morales
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism; Institute for Human Genetics; and Program in Craniofacial Biology (C.J.C., S.H., K.J., A.M., B.M.M., and E.C.H.); and the Biomedical Sciences Graduate Program (J.T.V. and E.C.H.); University of California, San Francisco, San Francisco, California 94143-0794.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Hsiao
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism*; D004435:Eating / Q000235:genetics / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D015870:Gene Expression; D020738:Leptin / Q000097:blood; D008297:Male; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism*; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014280:Triglycerides / Q000097:blood
chemical_list: D052242:Adiponectin; D020738:Leptin; D043562:Receptors, G-Protein-Coupled; D014280:Triglycerides; D019205:GTP-Binding Protein alpha Subunits, Gs