PMID- 21520275 OWN - NLM STAT- MEDLINE DCOM- 20111109 LR - 20110722 IS - 1523-4681 (Electronic) IS - 0884-0431 (Linking) VI - 26 IP - 8 DP - 2011 Aug TI - Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice. PG - 1710-20 LID - 10.1002/jbmr.406 [doi] AB - Both central and peripheral leptin administrations reduce body weight, food intake, and adiposity in ob/ob mice. In this study we compared effects of intracerebroventricular (ICV) and subcutaneous (SC) administration of leptin on bone metabolism in the appendicular and axial skeleton and adipose tissue gene expression and determined the effects of ICV leptin on bone marrow gene expression in ob/ob mice. In experiment 1, leptin (1.5 or 0.38 microg/d) or control was continuously injected ICV for 12 days. Gene expression analysis of femoral bone marrow stromal cells showed that expression of genes associated with osteogenesis was increased after ICV injection, whereas those associated with osteoclastogenesis, adipogenesis, and adipocyte lipid storage were decreased. In experiment 2, leptin was injected continuously ICV (0.0 or 1.5 microg/d) or SC (0.0 or 10 microg/d) for 12 days. In both experiments, regardless of mode of administration, leptin decreased body weight, food intake, and body fat and increased muscle mass, bone mineral density, bone mineral content, bone area, marrow adipocyte number, and mineral apposition rate. Serum insulin was decreased, whereas serum osteocalcin, insulin-like growth factor 1, osteoprotegerin, pyridinoline, and receptor activator of nuclear factor kappaB ligand concentrations were increased. In experiment 2, expression of genes in adipose tissue associated with apoptosis, lipid mobilization, insulin sensitivity, and thermogenesis was increased, whereas expression of genes associated with cell differentiation and maturation was decreased regardless of mode of administration. Thus ICV injection of leptin promotes expression of pro-osteogenic factors in bone marrow, leading to enhanced bone formation in ob/ob mice. CI - Copyright (c) 2011 American Society for Bone and Mineral Research. FAU - Bartell, Shoshana M AU - Bartell SM AD - Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA. FAU - Rayalam, Srujana AU - Rayalam S FAU - Ambati, Suresh AU - Ambati S FAU - Gaddam, Dhanunjaya R AU - Gaddam DR FAU - Hartzell, Diane L AU - Hartzell DL FAU - Hamrick, Mark AU - Hamrick M FAU - She, Jin-Xiong AU - She JX FAU - Della-Fera, Mary Anne AU - Della-Fera MA FAU - Baile, Clifton A AU - Baile CA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Bone Miner Res JT - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JID - 8610640 RN - 0 (Leptin) RN - 67763-96-6 (Insulin-Like Growth Factor I) SB - IM CIN - J Bone Miner Res. 2011 Aug;26(8):1694-7. PMID: 21698664 MH - Adipocytes/cytology/drug effects/metabolism MH - Animals MH - Body Weight/drug effects MH - Bone Density/*drug effects MH - Bone Marrow/drug effects/metabolism MH - Cell Count MH - Feeding Behavior/drug effects MH - Female MH - Femur/drug effects/metabolism MH - Gene Expression Regulation/drug effects MH - Injections, Intraventricular MH - Insulin-Like Growth Factor I/*metabolism MH - Leptin/administration & dosage/*deficiency/*pharmacology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Obese MH - Muscles/*anatomy & histology/drug effects MH - Organ Size/drug effects MH - Osteogenesis/*drug effects/*genetics MH - Tibia/anatomy & histology/drug effects/metabolism EDAT- 2011/04/27 06:00 MHDA- 2011/11/10 06:00 CRDT- 2011/04/27 06:00 PHST- 2011/04/27 06:00 [entrez] PHST- 2011/04/27 06:00 [pubmed] PHST- 2011/11/10 06:00 [medline] AID - 10.1002/jbmr.406 [doi] PST - ppublish SO - J Bone Miner Res. 2011 Aug;26(8):1710-20. doi: 10.1002/jbmr.406.