title: 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.
abstract: 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 µg/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 µg/d) or SC (0.0 or 10 µg/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 κB 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.
authors.affiliation: Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602, USA.
authors.forename: Shoshana M
authors.initials: SM
authors.lastname: Bartell
authors.forename: Srujana
authors.initials: S
authors.lastname: Rayalam
authors.forename: Suresh
authors.initials: S
authors.lastname: Ambati
authors.forename: Dhanunjaya R
authors.initials: DR
authors.lastname: Gaddam
authors.forename: Diane L
authors.initials: DL
authors.lastname: Hartzell
authors.forename: Mark
authors.initials: M
authors.lastname: Hamrick
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Della-Fera
authors.forename: Clifton A
authors.initials: CA
authors.lastname: Baile
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007276:Injections, Intraventricular; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020738:Leptin / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009132:Muscles / Q000033:anatomy & histology* / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics*; D013977:Tibia / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism
chemical_list: D020738:Leptin; D007334:Insulin-Like Growth Factor I