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
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
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DOI：
10.1002/jbmr.406
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发表时间：
2011-08-01
影响因子：
6.2
通讯作者：
Baile, Clifton A.
中科院分区：
文献类型：
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作者：
Bartell, Shoshana M.;Rayalam, Srujana;Baile, Clifton A.
中枢和外周瘦素给药均可减轻 ob/ob 小鼠的体重、食物摄入量和肥胖。在本研究中，我们比较了脑室内 (ICV) 和皮下 (SC) 施用瘦素对四肢和轴骨骨代谢以及脂肪组织基因表达的影响，并确定了 ICV 瘦素对 ob/ob 小鼠骨髓基因表达的影响。在实验1中，瘦素(1.5或0.38μg/d)或对照连续注射ICV 12天。股骨骨髓基质细胞的基因表达分析显示，注射ICV后，与成骨相关的基因表达增加，而与破骨细胞生成、脂肪生成和脂肪细胞脂质储存相关的基因表达减少。在实验2中，瘦素连续注射ICV（0.0或1.5μg/d）或SC（0.0或10μg/d）12天。在这两个实验中，无论给药方式如何，瘦素都会降低体重、食物摄入量和体脂，并增加肌肉质量、骨矿物质密度、骨矿物质含量、骨面积、骨髓脂肪细胞数量和矿物质沉积率。血清胰岛素降低，而血清骨钙素、胰岛素样生长因子1、骨保护素、吡啶啉和核因子κB配体受体激活剂浓度升高。在实验2中，无论给药方式如何，脂肪组织中与细胞凋亡、脂质动员、胰岛素敏感性和产热相关的基因表达增加，而与细胞分化和成熟相关的基因表达减少。因此，ICV注射瘦素可促进骨髓中促成骨因子的表达，从而增强ob/ob小鼠的骨形成。 (C) 2011 年美国骨与矿物质研究学会。
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 mu g/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 mu g/d) or SC (0.0 or 10 mu g/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 kappa B 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. (C) 2011 American Society for Bone and Mineral Research.