Leptin deficiency produces contrasting phenotypes in bones of the limb and spine
Leptin deficiency produces contrasting phenotypes in bones of the limb and spine
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DOI：
10.1016/j.bone.2003.11.020
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发表时间：
2004-03-01
期刊：
影响因子：
4.1
通讯作者：
Isales, C
中科院分区：
文献类型：
--
作者：
Hamrick, MW;Pennington, C;Isales, C
瘦素是一种由脂肪细胞分泌的激素，可以通过中枢神经内分泌信号通路调节骨量。我们测试了这样的假设：骨组织对瘦素信号改变的反应在整个骨骼中并不均匀，但在不同的骨骼区域之间以及皮质和小梁部分之间可能会有所不同。我们研究了瘦素缺乏对肥胖、瘦素缺乏 (ob/ob) 小鼠和瘦对照小鼠肌肉质量和骨骼结构的影响。结果表明，肥胖小鼠的体重大约是瘦小鼠的两倍，但 ob/ob 小鼠的股四头肌比对照组小 40%。与瘦小鼠相比，瘦素缺陷小鼠的股骨明显较短，股骨骨矿物质含量 (BMC)、骨矿物质密度 (BMD)、皮质厚度和骨小梁体积较低。与正常小鼠相比，ob/ob 小鼠股骨的骨髓组织中脂肪细胞数量也显着增加。与股骨中观察到的模式相反，与瘦对照组相比，ob/ob 小鼠的椎骨长度、腰椎 BMC、腰椎 BMD 和小梁骨体积显着增加。尽管股骨骨髓中有大量脂肪细胞，但 ob/ob 小鼠腰椎骨髓中观察到的脂肪细胞很少。然而，与股骨一样，脊柱中也观察到皮质显着变薄。这些结果表明，瘦素信号传导改变对骨骼的影响在中轴区域和四肢区域之间显着不同，并且可能部分由肌肉质量介导。随着人类衰老，ob/ob小鼠后肢也观察到肌肉发育不全、骨髓脂肪生成增加和骨量减少，这表明ob/ob小鼠可能是研究骨髓脂肪生成与骨质减少之间关系的新的、有用的动物模型。 (C) 2004 Elsevier Inc. 保留所有权利。
Leptin is a hormone secreted by adipocytes that can regulate bone mass through a central, neuroendocrine signaling pathway, We tested the hypothesis that the response of bone tissue to altered leptin signaling is not uniform throughout the skeleton, but may vary between different skeletal regions and between cortical and trabecular moieties. We investigated the effects of leptin deficiency on muscle mass and bone architecture in obese, leptin-deficient (ob/ob) mice, and in lean controls. Results indicate that the obese mice weigh approximately twice as much as the lean mice, but the quadriceps muscles of the ob/ob mice are 40% smaller than those of controls. Leptin-deficient mice have significantly shorter femora, lower femoral bone mineral content (BMC), bone mineral density (BMD), cortical thickness, and trabecular bone volume compared to lean mice. Marrow tissue from the femora of ob/ob mice also shows a marked increase in adipocyte number compared to that of normal mice. In contrast to the pattern observed in the femur, ob/ob mice have significantly increased vertebral length, lumbar BMC, lumbar BMD, and trabecular bone volume compared to lean controls. Few adipocytes are observed in bone marrow from lumbar vertebrae of ob/ob mice, despite being numerous in marrow of the femur. However, like the femur, significant cortical thinning is also observed in the spine. These results indicate that the effects of altered leptin signaling on bone differ significantly between axial and appendicular regions, and may be mediated in part by muscle mass. The muscle hypoplasia, increased marrow adipogenesis, and decreased bone mass observed in the hindlimbs of ob/ob mice are also observed with aging in humans, suggesting that the ob/ob mouse may be a new and useful animal model for studying the relationship between bone marrow adipogenesis and osteopenia. (C) 2004 Elsevier Inc. All rights reserved.