High bone mass in adult mice with diet-induced obesity results from a combination of initial increase in bone mass followed by attenuation in bone formation; implications for high bone mass and decreased bone quality in obesity
High bone mass in adult mice with diet-induced obesity results from a combination of initial increase in bone mass followed by attenuation in bone formation; implications for high bone mass and decreased bone quality in obesity
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DOI：
10.1016/j.mce.2015.01.001
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发表时间：
2015-07-15
影响因子：
4.1
通讯作者：
Dowling, A. R.
中科院分区：
文献类型：
--
作者：
Lecka-Czernik, B.;Stechschulte, L. A.;Dowling, A. R.
肥胖通常被认为是一种对骨量和骨矿物质密度（BMD）有积极影响的疾病。高体重指数（BMI）对骨骼的积极影响已被公认为是骨骼上施加的机械负荷增加的结果。然而，流行病学研究表明，肥胖与骨折发生率增加有关。本研究结果为骨质量增加和骨质量下降的机制提供了新的视角。两组12周龄的C57 BL/6雄性动物饲喂高脂饮食（HFD）或普通饮食（RD）11周。在实验结束时评估这些组中的代谢谱、骨参数和基因表达。此外，在第三组12周龄动物中评价骨状态，对应于饲喂期开始时的动物。与喂食RD的年龄匹配对照动物相比，HFD给药导致饮食诱导的肥胖（DIO）、葡萄糖耐受不良、能量代谢改变和WAT功能受损。在DIO动物的WAT中，脂联素、FABP 4/aP 2、DIO 2和FoxC 2的表达以及IGFBP 2的转录水平降低，IGFBP 2是调节能量代谢和骨量的细胞因子。在实验结束时，DIO小鼠在RD时具有比两个对照组更高的骨量，然而，如通过钙黄绿素标记所评估的，它们具有减少的骨形成，并且骨髓脂肪细胞含量增加。这项研究表明，在肥胖症中获得的骨量是一个两阶段过程的结果。第一阶段将包括脂肪膨胀的有益作用，通过增加机械负荷和/或增加骨合成代谢脂肪因子的产生和/或脂肪酸的营养作用来增加骨量。随后是第二阶段，其特征在于由代谢障碍的发展引起的骨形成和骨转换减少。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Obesity is generally recognized as a condition which positively influences bone mass and bone mineral density (BMD). Positive effect of high body mass index (BMI) on bone has been recognized as a result of increased mechanical loading exerted on the skeleton. However, epidemiologic studies indicate that obesity is associated with increased incidence of fractures. The results presented here offer a new perspective regarding the mechanisms which may be responsible for the increase of bone mass and concurrent decrease in bone quality. Two groups of 12 week old C57BL/6 males were fed either high fat diet (HFD) or regular diet (RD) for 11 weeks. Metabolic profile, bone parameters and gene expression were assessed in these groups at the end of the experiment. Additionally, bone status was evaluated in a third group of 12 week old animals corresponding to animals at the start of the feeding period. Administration of HFD resulted in development of a diet-induced obesity (DIO), glucose intolerance, alteration in energy metabolism, and impairment in WAT function, as compared to the age-matched control animals fed RD. The expression of adiponectin, FABP4/aP2, DIO2 and FoxC2 were decreased in WAT of DIO animals, as well as transcript levels for IGFBP2, the cytokine regulating both energy metabolism and bone mass. At the end of experiment, DIO mice had higher bone mass than both control groups on RD, however they had decreased bone formation, as assessed by calcein labeling, and increased marrow adipocyte content. This study suggests that the bone mass acquired in obesity is a result of a two-phase process. First phase would consist of either beneficial effect of fat expansion to increase bone mass by increased mechanical loading and/or increased production of bone anabolic adipokines and/or nutritional effect of fatty acids. This is followed by a second phase characterized by decreased bone formation and bone turnover resulting from development of metabolic impairment. (C) 2015 Elsevier Ireland Ltd. All rights reserved.