Department of Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Bone. 2012 Jul;51(1):46-53. doi: 10.1016/j.bone.2012.03.031. Epub 2012 Apr 6.
Obesity, in addition to being associated with metabolic diseases, such as diabetes, has also been found to lower the risk of osteoporotic fractures. The relationship between obesity and bone trabecular structure is complex, involving responses to mechanical loading and the effects of adipocyte-derived hormones, both directly interacting with bone tissue and indirectly through central nervous system signaling. Here we examine the effects of sex, a high fat diet, and genetics on the trabecular density and structure of the lumbar and caudal vertebra and the proximal tibia along with body weight, fat pad weight, and serum leptin levels in a murine obesity model, the LGXSM recombinant inbred (RI) mouse strains. The sample included 481 mice from 16 RI strains. We found that vertebral trabecular density was higher in males while the females had higher tibial trabecular density. The high fat diet led to only slightly higher trabecular density in both sexes despite its extreme effects on obesity and serum leptin levels. Trait heritabilities are moderate to strong and genetic correlations among trabecular features are high. Most genetic variation contrasts strains with large numbers of thick, closely-spaced, highly interconnected, plate-like trabeculae with a high bone volume to total volume ratio against strains displaying small numbers of thin, widely-spaced, sparsely connected, rod-like trabeculae with a low bone volume to total volume ratio. Genetic correlations between trabecular and obesity-related traits were low and not statistically significant. We mapped trabecular properties to 20 genomic locations. Only one-quarter of these locations also had effects on obesity. In this population obesity has a relatively minor effect on trabecular bone morphology.
肥胖症除了与糖尿病等代谢性疾病有关外，还被发现降低了骨质疏松性骨折的风险。肥胖症与骨小梁结构之间的关系很复杂，涉及到对机械负荷的反应和脂肪细胞衍生激素的作用，这两者都直接与骨组织相互作用，并通过中枢神经系统信号间接作用。在这里，我们研究了性别、高脂肪饮食和遗传对腰椎和尾椎以及胫骨近端小梁密度和结构的影响，同时还研究了体重、脂肪垫重量和血清瘦素水平在肥胖模型 LGXSM 重组近交系（RI）小鼠中的变化。样本包括 16 个 RI 系的 481 只小鼠。我们发现，雄性的椎体小梁密度较高，而雌性的胫骨小梁密度较高。尽管高脂肪饮食对肥胖症和血清瘦素水平有极端影响，但它只导致了两性的小梁密度略有升高。表型遗传力为中度到高度，小梁特征之间的遗传相关性很高。大多数遗传变异都将具有大量厚、紧密间隔、高度互联、板状小梁和高骨体积与总体积比的品系与具有少量薄、广泛间隔、稀疏连接、杆状小梁和低骨体积与总体积比的品系区分开来。小梁特征与肥胖相关特征之间的遗传相关性较低，且无统计学意义。我们将小梁特性映射到 20 个基因组位置。其中只有四分之一的位置也对肥胖有影响。在该人群中，肥胖症对小梁骨形态的影响相对较小。
