Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Texas Health Science Center at San Antonio, TX 78229-3900, USA.
J Nutr Biochem. 2010 Dec;21(12):1162-9. doi: 10.1016/j.jnutbio.2009.10.002. Epub 2010 Feb 10.
Osteoporosis and obesity remain a major public health concern through its associated fragility and fractures. Several animal models for the study of osteoporotic bone loss, such as ovariectomy (OVX) and denervation, require unique surgical skills and expensive set up. The challenging aspect of these age-associated diseases is that no single animal model exactly mimics the progression of these human-specific chronic conditions. Accordingly, to develop a simple and novel model of post menopausal bone loss with obesity, we fed either a high fat diet containing 10% corn oil (CO) or standard rodent lab chow (LC) to 12-month-old female C57Bl/6J mice for 6 months. As a result, CO fed mice exhibited increased body weight, total body fat mass, abdominal fat mass and reduced bone mineral density (BMD) in different skeletal sites measured by dual energy X-ray absorptiometry. We also observed that decreased BMD with age in CO fed obese mice was accompanied by increased bone marrow adiposity, up-regulation of peroxisome proliferator-activated receptor γ, cathepsin k and increased proinflammatory cytokines (interleukin 6 and tumor necrosis factor α) in bone marrow and splenocytes, when compared to that of LC fed mice. Therefore, this appears to be a simple, novel and convenient age-associated model of post menopausal bone loss, in conjunction with obesity, which can be used in pre-clinical drug discovery to screen new therapeutic drugs or dietary interventions for the treatment of obesity and osteoporosis in the human population.
骨质疏松症和肥胖症仍然是一个主要的公共健康问题，因为它们与骨折相关的脆弱性有关。有几种研究骨质疏松性骨丢失的动物模型，如卵巢切除术（OVX）和去神经支配，需要独特的手术技能和昂贵的设置。这些与年龄相关的疾病的挑战性在于，没有一种单一的动物模型能完全模拟这些人类特有的慢性疾病的进展。因此，为了开发一种简单而新颖的绝经后肥胖性骨丢失模型，我们给 12 个月大的 C57Bl/6J 雌性小鼠喂食含有 10%玉米油（CO）的高脂肪饮食或标准啮齿动物实验室饲料（LC）6 个月。结果，CO 喂养的小鼠体重增加，全身脂肪量、腹部脂肪量增加，不同骨骼部位的骨矿物质密度（BMD）降低，通过双能 X 射线吸收仪测量。我们还观察到，与 LC 喂养的小鼠相比，CO 喂养的肥胖小鼠随着年龄的增长，BMD 降低，骨髓脂肪增多，过氧化物酶体增殖物激活受体 γ、组织蛋白酶 K 上调，以及骨髓和脾细胞中的促炎细胞因子（白细胞介素 6 和肿瘤坏死因子 α）增加。因此，这似乎是一种简单、新颖、方便的与年龄相关的绝经后骨质疏松症合并肥胖症模型，可以在临床前药物发现中用于筛选新的治疗药物或饮食干预措施，以治疗肥胖症和骨质疏松症患者。
