High fat diet-induced animal model of age-associated obesity and osteoporosis.

High fat diet-induced animal model of age-associated obesity and osteoporosis.
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DOI:
10.1016/j.jnutbio.2009.10.002
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发表时间:
2010-12
影响因子:
5.6
通讯作者:
Fernandes, Gabriel
Fernandes, Gabriel
中科院分区:
医学2区
文献类型:
--
作者:
Halade, Ganesh V.;Rahman, Md M.;Williams, Paul J.;Fernandes, Gabriel

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骨质疏松症和肥胖症由于其相关的脆弱性和骨折,仍然是一个主要的公共卫生问题。几种研究骨质疏松性骨丢失的动物模型,如卵巢切除(OVX)和去神经治疗,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具有挑战性的方面是,没有一个单一的动物模型能够准确地模拟这些人类特有的慢性病的进展。因此,为了建立一种简单而新颖的绝经后肥胖骨丢失模型,我们用含10%玉米油的高脂饲料(CO)或标准的啮齿动物饲料(LC)喂养12月龄雌性C57BL/6J小鼠6个月。结果表明,饲喂CO的小鼠体重、全身脂肪质量(BFM)、腹部脂肪质量和不同骨骼部位的骨密度(BMD)均增加,双能X射线骨密度仪(DXA)测量的骨密度(BMD)降低。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加,骨密度下降伴随着骨髓肥胖度的增加,骨髓和脾细胞中PPARγ和组织蛋白酶K的上调,以及促炎细胞因子(IL-6和肿瘤坏死因子-α)的增加。因此,这似乎是一种简单、新颖和方便的绝经后骨丢失与肥胖相关的年龄相关模型,可用于临床前药物开发,以筛选治疗人类肥胖和骨质疏松症的新治疗药物或饮食干预措施。
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 (BFM), abdominal fat mass and reduced bone mineral density (BMD) in different skeletal sites measured by Dual Energy X-ray Absorptiometry (DXA). We also observed that decreased bone mineral density (BMD) with age in CO fed obese mice was accompanied by increased bone marrow adiposity, up-regulation of PPARγ, cathepsin k and increased pro-inflammatory cytokines (IL-6 and TNF-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.
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