Department of Molecular Physiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Dis Model Mech. 2010 Mar-Apr;3(3-4):156-66. doi: 10.1242/dmm.003467.
The metabolic syndrome (MetS) is characterized by obesity concomitant with other metabolic abnormalities such as hypertriglyceridemia, reduced high-density lipoprotein levels, elevated blood pressure and raised fasting glucose levels. The precise definition of MetS, the relationships of its metabolic features, and what initiates it, are debated. However, obesity is on the rise worldwide, and its association with these metabolic symptoms increases the risk for diabetes and cardiovascular disease (among many other diseases). Research needs to determine the mechanisms by which obesity and MetS increase the risk of disease. In light of this growing epidemic, it is imperative to develop animal models of MetS. These models will help determine the pathophysiological basis for MetS and how MetS increases the risk for other diseases. Among the various animal models available to study MetS, mice are the most commonly used for several reasons. First, there are several spontaneously occurring obese mouse strains that have been used for decades and that are very well characterized. Second, high-fat feeding studies require only months to induce MetS. Third, it is relatively easy to study the effects of single genes by developing transgenic or gene knockouts to determine the influence of a gene on MetS. For these reasons, this review will focus on the benefits and caveats of the most common mouse models of MetS. It is our hope that the reader will be able to use this review as a guide for the selection of mouse models for their own studies.
代谢综合征(MetS)的特征是肥胖,同时伴有其他代谢异常,如高甘油三酯血症、高密度脂蛋白水平降低、血压升高和空腹血糖升高。MetS 的精确定义、其代谢特征的关系以及其引发因素仍存在争议。然而,肥胖在全球范围内呈上升趋势,其与这些代谢症状的关联增加了患糖尿病和心血管疾病(以及许多其他疾病)的风险。研究需要确定肥胖和 MetS 增加疾病风险的机制。鉴于这种日益严重的流行,有必要开发代谢综合征的动物模型。这些模型将有助于确定 MetS 的病理生理基础以及 MetS 如何增加患其他疾病的风险。在用于研究 MetS 的各种动物模型中,由于以下几个原因,小鼠是最常用的模型之一。首先,有几种自发肥胖的小鼠品系已经使用了几十年,并且特征非常明显。其次,高脂肪喂养研究仅需数月即可诱导 MetS。第三,通过开发转基因或基因敲除来研究单个基因的影响相对容易,以确定一个基因对 MetS 的影响。基于这些原因,本综述将重点介绍最常见的 MetS 小鼠模型的优点和局限性。我们希望读者能够将本综述作为选择适合自己研究的小鼠模型的指南。