Assessment of diet-induced obese rats as an obesity model by comparative functional genomics
Assessment of diet-induced obese rats as an obesity model by comparative functional genomics
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DOI：
10.1038/oby.2007.116
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发表时间：
2008-04-01
期刊：
影响因子：
6.9
通讯作者：
Chen, Yanyun
中科院分区：
文献类型：
--
作者：
Li, Shuyu;Zhang, Hong-Yan;Chen, Yanyun
目的：我们应用比较功能基因组学方法来评估饮食诱导肥胖（DIO）大鼠是否是一种有效的肥胖模型。方法和步骤：使用微阵列生成DIO和瘦大鼠附睾脂肪的基因表达谱，并与已发表的肥胖和非肥胖人类皮下脂肪细胞的阵列数据进行比较。DIO大鼠的热量摄入和燃料效率显著较高，导致体重增加和肥胖。DIO大鼠的循环葡萄糖、胆固醇、甘油三酯、胰岛素和瘦素水平显著高于瘦对照组。DIO大鼠也表现出受损的胰岛素敏感性。DIO和瘦大鼠的基因表达谱与肥胖和非肥胖人类的基因表达谱的直接比较显示，DIO大鼠脂肪中的全球基因表达模式与肥胖人类脂肪细胞的基因表达模式相似。在人类和大鼠研究中，肥胖和非肥胖受试者之间的差异表达基因被鉴定，并通过将基因映射到基因本体（GO）类别来与生物学途径相关联。与非肥胖对照组相比，肥胖人和DIO大鼠的免疫应答相关基因和血管生成相关基因均显著上调。然而，脂肪酸代谢和氧化的基因表现出广泛的下调，只有在肥胖的人脂肪细胞，但不是在DIO大鼠附睾fat.Discussion：我们的研究的基础上基因表达谱表明，DIO大鼠一般代表一个适当的肥胖模型。然而，DIO大鼠和肥胖人类之间基因表达改变的差异，特别是在代谢途径中，可以解释在肥胖研究和药物发现中使用DIO啮齿动物模型的局限性。
Objective: We applied a comparative functional genomics approach to evaluate whether diet-induced obese ( DIO) rats serve as an effective obesity model.Methods and Procedures: Gene-expression profiles of epididymal fat from DIO and lean rats were generated using microarrays and compared with the published array data of obese and non-obese human subcutaneous adipocytes.Results: Caloric intake and fuel efficiency were significantly higher in DIO rats, which resulted in increased body weight and adiposity. Circulating glucose, cholesterol, triglyceride, insulin, and leptin levels in DIO rats were significantly higher than those in the lean controls. DIO rats also exhibited impaired insulin sensitivity. A direct comparison of gene-expression profiles from DIO and lean rats and those from obese and non-obese humans revealed that global gene-expression patterns in DIO rat fat resemble those of obese human adipocytes. Differentially expressed genes between obese and non-obese subjects in both human and rat studies were identified and associated with biological pathways by mapping genes to Gene Ontology ( GO) categories. Immune response-related genes and angiogenesis-related genes exhibited significant upregulation in both obese humans and DIO rats when compared with non-obese controls. However, genes in fatty acid metabolism and oxidation exhibited a broad downregulation only in obese human adipocytes but not in DIO rat epididymal fat.Discussion: Our study based on gene-expression profiling suggested that DIO rats in general represent an appropriate obesity model. However, the discrepancies in gene-expression alterations between DIO rats and obese humans, particularly in the metabolic pathways, may explain the limitations of using DIO rodent models in obesity research and drug discovery.