Sakamuri Siva Sankara Vara Prasad, Putcha Uday Kumar, Veettil Giridharan Nappan, Ayyalasomayajula Vajreswari
Department of Biochemistry, National Institute of Nutrition (ICMR), Hyderabad, India.
Department of Pathology, National Institute of Nutrition (ICMR), Hyderabad, India.
Indian J Med Res. 2016 Sep;144(3):409-423. doi: 10.4103/0971-5916.198667.
BACKGROUND & OBJECTIVES: Adipose tissue dysfunction in obesity is linked to the development of type 2 diabetes and cardiovascular diseases. We studied the differential gene expression in retroperitoneal adipose tissue of a novel obese rat model, WNIN/Ob, to understand the possible underlying transcriptional changes involved in the development of obesity and associatedcomorbidities in this model.
Four month old, male WNIN/Ob lean and obese rats were taken, blood was collected and tissues were dissected. Body composition analysis and adipose tissue histology were performed. Global gene expression in retroperitoneal adipose tissue of lean and obese rats was studied by microarray using Affymetrix GeneChips.
One thousand and seventeen probe sets were downregulated and 963 probe sets were upregulated (more than two-fold) in adipose tissue of WNIN/Ob obese rats when compared to that of lean rats. Small nucleolar RNA (SnoRNA) made most of the underexpressed probe sets, whereas immune system-related genes werethe most overexpressed in the adipose tissues of obese rats. Genes coding for cytoskeletal proteinswere downregulated, whereas genes related to lipid biosynthesis were elevated in the adipose tissue of obese rats.
INTERPRETATION & CONCLUSIONS: Majority of the altered genes and pathways in adipose tissue of WNIN/Ob obese rats were similar to the observations in other obese animal models and human obesity. Based on these observations, it is proposed that WNIN/Ob obese rat model may be a good model to study the mechanisms involved in the development of obesity and its comorbidities. Downregulation of SnoRNA appears to be a novel feature in this obese rat model.
肥胖状态下的脂肪组织功能障碍与2型糖尿病和心血管疾病的发生发展相关。我们研究了一种新型肥胖大鼠模型WNIN/Ob腹膜后脂肪组织中的基因差异表达,以了解该模型中肥胖及其相关合并症发生发展过程中可能涉及的潜在转录变化。
选取4月龄的雄性WNIN/Ob瘦鼠和肥胖鼠,采集血液并解剖组织。进行身体成分分析和脂肪组织组织学检查。使用Affymetrix基因芯片通过微阵列研究瘦鼠和肥胖鼠腹膜后脂肪组织中的整体基因表达。
与瘦鼠相比,WNIN/Ob肥胖鼠脂肪组织中有1017个探针集下调,963个探针集上调(超过两倍)。小核仁RNA(SnoRNA)构成了大部分表达下调的探针集,而免疫系统相关基因在肥胖鼠的脂肪组织中表达上调最为明显。编码细胞骨架蛋白的基因下调,而与脂质生物合成相关的基因在肥胖鼠的脂肪组织中升高。
WNIN/Ob肥胖鼠脂肪组织中大多数改变的基因和途径与其他肥胖动物模型和人类肥胖中的观察结果相似。基于这些观察结果,提出WNIN/Ob肥胖大鼠模型可能是研究肥胖及其合并症发生发展机制的良好模型。SnoRNA的下调似乎是该肥胖大鼠模型的一个新特征。