高脂肪喂养对糖尿病后崎大鼠肝脏基因表达的影响。

Gene regulation and systems biology Pub Date : 2012-01-01 Epub Date: 2012-11-28 DOI:10.4137/GRSB.S10371
Richard R Almon, Debra C Dubois, Siddharth Sukumaran, Xi Wang, Bai Xue, Jing Nie, William J Jusko
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引用次数: 12

摘要

在人类和啮齿类动物中,高脂肪饮食(HFD)对肥胖以及随后对糖尿病的影响是高度可变的,并受到基因的调节。在本报告中,我们描述了Goto-Kakizaki (GK)大鼠(一种自发性多基因模型,用于瘦型糖尿病和健康Wistar-Kyoto (WKY)对照)从断奶到20周龄对高脂肪喂养的反应。分别在4、8、12、16和20周龄时处死正常饮食或高热量饮食的动物,并使用Affymetrix基因阵列芯片进行广泛的生理测量和基因表达谱分析。对微阵列数据的挖掘发现了糖尿病动物中差异调节的基因(涉及炎症、代谢、转录调节和信号传导),以及两种菌株对HFD的反应。功能注释表明HFD增加了两株之间的炎症差异。由先天免疫反应增强引起的慢性炎症被确定存在于GK动物中,与饮食无关。此外,我们还发现了使用HFD的WKY动物抵抗糖尿病发展的代偿机制,从而说明了糖尿病疾病进展的复杂性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Effects of high fat feeding on liver gene expression in diabetic goto-kakizaki rats.

Effects of high fat diet (HFD) on obesity and, subsequently, on diabetes are highly variable and modulated by genetics in both humans and rodents. In this report, we characterized the response of Goto-Kakizaki (GK) rats, a spontaneous polygenic model for lean diabetes and healthy Wistar-Kyoto (WKY) controls, to high fat feeding from weaning to 20 weeks of age. Animals fed either normal diet or HFD were sacrificed at 4, 8, 12, 16 and 20 weeks of age and a wide array of physiological measurements were made along with gene expression profiling using Affymetrix gene array chips. Mining of the microarray data identified differentially regulated genes (involved in inflammation, metabolism, transcription regulation, and signaling) in diabetic animals, as well as the response of both strains to HFD. Functional annotation suggested that HFD increased inflammatory differences between the two strains. Chronic inflammation driven by heightened innate immune response was identified to be present in GK animals regardless of diet. In addition, compensatory mechanisms by which WKY animals on HFD resisted the development of diabetes were identified, thus illustrating the complexity of diabetes disease progression.

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