Dietary effects of arachidonate-rich fungal oil and fish oil on murine hepatic and hippocampal gene expression.

Dietary effects of arachidonate-rich fungal oil and fish oil on murine hepatic and hippocampal gene expression.
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DOI:
10.1186/1476-511x-1-2
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发表时间:
2002-10-21
影响因子:
4.5
通讯作者:
Roberts, Matthew A
Roberts, Matthew A
中科院分区:
医学3区
文献类型:
--
作者:
Berger, Alvin;Mutch, David M;Roberts, Matthew A

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背景技术背景:鱼油和其他来源的长链多不饱和脂肪酸(LC-PUFA)的消费影响组织代谢的功能,作用和调节仍然知之甚少;特别是LC-PUFA如何影响参与调节代谢的基因的转录。在目前的工作中,小鼠的饮食中含有富含二十碳五烯酸和二十二碳六烯酸的鱼油,富含花生四烯酸的真菌油,或两者的组合。肝脏和海马组织,然后分析通过相结合的基因表达和脂质谱的策略,以注释的分子功能和目标的饮食LC-PUFA.RESULTS:使用微阵列技术,329和356饮食调节转录本确定在肝脏和海马,分别。所有选择为差异表达的基因通过组合的k-means/分层聚类方法按表达模式分组,并使用基因本体分类进行注释。在肝脏中,基因组与转录因子PPARalpha、HNF alpha和SREBP-1相关;这些转录因子已知控制脂质代谢。差异调节基因的模式,进一步支持定量脂质分析,表明实验饮食增加肝脏β-氧化和脂肪生成,同时减少脂肪酸合成。最后,新的海马基因的变化被identified.CONCLUSIONS:检查广泛的LC-PUFAs的转录效应证实了先前确定的PUFA介导的基因表达的变化,并确定了新的基因靶点。基因表达谱显示了一个复杂和多样的基因模式的生物反应饮食LC-PUFA。研究饮食变化的结果突出了对主要真核脂质代谢转录因子的广谱影响。进一步的重点研究,源于这样的转录组学数据,将需要剖析转录因子信号通路,以充分解释鱼油和花生四烯酸如何实现其对健康的特定影响。
BACKGROUND: The functions, actions, and regulation of tissue metabolism affected by the consumption of long chain polyunsaturated fatty acids (LC-PUFA) from fish oil and other sources remain poorly understood; particularly how LC-PUFAs affect transcription of genes involved in regulating metabolism. In the present work, mice were fed diets containing fish oil rich in eicosapentaenoic acid and docosahexaenoic acid, fungal oil rich in arachidonic acid, or the combination of both. Liver and hippocampus tissue were then analyzed through a combined gene expression- and lipid- profiling strategy in order to annotate the molecular functions and targets of dietary LC-PUFA.RESULTS: Using microarray technology, 329 and 356 dietary regulated transcripts were identified in the liver and hippocampus, respectively. All genes selected as differentially expressed were grouped by expression patterns through a combined k-means/hierarchical clustering approach, and annotated using gene ontology classifications. In the liver, groups of genes were linked to the transcription factors PPARalpha, HNFalpha, and SREBP-1; transcription factors known to control lipid metabolism. The pattern of differentially regulated genes, further supported with quantitative lipid profiling, suggested that the experimental diets increased hepatic beta-oxidation and gluconeogenesis while decreasing fatty acid synthesis. Lastly, novel hippocampal gene changes were identified.CONCLUSIONS: Examining the broad transcriptional effects of LC-PUFAs confirmed previously identified PUFA-mediated gene expression changes and identified novel gene targets. Gene expression profiling displayed a complex and diverse gene pattern underlying the biological response to dietary LC-PUFAs. The results of the studied dietary changes highlighted broad-spectrum effects on the major eukaryotic lipid metabolism transcription factors. Further focused studies, stemming from such transcriptomic data, will need to dissect the transcription factor signaling pathways to fully explain how fish oils and arachidonic acid achieve their specific effects on health.