Analysis of sterol-regulatory element-binding protein 1c target genes in mouse liver during aging and high-fat diet.

Q Agricultural and Biological Sciences

Journal of Nutrigenetics and Nutrigenomics Pub Date : 2013-01-01 Epub Date: 2013-06-12 DOI:10.1159/000350751

Frédéric Capel, Gaëlle Rolland-Valognes, Catherine Dacquet, Manuel Brun, Michel Lonchampt, Alain Ktorza, Brian Lockhart, Jean-Pierre Galizzi

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引用次数: 19

Abstract

Background: The sterol regulatory element-binding protein (SREBP) 1c contributes to the transcriptional coordination of cholesterol, fatty acid, and carbohydrate metabolisms. Alterations in these processes accelerate the progression of hepatic steatosis and insulin resistance during aging and obesity.

Methods: Using an ex vivo chromatin immunoprecipitation coupled to microarray (ChIP-on-chip) technique combined with genome-wide gene expression analysis, we analyzed the transcriptomic adaptations mediated by Srebp-1c binding to gene promoters in the liver of mice fed with a low-fat diet or a high-fat diet (HFD) for either 1 or 12 months.

Results: Aging had a higher transcriptional impact than HFD and modified the expression of genes involved in fatty acid oxidation and oxidative stress. HFD was associated with a marked induction of genes involved in lipid and cholesterol metabolism. The prolonged high-fat feeding together with the aging effects stimulates inflammatory pathways. ChIP-on-chip applied to aging and HFD analyses revealed that the binding of SREBP-1c to a series of promoters accompanied a paralleled modification of gene expression. Therefore, SREBP-1c could play a role in aging and high-fat feeding through the regulation of genes involved in lipid metabolism and inflammatory response.

Conclusions: This study represents an original ex vivo experiment to elucidate the molecular events involved in metabolic disorders.

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衰老和高脂饮食小鼠肝脏中胆固醇调节元件结合蛋白1c靶基因的分析。

背景:甾醇调节元件结合蛋白(SREBP) 1c参与胆固醇、脂肪酸和碳水化合物代谢的转录协调。在衰老和肥胖过程中，这些过程的改变加速了肝脂肪变性和胰岛素抵抗的进展。方法:采用体外染色质免疫沉淀耦合微阵列(ChIP-on-chip)技术结合全基因组基因表达分析，我们分析了在低脂饮食或高脂饮食(HFD)喂养1或12个月的小鼠肝脏中，Srebp-1c结合基因启动子介导的转录组适应。结果:衰老对转录的影响高于HFD，并改变了脂肪酸氧化和氧化应激相关基因的表达。HFD与参与脂质和胆固醇代谢的基因显著诱导相关。长时间的高脂肪喂养加上衰老效应刺激了炎症途径。ChIP-on-chip应用于衰老和HFD分析显示，SREBP-1c与一系列启动子的结合伴随着基因表达的平行修饰。因此，SREBP-1c可能通过调控脂质代谢和炎症反应相关基因，在衰老和高脂喂养中发挥作用。结论:本研究是一项原始的离体实验，旨在阐明代谢紊乱所涉及的分子事件。

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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来源期刊

Journal of Nutrigenetics and Nutrigenomics GENETICS & HEREDITY-NUTRITION & DIETETICS

CiteScore

1.86

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The emerging field of nutrigenetics and nutrigenomics is rapidly gaining importance, and this new international journal has been established to meet the needs of the investigators for a high-quality platform for their research. Endorsed by the recently founded "International Society of Nutrigenetics/Nutrigenomics", the ‘Journal of Nutrigenetics and Nutrigenomics’ welcomes contributions not only investigating the role of genetic variation in response to diet and that of nutrients in the regulation of gene expression, but is also open for articles covering all aspects of gene-environment interactions in the determination of health and disease.