Identification of the principal transcriptional regulators for low-fat and high-fat meal responsive genes in small intestine.
Identification of the principal transcriptional regulators for low-fat and high-fat meal responsive genes in small intestine.
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DOI：
10.1186/s12986-017-0221-3
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发表时间：
2017
影响因子：
4.5
通讯作者：
St-Amand J
中科院分区：
文献类型：
--
作者：
Mucunguzi O;Melouane A;Ghanemi A;Yoshioka M;Boivin A;Calvo EL;St-Amand J
高脂肪（HF）饮食是众所周知的肥胖原因。为了确定可能成为肥胖症治疗靶点的主要转录调节因子，我们研究了低脂（LF）和HF餐摄入后十二指肠粘膜中的转录组学调节。一组小鼠禁食后处死，另一组小鼠自由进食LF或HF餐，并在开始进餐后30 min、1 h和3 h处死。使用基因表达的微阵列和系列分析（SAGE）方法以及随后的不相容性途径分析（IPA）对7组的十二指肠粘膜进行转录组分析。SAGE和微阵列显示，与禁食条件相比，LF和/或HF餐后十二指肠粘膜中总共896个转录本的调节。IPA将脂质代谢、分子转运和小分子生物化学确定为HF-应答、HF-特异性、HF-延迟和LF-HF不同基因的前三大分子和细胞功能。此外，HF反应性和HF特异性基因的最高转录调节因子是过氧化物酶体增殖物激活受体α（PPARα）。另一方面，LF响应和LF特异性基因与碳水化合物代谢、细胞功能和维持以及细胞死亡/细胞生长和增殖相关，并且顶部转录调控因子分别是叉头盒蛋白O 1（FOXO 1）和cAMP响应元件结合蛋白1（CREB 1）。这些结果将有助于了解LF和HF摄入后肠道反应的分子机制，并有助于确定肥胖和肥胖相关疾病的治疗靶点。本文的在线版本（10.1186/s12986-017-0221-3）包含补充材料，可供授权用户使用。
High-fat (HF) diet is a well-known cause of obesity. To identify principle transcriptional regulators that could be therapeutic targets of obesity, we investigated transcriptomic modulation in the duodenal mucosa following low-fat (LF) and HF meal ingestion. Whereas one group of mice was sacrificed after fasting, the others were fed ad libitum with LF or HF meal, and sacrificed 30 min, 1 h and 3 h after the beginning of the meal. A transcriptome analysis of the duodenal mucosa of the 7 groups was conducted using both microarray and serial analysis of gene expression (SAGE) method followed by an Ingenuity Pathways Analysis (IPA). SAGE and microarray showed that the modulation of a total of 896 transcripts in the duodenal mucosa after LF and/or HF meal, compared to the fasting condition. The IPA identified lipid metabolism, molecular transport, and small molecule biochemistry as top three molecular and cellular functions for the HF-responsive, HF-specific, HF-delay, and LF-HF different genes. Moreover, the top transcriptional regulator for the HF-responsive and HF-specific genes was peroxisome proliferator-activated receptor alpha (PPARα). On the other hand, the LF-responsive and LF-specific genes were related to carbohydrate metabolism, cellular function and maintenance, and cell death/cellular growth and proliferation, and the top transcriptional regulators were forkhead box protein O1 (FOXO1) and cAMP response element binding protein 1 (CREB1), respectively. These results will help to understand the molecular mechanisms of intestinal response after LF and HF ingestions, and contribute to identify therapeutic targets for obesity and obesity-related diseases. The online version of this article (10.1186/s12986-017-0221-3) contains supplementary material, which is available to authorized users.
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影响因子：
4.4
作者：
de Vogel-van den Bosch HM;Bünger M;de Groot PJ;Bosch-Vermeulen H;Hooiveld GJ;Müller M
通讯作者：
Müller M
DOI：
10.1016/j.bbadis.2010.12.010
发表时间：
2011-08
影响因子：
6.2
作者：
Fernandez-Marcos, Pablo J.;Auwerx, Johan;Schoonjans, Kristina
通讯作者：
Schoonjans, Kristina
影响因子：
7.1
作者：
SCHUTZ, Y;FLATT, JP;JEQUIER, E
通讯作者：
JEQUIER, E
影响因子：
4.8
作者：
Schmoll, D;Walker, KS;Unterman, TG
通讯作者：
Unterman, TG
DOI：
10.1073/pnas.0908641106
发表时间：
2009-10-13
影响因子：
11.1
作者：
Ruffell, Daniela;Mourkioti, Foteini;Nerlov, Claus
通讯作者：
Nerlov, Claus