Sugar sensor genes in the murine gastrointestinal tract display a cephalocaudal axis of expression and a diurnal rhythm
Sugar sensor genes in the murine gastrointestinal tract display a cephalocaudal axis of expression and a diurnal rhythm
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DOI：
10.1152/physiolgenomics.00139.2017
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发表时间：
2018-06-01
影响因子：
4.6
通讯作者：
Corpe, Christopher
中科院分区：
文献类型：
--
作者：
O'Brien, Patrick;Hewett, Rhys;Corpe, Christopher
营养感应细胞分布在胃肠道中，它们释放大量影响胃肠道功能、营养稳态和能量平衡的信号肽。最近的研究表明，胃肠道营养感知具有昼夜节律。但是对节律的机制却知之甚少。在本报告中，我们研究了小鼠GI糖传感器基因和蛋白在早上（上午7点）和晚上（晚上7点）的表达水平。甜味受体（tas1r2/tas1r3/gnat3/gnat1）糖转运体（slc5a1、slc2a2、slc2a5）和推测糖传感器（slc5a4a和slc5a4b）基因在舌头和小肠近端和远端表达水平最高。时钟基因（cry2/arntl）在所有研究区域均检测到活性。Slc5a4a和slc5a4b基因在小肠和胃中分别表现出明显的昼夜节律性，而SGLT3蛋白的表达没有节律性。Tas1r2、tas1r3、gnat1和gcg基因在近端小肠中的表达节律有限。微阵列分析显示舌头肠道肽基因表达的昼夜节律（上午7点与晚上7点），硅启动子分析表明肠道糖传感器和转运体具有时钟基因控制基因转录所需的典型E盒元件。在本报告中，我们提出的证据表明，负责肠道营养感知的基因的昼夜节律最有可能由时钟基因活性控制。时钟基因/营养感知相互作用的干扰可能在饮食相关疾病（如肥胖和糖尿病）的发展中很重要。
Distributed along the length of the gastrointestinal (GI) tract are nutrient sensing cells that release numerous signaling peptides influencing GI function, nutrient homeostasis and energy balance. Recent studies have shown a diurnal rhythm in GI nutrient sensing. but the mechanisms responsible for rhythmicity arc poorly understood. In this report we studied murine GI sugar sensor gene and protein expression levels in the morning (7 AM) and evening (7 PM). Sweet taste receptor (tas1r2/tas1r3/gnat3/gnat1) sugar transporter (slc5a1, slc2a2, slc2a5) and putative sugar sensor (slc5a4a and slc5a4b) gene expression levels were highest in tongue and proximal and distal small intestine, respectively. Clock gene (cry2/arntl) activity was detected in all regions studied. Slc5a4a and slc5a4b gene expression showed clear diurnal rhythmicity in the small intestine and stomach, respectively, although no rhythmicity was detected in SGLT3 protein expression. Tas1r2, tas1r3, gnat1, and gcg displayed a limited rhythm in gene expression in proximal small intestine. Microarray analysis revealed a diurnal rhythm in gut peptide gene expression in tongue (7 AM vs. 7 PM) and in silico promoter analysis indicated intestinal sugar sensors and transporters possessed the canonical E box elements necessary for clock gene control over gene transcription. In this report we present evidence of a diurnal rhythm in genes that are responsible for intestinal nutrient sensing that is most likely controlled by clock gene activity. Disturbances in clock gene/nutrient sensing interactions may be important in the development of diet-related diseases, such as obesity and diabetes.