Induction of fatty acid synthase and S14 gene expression by glucose, xylitol and dihydroxyacetone in cultured rat hepatocytes is closely correlated with glucose 6-phosphate concentrations
Induction of fatty acid synthase and S14 gene expression by glucose, xylitol and dihydroxyacetone in cultured rat hepatocytes is closely correlated with glucose 6-phosphate concentrations
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DOI：
10.1042/bj3260345
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发表时间：
1997-09-01
影响因子：
4.1
通讯作者：
Ferre, P
中科院分区：
文献类型：
--
作者：
Mourrieras, F;Foufelle, F;Ferre, P
现在已经确定，在脂肪细胞和肝细胞中存在高浓度葡萄糖时，属于糖酵解和脂肪生成途径的几种基因的转录受到刺激。我们先前提出葡萄糖6-磷酸可能是转导葡萄糖效应的信号代谢物。这一提议最近受到了挑战，并且已经提出了戊糖磷酸途径的中间体木酮糖5-磷酸和糖酵解后期部分的代谢物（3-磷酸甘油酸和磷酸烯醇丙酮酸）。为了区分这些可能性，我们同时测量了成年大鼠肝细胞的原代培养物中脂肪酸合成酶（FAS）和S14基因的表达以及葡萄糖代谢产物的浓度。我们已经使用了在糖酵解途径（葡萄糖、二羟基丙酮）和磷酸戊糖途径（木糖醇）的不同步骤进入的各种底物。与5 mM葡萄糖相比，25 mM葡萄糖诱导S14和FAS基因表达显著增加，早在2 h即可检测到，并在6 h达到峰值。在5 mM葡萄糖存在下，增加木糖醇和二羟基丙酮的浓度（1-5 mM）也能够逐渐诱导S14和FAS基因表达。在测量的各种葡萄糖代谢产物中，葡萄糖6-磷酸与木酮糖5-磷酸和糖酵解下部的代谢产物相反，是唯一一种显示其浓度与S14和FAS基因表达程度之间的明确平行性的葡萄糖6-磷酸。我们的结论是，葡萄糖6-磷酸是最有可能的信号代谢产物的葡萄糖诱导的这组基因的转录。
It is now well established that the transcription of several genes belonging to the glycolytic and lipogenic pathway is stimulated in the presence of a high glucose concentration in adipocytes and hepatocytes. We have previously proposed that glucose 6-phosphate could be the signal metabolite that transduces the glucose effect. This proposal has recently been challenged and both an intermediate of the pentose phosphate pathway, xylulose 5-phosphate, and metabolites of the later part of glycolysis (3-phosphoglycerate and phosphoenolpyruvate) have been proposed. To discriminate between these possibilities, we have measured concomitantly, in primary cultures of adult rat hepatocytes, the expression of the fatty acid synthase (FAS) and S14 genes and the concentration of glucose metabolites. We have used various substrates entering at different steps of the glycolytic pathway (glucose, dihydroxyacetone) and the pentose phosphate pathway (xylitol). When compared with 5 mM glucose, 25 mM glucose induces a marked increase in both S14 and FAS gene expression, detectable as early as 2 h and peaking at 6 h. Increasing concentrations (1-5 mM) of xylitol and dihydroxyacetone in the presence of 5 mM glucose are also able to induce S14 and FAS gene expression progressively. Among the various glucose metabolites measured, glucose 6-phosphate, in contrast with xylulose 5-phosphate and metabolites of the lower part of glycolysis, is the only one that shows a clear-cut parallelism between its concentration and the degree of S14 and FAS gene expression. We conclude that glucose 6-phosphate is the most likely signal metabolite for the glucose-induced transcription of this group of genes.