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

Mourrieras, Florence; Foufelle, Fabienne; Foretz, Marc; Morin, Jean Paul; Bouche, Sandrine; Ferré, Pascal

doi:10.1042/bj3260345

Cited by 71 publications

(57 citation statements)

References 33 publications

(37 reference statements)

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“…The effect of glucose is mimicked by 2-deoxyglucose, a glucose analogue which is not further metabolized after its phosphorylation into 2-deoxyglucose-6-phosphate, which accumulates in the cell (Foufelle et al 1992). Intracellular glucose-6-phosphate concentration varies in parallel with the expression of FAS, whereas that of other potential metabolites does not (Mourrieras et al 1997). Moreover, in vivo, the kinetics of hexose phosphate concentration fit with the time-related pattern of FAS gene induction.…”

Section: Glucose-6-phosphate Could Be the Signal Metabolitementioning

confidence: 80%

Regulation of gene expression by glucose

Ferré¹

1999

Proc. Nutr. Soc.

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Fatty acid synthase (EC 2.3.1.85) is an enzyme involved in the lipogenic pathway allowing fatty acid synthesis from glucose. Glucose up-regulates the transcription of the fatty acid synthase gene in both adipocytes and hepatocytes, with insulin having only an indirect role. The signal metabolite could be glucose-6-phosphate rather than glucose itself. The glucose response element of the fatty acid synthase gene has not yet been precisely identified, although a −2 kb region of the fatty acid synthase promoter is sufficient to confer nutritional responsiveness to a reporter gene. ADD1/SREBP1, a b-HLH-LZ transcription factor belonging to the sterol regulatory element-binding protein family might be involved in the transduction of the glucose effect. Finally, the stimulatory effect of glucose on the expression of the fatty acid synthase gene is inhibited by the activation of AMP-activated protein kinase. Interestingly enough, AMP-activated protein kinase is structurally and functionally related to the yeast SNF1 protein kinase complex which is essential for the transcriptional activation of glucose-repressed genes in Saccharomyces cerevisiae.

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Section: Glucose-6-phosphate Could Be the Signal Metabolitementioning

confidence: 80%

Regulation of gene expression by glucose

Ferré¹

1999

Proc. Nutr. Soc.

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“…Moreover, xylitol induces the expression of ChREBP target genes such as Pklr, S14 and Fasn in rat primary hepatocytes [33,34]. Thus, X5P is a glucose signal regulating the expression of glucose and lipid metabolism genes in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…In primary hepatocytes, xylitol is converted into X5P by XYLB, and X5P enters the non-oxidative branch of the pentose phosphate pathway [31][32][33][34]. Moreover, xylitol induces the expression of ChREBP target genes such as Pklr, S14 and Fasn in rat primary hepatocytes [33,34].…”

Section: Discussionmentioning

confidence: 99%

Role of glucose-6-phosphate and xylulose-5-phosphate in the regulation of glucose-stimulated gene expression in the pancreatic β cell line, INS-1E

Iizuka

Horikawa

et al. 2013

Endocr J

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“…Glycerol (2 mM) was also able to elicit a small increase in Glc-6-Pase mRNA; however, higher concentrations (Ͼ2 mM) of glycerol had an inhibitory effect. (26) have recently challenged the idea of Glc-6-P (27,28) as the signaling molecule that transduces the effect of glucose in regulating the expression of certain genes. Instead, they propose that xylulose 5-phosphate, a metabolite in the pentose phosphate pathway, may be the major messenger candidate that transduces the effect of glucose.…”

Section: Glucose Induces Glc-6-pase Mrna Production In Primarymentioning

confidence: 99%

Regulation of the Glucose-6-phosphatase Gene by Glucose Occurs by Transcriptional and Post-transcriptional Mechanisms

Massillon¹

2001

Journal of Biological Chemistry

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To understand how glucose regulates the expression of the glucose-6-phosphatase gene, the effect of glucose was studied in primary cultures of rat hepatocytes. Glucose-6-phosphatase mRNA levels increased about 10-fold when hepatocytes were incubated with 20 mM glucose. The rate of transcription of the glucose-6-phosphatase gene increased about 3-fold in hepatocytes incubated with glucose. The half-life of glucose-6-phosphatase mRNA was estimated to be 90 min in the absence of glucose and 3 h in its presence. Inhibition of the oxidative and the nonoxidative branches of the pentose phosphate pathway blocked the stimulation of glucose-6-phosphatase expression by glucose but not by xylitol or carbohydrates that enter the glycolytic/gluconeogenic pathways at the level of the triose phosphates. These results indicate that (i) the glucose induction of the mRNA for the catalytic unit of glucose-6-phosphatase occurs by transcriptional and post-transcriptional mechanisms and that (ii) xylitol and glucose increase the expression of this gene through different signaling pathways.Glc-6-Pase 1 (EC 3.1.3.9) is a multicomponent protein complex comprising catalytic and transporting entities (1-5). The complex is tightly associated with the endoplasmic reticulum, and the enzymatic component catalyzes the hydrolysis of glucose 6-phosphate to glucose, a final common step to both the pathways of glycogenolysis and gluconeogenesis. Hepatic Glc-6-Pase activity is effectively regulated by hormonal and nutritional status. For example, fasting and hormones that increase cAMP concentration stimulate its gene expression while refeeding and insulin decrease it (1, 2, 6 -12).The expression of the genes for several other proteins is regulated by glucose; these include genes for L-type pyruvate kinase (13, 14), fatty-acid synthase (15, 16), PEPCK (17, 18), and the type 2 glucose transporter (GLUT-2) (19,20). The mechanism by which glucose regulates the expression of these genes remains largely unknown. Recently, Kahn and colleagues (21, 22) have proposed a signaling pathway model to explain the molecular mechanism by which glucose regulates the expression of the L-type pyruvate kinase. This model consists of the following details: (i) the presence of glucose is sensed in the cell; (ii) this information is transduced by intracellular messengers; (iii) a second messenger, presumably xylulose 5-phosphate, rises and then modulates the activity of protein kinase and protein phosphatase involved in a cascade of phosphorylation/dephosphorylation. This cascade then leads to a modification of the phosphorylation state of the glucoseresponsive complex, followed by an increase in the transcriptional rate of the target gene. In this model, the presence of an active glucokinase that phosphorylates glucose to glucose 6-phosphate (Glc-6-P) is paramount.The molecular mechanism by which glucose regulates the expression of the Glc-6-Pase gene is currently unknown. Here we show that glucose regulation of the expression of this gene involves metabolism of glucose...

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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

Cited by 71 publications

References 33 publications

Regulation of gene expression by glucose

Regulation of gene expression by glucose

Role of glucose-6-phosphate and xylulose-5-phosphate in the regulation of glucose-stimulated gene expression in the pancreatic β cell line, INS-1E

Regulation of the Glucose-6-phosphatase Gene by Glucose Occurs by Transcriptional and Post-transcriptional Mechanisms

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