Several Transcription Factors Are Recruited to the Glucose-6-Phosphatase Gene Promoter in Response to Palmitate in Rat Hepatocytes and H4IIE Cells

Xu, Chuang; Chakravarty, Kaushik; Kong, Xiaoying; Tuy, Tertius; Arinze, Ifeanyi J.; Bone, Frederic; Massillon, Duna

doi:10.1093/jn/137.3.554

Cited by 27 publications

(21 citation statements)

References 37 publications

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“…1A). Oleate was used as a positive control for nutrient-induced G6pc expression (26). As expected, 20 mM glycerol administration (for 2 h) significantly increased endogenous G6pc expression 1.44 fold (compared with vehicle moter region (−143/+72).…”

Section: Effects Of Glycerol And/or Oleate On G6pc Expression In Fao supporting

confidence: 61%

“…Using several deletion-or chimeric-constructs of the G6pc promoter, we found that the DNA response element for HNF4α (−77/−65) is critical in the transactivation by glycerol. Administration of a saturated long-chain fatty acid, palmitate, has been shown to increase G6pc transcription by inducing the recruitment of HNF4α to the promoter (26). That study also found that oleate increases G6pc transcription.…”

Section: Temporal Changes Of G6pc Expression By Glycerol And/or Oleatementioning

confidence: 68%

“…In addition, several metabolites (such as glucose and fatty acids) are known to stimulate G6pc expression. In regard to the effects of fatty acids, Xu et al examined the transactivation mechanism of G6pc by palmitate (a saturated long-chain fatty acid) and oleate (a mono-unsaturated fatty acid) and found that several transcription factors such as HNF4α, peroxisome proliferator-activated receptor α (PPARα), CAAT/enhancer binding protein (C/EBP) and cAMP regulatory element binding protein (CREB) are involved in the regulation (26). However, the effect of glycerol on G6pc transcription has not been reported.…”

Section: Temporal Changes Of G6pc Expression By Glycerol And/or Oleatementioning

confidence: 99%

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Importance of Hepatocyte Nuclear Factor 4α in Glycerol-induced Glucose-6-phosphatase Expression in Liver

et al. 2016

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Glucose-6-phosphatase (G6Pase) is a key regulator of gluconeogenesis. We previously found that administration of glycerol, a substrate for gluconeogenesis, transactivates G6Pase in the mouse liver. To clarify its cell-autonomous transcriptional activation in hepatocytes, we examined the mechanism of expression of the gene G6pc, which encodes G6Pase, in rat hepatoma cell line FAO cells. Endogenous G6pc expression in FAO cells was increased by glycerol administration as well as by the fatty acid oleate. Luciferase reporter assay revealed that the ~2.0 kb mouse G6pc promoter contains the element(s) responsible for glycerol-stimulated G6pc transactivation. Using several deletion-or chimeric-constructs of G6pc promoter, we found that the DNA response element for hepatocyte nuclear factor 4α (HNF4α) (−77/−65) in the G6pc promoter is essential for transactivation by glycerol. Similarly to glycerol, oleate also increased G6pc expression through its action on the HNF4α element (−77/−65). Furthermore, the reporter activities were higher in the cells co-treated with glycerol plus oleate than in those singly treated with glycerol or oleate. In addition, the temporal profiles of G6pc expression differed between glycerol and oleate administration. Our present results suggest that glycerol and oleate induce G6pc expression both via the HNF4α element (−77/−65) and also through other regulatory mechanisms.

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Section: Effects Of Glycerol And/or Oleate On G6pc Expression In Fao supporting

confidence: 61%

Section: Temporal Changes Of G6pc Expression By Glycerol And/or Oleatementioning

confidence: 68%

Section: Temporal Changes Of G6pc Expression By Glycerol And/or Oleatementioning

confidence: 99%

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Importance of Hepatocyte Nuclear Factor 4α in Glycerol-induced Glucose-6-phosphatase Expression in Liver

et al. 2016

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“…In the liver, HNF4α is believed to be involved in protein kinase A regulation of the G6Pase gene (5,23), and its down-regulation is expected to cause the decrease in G6Pase expression. Although the difference was without a statistical significance, the present result of Q-PCR showed that the gene expression of HNF4α tended to be reduced in the green tea group (Fig.…”

Section: Resultsmentioning

confidence: 99%

Effects of chronic ingestion of catechin-rich green tea on hepatic gene expression of gluconeogenic enzymes in rats

et al. 2009

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Normal rats were given catechin-rich green tea as drinking fluid and the effects on hepatic gene expression were examined. The results of DNA microarray analysis and quantitative real-time reverse transcription-polymerase chain reaction indicated the down-regulated expression of genes for glucose-6-phosphatase (G6Pase) and fatty acid synthase, and the up-regulated expression of peroxisome proliferator activated receptor α in the rats given green tea for 4 weeks as compared with the water-given animals. One may expect anti-diabetic activity by catechin-rich green tea through its chronic down-regulatory effect on G6Pase expression.

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“…HNF4α gene expression was also down-regulated by GTB, suggesting an association with the down-regulated gene expression of gluconeogenic enzymes. HNF4α is believed to be involved in protein kinase A's regulation of the G6Pase gene (6,19) and has a key role in regulating the PEPCK gene (9,14). Therefore, its down-regulation is expected to cause a decrease in G6Pase and PEPCK expression.…”

Section: Effects Of Fractions Derived From Gtb On Gene Expression In mentioning

confidence: 99%

Effects of catechin-rich green tea on gene expression of gluconeogenic enzymes in rat hepatoma H4IIE cells

et al. 2010

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Rat hepatoma H4IIE cells were stimulated with dexamethasone and dibutyryl cAMP to increase gene expressions of gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Inclusion of catechin-rich green tea beverage (GTB) in the culture medium reduced the up-regulation of these genes as well as that of hepatocyte nuclear factor 4 alpha (HNF4α) gene. GTB was fractionated into chloroform-soluble (Fraction I), ethyl acetatesoluble (Fraction II), methanol-soluble (Fraction III) and residual (Fraction IV) fractions. Fractions II and III containing catechins caused an attenuation of the up-regulated expression of these genes as well as the down-regulation of HNF4α gene expression. Fraction IV had a synergistic effect on the up-regulation by dexamethasone/dibutyryl cAMP of the PEPCK gene expression and upregulated HNF4α gene expression. These results suggest that GTB down-regulated the expression of the HNF4α gene to cause the down-regulated gene expression of gluconeogenic enzymes. One reason why GTB did not down-regulate hepatic PEPCK gene expression in previous animal experiments may be that the component(s) acting to up-regulate PEPCK gene expression was more effective in vivo than in cultured cells.Tea is one of the world's most popular beverages and has been regarded to possess anti-cancer, antiobesity, anti-atherosclerotic, anti-diabetic, anti-bacterial, and anti-viral effects (4,7,8,17). Recently, it has been demonstrated that (−)-epigallocatechin gallate (EGCG), a major component of green tea catechins, represses glucose production in rat hepatoma H4IIE cells through down-regulation of the gene expression of gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), suggesting a beneficial effect of green tea on type 2 diabetes, since the disease is associated with enhanced glucose production in the post-absorptive state (16). Previously, we reported that the administration of catechin-rich green tea beverage (GTB) for 4 weeks caused a reduction in the gene expression of G6Pase, but not PEPCK, in the rat liver (1). The findings suggest that some component(s) of the green tea beverage other than catechins might affect the gene expression of PEPCK. We have also posed the possibility that forkhead box transcription factor 1a (Foxo1a) and hepatocyte nuclear factor 4α (HNF4α) may contribute to the down-regulated expression of G6Pase in the liver of GTB-treated rats (1).To answer these questions, we examined effects of GTB on the gene expression of gluconeogenic enzymes in rat hepatoma H4IIE cells using the quantitative real-time reverse transcription-polymerase chain reaction (Q-PCR). Our results suggest that the down-regulation of HNF4α by GTB is relat-

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Several Transcription Factors Are Recruited to the Glucose-6-Phosphatase Gene Promoter in Response to Palmitate in Rat Hepatocytes and H4IIE Cells

Cited by 27 publications

References 37 publications

<b>Importance of Hepatocyte Nuclear Factor 4α in Glycerol-induced Glucose-6-phosphatase Expression in </b><b>Liver </b>

<b>Importance of Hepatocyte Nuclear Factor 4α in Glycerol-induced Glucose-6-phosphatase Expression in </b><b>Liver </b>

Effects of chronic ingestion of catechin-rich green tea on hepatic gene expression of gluconeogenic enzymes in rats

Effects of catechin-rich green tea on gene expression of gluconeogenic enzymes in rat hepatoma H4IIE cells

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