The Effect of Dietary Fat or Cholesterol and Cholic Acid on the Rate of Synthesis of Rat Liver Glucose-6-P Dehydrogenase

Wolfe, Ronald G.; Holten, Darold

doi:10.1093/jn/108.10.1708

Cited by 15 publications

(6 citation statements)

References 23 publications

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“…It and a number of other key enzymes in fatty acid synthesis are regulated in co-ordinate fashion by the dietary and hormonal state of the animal. G6PD levels decrease during fasting [2][3][4], feeding on a high-fat diet [5][6][7], in alloxaninduced diabetes [2,8], with glucagon injections [9] and after thyroidectomy [10]. G6PD activity shows a strong positive correlation with the fraction of carbohydrate in the diet [11,12], and increases with exogenously administered hormones such as insulin [12,13] and thyroid hormones [2,14].…”

Section: Introductionmentioning

confidence: 99%

Regulation of glucose-6-phosphate dehydrogenase synthesis and mRNA abundance in cultured rat hepatocytes

Manos

Nakayama

Holten

1991

Biochemical Journal

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Conditions were identified which, for the first time, demonstrate that primary hepatocytes can express the same range of glucose-6-phosphate dehydrogenase (G6PD) synthesis and mRNA as in live rats. Primary hepatocytes were cultured without prior exposure to serum, hormones or carbohydrates. Five modulators implicated in G6PD induction in vivo were examined: insulin, dexamethasone, tri-iodothyronine (T3), glucose and fructose, T3 did not affect G6PD activity, and did not interact with carbohydrate to affect the activity of G6PD. Neither glucose nor fructose alone affected G6PD activity, and they did not interact with insulin to increase G6PD activity. Hepatocytes isolated from fasted rats and cultured in serum-free media with amino acids ad the only energy source how a 12-fold increase in G6PD synthesis and mRNA (measured by a solution-hybridization assay). This induction does not require added hormones or carbohydrate. The addition of insulin alone caused another increase in G6PD synthesis and mRNA. There are at least three distinct phases to G6PD induction under these conditions. The largest increase in G6PD synthesis (12-fold) occurs in the absence of any hormones and with amino acids as the only energy source. This phase is due to increased G6PD mRNA. Insulin causes an additional 2-3-fold increase in G6PD synthesis and mRNA. However, dexamethasone and insulin are both required before G6PD synthesis is equal to that in rats which are fasted and refed on a high-carbohydrate diet.

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Section: Introductionmentioning

confidence: 99%

Regulation of glucose-6-phosphate dehydrogenase synthesis and mRNA abundance in cultured rat hepatocytes

Manos

Nakayama

Holten

1991

Biochemical Journal

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“…These nutritionally induced changes in G6PD activity are pretranslational (17)(18)(19)(20)(21). Despite the 12-15-fold increase in G6PD mRNA abundance in the refed mouse, the transcriptional activity of the gene is not changed (22).…”

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confidence: 99%

Regulation of the Processing of Glucose-6-phosphate Dehydrogenase mRNA by Nutritional Status

Amir-Ahmady

Salati

2001

Journal of Biological Chemistry

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Expression of glucose-6-phosphate dehydrogenase (G6PD) gene during starvation and refeeding is regulated by a posttranscriptional mechanism occurring in the nucleus. The amount of G6PD mRNA at different stages of processing was measured in RNA isolated from the nuclear matrix fraction of mouse liver. This nuclear fraction contains nascent transcripts and RNA undergoing processing. Using a ribonuclease protection assay with probes that cross an exon-intron boundary in the G6PD transcript, the abundance of mRNAs that contain the intron (unspliced) and without the intron (spliced) was measured. Refeeding resulted in 6-and 8-fold increases in abundance of G6PD unspliced and spliced RNA, respectively, in the nuclear matrix fraction. However, the amount of G6PD unspliced RNA was at most 15% of the amount of spliced RNA. During refeeding, G6PD spliced RNA accumulated at a rate significantly greater than unspliced RNA. Further, the amount of partially spliced RNA exceeded the amount of unspliced RNA indicating that the enhanced accumulation occurs early in processing. Starvation and refeeding did not regulate either the rate of polyadenylation or the length of the poly(A) tail. Thus, the G6PD gene is regulated during refeeding by enhanced efficiency of splicing of its RNA, and this processing protects the mRNA from decay, a novel mechanism for nutritional regulation of gene expression.Glucose-6-phosphate dehydrogenase (G6PD, 1 EC 1.1.1.49) is the rate-limiting enzyme of the pentose phosphate pathway. All cells contain G6PD activity; however, nutritional and hormonal factors only regulate the expression of the enzyme in liver and adipose tissue (1-3). Regulation of G6PD activity in these tissues is because it plays a critical role in the de novo synthesis of fatty acids by providing 50 -75% of the NADPH for the fatty acid synthase reaction (4). Thus, G6PD is a member of the lipogenic enzyme family. The activities of the lipogenic enzymes are coordinately regulated so that flux of substrate through the fatty acid biosynthetic pathway is high when animals consume a diet rich in carbohydrate and flux is decreased by starvation or the addition of polyunsaturated fat to the diet (reviewed in Ref. 5). However, the molecular mechanisms causing these changes in flux vary considerably between enzymes.The enzymes of the fatty acid biosynthetic pathway are regulated at both transcriptional and posttranscriptional steps. Fatty acid synthase (6 -8), acetyl-CoA carboxylase (9, 10), stearoyl-CoA desaturase (11), and ATP-citrate lyase (12) undergo large changes in their transcriptional rates in response to dietary manipulations. Regulation of malic enzyme expression during a chow to fat-free diet transition occurs by changes in mRNA stability in the cytoplasm (13). In addition, cytoplasmic mRNA stability is also involved in the regulation of stearoylCoA desaturase expression by fatty acids in yeast (14) and in adipocytes (15). Posttranscriptional regulation is the primary mechanism involved in the nutritional regulation of G6PD expressi...

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“…Tissue-specific regulation of G6PD mRNA abundance Nutritionally induced changes in the activity of G6PD in liver are accompanied by comparable changes in G6PD concentra¬ tion (Gozukara et al, 1972;Peavy and Hansen, 1975;Watanabe and Taketa, 1973), rate of synthesis of G6PD protein (Miksicek and Towle, 1982;Winberry and Holten, 1977;Wolfe and Holten, 1978), and abundance of G6PD mRNA (Stabile et al, 1996;Tomlinson et al, 1988). To determine if tissue-specific regulation of G6PD expression was also pretranslational, G6PD mRNA abundance was measured in various tissues of mice con¬ suming different amounts of dietary fat and during starvation and refeeding.…”

Section: Resultsmentioning

confidence: 99%

Structural Characterization and Tissue-Specific Expression of the MouseGlucose-6-Phosphate DehydrogenaseGene

Hodge¹,

Charron²,

Stabile³

et al. 1998

DNA and Cell Biology

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Glucose-6-phosphate dehydrogenase (G6PD) activity differs among tissues and, in liver, with the dietary state of the mouse. Tissue-specific differences in G6PD activity in adipose tissue, liver, kidney, and heart were associated with similar differences in the amount of G6PD mRNA. Regulation of mRNA amount by dietary fat was only observed in liver. In mice fed a low-fat diet, the relative amounts of G6PD mRNA were 3:1:1:0.38, respectively, in the four tissues. Further, the amount of precursor mRNA for G6PD in liver, kidney, and heart reflected the amount of mature mRNA in these tissues, suggesting differing transcriptional activity. Our S1 nuclease and primer-extension analyses indicated that the same transcriptional start site is used in liver, kidney, and adipose tissue, resulting in a common 5' end of the mRNA in these tissues. Thus, differential regulation is not attributable to alternate promoter usage. A DNase hypersensitivity analysis of the 5' end of the G6PD gene identified three hypersensitive sites (HS): HS 1 and HS 2 were present in all tissues, whereas HS 3 was liver specific. Thus, regulation of G6PD expression involves both dietary and tissue-specific signals that appear to act via different mechanisms.

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The Effect of Dietary Fat or Cholesterol and Cholic Acid on the Rate of Synthesis of Rat Liver Glucose-6-P Dehydrogenase

Cited by 15 publications

References 23 publications

Regulation of glucose-6-phosphate dehydrogenase synthesis and mRNA abundance in cultured rat hepatocytes

Regulation of glucose-6-phosphate dehydrogenase synthesis and mRNA abundance in cultured rat hepatocytes

Regulation of the Processing of Glucose-6-phosphate Dehydrogenase mRNA by Nutritional Status

Structural Characterization and Tissue-Specific Expression of the MouseGlucose-6-Phosphate DehydrogenaseGene

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