Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was conducted to determine the chronic effects of porcine growth hormone administration on fatty acid synthase (FAS) mRNA abundance and gene transcription in growing rats. Growth hormone treatment increased growth rate approximately 27% (P<0.01). Porcine growth hormone decreased FAS mRNA levels by 55%. The reduction in FAS mRNA was due to a marked decrease in transcription of the FAS gene (decreased by 80%). In contrast, porcine growth hormone did not affect mRNA abundance or transcription rate of another insulin-regulated gene, phosphoenolpyruvate carboxykinase. In summary, our results have established that chronic treatment with growth hormone decreases FAS mRNA by decreasing the transcription rate of the gene. Furthermore, they suggest that the effects of growth hormone are specific and are not mediated by general changes in insulin-responsive gene expression in liver.
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PMID:The growth hormone-dependent decrease in hepatic fatty acid synthase mRNA is the result of a decrease in gene transcription. 915 18

A dietary copper (Cu) deficiency is associated with a twofold increase in hepatic fatty acid biosynthesis. We hypothesized that the induction of hepatic lipogenesis associated with a dietary Cu deficiency reflected an enhanced expression of genes encoding lipogenic enzymes, i.e., fatty acid synthase (FAS). Male weanling rats were pair-meal fed for 42 days a high-sucrose diet that was Cu deficient (CuD; 0.7 microgram Cu/g) or Cu adequate (CuA; 5.0 micrograms Cu/g). The CuD diet increased FAS enzymatic activity twofold (P < 0.05). This rise in enzymatic activity was accompanied by a threefold increase in FAS mRNA and a 2.5-fold increase in FAS gene transcription (P < 0.05). Neither the mRNA abundance nor the rate of gene transcription for phosphoenolpyruvate carboxykinase or beta-actin was affected by the CuD diet. The induction of FAS gene transcription was associated with a 65-85% increase in hepatic reduced glutathione (GSH; P < 0.05). When hepatic GSH synthesis was suppressed by treating CuD rats with L-buthionine sulfoximine, the induction of FAS expression was completely prevented. Similarly, feeding N-acetylcysteine to CuA rats increased hepatic GSH levels 2.5-fold, and this was accompanied by a significant induction in FAS expression. These data indicate that the increase in hepatic lipogenesis associated with a Cu deficiency reflects an induction in hepatic lipogenic gene transcription (i.e., FAS) and that the rate of gene transcription may be dependent on hepatic thiol redox.
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PMID:Hepatic fatty acid synthase gene transcription is induced by a dietary copper deficiency. 922 60

Thiazolidinediones are potent antidiabetic compounds, in both animal and human models, which act by enhancing peripheral sensitivity to insulin. Thiazolidinediones are high-affinity ligands for peroxisome proliferator-activated receptor-gamma, a key factor for adipocyte differentiation, and they are efficient promoters of adipocyte differentiation in vitro. Thus, it could be questioned whether a thiazolidinedione therapy aimed at improving insulin sensitivity would promote the recruitment of new adipocytes in vivo. To address this problem, we have studied the in vivo effect of pioglitazone on glucose metabolism and gene expression in the adipose tissue of an animal model of obesity with insulin resistance, the obese Zucker (fa/fa) rat. Pioglitazone markedly improves insulin action in the obese Zucker (fa/fa) rat, but doubles its weight gain after 4 weeks of treatment. The drug induces a large increase of glucose utilization in adipose tissue, where it stimulates the expression of genes involved in lipid metabolism such as the insulin-responsive GLUT, fatty acid synthase, and phosphoenolpyruvate carboxykinase genes, but decreases the expression of the ob gene. These changes are related to both an enhanced adipocyte differentiation, as shown by the large increase in the number of small adipocytes in the retroperitoneal fat pad, and a direct effect of pioglitazone on specific gene expression (phosphoenolpyruvate carboxykinase and ob genes) in mature adipocytes.
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PMID:Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa rat. 928 37

Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) limit abdominal fat depot hypertrophy. This could be due to regulation of the expression of proteins involved in adipose tissue metabolism. We investigated in vivo whether fatty acid synthase (FAS), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL), phosphoenolpyruvate carboxykinase (PEPCK), CCAAT/enhancer binding protein alpha (C/EBP alpha), and leptin mRNA levels are affected in retroperitoneal (RP) and subcutaneous adipose tissues (SC) of rats fed n-3 PUFAs. For 4 weeks rats were fed high fat diets (20% fat) containing n-3 PUFAs given as eicosapentaenoic acid (EPA group), docosahexaenoic acid (DHA group), a mixture of these two fatty acids (MIX group), or native fish oil (FO group). A control group was fed with lard plus olive oil (LOO group). Final mean fat cell weight in RP ranged according to: LOO > or = EPA > or = DHA = FO = MIX. There was no difference in fat cell size of SC when comparing the LOO and MIX groups. The fatty acid compositions of RP and SC were similar and resemble that of dietary fat within each experimental group. In RP and compared to the LOO group, FAS, HSL, PEPCK, LPL, C/EBP alpha, and leptin mRNA levels decreased although not significantly in the EPA group, and were 40-75% lower in the DHA and MIX groups. mRNA levels were positively correlated to fat cell size in RP. In contrast, n-3 PUFAs had no effect on gene expression in SC. We conclude that n-3 PUFAs and mainly 22:6n-3 affect gene expression in a site-dependent manner in white adipose tissues via possible antiadipogenic effects.
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PMID:Site-specific regulation of gene expression by n-3 polyunsaturated fatty acids in rat white adipose tissues. 937 19

1. The effects of dietary polychlorinated biphenyls (PCBs) (30-2000 ppm) on activities of gluconeogenic (phosphoenolpyruvate carboxykinase-PEPCK, and fructose 1,6-bisphosphatase-FdPase) and lipogenic enzymes (fatty acid synthase-FAS, ATP citrate lyase-ACL, malic enzyme-ME, glucose 6-phosphate dehydrogenase-G6PDH, and 6-phosphogluconate dehydrogenase-PGDH) were studied in livers of the female Sprague-Dawley and Wistar rat. 2. PCB amounts accumulating in the liver reflected the extent of dietary exposure. The Wistar strain was more sensitive to PCBs than the Sprague-Dawley strain. Of the Clophentype PCBs those containing 60 and 64% chlorine displayed the most pronounced effects. 3. Activities of gluconeogenic enzymes (PEPCK and FdPase) were dose-dependently decreased by PCBs, PEPCK being considerably more sensitive. This decrease was also found under conditions where the activity of PEPCK was induced (administration of adrenalin, glucagon or cAMP, feeding high protein diets, starvation). 4. Activities of lipogenic enzymes were induced by PCBs. The increase was much greater with ME, G6PDH and PGDH (up to 10-fold) than with FAS and ACL (approximately 2-fold). PCB effects were dose-dependent, but transient. 5. In cultured hepatocytes basal activities of lipogenic enzymes were induced by PCBs in the absence of hormones. With saturating levels of insulin or triiodothyronine, enzyme activities were also induced, but addition of PCBs resulted in an additive effect. 6. These results suggest that in the female rat PCBs can mimic the actions of certain hormones by affecting either hormone levels, hormone receptor systems or regulatory systems.
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PMID:Polychlorinated biphenyls affect the activities of gluconeogenic and lipogenic enzymes in rat liver: is there an interference with regulatory hormone actions? 962 50

The of this study was to evaluate the chronic effects of a high (waxy corn) vs. a low (mung beans) glycemic index starch diet on the lipogenic enzymes, fatty acid synthase (FAS) and lipoprotein lipase (LPL). Normal and diabetic (streptozotocin-injected on d 2 of life) male Sprague-Dawley rats consumed a diet containing 575 g/kg carbohydrates either as waxy cornstarch (WCS) or as mung bean starch (MBS). After 3 wk, neither body weights nor relative epididymal fat pad weights differed. In diabetic rats, the WCS diet induced high basal plasma insulin levels. Plasma triglycerides were not significantly affected by diet in either normal or diabetic rats. Adipose tissue and liver LPL activities were not modified by the type of starch in the diet. In normal rats, FAS activity and gene expression in epididymal adipose tissue but not in liver were greater in rats consuming the WCS diet than in those consuming MBS. To evaluate the implication of insulin in this regulation, two genes regulated by insulin [GLUT4 and phosphoenolpyruvate carboxykinase (PEPCK)] were also studied. The high glycemic index WCS diet compared with the low glycemic index MBS diet resulted in lower hepatic PEPCK mRNA in both normal and diabetic rats. Normal, but not diabetic rats fed WCS had greater GLUT4 gene expression in adipocytes than did those fed MBS. We conclude that the total replacement of 575 g/kg low glycemic index starch by a high glycemic index starch for 3 wk caused the following in normal rats: 1) high FAS activity and mRNA in adipose tissue but not in liver and 2) high GLUT4 gene expression in adipose tissue. In both normal and diabetic rats this same diet resulted in lower hepatic PEPCK mRNA. Therefore, high glycemic index starch diet is implicated in stimulating FAS activity and lipogenesis and might have undesirable long-term metabolic effects.
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PMID:A high glycemic index starch diet affects lipid storage-related enzymes in normal and to a lesser extent in diabetic rats. 980 37

This study was designed to determine the level of inhibition of gene transcription by the reduction in insulin levels upon the onset of diabetes in spontaneously diabetic B/B rats and if reducing the level of polyunsaturated fatty acids (PUFA) in the diet will increase lipogenic enzyme activity. Control (eight animals per group) and spontaneously diabetic B/B male weanling rats (25 animals per group) were fed semipurified diets containing 20% (w/w) fat of either low (0.25) or high (1.0) polyunsaturated to saturated (P/S) fatty acid ratio. Rats were killed at the onset of diabetes [blood glucose level of approximately/= 100 mg/dL (5.55 mM)] and as they became highly diabetic [blood glucose level of approximately/= 400 mg/dL (22.22 mM)]. Total RNA was extracted from liver, and the relative amount of mRNA coding for fatty acid synthase (FAS), acetyl-CoA carboxylase, malic enzyme, pyruvate kinase, and phosphoenolpyruvate carboxykinase was determined. Liver enzyme activities were also measured. The mRNA levels for FAS, acetyl-CoA carboxylase, and malic enzyme decreased compared to control animals. The mRNA level for pyruvate kinase decreased at the onset of diabetes as compared to control animals. Feeding animals the low P/S diet treatment elevated the level of mRNA and lipogenic enzyme activity compared to animals fed the high P/S diet treatment, suggesting that the effect of PUFA on lipogenic enzymes is through a direct effect on gene expression.
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PMID:Dietary fat-induced suppression of lipogenic enzymes in B/B rats during the development of diabetes. 1085 27

Tungstate was orally administered to 7.5-week-old male Zucker diabetic fatty (ZDF) rats that already showed moderate hyperglycemia (180 +/- 16 mg/dl). The animals became normoglycemic for approximately 10 days. Then, glycemia started to rise again, although it did not reach the initial values until day 24, when levels stabilized at approximately 200 mg/dl for the duration of the experiment. Untreated ZDF rats showed steadily increased blood glucose levels between 7.5 and 10 weeks of age, when they reached a maximum value of 450 +/- 19 mg/dl, which was maintained throughout the experiment. In addition, tolerance to intraperitoneal glucose load improved in treated diabetic rats. Serum levels of triglycerides were elevated in untreated diabetic rats compared with their lean counterparts (ZLC). In the liver of diabetic animals, glucokinase (GK), glycogen phosphorylase a (GPa), liver-pyruvate kinase (L-PK), and fatty acid synthase (FAS) activities decreased by 81, 30, 54, and 35%, respectively, whereas phosphoenolpyruvate carboxykinase (PEPCK) levels increased by 240%. Intracellular glucose-6-phosphate (G6P) decreased by 40%, whereas glycogen levels remained unaffected. Tungstate treatment of these rats induced a 42% decrease in serum levels of triglycerides and normalized hepatic G6P concentrations, GPa activity, and PEPCK levels. GK activity in treated diabetic rats increased to 50% of the values of untreated ZLC rats. L-PK and FAS activity increased to higher values than those in untreated lean rats (1.7-fold L-PK and 2.4-fold FAS). Hepatic glycogen levels were 55% higher than those in untreated diabetic and healthy rats. Tungstate treatment did not significantly change the phosphotyrosine protein profile of primary cultured hepatocytes from diabetic animals. These data suggest that tungstate administration to ZDF rats causes a considerable reduction of glycemia, mainly through a partial restoration of hepatic glucose metabolism and a decrease in lipotoxicity.
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PMID:Effects of tungstate, a new potential oral antidiabetic agent, in Zucker diabetic fatty rats. 1114 78

We have assessed the potential role of sterol regulatory element-binding protein-1c (SREBP-1c) on the transcription of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC ) (PEPCK-C). SREBP-1c introduced into primary hepatocytes with an adenovirus vector caused a total loss of PEPCK-C mRNA and a marked induction of fatty acid synthase mRNA that directly coincided with the appearance of SREBP-1c in the hepatocytes. It also blocked the induction of PEPCK-C mRNA by cAMP and dexamethasone in these cells. In contrast, a dominant negative form of SREBP-1c (dnSREBP-1c) stimulated the accumulation of PEPCK-C mRNA in these cells. SREBP-1c completely blocked the induction of PEPCK-C gene transcription by the catalytic subunit of protein kinase A (PKA), and increasing concentrations of dnSREBP-1c reversed the negative effect of insulin on transcription from the PEPCK-C gene promoter in WT-IR cells. The more than 10-fold induction of PKA-stimulated PEPCK-C gene transcription caused by the co-activator CBP, was also blocked by SREBP-1c. In addition, dnSREBP-1c reversed the strong negative effect of E1A and NF1 on PKA-stimulated transcription from the PEPCK-C gene promoter. An analysis of the possible site of action of SREBP-1c using stepwise truncations of the PEPCK-C gene promoter indicated that the negative effect of SREBP-1c on transcription is exerted at a site between -355 and -277. We conclude that SREBP-1c is an intermediate in the action of insulin on PEPCK-C gene transcription in the liver and acts by blocking the stimulatory effect cAMP that is mediated via an interaction with cAMP-binding protein.
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PMID:Sterol regulatory element-binding protein-1c mimics the negative effect of insulin on phosphoenolpyruvate carboxykinase (GTP) gene transcription. 1144 21

Besides their role as energetic molecules, fatty acids (FAs) also act as signals involved in regulating gene expression. This review focuses on a few examples of FA regulation. The hepatic lipogenic enzyme, fatty acid synthase (FAS) is negatively regulated by polyunsaturated FAs (PUFAs) which suppress sterol regulatory element-binding protein 1 (SREBP 1) gene expression and nuclear content in hepatocytes, thereby reducing FAS gene transcription. It was proposed recently that this reduction in SREBP 1 was the result of a PUFA-induced antagonism of ligand-dependent activation of the liver X nuclear receptor (LXR), known to be an inducer of the SREBP 1 gene. In contrast, several genes are turned on by long-chain (LCFAs) and nonmetabolized FAs in a physiologically relevant manner. These include the acyl-CoA oxidase (AOX), the liver carnitine palmitoyltransferase 1 (L-CPT 1) and the liver fatty acid binding protein (L-FABP). While induction of AOX gene transcription appears to be PPARalpha-dependent, that of the L-CPT 1 gene seems disconnected from PPAR activation. Results obtained in preadipocytes and in intestine cells are in support of a key role played by the beta/delta isoform of PPAR in LCFA induction of the FABP gene. Transcription of the phosphoenolpyruvate carboxykinase (PEPCK) gene is stimulated by unsaturated and nonmetabolized LCFAs specifically in adipocytes. Our results reported here support the notion that the mechanisms by which PPARgamma activators and FAs induce transcription of the PEPCK gene are distinct. Altogether these data argue that several FA effects are PPAR-independent. Evidences suggesting that other transcription factors might be involved are debated. It seems now clear that depending upon the cell-specific context and the target gene, FAs can take very different routes to alter transcription.
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PMID:Is there a single mechanism for fatty acid regulation of gene transcription? 1221 84


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