Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of nutrients and hormones on the mRNA levels of acetyl-CoA carboxylase, fatty acid synthase, malic enzyme, and glucose 6-phosphate dehydrogenase were examined in primary cultures of rat hepatocytes during the process of induction. The addition of both glucose and insulin to the culture medium markedly enhanced the lipogenic enzyme mRNA induction due to either of them, in 16 h. Fructose or glycerol proved to be an effective substitute for glucose, suggesting that glycolytic metabolites were involved in the mRNA induction. It is remarkable that mRNA induction of acetyl-CoA carboxylase was the most sensitive to glucose and also to insulin among the lipogenic enzymes. Polyunsaturated fatty acids markedly reduced the mRNA induction of lipogenic enzymes. Dexamethasone enhanced all the lipogenic enzyme mRNA induction by insulin. On the other hand, triiodothyronine addition greatly increased the mRNA concentrations of lipogenic enzymes, but dexamethasone decreased rather than increased the mRNA induction by triiodothyronine. The effects of insulin on the induction of the lipogenic enzyme mRNAs were similar, but those of triiodothyronine were not. Triiodothyronine markedly enhanced malic enzyme mRNA induction by insulin with dexamethasone, and tended to enhance the induction of the acetyl-CoA carboxylase and fatty acid synthase mRNAs, but not that of glucose 6-phosphate dehydrogenase mRNA. It appeared that insulin and triiodothyronine synergistically enhanced lipogenic enzyme mRNA induction by glucose, but the mechanisms were different.
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PMID:Nutritional and hormonal regulation of mRNA levels of lipogenic enzymes in primary cultures of rat hepatocytes. 135 82

The expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) is low in the adipose tissue of suckling rats and increases markedly at weaning to a high carbohydrate diet. We have studied in vitro the factors regulating this phenomenon. Inguinal adipose tissue pieces from 19-day-old suckling rats were cultured for 6 or 24 h in minimal essential medium. Insulin (100 nM) added in the presence of lactate and pyruvate did not stimulate the expression of FAS and ACC. Glucose (20 mM) alone resulted in a 5-7-fold increase of FAS and ACC mRNA. Insulin potentiated the effect of glucose. 3-O-Methylglucose, a glucose analog that is transported into the cell but not metabolized, had no effect on FAS and ACC mRNA accumulation. However, 2-deoxyglucose (1 mM), a glucose analog which is phosphorylated to 2-deoxyglucose 6-phosphate, stimulated the expression of FAS and ACC to the same extent as 20 mM glucose. Glucose 6-phosphate concentrations in adipose tissue pieces cultured in various conditions changed in parallel with the FAS and ACC mRNA levels. We conclude that glucose 6-phosphate could be the metabolite involved in the stimulation of lipogenic enzyme gene expression in response to glucose.
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PMID:Glucose stimulation of lipogenic enzyme gene expression in cultured white adipose tissue. A role for glucose 6-phosphate. 135 82

We have previously shown that rats made obese by lesion of ventromedial hypothalamus (VMH) nuclei, demonstrate an hyper-responsiveness to insulin with regard to whole-body glucose utilization one week after injury. This is mainly due to an increased glucose uptake in white adipose tissue. Six weeks after the lesion, glucose utilization in white adipose tissue returns to normal values. These modifications in insulin responsiveness could be mediated by altered activity and/or concentration of intracellular insulin effectors. In this study, we have measured the expression of the insulin-sensitive glucose transporter, Glut 4 and the activities and expression of key lipogenic enzymes (fatty-acid synthase and acetyl-CoA carboxylase) in white adipose tissue, one and six weeks after the lesion. All these parameters, as well as glucose transport and metabolism determined in white adipocytes, were markedly increased one week after the lesion. They returned to control values within six weeks in VMH-lesioned rats. These results indicate the existence of an increased expression of Glut 4 and lipogenic enzymes in white adipose tissue of VMH-lesioned rats which decreased with time and were parallel to glucose utilization determined in vivo.
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PMID:Molecular and metabolic changes in white adipose tissue of the rat during development of ventromedial hypothalamic obesity. 137 5

Previous experiments have shown that insulin-induced glucose utilization is increased in white adipose tissue of young obese Zucker rats. We have investigated the possible role of over-expression of the muscle/fat glucose transporter (Glut 4) and key lipogenic enzymes in this increased insulin-responsiveness. The amount or activity and the mRNA concentrations of Glut 4, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were measured before and after weaning in white adipose tissue of obese and lean Zucker rats. Comparison of the levels of Glut 4 and lipogenic-enzyme expression in 15-day-old suckling and 30-day-old weaned rats on a high-carbohydrate diet shows a marked increase in the latter group. The increase was, in lean and obese rats respectively, 6- and 7-fold for the amount of Glut 4 and 2- and 3-fold for its mRNA concentrations, 40- and 100-fold for the activity of lipogenic enzymes (FAS and ACC) and 30- and 10-fold for their mRNA concentrations. Furthermore, all these parameters, except the amount of Glut 4, were 2-5-fold higher in obese rats, both before and after weaning. Changes at weaning were largely blunted when rats were weaned on to a high-fat diet, although the differences between lean and obese rats persisted, and even became significant for the amount of Glut 4. Whatever the experimental conditions, plasma insulin levels were significantly higher in obese than in lean rats. These results indicate the existence of an enhanced expression of Glut 4, FAS and ACC in white adipose tissue of young obese fa/fa rats which could be related to the increased plasma insulin levels.
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PMID:Increased gene expression of lipogenic enzymes and glucose transporter in white adipose tissue of suckling and weaned obese Zucker rats. 168 2

1. Withdrawal of food from lactating rats produced a rapid and dramatic decrease in the uptake of glucose by the mammary gland and an inhibition of the rate of fatty acid synthesis that could not be explained alone by decreased substrate supply to the tissue. 2. Within the first 6 hr starvation, fatty acid synthesis and pyruvate dehydrogenase activity were inhibited by 87 and 80%, respectively, but acetyl-CoA carboxylase activity did not change significantly. 3. Between 6 and 24 hr starvation, total and expressed activities of acetyl-CoA carboxylase decreased by 62 and 55%, respectively. 4. The ratio of fructose-6-phosphate/fructose-1,6-bisphosphate concentration in mammary tissue increased 9-fold during the first 6 hr starvation, indicating an inhibition of 6-phosphofructo-1-kinase. However, the major inhibition of this enzyme occurred between 6 and 24 hr starvation when this metabolite ratio increased a further 160-fold in parallel with increased tissue citrate concentration. 5. The increase in citrate concentration between 6 and 24 hr starvation correlated with acetyl-CoA carboxylase inactivation and ketone body accumulation in the mammary gland. 6. This study confirms the asynchronous control of three important regulatory steps in the pathway of glucose utilization and fatty acid synthesis in the lactating rat mammary gland.
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PMID:Regulation of fatty acid synthesis in lactating rat mammary gland in the fed to starved transition: asynchronous control of pyruvate dehydrogenase, phosphofructokinase and acetyl-CoA carboxylase. 168 75

With metabolically active, saponin-permeabilized adipocytes, in situ pathway metabolism, which was distal to glucose transport, was examined in acute streptozocin-induced diabetic (STZ-D) rats. Metabolic reactions were initiated with selectively radiolabeled glucose-6-phosphate (G6P), an otherwise inert substrate with intact cells. Thus, the membrane pores permitted a direct comparison of cellular flux between control and STZ-D adipocytes at identical initial substrate concentrations. Three metabolic pathways were studied: 1) proximal glycolysis through the triosephosphates ([3-3H]G6P to 3H2O), 2) glycolysis-Krebs ([6-14C]G6P) oxidation, and 3) lipogenesis ([6-14C]G6P incorporation into triglyceride). The extent of membrane porosity was assessed by both propidium iodide staining and lactate dehydrogenase leakage to assure that porosity was comparable between the cell groups. Porous adipocytes from STZ-D rats had markedly attenuated rates of G6P metabolism compared with controls. At enzyme-saturating concentrations of G6P (4 mM), this deficit ranged from 44% for glycolysis-Krebs oxidation to 88% for lipogenesis. The reduction in glycolysis-Krebs oxidation was also evident between 0.5 and 6 mM G6P. These porous-cell data were compared with parallel studies of glucose metabolism and clearance in intact adipocytes. Finally, several glycolytic enzymes and acetyl-CoA carboxylase were measured in cell-free (sonicated) extracts with traditional in vitro methods under Vmax conditions. Overall, the in situ porous-cell flux measurements uncovered larger deficits in posttransport cellular metabolism than were apparent in the cell-free, in vitro assays. We conclude that, in actively metabolizing porous rat adipocytes, there exists a striking and unequivocal transport-independent defect in intermediary metabolism after acute STZ-D.
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PMID:Diminished in situ glucose-6-phosphate flux in permeabilized adipocytes from streptozocin-induced diabetic rats. 183 3

The utilization of lactate, glucose, 3-hydroxybutyrate, and glutamine has been studied in isolated brain cells from early newborn rats. Isolated brain cells actively utilized these substrates, showing saturation at concentrations near physiological levels during the perinatal period. The rate of lactate utilization was 2.5-fold greater than that observed for glucose, 3-hydroxybutyrate, or glutamine, suggesting that lactate is the main metabolic substrate for the brain immediately after birth. The apparent Km for glucose utilization suggested that this process is limited by the activity of hexokinase. However, lactate, 3-hydroxybutyrate, and glutamine utilization seems to be limited by their transport through the plasma membrane. The presence of fatty acid-free bovine serum albumin (BSA) in the incubation medium significantly increased the rate of lipogenesis from lactate or 3-hydroxybutyrate, although this was balanced by the decrease in their rates of oxidation in the same circumstances. BSA did not affect the rate of glucose utilization. The effect of BSA was due not to the removal of free fatty acid, but possibly to the binding of long-chain acyl-CoA, resulting in the disinhibition of acetyl-CoA carboxylase and citrate carrier.
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PMID:Lactate utilization by isolated cells from early neonatal rat brain. 191 82

The activities and mRNA concentrations of two lipogenic enzymes, fatty acid synthetase and acetyl-CoA carboxylase, and one enzyme involved in glyceroneogenesis, phosphoenolpyruvate carboxykinase (PEPCK), were measured in rat white adipose tissue during the suckling-weaning transition. Activities and mRNA concentrations of lipogenic enzymes were low in suckling rats, whereas activity and mRNA concentration of PEPCK were high. At weaning to a high-carbohydrate diet, the rapid increase in lipogenic enzymes mRNA (10- to 20-fold) and decrease in PEPCK mRNA (10-fold) were followed by parallel changes in enzyme activities. In contrast, weaning to a high-fat diet prevented these modifications. Force feeding suckling rats with carbohydrates induced a rise in blood glucose and plasma insulin concentrations. During these experiments, mRNA concentrations increased 10- to 20-fold for lipogenic enzymes and decreased 5-fold for PEPCK in less than 6 h, whereas all enzyme activities did not vary. This suggests a pretranslational regulation of gene expression. Force feeding suckling rats with a mixture of fat devoid of carbohydrate induced a slight increase in plasma insulin concentration and a fall in PEPCK mRNA but was not accompanied by a rise in lipogenic enzyme mRNAs. This suggested that insulin is a prime regulator of PEPCK gene expression, whereas glucose and insulin act synergistically in the regulation of lipogenic enzyme gene expression.
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PMID:Lipogenic enzyme activities and mRNA in rat adipose tissue at weaning. 196 6

The effects of two preparations of highly purified human GH (hGH) on lipid metabolism were studied in the GH-deficient little mouse (50-60 days old). Marked decreases in incorporation of [14C]glucose into fatty acid and in the activity of acetyl-CoA carboxylase in the epididymal fat pads were observed after i.p. injection of hGH at a dose of 1.0 microgram/g body weight or after continuous infusion of hGH by osmotic minipump. The rate of glucose incorporation into fatty acid decreased from 107.0 +/- 27.6 (S.E.M.) to 38.1 +/- 19.6 mumol/g tissue per h after a single injection of hGH and from 174.1 +/- 28.5 to 56.3 +/- 20.3 mumol/g tissue per h after continuous infusion of hGH for 2 days. Activity of the lipogenic enzyme acetyl-CoA carboxylase was also reduced by more than 50% in the epididymal fat pad from hGH-treated mice in comparison with the corresponding control animals. Incubation of isolated fat pads with hGH (0.1 microgram/ml) revealed similar inhibitory effects of the hormone on fatty acid synthesis and acetyl-CoA carboxylase activity. No lipolytic effect of hGH was found as determined by the rate of glycerol release from epididymal fat pads of little mice following hormone treatment in vivo or in vitro. The results lend strong support to the conclusion that GH inhibits lipogenesis but has no effect on lipolysis in adipose tissues, and indicate that the physiological role of GH in lipid metabolism is concerned mainly with the regulation of anabolic rather than catabolic processes.
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PMID:Effects of exogenous growth hormone on lipid metabolism in the isolated epididymal fat pad of the growth hormone-deficient little mouse. 196 38

Food intake, plasma glucose, insulin (I) and triiodothyronine (T3) and liver glucose 6-phosphate dehydrogenase (G6P-DH), malic enzyme (ME). ATP-citrate lyase, acetyl-CoA carboxylase (AcCoACx) and fatty acid synthase (FAS) activities were measured in 2 and 22 months old rats before, after 3 d starvation and 2,4,6. 24 and 48 h refeeding a high carbohydrate (74% w/w) diet. Expressed per 100 g of body weight, the carbohydrate intake of old rats was 55% lower than that of young rats. Plasma insulin was higher in old than in young rats and decreased (-40%) after starvation and returned to control values 4 h after refeeding. In young rats plasma insulin fell after starvation (-85%) and returned to normal values 2 h after refeeding. No significant differences were observed in plasma [T3] between the two groups. During the first 6 h of refeeding, plasma glucose increased 2-fold and returned to control values after 24 h in young rats. In old rats, plasma glucose returned to its control value after 2 h. Compared to the starved level, 48 h after refeeding, G6P-DH, ME, ATP-citrate lyase, AcCoACx and FAS activities increased 5- to 6-fold in young rats, while in old rats the increase was much smaller and represented 35% of that observed in young rats. These results suggest, that the age-related reduction in inducibility of hepatic lipogenic enzymes of rats refed a high carbohydrate diet after starvation may be due to a spontaneous decrease in the carbohydrate intake and to a decrease effectiveness of insulin (insulin resistance).
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PMID:Age-dependent hepatic lipogenic enzyme activities in starved-refed rats. 197 51


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