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)

Acarbose is a potent intestinal glucosidase inhibitor which could have an anti-obesity property by reducing postprandial plasma glucose and insulin levels, potentially responsible for high rates of lipid synthesis in adipose tissue. We have tested this hypothesis by studying rats during the weaning period, when the lipogenic capacity of the adipose tissue develops. Rats were treated from age 19 days onwards with acarbose (10 mg/100 g diet) and studied at age 30 days. Acarbose was efficient in reducing postprandial excursions of both blood glucose and plasma insulin. Acarbose-treated rats behave like rats continuously infused with glucose with no metabolic signs of carbohydrate deprivation since gluconeogenesis was not activated. There was no massive caecal fermentation of carbohydrate since volatile fatty acids did not significantly increase in the portal blood. One of the most striking features of the acarbose-treated rats was the reduction of adipose tissue weight due to a reduced adipocyte size. This was concomitant with a reduced lipogenic capacity from glucose in isolated adipocytes under insulin stimulation. The activity of fatty acid synthase and acetyl-CoA carboxylase was decreased concomitantly with a reduced expression of their specific mRNA. This study allows the conclusion that postprandial hyperinsulinaemia and hyperglycaemia have a major role in the control of expression of lipogenic enzymes and thus on adipose tissue lipogenic capacity.
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PMID:Effect of acarbose on glucose homeostasis, lipogenesis and lipogenic enzyme gene expression in adipose tissue of weaned rats. 810 98

The time courses and the regulation of lipogenic enzyme gene expression during development after birth have been investigated. The mRNA concentrations and activities of liver lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase, malic enzyme, glucose-6-phosphate dehydrogenase, and ATP-citrate lyase) were very low in all the suckling rats, regardless of dietary fat of the mothers. After weaning to the same diet as the mothers, the mRNA and enzyme levels were greatly increased by the fat-free or hydrogenated fat diet but not so greatly increased by the corn or fish oil diet. The mRNA concentrations of all the groups reached maximum at 4-6 weeks old and then decreased, usually to 40-60% of the maximal levels. It appeared that the gene expression after weaning is subject to strong nutritional regulation, as well as developmental regulation. The plasma levels of triiodothyronine and insulin were low during suckling. Malic enzyme mRNA level was increased by triiodothyronine treatment even during suckling, but the absolute increase was much less than after weaning. Thus, the gene expression of lipogenic enzymes during suckling appeared to be suppressed by nutritional and hormonal regulation, or may not be sufficiently developed. On the other hand, the hepatic triacylglycerol levels were increased slightly at 2 weeks old and greatly at 3 weeks. As the gene expression of lipogenic enzymes was still low at that time, the major triacylglycerols appear to be obtained from milk and accumulated in preparation for weaning.
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PMID:Lipogenic enzyme gene expression in rat liver during development after birth. 810 37

Proglycosyn (LY177507) belongs to a series of powerful agents that stabilize liver glycogen stores by promoting glycogen synthesis from different precursors and inhibiting glycogenolysis and glycolysis. In the present study we have examined the effects of proglycosyn on fatty acid metabolism in isolated hepatocytes. Preincubation of hepatocytes with medium containing proglycosyn led to a marked inhibition of fatty acid synthesis de novo and acetyl-CoA carboxylase activity without affecting fatty acid synthase. Likewise, proglycosyn depressed the synthesis of triacylglycerols and phospholipids from labeled palmitate. Although octanoate oxidation was unaffected by proglycosyn, mitochondrial palmitate oxidation was notably stimulated. This effect may be attributed to the proglycosyn-induced decrease of intracellular malonyl-CoA levels relative to control incubations and the concomitant relieve of the inhibition of the mitochondrial-outer-membrane carnitine palmitoyl-transferase by malonyl-CoA. By contrast, neither peroxisomal palmitate oxidation nor peroxisomal carnitine palmitoyltransferase activity was changed upon hepatocyte incubation with proglycosyn. Results thus indicate that proglycosyn increases the fatty-acid-oxidation efficiency of the liver at the expense of lipogenesis, and this may contribute to the proglycosyn-induced sparing of liver glycogen stores.
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PMID:Effects of proglycosyn (LY177507) on fatty acid metabolism in rat hepatocytes. 810 45

1. Viable myocytes were obtained from rat hearts. Oxidation of [1-14C]palmitate by these cells could be decreased by the addition of glucose (5 mM) or lactate (2 mM). In the presence of glucose, insulin decreased and adrenaline increased palmitate oxidation. 2. The myocytes contained activities of ATP citrate-lyase, acetyl-CoA carboxylase and the condensing enzyme of the fatty acid elongation system. No fatty acid synthase activity was demonstrable in myocytes. 3. In rat hearts perfused with 5 mM glucose, malonyl-CoA content was acutely raised by insulin. In the presence of glucose+insulin, perfusion with palmitate or adrenaline decreased the malonyl-CoA content. 4. It is concluded that malonyl-CoA can be synthesized within cardiac myocytes and that the level of this metabolite can be acutely regulated. This is likely to have consequences for the regulation of carnitine palmitoyltransferase in the heart.
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PMID:Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation. 821 40

There are developmental and glucocorticoid-induced increases in the rate of fatty acid biosynthesis and in the activity of fatty acid synthase in late gestation fetal lung. We have now measured mRNA levels of fatty acid synthase and of two other enzymes of fatty acid biosynthesis, ATP citrate lyase and acetyl-CoA carboxylase, in developing fetal and postnatal rat lung and in fetal lung explants cultured with and without dexamethasone. There was a developmental increase in the mRNA for fatty acid synthase with the maximum level being reached on fetal day 21 (term is fetal day 22). This profile was similar to that reported for de novo fatty acid synthesis and fatty acid synthase activity. There was a similar but less pronounced developmental increase in the mRNA for ATP citrate lyase and a corresponding increase in its activity. There was no developmental change in the mRNA for acetyl-CoA carboxylase. Dexamethasone increased the level of fatty acid synthase mRNA approximately threefold but had no effect on those for ATP citrate lyase and acetyl-CoA carboxylase. The effect of dexamethasone on fatty acid synthase mRNA was rapid, biphasic, and partly inhibited by actinomycin D and cycloheximide. We conclude that glucocorticoids increase expression of the gene for fatty acid synthase in fetal lung. The effect of the hormone appears to be due to increased transcription and post-transcriptional events and is dependent on protein synthesis.
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PMID:Glucocorticoid regulation of fatty acid synthase gene expression in fetal rat lung. 836 27

Sulfur-substituted fatty acid analogues have been administered to rats fed a high carbohydrate diet, and the effect on plasma and hepatic lipid metabolism was investigated. Two of the analogues studied, 3-thiadicarboxylic acid and tetradecylthioacetic acid, reduced the plasma cholesterol level significantly, whereas the effect on plasma triacylglycerol level was only marginal. 3-Thiadicarboxylic acid was the most potent, decreasing the cholesterol level faster and at a lower dose than tetradecylthioacetic acid. The relative effects on plasma cholesterol and triacylglycerol levels were different from what have been observed in rats fed a conventional pellet diet. Tetradecylthiopropionic acid had no hypocholesterolemic effect. The activities of three lipogenic enzymes: ATP-citrate lyase, acetyl-CoA carboxylase and fatty acid synthase was measured. The two hypocholesterolemic analogues reduced the activities of these enzymes in a coordinated manner. The enzyme activities was found to correlate with the the plasma cholesterol level, indicating a coordinated regulation of these enzymes and cholesterol synthesis or secretion. The effect on two enzymes involved in cholesterol metabolism was also studied. The activity of acyl-CoA:cholesterol acyltransferase (ACAT) was reduced by the two hypocholesterolemic analogues, in contrast to the rate-limiting enzyme in cholesterol biosynthesis, HMG-CoA reductase, which tended to increase. The cholesterol lowering effect of 3-thiadicarboxylic acid and tetradecylthioacetic acid can probably be ascribed to diminished cholesterol synthesis due to a reduced availability of acetyl-CoA. A reduction in the esterification of hepatic cholesterol may be a contributing factor.
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PMID:The hypocholesterolemic effect of sulfur-substituted fatty acid analogues in rats fed a high carbohydrate diet. 846 46

In fetal lung the amounts of mRNAs encoding fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and ATP citrate lyase (ACL) increase in late gestation and drop around birth. To study the mechanism of the perinatal decrease, pregnancy was prolonged from 22 (term) to 25 days in rats with daily injections of progesterone. Progesterone did not affect the levels of lipogenic enzyme mRNAs in fetal lung prior to term, but significantly delayed the perinatal decrease in the levels of lung FAS and ACC mRNA. Although for ACL mRNA abundance the differences were not statistically significant, its pattern in the control and progesterone groups were similar to those of FAS and ACC mRNA. Malic enzyme mRNA did not change between 20 and 25 days after conception in either group. These results suggest that the decrease in FAS and ACC mRNA at term can be partially explained by labor, delivery, air-breathing or switch from carbohydrate to fat metabolism.
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PMID:Gene expression of fatty acid synthesizing enzymes in fetal rat lung in prolonged pregnancy. 853 72

Prodigiosin 25-C had little effect on DNA, RNA, and protein synthesis, and cellular ATP content, but the drug markedly inhibited the incorporation of acetate into lipid fractions. Under the same conditions, the incorporation of other lipid precursors including glycerol, mevalonate, palmitate, and oleate was not affected. A decrease in the incorporation of acetate was not due to the inhibition of fatty acid biosynthesis, because prodigiosin 25-C did not affect the activity of acetyl-CoA synthetase, acetyl-CoA carboxylase or fatty acid synthase in cell-free assay systems prepared from rat liver cytosol. In contrast, prodigiosin 25-C strongly inhibited the rapid uptake of acetate into acid-soluble fraction in intact cells. The results suggest that prodigiosin 25-C specifically perturbs the permeation of acetate through plasma membranes.
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PMID:Prodigiosin 25-C perturbs permeation of acetate in a cultured cell line. 853 81

A metabolic model of fuel sensing has been proposed in which malonyl-CoA and long-chain acyl-CoA esters may act as coupling factors in nutrient-induced insulin release (Prentki M, Vischer S, Glennon MC, Regazzi R, Deeney J, Corkey BE: Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion. J Biol Chem 267:5802-5810, 1992). To gain further insight into the control of malonyl-CoA content in islet tissue, we have studied the short- and long-term regulation of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in the beta-cell. These enzymes catalyze the formation of malonyl-CoA and its usage for de novo fatty acid biogenesis. ACC mRNA, protein, and enzymatic activity are present at appreciable levels in rat pancreatic islets and clonal beta-cells (HIT cells). Glucose addition to HIT cells results in a marked increase in ACC activity that precedes the initiation of insulin release. Fasting does not modify the ACC content of islets, whereas it markedly downregulates that of lipogenic tissues. This indicates differential regulation of the ACC gene in lipogenic tissues and the islets of Langerhans. FAS is very poorly expressed in islet tissue, yet ACC is abundant. This demonstrates that the primary function of malonyl-CoA in the beta-cells is to regulate fatty acid oxidation, not to serve as a substrate for fatty acid biosynthesis. The anaplerotic enzyme pyruvate carboxylase, which allows the replenishment of citric acid cycle intermediates needed for malonyl-CoA production via citrate, is abundant in islet tissue. Glucose causes an elevation in beta (HIT)-cell citrate that precedes secretion, and only those nutrients that can elevate citrate induce effective insulin release. The results provide new evidence in support of the model and explain why malonyl-CoA rises markedly and rapidly in islets upon glucose stimulation: 1) glucose elevates citrate, the precursor of malonyl-CoA; 2) glucose enhances ACC enzymatic activity; and 3) malonyl-CoA is not diverted to lipids. The data suggest that ACC is a key enzyme in metabolic signal transduction of the beta-cell and provide evidence for the concept that an anaplerotic/malonyl-CoA pathway is implicated in insulin secretion.
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PMID:Evidence for an anaplerotic/malonyl-CoA pathway in pancreatic beta-cell nutrient signaling. 854 64

We have previously shown that the effects of a high carbohydrate, fat-free diet and 24-h starvation on fatty acid synthesis in rats are tissue specific. In the present study we examine the tissue-specific pretranslational effects of high carbohydrate feeding, starvation and refeeding a high carbohydrate diet after starvation on the lipogenic pathway by measuring the levels of mRNA encoding acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) using Northern analysis. Additionally, we measured mRNA S14, a sequence tightly associated with lipogenesis. In rats fed the high carbohydrate diet, hepatic levels of the three mRNA were 3-5 fold higher than in controls. The level of S14 mRNA was doubled in epididymal fat, but other effects of this diet in adipose tissues were not significant. Expression in kidney, heart, lung and brain was not altered. Starvation significantly reduced the level of these mRNA in all tissues examined except brain. In liver, refeeding the high carbohydrate diet induced the expression of ACC, FAS and S14 mRNA 20-30 fold compared with the values found in 48-h starved animals. Hyperinduction of ACC and FAS, but not S14 mRNA expression was also observed in adipose tissues. The tissue-specific nature of these effects is consistent with previous measurements of fatty acid synthesis and confirm that this regulation occurs at the pretranslational level.
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PMID:High carbohydrate diet and starvation regulate lipogenic mRNA in rats in a tissue-specific manner. 859 45


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