UMLS:C0038187 - FACTA Search

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Query: UMLS:C0038187 (starvation)
24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The activity of acetyl-CoA carboxylase (EC 6.4.1.2) in extracts of freeze-clamped liver samples from fed or 24 h-starved virgin, pregnant, lactating and weaned rats was measured (i) immediately after preparation of extracts (;I activity'), (ii) after incubation of extracts with partially purified preparations of either rabbit muscle protein phosphatase 1 [Antoniw, Nimmo, Yeaman & Cohen (1977) Biochem. J.162, 423-433] or rabbit liver phosphatase [Brandt, Capulong & Lee (1975) J. Biol. Chem.250, 8038-8044] (;A activity') and (iii) after incubation with 20mm-potassium citrate before or after incubation with phosphatases (;C activity'). 2. Incubation of liver extracts at 30 degrees C without any additions resulted in activation of acetyl-CoA carboxylase that was shown to be due to dephosphorylation of the enzyme by endogenous protein phosphatase activity. This latter activity was not stimulated by Ca(2+) and/or Mg(2+) but was stimulated by 1 mm-Mn(2+). Incubation of extracts with either of the partially purified phosphatases (0.2-0.5 unit) resulted in faster dephosphorylation and activation. The activity achieved after incubation with either of the exogenously added phosphatases was similar. 3. The A and C activities increased during late pregnancy, were lower than in the virgin rat liver during early lactation and increased by 2-fold in liver of mid-lactating rats. Weaning of mid-lactating rats for 24 h resulted in no change in A and C activities but after 48 h weaning they were significantly lower than those in livers from suckled mothers. 4. The I activity followed a similar pattern of changes as the A and C activities during pregnancy and lactation such that, although the I/A and I/C activity ratios tended to be lower during late pregnancy and early lactation, there were no significant changes in I/A and I/C ratios between lactating and virgin animals. However, these ratios were significantly higher in liver from fed 24 h-weaned animals. 5. Starvation (24 h) resulted in a marked decrease in I activity for all animals studied except early-lactating rats. This was due to a combination of a decrease in the concentration of acetyl-CoA carboxylase in liver of starved animals (A and C activities) and a decrease in the fraction of the enzyme in the active form (lower I/C and I/A ratios). The relative importance of the two forms of regulation in mediating the starvation-induced fall in I activity was about equal in livers of virgin, pregnant and lactating animals. However, the decrease in I/A and I/C ratios was of dominating importance in livers of weaned animals. The A/C activity ratios were the same for livers from all animals studied. 6. The maximal activity of fatty acid synthase was also measured in livers and was highly and positively correlated with the A and C activities of acetyl-CoA carboxylase, suggesting that the concentrations of the two enzymes in the liver were controlled coordinately. 7. It is suggested that the lack of correlation between plasma insulin levels and rates of lipogenesis in the transition from the virgin to the lactating state may be explained by different effects of insulin and prolactin on the concentration of acetyl-CoA carboxylase in the liver and on the fraction of the enzyme in the active form.
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PMID:Changes in the proportion of acetyl-CoA carboxylase in the active form in rat liver. Effect of starvation, lactation and weaning. 612 71

Periportal and perivenous hepatocytes were isolated from rats subjected to different treatments that induce (starvation, cold exposure) or depress (refeeding after starvation) hepatic fatty acid oxidation. These experiments were designed to determine factors that may be involved in creating and maintaining the asymmetrical distribution of this metabolic pathway in the acinus of the liver. The uneven distribution of mitochondrial [14C]-palmitate oxidation within the acinus (i) was very flexible and changed markedly with the physiological status of the animal (periportal/perivenous ratio: 1.5, 2.0, 1.0 and 0.4 for fed, starved, refed and cold-exposed animals respectively), (ii) coincided with a similar zonation of carnitine palmitoyltransferase I activity in fed as well as in cold-exposed animals, (iii) was paralleled by a comparable zonation of mitochondrial 3-hydroxy-3-methyl-glutaryl-CoA synthase activity in starved animals, and (iv) was not determined by zonal differences in any of the following parameters: sensitivity of carnitine palmitoyltransferase I to malonyl-CoA, intracellular concentration of malonyl-CoA, fatty acid synthesizing capacity, acetyl-CoA carboxylase activity, fatty acid synthase activity or relative content of the two hepatic acetyl-CoA carboxylase isoforms. Unlike mitochondrial oxidation, peroxisomal [14C]palmitate oxidation was always zonated towards the perivenous zone of the liver irrespective of the physiological status of the animal. The data presented show that changes in the acinar distribution of mitochondrial long-chain fatty acid oxidation involve specific long-term mechanisms under different physiological conditions.
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PMID:Flexibility of zonation of fatty acid oxidation in rat liver. 748 41

We previously isolated a mutant of Escherichia coli that is preferentially affected in the synthesis of rRNA and has a mutation in the gene (accD) encoding a subunit of acetyl-CoA carboxylase. Using this mutant and other mutants of the pathway for fatty acid and phospholipid biosynthesis as well as cerulenin, a specific inhibitor of fatty acid synthesis, we show that (i) inhibition of fatty acid synthesis in the presence of both a carbon source and all 20 amino acids stimulates the accumulation of guanosine tetraphosphate (ppGpp) and leads to preferential inhibition of rRNA synthesis, (ii) this ppGpp accumulation is spoT dependent, and (iii) the generation of the metabolic signal that stimulates this spoT-mediated response probably does not depend on either phospholipid starvation or a significant reduction in the level of ATP.
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PMID:spoT-dependent accumulation of guanosine tetraphosphate in response to fatty acid starvation in Escherichia coli. 750 90

The effects of the ingestion of a meal on the partitioning of hepatic fatty acids between oxidation and esterification were studied in vivo for meal-fed rats. The time course for the reversal of the starved state was extremely rapid and the process was complete within 2 h, in marked contrast with the reversal of the effects of starvation in rats fed ad libitum [A. M. B. Moir and V. A. Zammit (1993) Biochem. J. 289, 49-55]. This rapid reversal occurred in spite of the fact that, in the liver of the meal-fed animals before feeding, a similar degree of partitioning of fatty acids in favour of oxidation was observed as in 24 h-starved rats (previously fed ad libitum). This suggested that the lower degree of ketonaemia observed in meal-fed rats before a meal is not due to the inability of acylcarnitine formation to compete successfully with esterification of fatty acids to the glycerol moiety. Investigation of the possible mechanisms that could contribute towards the rapid switching-off of fatty acid oxidation revealed that this was correlated with a very rapid rise and overshoot in hepatic malonyl-CoA concentration, but not with any change in the activity, or sensitivity to malonyl-CoA, of the mitochondrial overt carnitine palmitoyltransferase (CPT I). The role of these two parameters in the reversal of fasting-induced hepatic fatty acid oxidation was thus the inverse of that observed previously for refed 24 h-starved rats. The rapid increase in [malonyl-CoA] was accompanied by an immediate and complete reversion of the kinetic characteristics (Ka for citrate, expressed/total activity ratio) of acetyl-CoA carboxylase to those found in the post-meal animals, again in contrast with the time course observed in refed 24 h-starved rats [A. M. B. Moir and V. A. Zammit (1990) Biochem. J. 272, 511-517]. The rapidity with which these changes occurred was specific to the partitioning of acyl-CoA; the meal-induced diversion of glycerolipids towards phospholipid synthesis and the acute inhibition of the fractional rate of triacylglycerol secretion occurred with very similar time courses to those observed upon refeeding of 24 h-starved rats. The results confirm the central role played by differences in the dynamics of changes in hepatic malonyl-CoA concentration, and CPT I sensitivity to it, in determining the route through which ingested glucose is converted into hepatic glycogen upon refeeding of starved rats which had previously been meal-fed or fed ad libitum.
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PMID:Rapid switch of hepatic fatty acid metabolism from oxidation to esterification during diurnal feeding of meal-fed rats correlates with changes in the properties of acetyl-CoA carboxylase, but not of carnitine palmitoyltransferase I. 809 87

In this review, we evaluate the relative regulatory importance of specific strategic enzymes (in particular glycogen synthase, acetyl-CoA carboxylase [ACC] and the pyruvate dehydrogenase complex [PDH]) for carbohydrate utilization as an anabolic precursor and as an energy substrate during the nutritional transitions between the fed and fasted states. The involvement of the specific protein kinases contributing to the inactivation of these enzymes by phosphorylation [cyclic AMP-dependent protein kinase, AMP-activated protein kinase and PDH kinase] in achieving each regulatory response is also assessed. We demonstrate a striking temporal correlation between hepatic glycogen mobilization and PDH and ACC inactivation by phosphorylation during the immediate postabsorptive period; in contrast, rates of hepatic glycogen synthesis and PDH and ACC expressed activities do not change in parallel during refeeding. The results are consistent with shifting of the primary sites of control for overall hepatic carbon flux during the fed-to-starved and starved-to-fed nutritional transitions achieved, at least in part, by a complex pattern of regulation by protein phosphorylation and metabolites which is critically dependent on the precise nutritional status. Data are also presented that demonstrate asynchronous suppression of glucose uptake/phosphorylation and pyruvate oxidation in cardiac and skeletal muscle during progressive starvation. Analogous asynchrony is observed in the reactivation of these processes in cardiac and skeletal muscle during refeeding after starvation. We provide evidence in support of the concept that selective suppression of pyruvate oxidation in oxidative muscles during early starvation and during the initial phase of refeeding is achieved because of differential sensitivity of glucose uptake/phosphorylation and pyruvate oxidation to lipid-fuel utilization. We discuss the relative importance of regulatory events governing local fatty acid production and utilization (via lipoprotein lipase and carnitine palmitoyltransferase 1, respectively) or overall fatty acid supply (dictated by events at the adipocyte) for fuel utilization by muscle during nutritional transitions. Finally, we assess the regulatory importance of glycogen synthesis in determining overall rates of glucose clearance by skeletal muscle during alimentary hyperglycemia and hyperinsulinemia.
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PMID:Mechanisms involved in the coordinate regulation of strategic enzymes of glucose metabolism. 810 32

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

Feeding previously starved chicks with a high-carbohydrate, low-fat diet stimulates a 9-fold increase in both the rate of synthesis of acetyl-CoA carboxylase (ACC) and the abundance of its mRNA in liver. To define the steps involved in mediating diet-induced changes in the abundance of ACC mRNA, transcriptional activity was measured with the nuclear run-on assay and multiple DNA probes specific to the ACC gene. ACC transcription was low in livers of starved chicks; feeding them with a high-carbohydrate, low-fat diet induced ACC transcription, increasing it 11-fold. An increase in transcription was detectable at 1 h, was maximal at 5 h and remained high for 26 h. Feeding previously starved chicks with a low-carbohydrate, high-fat diet stimulated a smaller increase (4-fold) in the abundance of ACC mRNA and the transcription of ACC than feeding with a high-carbohydrate, low-fat diet. The half-life of ACC mRNA in liver, as estimated from the kinetics of accumulation and decay of ACC mRNA during high-carbohydrate feeding and starvation, was not changed significantly by dietary manipulation. ACC mRNA was expressed at low levels in heart, pectoral muscle, kidney and brain. The abundance of ACC mRNA in these tissues was not affected by nutritional manipulation. These results demonstrate that nutritional control of the abundance of ACC mRNA in the chicken is liver-specific and is mediated primarily by changes in the rate of transcription of the ACC gene.
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PMID:Alterations in nutritional status regulate acetyl-CoA carboxylase expression in avian liver by a transcriptional mechanism. 887 Jun 77

The time courses of gene expression, and the nutritional regulation of gene expression of lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase, ATP citrate-lyase, malic enzyme, and glucose-6-phosphate dehydrogenase) in epididymal adipose tissue after refeeding food-deprived rats have been investigated and compared with those in liver (previously reported). The mRNA concentrations of lipogenic enzymes reached maximum levels at 24 h after the refeeding in adipose tissue and at 8-16 h in liver, while the enzyme induction reached maximum at 48-72 h in both tissues. Moreover, the mRNAs were more strongly induced in adipose tissue than in liver, whereas the enzyme induction (except malic enzyme) was lower. In adipose tissue of rats fed a carbohydrate diet without protein, the mRNA concentrations of acetyl-CoA carboxylase, ATP-citrate lyase, malic enzyme, and fatty acid synthase reached comparable levels to those of the carbohydrate/protein diet group. The protein feeding increased the enzyme induction in adipose tissue. As regards reduction of gene expression, lipogenic enzyme mRNA concentrations were not so markedly reduced by starvation or polyunsaturated fatty acids in adipose tissue as in liver. The differences in regulation of lipogenic enzyme gene expression and induction between adipose tissue and liver can be ascribed to tissue specificity.
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PMID:Nutritional regulation of lipogenic enzyme gene expression in rat epididymal adipose tissue. 888 6

A single entity, the AMP-activated protein kinase (AMPK), phosphorylates and regulates in vivo hydroxymethylglutaryl-CoA reductase and acetyl-CoA carboxylase (key regulatory enzymes of sterol synthesis and fatty acid synthesis, respectively), and probably many additional targets. The kinase is activated by high AMP and low ATP via a complex mechanism, which involves allosteric regulation, promotion of phosphorylation by an upstream protein kinase (AMPK kinase), and inhibition of dephosphorylation. This protein-kinase cascade represents a sensitive system, which is activated by cellular stresses that deplete ATP, and thus acts like a cellular fuel gauge. Our central hypothesis is that, when it detects a 'low-fuel' situation, it protects the cell by switching off ATP-consuming pathways (e.g. fatty acid synthesis and sterol synthesis) and switching on alternative pathways for ATP generation (e.g. fatty acid oxidation). Native AMP-activated protein kinase is a heterotrimer consisting of a catalytic alpha subunit, and beta and gamma subunits, which are also essential for activity. All three subunits have homologues in budding yeast, which are components of the SNF1 protein-kinase complex. SNF1 is activated by glucose starvation (which in yeast leads to ATP depletion) and genetic studies have shown that it is involved in derepression of glucose-repressed genes. This raises the intriguing possibility that AMPK may regulate gene expression in mammals. AMPK/SNF1 homologues are found in higher plants, and this protein-kinase cascade appears to be an ancient system which evolved to protect cells against the effects of nutritional or environmental stress.
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PMID:The AMP-activated protein kinase--fuel gauge of the mammalian cell? 920 14

Transcription of acetyl-CoA carboxylase in avian liver is low during starvation or after consumption of a low-carbohydrate, high-fat diet and high during consumption of a high-carbohydrate, low-fat diet. The role of fatty acids or metabolites derived from fatty acids in the nutritional control of acetyl-CoA carboxylase transcription was investigated by determining the effects of long- and medium-chain fatty acids on acetyl-CoA carboxylase expression in primary cultures of chick embryo hepatocytes. Palmitate, oleate, and arachidonate caused a decrease in acetyl-CoA carboxylase activity in hepatocytes incubated with triiodothyronine (T3). The inhibition of acetyl-CoA carboxylase activity caused by arachidonate was accompanied by a similar decrease in transcription of the acetyl-CoA carboxylase gene. In contrast, neither palmitate nor oleate were effective in modulating acetyl-CoA carboxylase transcription. These results are consistent with arachidonate or a metabolite derived therefrom mediating the effects of diets containing high levels of n-6 polyunsaturated fatty acids on acetyl-CoA carboxylase transcription in liver. Hexanoate and octanoate also inhibited acetyl-CoA carboxylase activity in the presence of T3. The magnitude of the hexanoate- or octanoate-induced decrease in acetyl-CoA carboxylase activity was greater than that observed for long-chain fatty acids. Hexanoate and octanoate inhibited acetyl-CoA carboxylase activity at a transcriptional step, and did so within 2 h of addition of fatty acid. Addition of carnitine partially reversed the inhibitory effects of octanoate on acetyl-CoA carboxylase expression, suggesting that a metabolite of octanoate is involved in mediating this response. 2-Bromooctanoate was a more potent inhibitor of acetyl-CoA carboxylase expression than octanoate or hexanoate. We postulate that a metabolite of hexanoate and octanoate, possibly a six or eight carbon acyl-CoA, plays a role in the nutritional regulation of acetyl-CoA carboxylase transcription.
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PMID:Arachidonate and medium-chain fatty acids inhibit transcription of the acetyl-CoA carboxylase gene in hepatocytes in culture. 945 78

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