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

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

Hepatic fatty acid synthase is regulated by nutritional state. Starvation decreases and refeeding increases the activity of avian fatty acid synthase, principally by regulating transcription of the gene (Back, B. W., Goldman, M. J., Fisch, J.E., Ochs, R.A., and Goodridge, A.G. (1986) J. Biol. Chem. 261, 4190-4197). In chick embryo hepatocytes in culture, the stimulatory effect of feeding on fatty acid synthase activity is mimicked by adding triiodothyronine and insulin; the inhibitory effect of starvation is mimicked by adding glucagon or cyclic AMP. We now show that triiodothyronine alone stimulates transcription of fatty acid synthase by 4- to 6-fold, about the same as the increase in fatty acid synthase mRNA. When added alone, insulin has little or no effect on transcription, mRNA level, or enzyme activity. In combination with triiodothyronine, however, insulin amplifies the response to triiodothyronine by about 2-fold, leading to an overall increase of about 10-fold. Insulin-like growth factor 1 (IGF-1) has the same effect as insulin, no effect by itself, and amplification of the stimulation by triiodothyronine. A maximally effective dose of insulin has no effect in the presence of a maximally effective dose of IGF-1, suggesting regulation by a common pathway. It takes much less IGF-1 than insulin to achieve a given effect, suggesting that both insulin and IGF-1 may act through IGF-1 receptors. Plasma levels of IGF-1 are decreased by starvation and increased by feeding (reviewed by Froesch, E.R., and Zapf, J. (1985) Diabetologia 28, 485-493). Thus, IGF-1 may play a physiological role in the regulation of hepatic fatty acid synthase during transitions between the starved and fed states, roles previously assigned primarily to insulin and glucagon. IGF-1 regulates transcription of the fatty acid synthase gene. Insulin and IGF-1 also have similar effects on activity, mRNA abundance, and transcription of the malic enzyme gene. Glucagon or dibutyryl cyclic AMP inhibit fatty acid synthase activity and mRNA level in hepatocytes in culture by 70-80% and 60%, respectively, but have no effect on transcription of the fatty acid synthase gene, suggesting a post-transcriptional mode of regulation for cyclic AMP.
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PMID:Triiodothyronine stimulates transcription of the fatty acid synthase gene in chick embryo hepatocytes in culture. Insulin and insulin-like growth factor amplify that effect. 217 Apr 11

We have examined the effects of starvation, normal lab chow and low-fat carbohydrate-rich diet on rat fatty acid synthase (FAS, EC 2.3.1.85). Under each of the dietary conditions the amount of FAS mRNA is different, the most being produced after a low-fat carbohydrate-rich diet. There is also an increase in the amount of FAS protein under the same conditions. To complete the picture we determined the incorporation of [14C]acetate into palmitate as a measure of enzyme activity. Data for cardiac and renal tissue also reflect a dietary influence on FAS. Therefore FAS mRNA, FAS protein and FAS activity are all responsive to dietary-induced signals, and our results suggest a pre-translational regulation.
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PMID:Dietary-induced pre-translational control of rat fatty acid synthase. 232 66

1. A sensitive radiochemical assay was established to determine the activity of fatty acid synthase in microdissected liver tissue of less than 1 microgram dry mass. 2. In female rats, the enzyme activity in perivenous tissue was twice that in periportal liver tissue while it was homogeneously distributed in livers of male animals. The overall activity was higher in female than in male animals. 3. The absolute activity, as well as the perivenous/periportal ratio, was reduced during starvation and in diabetes. They were greatly increased after refeeding to values above those observed in animals during normal feeding. 4. Ovariectomy or administration of testosterone to female rats resulted in a significant reduction of the zonal heterogeneity. 5. Castration or administration of estradiol to male animals was followed by an increase in the enzyme activity exclusively in the perivenous tissue, resulting in a zonal heterogeneity as observed in female rats.
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PMID:Zonal distribution of fatty acid synthase in liver parenchyma of male and female rats. 270 60

The rates of synthesis of fatty acid synthase and the levels of its mRNA are high in livers of chicks, ducklings, or goslings fed high-carbohydrate mash diets and low in livers of starved birds, indicating pretranslational regulation of fatty acid synthase activity. Determination of the step(s) at which the nutritional state regulates the fatty acid synthase mRNA level was the objective of this study. Total RNA extracted from gosling or duckling liver contains two discrete fatty acid synthase transcripts, one of about 12,200 nucleotides and the other about 10,800 nucleotides. Both mRNAs are transcribed from the same gene because there is only one fatty acid synthase gene/haploid genome. A combination of 1) comparison of restriction fragment lengths in genomic DNA and cloned fatty acid synthase cDNAs, 2) differential hybridization of cloned cDNAs to the two mRNAs, and 3) sequence analysis indicates that the longer mRNA is a 3'-extension of the shorter one. The half-lives for fatty acid synthase mRNAs in fed ducklings and in starved ducklings were estimated from the rate at which mRNA level approached steady state during starvation or refeeding. The amount of fatty acid synthase mRNA in total liver RNA increased rapidly when starved ducklings were fed a high-carbohydrate mash diet, reaching an apparent steady state of 10 times the initial level after 9 h. The kinetics of accumulation suggested a half-life of 4-6 h for fatty acid synthase mRNA in fed ducklings. When fed ducklings were starved, fatty acid synthase mRNA decayed with a half-life of about 3 h. Therefore, the half-life for fatty acid synthase mRNA appeared to be little affected by feeding or starvation. The levels of both mRNAs changed in parallel indicating that half-lives of the two mRNAs were not regulated differentially. Transcription of the fatty acid synthase gene, as measured in isolated nuclei, increased about 10-fold when starved ducklings were refed for 24-30 h. Most of the increase in transcription occurred within 45 min after feeding was initiated. However, when fed ducklings were starved, the initial decrease in fatty acid synthase mRNA level occurred more rapidly than the decrease in transcription of the fatty acid synthase gene, indicating some degree of post-transcriptional regulation. Nevertheless, after 48 h of starvation, both mRNA level and transcription were decreased to the same extent. Nutritional state, therefore, regulates the transcription of two fatty acid synthase mRNAs from a unique gene. In addition, transient regulation occurs at an as yet undefined post-transcriptional step.
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PMID:The fatty acid synthase gene in avian liver. Two mRNAs are expressed and regulated in parallel by feeding, primarily at the level of transcription. 300 24

Mechanisms involved in the multihormonal regulation of fatty acid synthase have been investigated by comparing levels of its mRNA with rates of enzyme synthesis in chick embryo hepatocytes in culture. Triiodothyronine or insulin caused about a 2.5-fold increase in the relative rate of synthesis of fatty acid synthase. Together, these hormones were synergistic, stimulating enzyme synthesis by nearly 40-fold (Fischer, P.W.F., and Goodridge, A.G. (1978) Arch. Biochem. Biophys. 190, 332-344). Addition of triiodothyronine stimulated increases in mRNA levels comparable to increases in enzyme synthesis whether insulin was present or not. Thus, triiodothyronine regulates fatty acid synthase primarily by controlling the amount of its mRNA. Addition of insulin, in the presence of triiodothyronine, stimulated enzyme synthesis by 14-fold and mRNA levels by only 2-fold. In the absence of triiodothyronine, insulin had no effect on mRNA levels. Thus, insulin has a major effect on the translation of fatty acid synthase mRNA. After the addition of triiodothyronine, fatty acid synthase mRNA accumulated with sigmoidal kinetics, approaching a new steady state about 48 h after the addition of hormone. Puromycin, an inhibitor of protein synthesis, blocked the effect of triiodothyronine. We suggest that the abundances of both fatty acid synthase and malic enzyme mRNAs are regulated by a common triiodothyronine-induced peptide intermediate which has a relatively long half-life. Glucagon caused an 80% decrease in the synthesis of fatty acid synthase (Fischer, P.W.F., and Goodridge, A.G. (1978) Arch. Biochem. Biophys. 190, 332-344) and a 60% decrease in the level of fatty acid synthase mRNA. Thus, glucagon regulates fatty acid synthase by controlling the concentration of its mRNA. The synthesis of malic enzyme also was inhibited by glucagon at a pretranslational step, but the inhibition was almost complete. Thus, despite coordinated regulation of the concentrations of these enzymes during starvation and refeeding, individual hormones sometimes regulate synthesis of the two enzymes at the same step and to about the same degree and sometimes at different steps or to very different degrees.
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PMID:Hormonal regulation of lipogenic enzymes in chick embryo hepatocytes in culture. Expression of the fatty acid synthase gene is regulated at both translational and pretranslational steps. 353 37

The levels of malic enzyme and fatty acid synthase are increased by feeding and decreased by starvation in liver in vivo and are increased by triiodothyronine and decreased by glucagon in hepatocytes in culture. Cloned malic enzyme and fatty acid synthase cDNAs are being used to analyze regulation of these unique genes. Dietary regulation of both enzymes occurs at pretranslational steps. Increased transcription and increased mRNA stability contribute about equally to a 20-fold increase in malic enzyme mRNA level when starved ducklings are refed. In contrast, a 10-fold increase in the level of fatty acid synthase mRNA is largely accounted for by increased transcription of this gene. In chick-embryo hepatocytes incubated in serum-free medium containing insulin, triiodothyronine causes a greater than 10-fold increase in levels of both malic enzyme and fatty acid synthase mRNAs. Kinetic and inhibitor experiments suggest a protein intermediate in the increases of malic enzyme and fatty acid synthase mRNAs caused by triiodothyronine. For malic enzyme, the stimulation by triiodothyronine is predominantly posttranscriptional. Glucagon decreases the level of malic enzyme mRNA by 90 to 95%, with regulation occurring at a posttranscriptional step. Inhibitor experiments suggest that stimulation of the degradation of malic enzyme mRNA is partially responsible. Glucagon inhibited fatty acid synthase mRNA level by less than 50%; the inhibited step has not been identified. Thus, the coordinated regulation of malic enzyme and fatty acid synthase proteins by nutritional state may involve different hormones regulating at different points. A surprisingly large component of the regulation is posttranscriptional.
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PMID:Regulation of genes for enzymes involved in fatty acid synthesis. 354 53

Protein synthesis in the rat mammary gland has been studied using acini isolated from mammary tissue by collagenase digestion. When the acini were incubated with radioactively labeled amino acids, both cellular and milk proteins were synthesized and milk proteins were secreted into the incubation medium. Antisera to the lipogenic enzyme, fatty acid synthase, and the milk proteins, alpha-lactalbumin and the caseins, raised in rabbits, were shown to be specific by analyzing immunoprecipitates on sodium dodecyl sulfate--polyacrylamide gels. The rates of synthesis and secretion of each protein by acini prepared from rats during late gestation and at specific stages of lactation reflect their previously observed concentration in the mammary gland or milk of rats at the corresponding stage of gestation or lactation. Rats were treated according to one of the following regimes between d 7 and 14 of lactation: they were fed a control (20% casein) or a low protein (10% casein) diet ad libitum, they were fed the control diet restricted to 25 g/d (40% of the voluntary intake), they were fed the control diet for 5 d and starved for 48 h or they were treated as in 3 and then refed the control diet ad libitum for 24 h. Food restriction and starvation both resulted in lowered rates of synthesis of all proteins examined compared with either the control or refed animals. Starvation also lowered the rates of secretion of the milk proteins. Consumption of the low protein diet caused a specific decrease in both the rates of synthesis and secretion of alpha-lactalbumin compared with the control rats without affecting the synthesis and secretion of the caseins.
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PMID:Protein synthesis in mammary acini isolated from lactating rats: effect of maternal diet. 358 28

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

The mRNAs for fatty acid synthase and malic enzyme were almost undetectable in total RNA extracted from the livers of 16-day old chick embryos. Both mRNAs increased in abundance between the 16th day of incubation and the day of hatching. In neonates, fatty acid synthase mRNA level was dependent on nutritional status, increasing slowly if the chicks were starved and rapidly if they were fed. The abundance of malic enzyme mRNA decreased in starved neonatal chicks and increased in fed ones. When neonates were first fed and then starved, starvation caused a large decrease in the abundance of both mRNAs. Conversely, feeding, after a period of starvation, resulted in a substantial increase in both mRNAs. The relative abundances of fatty acid synthase and malic enzyme mRNAs correlated positively with relative rates of enzyme synthesis. Thus, nutritional and hormonal regulation of the synthesis of these two 'lipogenic' enzymes is exerted primarily at a pre-translational level. The abundance of albumin mRNA decreased significantly between the 16th day of incubation and the day of hatching but did not change thereafter in fed or starved chicks. The relative stability of albumin mRNA levels after hatching attests to the selectivity of the nutritional regulation of fatty acid synthase and malic enzyme mRNAs. The decrease in albumin mRNA which occurred between 16 days of incubation and hatching contrasts with the increase in albumin mRNA sequences which occurred during late gestation in the fetal rat (20). High levels of albumin in the chick embryo may be related to the lack of an analogue of mammalian alpha-fetoprotein in birds.
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PMID:Developmental and nutritional regulation of the messenger RNAs for fatty acid synthase, malic enzyme and albumin in the livers of embryonic and newly-hatched chicks. 620 76


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