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PubMed2006

Starvation induces phase-specific changes in the proteome of mouse small intestine.

Food deprivation results in metabolic, structural, and functional changes in the small intestine that influences gut mucosal integrity, epithelial cell proliferation, mucin synthesis, and other processes. The underlying mechanisms are still unclear, which lead to the study of molecular effects of short-term and long-term starvation in the intestine of mice. A comparative proteomics approach, combining two-dimensional gel electrophoresis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, was used to identify intestinal proteins whose expression is changed under different starvation conditions (0, 12, 24, and 72 h). In total, the expression levels of 80 protein spots changed significantly between the different groups. The results demonstrate that after 12 h of starvation, mainly proteins involved in glycolysis and energy metabolism show decreased expression levels. Starvation for 24 h results in a down-regulation of proteins involved in protein synthesis and amino acid metabolism. Simultaneously, proteins with a protective role, e.g., reg I and II, glutathione peroxidase 3, and carbonic anhydrase 3, are clearly up-regulated. The last starvation phase (72 h) is characterized by increased ezrin expression, which may enhance villus morphogenesis critical for survival. Together, these results provide novel insights in the intestinal starvation response and may contribute to improved nutritional support during conditions characterized by malnutrition.

Animals↗
PubMed1975

Lipid metabolism in the cow during starvation-induced ketosis.

1. Concentrations and compositions of liver, serum and milk lipids of cows were measured during 6 days' starvation and serum lipids during 60 days' re-feeding. 2. The concentration of free fatty acid in serum increased fivefold during starvation. 3. The content of total lipid in liver (g/100g of liver dry matter) doubled owing to a 20-fold increase in triglyceride, an eightfold increase in cholesterol ester, a three fold increase in free fatty acid and a 20% increase in cholesterol. There were no changes in the content or composition of liver phospholipids. 4. Starvation lowered the concentrations of total lipid, phospholipid and cholesterol ester of dextran sulphate-precipitable serum lipoproteins. Total lipid and cholesterol ester concentrations in lipoproteins of d greater than 1.055 and in lipoproteins not precipitable by dextran sulphate decreased from day 4 of the starvation period and during the first 20 days' re-feeding. 5. During starvation there were decreases in percentages of stearic acid and increases in oleic acid in serum free fatty acids and triglycerides and in liver neutral lipid. 6. Throughout starvation total milk lipid yield decreased, yields and percentages of C4-14 fatty acids decreased and percentages of C18 fatty acids increased. 7. It is suggested that accumulation of triglyceride in liver may be caused by increased uptake of plasma free fatty acids without corresponding increase in lipoprotein secretion.

Acidosis↗
PubMed1979

Activities of enzymes of fat and ketone-body metabolism and effects of starvation on blood concentrations of glucose and fat fuels in teleost and elasmobranch fish.

1. Activities of 3-oxo acid CoA-transferase and carnitine palmitoyltransferase together with tri- and di-acylglycerol lipase were present in red and heart muscles of the teleost fish. However, d-3-hydroxybutyrate dehydrogenase activity was not detectable. These results suggest that the heart and red muscles of the teleosts should be able to utilize the fat fuels triacylglycerol, fatty acids or acetoacetate, but not hydroxybutyrate. The muscles from the elasmobranchs differed in that d-3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities were present, but carnitine palmitoyltransferase activity was not detectable. This suggests that ketone bodies are the most important fat fuels in elasmobranchs. 2. The concentrations of acetoacetate, 3-hydroxybutyrate, glycerol, non-esterified fatty acids and triacylglycerols were measured in blood or plasma of several species of fish (teleosts and elasmobranchs) in the fed state. Teleosts have a 10-fold higher concentration of plasma non-esterified fatty acids, but a lower blood concentration of ketone bodies; both acetoacetate and 3-hydroxybutyrate are present in blood of elasmobranchs, whereas 3-hydroxybutyrate is absent from that of the teleosts. 3. The effects of starvation (up to 150 days) on the concentrations of blood metabolites were studied in a teleost (bass) and an elasmobranch (dogfish). In the bass there was a 60% decrease in blood glucose after 100 and 150 days starvation. In dogfish there was a large increase in the concentration of ketone bodies, whereas in bass the concentration of acetoacetate (the only ketone body present) remained low (<0.04mm) throughout the period of starvation. The concentration of plasma non-esterified fatty acids increased in bass, but decreased in dogfish. These changes are consistent with the predictions based on the enzyme-activity data. 4. Starvation did not change the activities of ketone-body-utilizing enzymes or that of phosphoenolpyruvate carboxykinase in heart and red skeletal muscles of both fish, but it decreased markedly the activity of phosphoenolpyruvate carboxykinase in white skeletal muscle of both fish. However, in the liver of the dogfish, starvation resulted in a twofold increase in the activities of 3-hydroxybutyrate dehydrogenase and acetoacetyl-CoA thiolase, whereas in bass liver it decreased the activity of acetoacetyl-CoA thiolase and increased that of 3-oxo acid CoA-transferase. The activity of phosphoenolpyruvate carboxykinase was increased twofold in the liver of bass, but was unchanged in that of the dogfish. 5. The difference in changes in concentrations of blood metabolites and enzyme activities in the two fish support the suggestion that, in starvation, ketone bodies, but not non-esterified fatty acids, are an important fuel for muscle in elasmobranchs, whereas non-esterified fatty acids, but not ketone bodies, are an important fuel in teleosts. The results are discussed in relation to the evolution of a discrete lipid-storing adipose tissue in teleosts and higher vertebrates.

Animals↗
PubMed1991

Glucose disposal by skeletal muscle in response to re-feeding after progressive starvation.

We investigated the extent to which increases in glucose utilization indices (GUIs) in individual skeletal muscles during chow re-feeding after 6 h, 24 h or 48 h starvation are related to the antecedent duration of starvation. Chow re-feeding after either acute or prolonged starvation led to an increase in glucose disposal by the muscle mass. Glucose intolerance after prolonged starvation was not associated with lower values of GUI in skeletal muscle. In both working and non-working muscles, the increment in GUI during the first 2 h of re-feeding was less after acute than after prolonged starvation. In non-working muscles the differential responses to re-feeding were due to higher GUI values after re-feeding rather than lower pre-prandial GUI values. Therefore the contribution of non-working muscles to glucose clearance is higher as the antecedent period of starvation is extended. Rates of glycogen deposition in non-working muscles after refeeding were similar to absolute values of GUI, and a strong relationship existed between measured GUI values and rates of glycogen deposition.

Animals↗
PubMed2000

Semi-starvation alters myofibrillar mRNA concentrations to expedite rapid recovery of muscle protein stores following feeding.

BACKGROUND: Protein synthesis in skeletal muscle is reduced following starvation and restored by feeding. The mediators and mechanisms are incompletely understood. The aim of this study was to evaluate whether prolongation of undernutrition induced changes in muscle gene expression at the level of mRNA and protein. MATERIALS AND METHODS: The changes in myosin heavy-chain 2X mRNA in adult partially starved (50% of ad libitum standard rodent chow intake for 4 or 7 days) C57BL mice or subsequently refed mice were studied. Ad libitum-fed mice were used as controls. Protein synthesis, total RNA and myosin heavy-chain 2X mRNA concentrations were determined. Plasma concentrations of amino acids were measured by high-performance liquid chromatography. RESULTS: Partial starvation of 4 and 7 days reduced bodyweight by 15.6 +/- 1% and 17.1 +/- 2.1% (P < or = 0.05) vs. ad libitum fed controls. Protein synthesis was reduced by 32 +/- 9% and protein content by 20 +/- 4% (P < or = 0.05) following 7 days of partial starvation. Plasma amino acid concentrations were increased (6297 +/- 853) in refed animals vs. ad libitum-fed controls (3057 +/- 141, P < or = 0.05). Total RNA concentration (micrograms RNA micrograms(-1) DNA) in skeletal muscle was unchanged. Myosin heavy-chain 2X mRNA concentration did not change following 4 days of partial starvation but increased by 24 +/- 5% (P < or = 0.05) following 7 days of partial starvation, hence suggesting that expression of myosin mRNA was nutritionally altered. CONCLUSION: Postprandial stimulation of protein synthesis following starvation may thus be a combination of increased mRNA availability and increased translation. This effect may be activated by peak concentrations of amino acids in plasma following feeding.

Amino Acids↗
PubMed1997

Relationship between respiratory enzymes and survival of Escherichia coli under starvation stress in lake water.

Survival, electron transport system (ETS) activity and the activity of NADH and succinate dehydrogenase of Escherichia coli ML30 were studied under starvation stress at different temperatures in a filtered-autoclaved lake water microcosm. ETS activity in E. coli declined rapidly at 30 degrees C but more slowly at 4 degrees and 15 degrees C over a 20 d starvation period. The decrease in ETS activity in E. coli only started after 6 d of incubation at 4 degrees C and 15 degrees C. Viability of E. coli, as determined by plate counts, declined faster at 37 degrees C than at the other temperatures and remained highest at 4 degrees C in filtered-autoclaved lake water. There was also a significant cell size reduction at 37 degrees C in filtered-autoclaved lake water but not at 4 degrees C. ETS activity after up to 16 d of starvation increased after the addition of nutrient broth to the filtered-autoclaved lake water at 15 degrees C and 30 degrees C suggesting that cells were still able to respond to nutrients, even after prolonged starvation. The response to the addition of nutrient broth, however, declined with the length of the starvation period. The activity of both succinate and NADH dehydrogenase declined over a 13 d starvation period. The loss of activity was fastest at 37 degrees C compared to lower incubation temperatures but even at 4 degrees C, a significant proportion of the activity was lost over the 13 d period.

Colony Count, Microbial↗
PubMed2003

Alterations in the DNA binding activity of transcriptional factors activator protein-1, Sp1, and hepatocyte nuclear factor-1 in rat jejunum during starvation and refeeding.

BACKGROUND: The molecular processes leading to mucosal atrophy, regrowth, and functional changes with starvation and refeeding are largely unknown. There are many transcriptional factors that might be related to mucosal atrophy and proliferation. In contrast, we previously reported that H+/peptide transporter and aminopeptidase N messenger RNA in the intestinal mucosa were upregulated during starvation. Therefore, we selected and studied three transcriptional factors: activator protein (AP)-1, Sp1, and hepatocyte nuclear factor (HNF)-1, which not only play important roles for enterocytes proliferation, but also exist in promoter lesions of the brush border enzymes and peptide transporter. METHODS: In the present study, we performed electrophoretic mobility shift assays employing AP-1, Sp1, and HNF-1, and evaluated the changes in the DNA binding activities in rat jejunum during starvation and refeeding. RESULTS: Two days after starvation, the Sp1 binding activity was significantly decreased to 61.8% as compared with the control level, whereas AP-1 was 121.4% and HNF-1 was 77.5%. Two hours after refeeding, the AP-1 activity was significantly increased to 175.0% as compared with the control level, and the HNF-1 activity was significantly increased to 180.2%. In contrast, the decreased SP1 level did not recover until 24 h after refeeding. CONCLUSIONS: The DNA binding activities of these three transcriptional factors were significantly changed in the rat jejunum during starvation and refeeding. Our results provide insight into the molecular mechanisms of the transcriptional regulations associated with mucosal atrophy, regrowth, and functional changes of the jejunal epithelium in response to starvation and refeeding.

Animals↗
PubMed2000

Influence of pre-examination starvation on liver uptake of the hepatocyte-specific contrast medium FP 736-04 at CT. An experimental study in the rat.

PURPOSE: To investigate the effect of starvation on contrast-enhanced CT of the liver using the iodinated hepatocyte-specific lipid emulsion FP 736-04. MATERIAL AND METHODS: CT examination of the liver was performed in Sprague-Dawley rats before and after an i.v. infusion of 1.0 ml/kg b.w. of FP 736-04. The examination was preceded by a 15-h period of food withdrawal (the starvation group). A control group was subjected to the same CT examination protocol with use of FP 736-04 but without prior starvation. RESULTS: Liver attenuation values did not differ significantly between the starvation and the control group (p>0.05). CONCLUSION: A pre-examination period of starvation had no effect on FP 736-04 liver enhancement on CT However, liver attenuation tended to decrease more slowly in the starvation group than in the controls.

Animals↗
PubMed1989

Effects of acute starvation on vitamin A status in rats.

Maintenance of vitamin A stores in the body is dependent on a number of basic metabolic processes. These processes, such as protein and carbohydrate metabolism, are disrupted in acute starvation, and, as a result, alterations in vitamin A status may result. We investigated this possibility in 8-week-old Sprague-Dawley male rats. The rats were starved for 24, 48, and 72 hr but had free access to water. At 24 hours of starvation, the plasma retinol concentration was depressed, but not significantly so. After 48 and 72 hours of starvation, however, the plasma retinol concentration decreased to less than half of the control values (61 +/- 4 vs 124 +/- 12 nmol/dl at 72 hours, mean +/- SEM, (p less than 0.005). The hepatic retinoid (retinyl esters + retinol) concentration (nmol/g liver) was increased at 24 and 48 hours of starvation compared to controls (p less than 0.05), and by 72 hours the concentration was 56% greater in starved rats than in fed controls (p less than 0.001). The total hepatic retinoid content (mumol/total liver) was decreased moderately at all periods of starvation compared to controls (p less than 0.05). In both starved and fed animals, the total hepatic content per 100 g body weight, a measure of total vitamin A reserves, was statistically the same. These results demonstrate that acute starvation in rats alters the vitamin A equilibrium between the plasma and hepatic stores without affecting the overall vitamin A reserves.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed2003

Amino acid starvation and Gcn4p regulate adhesive growth and FLO11 gene expression in Saccharomyces cerevisiae.

In baker's yeast Saccharomyces cerevisiae, cell-cell and cell-surface adhesion are required for haploid invasive growth and diploid pseudohyphal development. These morphogenetic events are induced by starvation for glucose or nitrogen and require the cell surface protein Flo11p. We show that amino acid starvation is a nutritional signal that activates adhesive growth and expression of FLO11 in both haploid and diploid strains in the presence of glucose and ammonium, known suppressors of adhesion. Starvation-induced adhesive growth requires Flo11p and is under control of Gcn2p and Gcn4p, elements of the general amino acid control system. Tpk2p and Flo8p, elements of the cAMP pathway, are also required for activation but not Ste12p and Tec1p, known targets of the mitogen-activated protein kinase cascade. Promoter analysis of FLO11 identifies one upstream activation sequence (UASR) and one repression site (URS) that confer regulation by amino acid starvation. Gcn4p is not required for regulation of the UASR by amino acid starvation, but seems to be indirectly required to overcome the negative effects of the URS on FLO11 transcription. In addition, Gcn4p controls expression of FLO11 by affecting two basal upstream activation sequences (UASB). In summary, our study suggests that amino acid starvation is a nutritional signal that triggers a Gcn4p-controlled signaling pathway, which relieves repression of FLO11 gene expression and induces adhesive growth.

Amino Acids↗
PubMed1995

Starvation and refeeding regulate glycogen synthase gene expression in rat liver at the posttranscriptional level.

Starvation and refeeding affect glycogen metabolism. The effects of starvation and refeeding on the level of glycogen synthase (GS) gene expression were examined in rat liver. Depletion of hepatic glycogen stores by 72 h of starvation (7% of control) was supercompensated by 24 h of refeeding a standard laboratory diet (247% of control). Upon further refeeding, glycogen concentration gradually returned to control levels after 120 h. After 72 h of starvation, GS activity and immunoreactive protein in the liver were 60-64% lower than in control rats with free access to food. After 72 h of refeeding, GS activity and immunoreactive protein returned to control values. No significant differences in GS mRNA levels were found between fed, starved and refed rats, as determined by Northern blot analysis and PCR quantification, indicating that the long-term regulation of GS gene expression in starvation and refeeding occurs via a posttranscriptional mechanism. The amount of GS mRNA associated with polyribosomes was 90% lower in starved than in fed rats. These data indicate that the efficiency of GS mRNA translation, rather than its abundance, decreases during starvation.

Animals↗
PubMed2005

Evidence for a robust sex-specific trade-off between cold resistance and starvation resistance in Drosophila melanogaster.

In insects changes in lipid metabolism may underlie a trade-off between cold resistance and starvation resistance. To test this we examined correlated responses in independent sets of Drosophila melanogaster lines selected for increased cold resistance and increased starvation resistance. The starvation lines showed correlated patterns found in other D. melanogaster populations selected for this trait, including higher lipid levels and increased resistance to desiccation, although the selected lines did not show a longer development time as found in some other studies. Consistent with the trade-off hypothesis, selected lines with increased starvation resistance showed decreased resistance to a cold stress as measured by mortality, whereas selected lines with increased cold resistance showed a decrease in starvation resistance. To counter the possibility of inadvertent selection accounting for these patterns, selected and control lines from both selection regimes were crossed to form mass bred populations, which were left for four generations prior to establishing isofemale lines. By scoring starvation and cold resistance in these lines derived from both sets of selection regimes, we confirmed the negative association between resistance to these stresses in females but not in males. Potential implications of this trade-off for surviving cold conditions when food resources are limiting are discussed.

Adaptation, Physiological↗
PubMed1993

Resting oxygen consumption in rats during food restriction, starvation and refeeding.

Oxygen consumption was measured in male rats during starvation and during different regimens of restricted feeding and refeeding after starvation. Changes in oxygen consumption and body mass were mostly parallel, but rats with a very reduced food intake displayed the same reduction in oxygen consumption as starved rats, despite the smaller reduction in body mass. Also, rats fed different amounts of food after starvation had different oxygen consumptions, but displayed the same changes in body mass. Two different refeeding regimens with restricted food amounts either induced a further depression of oxygen consumption (i.e. below starvation oxygen consumption), or a stabilizing of oxygen consumption on the level of starvation. The changes in oxygen consumption during restriction and feeding after starvation indicate that reductions in resting metabolic rate may not always be predicted from either body mass change or food intake.

Animals↗
PubMed1991

Role of RpoH, a heat shock regulator protein, in Escherichia coli carbon starvation protein synthesis and survival.

Escherichia coli starvation proteins include several heat shock proteins whose induction by heat is controlled by the minor sigma factor, sigma 32. The level of sigma 32 increased in wild-type E. coli upon starvation, and three sigma 32-controlled heat shock proteins (DnaK, GroEL, and HtpG) were not induced during starvation in an isogenic delta rpoH strain, which is unable to synthesize sigma 32. Thus, sigma 32 plays a role in the induction of these proteins during both heat shock and starvation. The delta rpoH strain was more sensitive to starvation but could develop starvation-mediated cross protection against heat and oxidation.

Bacterial Proteins↗
PubMed1985

Dopamine in the pituitary adaptation to starvation in man.

To investigate the role of the dopaminergic system in the pituitary adaptation to energy deprivation, the effect of metoclopramide, a dopamine receptor blocker, on prolactin (PRL), TSH, FSH and LH secretion was investigated in 6 healthy men in the fed state and at 36 h starvation. All underwent a further 36 h of starvation on a separate occasion to assess the effect of starvation on the TSH and PRL responses to TRH and the LH and FSH responses to gonadotrophin releasing hormone (GnRH). In all subjects starvation produced the expected reduction in serum T3 and an average decrease of 53% in the cumulative TSH response to TRH. The basal serum PRL and its response to TRH and metoclopramide remained unchanged with 36 h starvation. The FSH response to GnRH also remained unchanged, but the LH response was significantly greater during starvation. We conclude that factor(s) other than dopamine influence not only thyrotrophic activity but also other aspects of pituitary function during energy deprivation.

Adaptation, Physiological↗
PubMed1979

Effects of starvation and diabetes on protein synthesis in lung.

Metabolism of lung proteins was investigated in rats starved 3 days or made diabetic with streptozotocin. Body weight was below normal in both groups, but lung weight decreased only in starved animals. Total lung protein and RNA (mg/lung) decreased during starvation and diabetes. Protein concentration (mg/g) was unchanged in either group of animals; RNA concentration decreased only during starvation. Protein synthesis, estimated in lungs perfused in situ, was reduced 22% in starvation, but remained unchanged in diabetes. Inhibition of protein synthesis was accounted for by loss of RNA. Ribosomal profiles were unchanged by starvation, suggesting an unaltered relationship between rates of peptide-chain initiation and elongation in vivo. Activity of an eIF-2-like initiation factor decreased during starvation in proportion to the loss of RNA. In diabetes, factor activity remained normal. Thus, starvation but not streptozotocin-induced diabetes, reduced the capacity of the lung to synthesize protein. No evidence for reduced efficiency of synthesis was observed.

Animals↗
PubMed1983

Interactions of cold exposure and starvation on glucose tolerance and insulin response.

The metabolic interactions of cold exposure, cold acclimation, and starvation on glucose tolerance and plasma insulin levels were studied in precannulated, unrestrained, and unanesthetized rats. Cold exposure (48 h at 5 degrees C) significantly reduced the insulin response to intravenous glucose injection (P less than 0.01) while improving glucose tolerance (P less than 0.01). Starvation (48 h at 25 degrees C) also reduced the insulin response (P less than 0.01) but did not significantly alter glucose tolerance. "Accelerated starvation" induced by starving rats for 48 h at 5 degrees C dramatically reduced both basal and glucose-stimulated insulin levels while even improving glucose tolerance, resulting in a 15-fold reduction in the insulinogenic index. Cold acclimation (3 wk at 5 degrees C) induced essentially the same alterations as cold exposure. Approximately reversed changes were observed when cold-acclimated rats were returned to a warm environment for 15-18 h. Results from these studies indicate that 1) cold exposure and starvation, but not cold acclimation, act synergistically in decreasing the sensitivity and/or the capacity of pancreatic islets for secreting insulin in response to glucose stimulation; 2) glucose tolerance and possibly insulin sensitivity of peripheral tissues are enhanced by cold exposure and starvation, although glucose tolerance is improved by cold exposure only, not by starvation; 3) an improved glucose tolerance with barely detectable plasma insulin levels was obtained in cold-starved rats under normal physiological conditions.

Acclimatization↗
PubMed1985

Effect of starvation on amino acid and peptide transport and peptide hydrolysis in humans.

Jejunal disappearance rates of glycine (a model for neutral amino acid absorption), triglycine (a model for peptide transport), and tetraglycine (a model for brush-border membrane hydrolysis) were investigated by an in situ perfusion technique before and after 2 wk of starvation in seven obese volunteers. The three test solutions of glycine, triglycine, and tetraglycine were equivalent in glycine content. Before starvation glycine absorption was greatest from the triglycine solution and smallest from the glycine solution. Starvation significantly decreased glycine absorption from both glycine and triglycine solutions, but not from the tetraglycine solution. However, glycine absorption was still significantly greater from the triglycine and tetraglycine solutions than from the glycine solution. Starvation had no significant effect on the disappearance rate of triglycine, but it increased the disappearance rate of tetraglycine. We conclude that a) starvation has different effects on functions of mucosal brush-border membrane, for example, it reduces amino acid absorption but enhances peptide hydrolysis; and b) the greater amino acid absorption from peptides is maintained even after 2 wk of starvation, suggesting that peptides are superior to free amino acids as the nitrogen source for enteral nutrition if employed in malnutrition.

Absorption↗