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Aerobic and anaerobic starvation metabolism in methanotrophic bacteria.

The capacity for anaerobic metabolism of endogenous and selected exogenous substrates in carbon- and energy-starved methanotrophic bacteria was examined. The methanotrophic isolate strain WP 12 survived extended starvation under anoxic conditions while metabolizing 10-fold less endogenous substrate than did parallel cultures starved under oxic conditions. During aerobic starvation, the cell biomass decreased by 25% and protein and lipids were the preferred endogenous substrates. Aerobic protein degradation (24% of total protein) took place almost exclusively during the initial 24 h of starvation. Metabolized carbon was recovered mainly as CO(inf2) during aerobic starvation. In contrast, cell biomass decreased by only 2.4% during anaerobic starvation, and metabolized carbon was recovered mainly as organic solutes in the starvation medium. During anaerobic starvation, only the concentration of intracellular low-molecular-weight compounds decreased, whereas no significant changes were measured for cellular protein, lipids, polysaccharides, and nucleic acids. Strain WP 12 was also capable of a limited anaerobic glucose metabolism in the absence of added electron acceptors. Small amounts of CO(inf2) and organic acids, including acetate, were produced from exogenous glucose under anoxic conditions. Addition of potential anaerobic electron acceptors (fumarate, nitrate, nitrite, or sulfate) to starved cultures of the methanotrophs Methylobacter albus BG8, Methylosinus trichosporium OB3b, and strain WP 12 did not stimulate anaerobic survival. However, anaerobic starvation of these bacteria generally resulted in better survival than did aerobic starvation. The results suggest that methanotrophic bacteria can enter a state of anaerobic dormancy accompanied by a severe attenuation of endogenous metabolism. In this state, maintenance requirements are presumably provided for by fermentation of certain endogenous substrates. In addition, low-level catabolism of exogenous substrates may support long-term anaerobic survival of some methanotrophic bacteria.

Journal Article↗

Starvation response of Saccharomyces cerevisiae grown in anaerobic nitrogen- or carbon-limited chemostat cultures.

Anaerobic starvation conditions are frequent in industrial fermentation and can affect the performance of the cells. In this study, the anaerobic carbon or nitrogen starvation response of Saccharomyces cerevisiae was investigated for cells grown in anaerobic carbon or nitrogen-limited chemostat cultures at a dilution rate of 0.1 h(-1) at pH 3.25 or 5. Lactic or benzoic acid was present in the growth medium at different concentrations, resulting in 16 different growth conditions. At steady state, cells were harvested and then starved for either carbon or nitrogen for 24 h under anaerobic conditions. We measured fermentative capacity, glucose uptake capacity, intracellular ATP content, and reserve carbohydrates and found that the carbon, but not the nitrogen, starvation response was dependent upon the previous growth conditions. All cells subjected to nitrogen starvation retained a large portion of their initial fermentative capacity, independently of previous growth conditions. However, nitrogen-limited cells that were starved for carbon lost almost all their fermentative capacity, while carbon-limited cells managed to preserve a larger portion of their fermentative capacity during carbon starvation. There was a positive correlation between the amount of glycogen before carbon starvation and the fermentative capacity and ATP content of the cells after carbon starvation. Fermentative capacity and glucose uptake capacity were not correlated under any of the conditions tested. Thus, the successful adaptation to sudden carbon starvation requires energy and, under anaerobic conditions, fermentable endogenous resources. In an industrial setting, carbon starvation in anaerobic fermentations should be avoided to maintain a productive yeast population.

Adenosine Triphosphate↗

Alanine dehydrogenase activity is required for adequate progression of phycobilisome degradation during nitrogen starvation in Synechococcus elongatus PCC 7942.

Degradation of the cyanobacterial light-harvesting antenna, the phycobilisome, is a general acclimation response that is observed under various stress conditions. In this study we identified a novel mutant of Synechococcus elongatus PCC 7942 that exhibits impaired phycobilisome degradation specifically during nitrogen starvation, unlike previously described mutants, which exhibit aberrant degradation under nitrogen, sulfur, and phosphorus starvation conditions. The phenotype of the new mutant, AldOmega, results from inactivation of ald (encoding alanine dehydrogenase). AldOmega is deficient in transcription induction of a number of genes during nitrogen starvation. These genes include the "general nutrient stress-related" genes, nblA and nblC, the products of which are essential for phycobilisome degradation. Furthermore, transcripts of several specific nitrogen-responsive genes accumulate at lower levels in AldOmega than in the wild-type strain. In contrast, ald inactivation did not decrease the accumulation of transcripts during sulfur starvation. Transcription of ald is induced upon nitrogen starvation, which is consistent with the ability of wild-type cells to maintain a low cellular content of alanine under these conditions. Unlike wild-type cells, AldOmega accumulates alanine upon nitrogen starvation. Our analyses suggest that alanine dehydrogenase activity is necessary for an adequate cellular response to nitrogen starvation. Decomposition of alanine may be required to provide a sufficient amount of ammonia. Furthermore, the accumulated alanine, or a related metabolite, may interfere with the cues that modulate acclimation during nitrogen starvation. Taken together, our results provide novel information regarding cellular responses to nitrogen starvation and suggest that mechanisms related to nitrogen-specific responses are involved in modulation of a general acclimation process.

Alanine Dehydrogenase↗

Starvation for different nutrients in Escherichia coli results in differential modulation of RpoS levels and stability.

Levels of RpoS increase upon glucose starvation in Escherichia coli, which leads to the transcription of genes whose products combat a variety of stresses. RpoS stability is a key level of control in this process, as SprE (RssB)-mediated degradation is inhibited under glucose starvation. Starvation for ammonia or phosphate also results in increased stress resistance and induction of RpoS-dependent genes. However, we demonstrate that RpoS levels following ammonia starvation are only slightly increased compared to growing cells and are 10-fold below the levels observed under glucose or phosphate limitation. This difference is largely due to regulated proteolysis of RpoS, as its stability in ammonia-starved cells is intermediate between that in logarithmic-phase cells and glucose-starved cells. Use of an rpoS construct that is devoid of the gene's native transcriptional and translational control regions reveals that stability differences are sufficient to explain the different levels of RpoS observed in logarithmic phase, ammonia starvation, and glucose starvation. Under phosphate starvation, however, rpoS translation is increased. The cellular response to nutrient limitation is much more complex than previously appreciated, as there is not simply one response that is activated by starvation for any essential nutrient. Our data support the hypothesis that SprE activity is the key level at which ammonia and glucose starvation signals are transmitted to RpoS, and they suggest that carbon source and/or energy limitation are necessary for full inactivation of the SprE pathway.

Adaptation, Physiological↗

Influence of starvation for methionine and other amino acids on subsequent bacterial deoxyribonucleic acid replication.

Billen, Daniel (University of Texas M. D. Anderson Hospital and Tumor Institute, Houston, Tex.), and Roger Hewitt. Influence of starvation for methionine and other amino acids on subsequent bacterial deoxyribonucleic acid replication. J. Bacteriol. 92:609-617. 1966.-A study has been made of the subsequent replicative fate of deoxyribonucleic acid (DNA) synthesized during amino acid starvation by several multiauxotrophic strains of Escherichia coli. Using radioisotopic and density labels and a procedure whereby total cellular DNA is analyzed, we have confirmed and extended a recent report that the DNA made during amino acid starvation behaves anomalously during subsequent DNA replication. When 5-bromouracil (BU) serves as the density lable, 40% or more of the DNA synthesized during starvation will subsequently fail to replicate during three cell generations. Selective amino acid effects were noted. In two methionine-requiring bacteria, methionine deprivation appeared to be of singular importance in influencing the subsequent replicative fate of the DNA made in its absence. When a non-BU density label (N(15), C(13)) was utilized, the effects of amino acid starvation were less obvious. Although the DNA synthesized during complete amino acid starvation in a methionine-requiring E. coli was subsequently more slowly replicated, most of the DNA was finally duplicated during three generations of growth. If methionine was present during starvation for other required amino acids, the subsequent replication rate of the DNA synthesized during this time was more nearly normal, and complete replication was observed. The results have been interpreted as indicating that DNA synthesized during amino acid starvation, and especially during methionine starvation, is somehow altered, and that BU substitution for thymine may interfere with the restoration of such DNA to its replicative state.

Amino Acids↗

Global gene expression profiling of Bacillus subtilis in response to ammonium and tryptophan starvation as revealed by transcriptome and proteome analysis.

The global gene expression profile of Bacillus subtilis in response to ammonium and tryptophan starvation was analyzed using transcriptomics and proteomics which gained novel insights into these starvation responses. The results demonstrate that both starvation conditions induce specific, overlapping and general starvation responses. The TnrA regulon, the glutamine synthetase (glnA) as well as the sigma(L)-dependent bkd and roc operons were most strongly and specifically induced after ammonium starvation. These are involved in the uptake and utilization of ammonium and alternative nitrogen sources such as amino acids, gamma-aminobutyrate, nitrate/nitrite, uric acid/urea and oligopeptides. In addition, several carbon catabolite-controlled genes (e.g. acsA, citB), the alpha-acetolactate synthase/-decarboxylase alsSD operon and several aminotransferase genes were specifically induced after ammonium starvation. The induction of sigma(F)- and sigma(E)-dependent sporulation proteins at later time points in ammonium-starved cells was accompanied by an increased sporulation frequency. The specific response to tryptophan starvation includes the TRAP-regulated tryptophan biosynthesis genes, some RelA-dependent genes (e.g. adeC, ald) as well as spo0E. Furthermore, we recognized overlapping responses between ammonium and tryptophan starvation (e.g. dat, maeN) as well as the common induction of the CodY and sigma(H) general starvation regulons and the RelA-dependent stringent response. Many genes encoding proteins of so far unknown functions could be assigned to specifically or commonly induced genes.

Ammonium Sulfate↗

Multitrait evolution in lines of Drosophila melanogaster selected for increased starvation resistance: the role of metabolic rate and implications for the evolution of longevity.

Starvation resistance is a trait often associated with longevity. Animals with increased longevity frequently show elevated starvation resistance and vice versa. Consequently, both life-history traits are thought to share genetic and physiological mechanisms, such as increased fat content and lowered metabolic rate. Here, we present results from 20 generations of selection on Drosophila melanogaster for increased starvation resistance at the time of adult eclosion. We observe that starvation resistance can be the result of more than one mechanism, all associated with an increase in fat resources. In general, metabolic rate is lowered under starved conditions relative to fed conditions. Metabolic rate in the starvation resistant lines is generally higher than in control lines under starved conditions. Starvation resistant flies are able to sustain a higher metabolic rate for a longer period of time when food is unavailable. This implies depletion of the increased fat reserves. However, longevity was not consistently affected by selection for increased starvation resistance. Similarly, paraquat resistance differed between selection lines and did not associate with starvation resistance, but rather with longevity. The results are discussed in relation to previous reported results on starvation resistance and its relation with mechanisms of aging and longevity.

Animals↗

[Adaptive changes in activity of tonoplast H(+)-ATPase from the roots of tomato seedlings under phosphorus starvation].

We studied the growth state of tomato seedlings and the adaptive changes in activity of tonoplast H(+)-ATPase on different days (5 d, 7 d, 9 d, 11 d, 13 d) sampling from the roots of tomato seedlings under phosphorus starvation. The results indicated that the average height of the seedlings decreased under phosphorus starvation, while the main roots of the seedlings were significantly longer than those of the control. The phosphorus uptake rates of tomato seedlings under phosphorus starvation significantly increased and were much higher than those of controls and reached maximum values under the starvation for 7 days. The tonoplast H(+)-ATPase activity in the roots of tomato seedlings increased under phosphorus starvation and reached maximum values under the starvation for 7 days, while the activity of the control changed little. Kinetic analysis of tonoplast H(+)-ATPase showed that phosphorus starvation significantly lowered the K(m) value, but had no significant effect on the V(max) value of the enzyme. The results showed that phosphorus starvation increased the affinity of the enzyme to its substrate. In addition, phosphorus starvation did not alter the optimum pH (7.5) of the ATPase activity.

Adaptation, Physiological↗

The effect of starvation on growth and plasma growth hormone concentrations of rainbow trout, Oncorhynchus mykiss.

Two experiments, one using 0+ the other 1+ rainbow trout, were conducted to investigate the effect of prolonged starvation on plasma growth hormone levels. The results from both experiments were essentially the same. As expected, starvation resulted in cessation of growth and in a lower coefficient of condition, whereas fed fish continued to grow and remained in good condition. Starvation had relatively little effect on the plasma cortisol level; in one experiment levels were elevated temporarily in starved fish, although by the end of the experiment there was no longer any difference between starved and fed fish, and in the other experiment plasma cortisol levels remained very low throughout the course of the experiment in both starved and fed fish. In contrast, in both experiments starvation had a pronounced effect on the plasma growth hormone level, which rose steadily during both experiments, such that it was six times higher after 1 month of starvation in 0+ fish, and five times higher after 6 weeks of starvation in 1+ fish. Thus, paradoxically, fed fish had very low plasma growth hormone levels and grew rapidly, whereas starved fish had elevated plasma growth hormone levels but did not grow. In both experiments a strong negative correlation was observed between the plasma growth hormone level and the coefficient of condition of the fish. The results are discussed with regard to the well-established metabolic changes that occur during starvation, and it is suggested that a major role of growth hormone during starvation is to aid in the mobilisation of fatty acids and glycerol from adipose stores.

Animals↗

The energy cost of triglyceride-fatty acid recycling in nonobese subjects after an overnight fast and four days of starvation.

The basal blood glycerol concentration was determined and the rate of glycerol turnover was assessed by a nonradioactive infusion technique in six healthy nonobese adults after an overnight fast and again after four days of total starvation. Simultaneously, estimates of total energy expenditure and net fat oxidation were made from measurements of oxygen consumption, carbon dioxide production, and urinary nitrogen excretion. The data were combined to provide quantitative estimates of the activity of the triglyceride/fatty acid cycle. The basal concentration of glycerol in venous blood rose from a mean value of 54 +/- 8 mumol/L (SEM) before starvation to 154 +/- 5 mumol/L on day 4 of starvation. Glycerol turnover rates correlated well with the basal blood glycerol concentration (r = .95) and increased from a mean value of 115 +/- 17 mumol/min before starvation (equivalent to mobilization of about 3.95 kJ triglyceride/min) to 304 +/- 20 mumol/min (equivalent to mobilization of about 18.41 kJ/min). The estimated rate of net fat oxidation was 3.00 +/- 0.47 kJ/min before starvation and 4.00 +/- 0.14 kJ/min on day +4 of starvation. The rate of triglyceride energy recycling or rate of deposition of triglyceride energy into fat stores was calculated from the difference in the rate of fat energy mobilization and the rate of energy released during net fat oxidation. The values were found to be 0.94 +/- 0.26 kJ/min before starvation and 6.29 +/- 0.54 kJ/min on day +4 of starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Induction and regulation of cytochrome P450 K-5 (lauric acid hydroxylase) in rat renal microsomes by starvation.

The effects of starvation on rat renal cytochrome P-450s were studied. The content of spectrally measured cytochrome P-450 in the renal microsomes of male rats increased 2-fold with 72 h starvation, but cytochrome b5 and NADPH-cytochrome P-450 reductase were not induced. 7-Ethoxycoumarin O-dealkylation and aniline hydroxylation activities of the renal microsomes of control male rats were very low but were induced 2.5-3-fold by 72 h starvation. Aminopyrine N-demethylation and lauric acid hydroxylation activities were induced 1.5-2-fold by 72 h starvation. The changes in catalytic activities suggested that the contents of individual cytochrome P-450s in the renal microsomes were altered by starvation. The contents of some cytochrome P-450s were measured by Western blotting. P450 DM (P450IIE1), a typical form of cytochrome P-450 induced by starvation in rat liver, was barely detected in rat kidney and was induced 2-fold by 72 h starvation. P450 K-5, a typical renal cytochrome P-450 and lauric acid hydroxylase, accounted for 81% of the spectrally measured cytochrome P-450 in the renal microsomes of control male rats and was induced 2-fold by 72 h starvation. P450 K-5 was not induced in rat kidney by treatment with chemicals such as acetone or clofibrate. The renal microsomes of male rats contained 6-times as much P450 K-5 as those of female rats. These results suggest that P450 K-5 is regulated by an endocrine factor.

Animals↗

Metabolic priorities during starvation: enzyme sparing in liver and white muscle of Atlantic cod, Gadus morhua L.

Atlantic cod, Gadus morhua, respond to starvation first by mobilising hepatic lipids, then muscle and hepatic glycogen and finally muscle proteins. The dual role of proteins as functional elements and energetic reserves should lead to a temporal hierarchy of mobilisation where the nature of a function dictates its conservation during starvation. We examined (1) whether lysosomal and anti-oxidant enzymes in liver and white muscle are spared during prolonged starvation, (2) whether the responses of these enzymes in muscle vary longitudinally. Hepatic contents of lysosomal proteases decreased with starvation, whereas those of catalase (CAT) increased and lysosomal enzymes of carbohydrate metabolism and glutathione S-transferase (GST) did not change. In white muscle, starvation decreased the specific activity of lysosomal enzymes of carbohydrate degradation and doubled that of cathepsin D (CaD). The activity of anti-oxidant enzymes and acid phosphatase in muscle was unchanged with starvation. In white muscle neither lysosomal enzymes nor anti-oxidant enzymes varied significantly with sampling position. In cod muscle, antioxidant enzymes, CaD and acid phosphatase are spared during a period of starvation that decreases lysosomal enzymes of carbohydrate metabolism and decreases glycolytic enzyme activities. In cod liver, the anti-oxidant enzymes, CAT and GST, were also spared during starvation.

Animals↗

Effect of starvation on free histidine and amino acids in white muscle of milkfish Chanos chanos.

Milkfish (Chanos chanos) decreased their body weight from 47 to 28 g over the 60-day period of starvation. Starvation also resulted in the reduction of muscle lipid and protein, and hepatosomatic index. The predominant free amino acid (FAA) in white muscle of milkfish was histidine, followed by taurine and glycine. In the first 25 days of starvation, no significant change in histidine was found. After 40 days of starvation, however, the histidine concentration was significantly decreased by 46%, and remained unchanged thereafter. As compared to control group fish, the 60-day-starved fish possessed only half the amount of histidine. Taurine and glycine, on the other hand, showed no significant changes throughout starvation. Taurine became the most predominant in the FAA pool after 40 days of starvation, and the concentration of 60-day-starved fish was two times higher than that of control group fish without starvation. The ratios of histidine, taurine, and glycine to total FAAs remained approximately the same although the individual contributions varied considerably to the total FAAs during starvation. The results of this study suggested that a good strategy would be to keep taurine and glycine in milkfish muscle at relatively high levels for physiological function as histidine decreased drastically for energy source under conditions of food deprivation.

Amino Acids↗

Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism.

Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged starvation and in response to hyperthyroidism is associated with enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4. The present study examined the potential role of peroxisome-proliferator-activated receptor alpha (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after starvation and in hyperthyroidism. PDK4 protein expression was analysed by immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with or without treatment with the PPARalpha agonist WY14,643. In addition, PDK4 protein expression was analysed in hearts from fed, 24 h-starved or 6 h-refed wild-type or PPARalpha-null mice. PPARalpha activation by WY14,643 in vivo over the timescale of the response to starvation failed to up-regulate cardiac PDK4 protein expression in rats maintained on standard diet (WY14,643, 1.1-fold increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response to starvation. By contrast, PPARalpha activation by WY14,643 in vivo significantly enhanced cardiac PDK4 protein expression in rats maintained on a high-fat diet, which itself increased cardiac PDK4 protein expression. PPARalpha deficiency did not abolish up-regulation of cardiac PDK4 protein expression in response to starvation (2.9-fold increases in both wild-type and PPARalpha-null mice). Starvation and hyperthyroidism exerted additive effects on cardiac PDK4 protein expression, but PPARalpha activation by WY14,643 did not influence the response of cardiac PDK4 protein expression to hyperthyroidism in either the fed or starved state. Our data support the hypothesis that cardiac PDK4 protein expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha-independent mechanism and strongly implicate a fall in insulin in either initiating or facilitating the response of cardiac PDK4 protein expression to starvation.

Animals↗

Lipid metabolism during the initiation of lactation in the rat. The effects of starvation and tumour growth.

1. The effects of starvation post partum (24 h) and tumour growth pre partum on the initiation of lactation in the rat were studied. 2. Tumour growth decreased food intake at 24 h, but not at 2 days post partum. 3. Pup growth rate increased with hyperphagia; starvation and tumour burden decreased pup growth, and starvation decreased maternal body weight. 4. Starvation decreased gastrointestinal-tract mass; tumour growth decreased gastrointestinal-tract and mammary-gland mass. 5. Mammary-gland DNA-synthesis rate was high immediately post partum, but decreased by day 3 of lactation; starvation and tumour burden decreased this rate, and also decreased gastrointestinal-tract DNA-synthesis rate. 6. Arteriovenous differences for glucose and lactate across the mammary gland did not change with time, nor were they affected by the tumour. Starvation decreased arterial glucose and lactate, and the gland extracted less glucose but produced lactate. 7. Mammary-gland lipogenesis was sensitive to starvation and to tumour growth. 8. In contrast with the gradual development of mammary-gland lipogenic enzyme activities, lipoprotein lipase activity was high in the gland by 2 days post partum; starvation or tumour burden decreased the activity. 9. The mammary gland is sensitive post partum to decreased food intake, and to tumour presence. The effects of the latter are apparently independent of hypophagia.

Animals↗

Differential neuropeptide responses to starvation with ageing.

During starvation, counterregulatory responses to loss of food (i.e. responses that lead to an increase in appetite) occur in the central nervous system (CNS). This study was designed to examine whether middle-aged rats show greater or smaller behavioural, peripheral and central hormonal responses during starvation compared to young rats. In experiment 1, refeeding following 4 days of starvation was measured in both middle-aged (72-week-old) and young (9-week-old) rats. The level of refeeding was similar to each prestarved level until 3 days after the end of starvation in both groups. From the 4th day, the level of refeeding in young rats increased and reached beyond the prestarved level, whereas refeeding in middle-aged rats remained similar to the prestarved level. Thus, overall refeeding throughout 7 days was greater in young rats than in middle-aged rats. In experiment 2, middle-aged and young rats were starved for 4 days and were killed in the morning. Middle-aged rats showed a smaller plasma corticosterone response than that of young rats. The magnitude of decreases in plasma glucose, insulin and leptin was similar in both groups. In the arcuate nucleus, the starvation-induced increase in neuropeptide Y (NPY) mRNA and the decrease in proopiomelanocortin (POMC) mRNA were smaller in middle-aged rats than in young rats. In contrast, the starvation-induced decrease in corticotrophin-releasing hormone (CRH) mRNA in the hypothalamic paraventricular nucleus was greater in middle-aged rats than young rats. The magnitude of decrease in type-2 CRH receptor mRNA in the ventromedial hypothalamus was similar in both groups. The results indicate that (a) ageing impaired refeeding response (b), middle-aged rats showed the same directional neuropeptide mRNA responses as seen in young rats during starvation and (c) the magnitude of these counterregulatory responses in the CNS in middle-aged versus young rats was not uniform, but rather was site-specific or neuropeptide-specific. This study suggests the importance of NPY and POMC responsiveness in the arcuate nucleus in the age-related differences resulting from starvation-induced refeeding.

Adrenocorticotropic Hormone↗

Immune mechanisms in leukemia: suppression of cellular immunity by starvation.

The effects of starvation on the cellular immune response of C58/Wm mice to syngeneic malignant lymphoid cells (1b cells) were studied. Mice were starved 1-3 days before or after immunization. The capacity of starved animals to survive immunization was used to quantify immunosuppression. When starvation bracketed immunization by -1 to +1 days, only 2 of 23 mice survived primary immunization, compared with 100% survival for nonstarved controls. A 2-day period of starvation +1 to +7 days after primary immunization reduced survival about 30%. For a test of the effect of starvation on the secondary immune response, mice were immunized, starved 2 days, and then challenged with viable lb cells. When mice were starved from -3 to +1 days before or after challenge, there was a 25-45% decrease in survival. Starvation caused a disproportionate depletion of lymphoid tissue elements. The proportional loss in the weight of the spleen and thymus was essentially twice as great as the loss in total body weight. The peripheral blood leukocyte count was reduced by about 20% when mice were starved 1 day and by approximately 50% when they were starved 2 days. When mice were starved 1-2 days, the differential leukocyte count did not shift and there was no significant change in the number of blood erythrocytes or in the hematocrit. Starvation for 2 days caused a 65-70% reduction in the number of viable mononuclear spleen cells. Starvation for 3 days caused about 90% reduction. Adoptive cell transfer experiments showed that the immunocompetence of individual spleen immunocytes was not reduced by starvation.

Animals↗

The influence of starvation on intestinal cholecystokinin-like activity and pancreatic growth.

1. This study examines the influence of starvation on intestinal CCK content and pancreatic growth. Intestinal CCK content was determined by measuring the CCK-like activity using an in vitro gall-bladder bio-assay. Starvation for up to 72 hr causes a parallel fall in intestinal CCK content and pancreatic DNA synthesis. Since there was no significant decrease in liver DNA synthesis, the effect of starvation was probably not simply a consequence of malnutrition. Furthermore there was little effect of starvation on pancreatic protein and DNA content, suggesting that pancreatic cell turnover is particularly sensitive to changes in dietary stimulation.2. With refeeding after starvation CCK-like activity in intestinal extracts gradually increased, approaching non-fasting levels 72 hr after refeeding. Pancreatic DNA synthesis also returned to non-fasting levels after feeding but this rose faster than the intestinal CCK content.3. Pentagastrin treatment prevented the atrophy of both the pancreas and the gastrointestinal tract with starvation without influencing the fall in intestinal CCK-like activity. This suggests that the control of CCK-containing cells is different from that of the surrounding intestinal parenchyma.4. The effect of starvation was also studied in antrectomized rats. Antrectomy alone did not reduce pancreatic DNA synthesis although DNA synthesis of the small intestine was significantly reduced. When antrectomized rats were starved pancreatic DNA synthesis fell to the same degree as was found in unoperated animals. The pancreatic atrophy was also accompanied by a drop in intestinal CCK content. Starvation of antrectomized rats, however, did not further depress the already greatly reduced plasma gastrin concentration.

Animals↗