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The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men.

To elucidate the role of leptin in regulating neuroendocrine and metabolic function during an acute fast, six to eight healthy, lean men were studied under four separate conditions: a baseline fed state and three 72-hour fasting studies with administration of either placebo, low-dose recombinant-methionyl human leptin (r-metHuLeptin), or replacement-dose r-metHuLeptin designed to maintain serum leptin at levels similar to those in the fed state. Replacement-dose r-metHuLeptin administered during fasting prevents the starvation-induced changes in the hypothalamic-pituitary-gonadal axis and, in part, the hypothalamic-pituitary-thyroid axis and IGF-1 binding capacity in serum. Thus, in normal men, the fall in leptin with fasting may be both necessary and sufficient for the physiologic adaptations of these axes, which require leptin levels above a certain threshold for activation. In contrast to findings in mice, fasting-induced changes in the hypothalamic-pituitary-adrenal, renin-aldosterone, and growth hormone-IGF-1 axes as well as fuel utilization may be independent of leptin in humans. The role of leptin in normalizing several starvation-induced neuroendocrine changes may have important implications for the pathophysiology and treatment of eating disorders and obesity.

Adult↗

Oxidative stress, growth factor starvation and Fas activation may all cause apoptosis through lysosomal leak.

Oxidative stress, growth factor starvation, and activation of the Fas/APO-1/CD95 receptor all induce apoptosis in a variety of cell-types, including the established human Jurkat T-cell line. Oxidative stress, in the form of exposure of the cells to a bolus dose of hydrogen peroxide, results in intralysosomal, iron-catalyzed oxidative reactions. This is accompanied by a time- and dose-dependent lysosomal destabilization--as evaluated by a decreased lysosomal uptake of the metachromatic fluorochrome, and weak base, acridine orange--in combination with leakage to the cytosol of lysosomal contents, including hydrolytic enzymes. Moderate lysosomal rupture is followed by apoptosis within initially intact plasma membranes, while necrosis and cell lysis are associated with a more complete lysosomal breach. Prior endocytosis of the potent iron-chelator desferrioxamine, resulting in binding of intralysosomal low molecular weight iron in a non-redox active form, largely prevents not only oxidative stress-induced lysosomal labilization, but apoptosis as well. When apoptosis is induced by the use of a monoclonal IgM anti-human Fas/APO-1/CD95 receptor antibody, the apoptotic process is again found to be accompanied by lysosomal leak. It is, however, not prevented by a preceding endocytosis of desferrioxamine and, consequently, could not be a function of intralysosomal iron-catalyzed oxidative reactions, but must be due to other mechanisms. Growth factor starvation of Jurkat cultures for a few days results in a high proportion of apoptotic cells, which contain lysosomes many of which have lost their proton gradient and appear to have released their contents. Overall, our results indicate that lysosomal leakage/rupture precedes apoptosis in Jurkat cells regardless of the initiating agent, but that such rupture may occur through multiple mechanisms. Lysosomal enzymes, leaking out of their normal vacuolar compartment, may then induce apoptosis, perhaps by proteolytic activation of the caspase-family of enzymes. Regardless of the precise mechanism, these observations suggest that partial rupture of the acidic vacuolar compartment may be one of the final pathways in apoptosis.

Apoptosis↗

A nitrogen starvation-induced dormant G0 state in fission yeast: the establishment from uncommitted G1 state and its delay for return to proliferation.

Fission yeast cells either remain in the mitotic cell cycle or exit to meiotic sporulation from an uncommitted G1 state dependent on the presence or absence of nitrogen source in the medium (Nurse and Bissett, 1981). We examined how heterothallic haploid cells, which cannot sporulate, behave under nitrogen-starvation for longer than 25 days at 26 degrees C. These cells were shown to enter a stable state (designated the dormant G0) with nearly full viability. Maintaining the dormant cells required glucose, suggesting that the cells remained metabolically active although cell division had ceased. They differed dramatically from mitotic and uncommitted G1 cells in heat resistance, and also in cytoplasmic and nuclear morphologies. After nitrogen replenishment, the initial responses of dormant G0 cells were investigated. The kinetics for reentry into the proliferative state were delayed considerably, and the changes in cell shape were enhanced particularly for those recovering from extended nitrogen starvation. A part of the delay could be accounted for by the duration of nuclear decondensation and cell elongation for the first cell division.

Cell Division↗

Euglena plasma membrane during normal and vitamin B12 starvation growth.

Freeze-fracture and optical diffraction techniques were used to study the organization of the Euglena pellicle during the normal and replicative stages of the cell cycle and during vitamin B12 starvation. It was shown that the diffuse layer underlying the tripartite structure has a fibrillar structure. Despite the absence of homology in the 2 fracture faces of the pellicle, the EF striated and the PF particulate ones appear complementary as shown by optical diffraction studies; it must therefore be considered as a true membrane. The grooves are free from such particles and striations. They appear as a specific pattern of the cortex, different from the ridges in their structural organization and their replicative capacity as observed during vitamin B12 starvation. This notion is confirmed by the mode of pellicular growth which is characterized by 2 steps. The first occurs during the early replicative stage (pre-mitotic phase of the cell cycle) when the formation of a new ridge is correlated with the appearance of the 'minor' orientation of a 2-dimensional lattice on the EF and the PF faces and the spread of the particles over the PF face of the space between the old ridges. The second takes place during the lengthening of the ridges from the initiating posterior side (non-replicative stage). During this second step, the 'major' orientation of the lattice is preferentially observed in control cells and exclusively in starved cells. The striking differences between the grooves and the ridges is discussed, as well as the 2 modes of growth and their significance in morphogenesis.

Animals↗

Calcium accumulation in vacuoles of Physarum polycephalum following starvation.

The plasmodium of Physarum polycephalum contained 15.3 mmol Ca/kg fresh weight of sample, 11.8 mmol Mg/kg, 24.5 mmol K/kg and 1.4 mmol Na/kg. When the plasmodium was starved of food, the Ca content increased gradually up to 71.9 mmol/kg during 5 days of starvation. The concentration of other elements changed only slightly. The endoplasm contained 23.0 mmol Ca/kg, 12.6 mmol Mg/kg, 26.6 mmol K/kg and 1.7 mmol Na/kg, but these contents changed only slightly during starvation. The Ca, Mg, K and Na contents of the slime and the soluble fraction were also determined. In order to clarify where the accumulated Ca was localized, Ca in the plasmodium was precipitated with potassium pyroantimonate and examined by electron microscopy. In the starved plasmodium, the vacuoles which contained the electron-opaque precipitates and were located in the ectoplasm increased in number, compared with the unstarved plasmodium. At the same time the large electron-opaque granules in the extracellular slime increased in number. The electron-opaque precipitates were identified as Ca pyroantimonate by its susceptibility to removal by chelation with ethyleneglycol bis (beta-aminoethyl ether) N, N, N', N'-tetraacetic acid (EGTA) and X-ray microprobe analysis.

Calcium↗

Feeding sugar overnight maintains metabolic homeostasis in rats and is preferable to overnight starvation.

Rats are often starved overnight for many different reasons. Overnight starvation causes loss of body and liver weights, depletion of liver glycogen, decrease of blood glucose and loss of amino acids because of gluconeogenesis. Providing pure sucrose cubes as the sole overnight nutrient is a simple, inexpensive way to empty the gastrointestinal (GI) tract, while minimizing liver changes and preventing decrease of blood glucose and loss of amino acids. Adding sugars to the overnight drinking water as the sole nutrient has the same beneficial effects, provided the type of sugar and its concentration allow for sufficient intake and provided hyponatremia is avoided. Feeding sucrose cubes or sugar solutions will empty the gastrointestinal tract as effectively as starvation. In all instances, simple precautions against coprophagy and pica should be taken in order to secure optimal benefit.

Animals↗

Involvement of a CCAAT-binding complex in the expression of a nitrogen-starvation-specific gene, isp6+, in Schizosaccharomyces pombe.

The fission yeast gene isp6+ is needed in nitrogen-starvation response but its transcriptional regulation has been unclear. isp6+ was repressed under nutrient conditions, in which cAMP-dependent protein kinase A, the stress-activated protein kinase cascade, and the CCAAT-binding complex were concerned. The CCAAT-binding complex also was involved in the induction of isp6+ during nitrogen starvation.

Blotting, Northern↗

Enhancement of Borna disease virus transcription in persistently infected cells by serum starvation.

Transcription of Borna disease virus (BDV) in persistently infected MDCK (MDCK/BDV) cells increased in the fetal bovine serum free media as detected by Northern blot analysis. Especially, the amount of 1.9-kb RNA without cap formation at the 5' end and polyadenylation at the 3' end, increased as compared to other mRNA molecules of BDV. Growth arrest of MDCK/BDV cells observed in the condition of serum starvation might be important for increasing viral transcription. Since N-cadherin is the responsible factor for cell-to-cell contact, MDCK/BDV cells were cultured in calcium free medium which inhibits the interaction of N-cadherin. However, inhibition of cell-to-cell contact by N-cadherin is not effective on up regulation of viral transcription. Our finding in this study indicates that enhancement of BDV transcription by serum starvation is a useful technique for further investigation in understanding of mechanisms of BDV transcription.

Animals↗

Effect of labor on maternal dehydration, starvation, coagulation, and fibrinolysis.

BACKGROUND: Dehydration, starvation, and enhanced blood coagulability may occur during labor. METHODS: We studied 60 women who gave birth vaginally to a healthy singleton infant at term. Sampling of urine and blood specimens was performed on admission to the hospital with labor pains and just after birth. Paired samples were available from 50 women for urine analysis and 29 women for blood analysis. Total fluid intake (oral and intravenous) during labor was recorded. Changes in various parameters in the urine and blood in relation to the total fluid intake were analyzed. RESULTS: Osmolality and creatinine concentration in the urine, red blood cell count, hemoglobin concentration, hematocrit value, thrombin-antithrombin III complex, plasmin-alpha 2-plasmin inhibitor complex and D dimer significantly increased during labor. Ketone bodies were absent in the urine in 84% (42/50) of women on admission to the hospital whereas these were present in 74% (37/50) of women just after delivery (p < 0.01). The degree of these changes appeared to be smaller with an increase in fluid intake. CONCLUSION: Concentrated urine, hemoconcentration, starvation, and activation of the thrombogenic and fibrinolytic system occur in parturient women. Sufficient fluid intake during labor may ameliorate these unfavorable changes.

Adolescent↗

The response of Gregarina niphandrodes (Apicomplexa: Eugregarinida: Septatina) to host starvation in Tenebrio molitor (Coleoptera: Tenebrionidae) adults.

Numerous studies of host starvation have emphasized pathological effects of parasites on their insect host, but little attention has been focused on the effects of host starvation on the parasites. This study addressed the possibility that parasite life-cycle events could be manipulated by withholding food from the host. The system used was Gregarina niphandrodes (Apicomplexa: Eugregarinida) in Tenebrio molitor (Coleoptera: Tenebrionidae) adults. Gregarine gametocyst formation and shedding ceased after 1 day in starved beetles but continued in fed controls. There were no statistically significant differences between total lengths of associated (3 of 5 trials) or unassociated (5 of 5 trials) gregarines found between experimental and control groups, but average numbers of the 2 life cycle events were generally higher in fed hosts than in starved ones. If infected, fed control beetles continued to form gametocysts throughout the 7-day trial periods, and gametocysts could be observed in the gut. Starved experimental beetles had no gametocysts in their guts. Refeeding of starved beetles after 4 days resulted in resumption of gametocyst formation and shedding. The studies demonstrated that the gregarine life cycle could be stopped and then started at the gametocyst formation stage like an off/on switch, simply by withholding food from, then refeeding, the host.

Analysis of Variance↗

The effect of partial starvation and glucagon treatment on intestinal villus morphology and cell migration.

Male Sprague-Dawley rats were either treated with repeated ip injections of glucagon every 6 hr or partially starved. After 7 days of partial starvation or 5 days of glucagon injections, a time period shown previously to induce increased transport, all animals were sacrificed and a segment of jejunum was removed, fixed in formalin, sectioned, and dipped in Kodak NTB-2 liquid emulsion. After 8 weeks of exposure the autoradiographs were developed; assessments of villus height and crypt depth and measurements of length of the column of exposed grains were made in a calibrated microscope. The mean villus length in both semistarved and glucagon-treated groups was found to be significantly reduced (p less than 0.001) when compared to control animals. The crypt-to-villus ratio was found to be unaltered by either treatment modality. The rate of cell migration was diminished by both partial starvation and glucagon treatment, but only glucagon therapy was found to cause a significant (p less than 0.01) reduction in the rate of cell movement when compared to controls.

Animals↗

Acid adaptation and starvation effects on Shiga toxin production by Escherichia coli O157:H7.

Reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and gene fusion were used to determine differences in the expression of stx-II mRNA and the production of mature Stx protein following acid adaptation or starvation of Escherichia coli O157:H7 (ATCC 43895) and an isogenic rpoS mutant (FRIK 816-3) under static conditions and with shaking. The expression of stx-II mRNA in acid-adapted and starved cells was more extensive than that in nonstressed control cells. This effect was more pronounced for the rpoS mutant. Oxygenation (incubation with shaking) increased stx-II mRNA expression for both strains relative to the level of expression obtained with static conditions. ELISA results indicated that Stx production was enhanced more in the rpoS mutant than in its wild-type parent strain and that oxygenation enhanced Stx production for both strains but there were no detectable differences between stressed and nonstressed cells of either strain. The monitoring of the gene product of Stx-II alone with the use of stx-IIAB::lacZ gene fusions confirmed the induction of aeration and the absence of a stress effect for both the wild type and the rpoS mutant. These results indicate that oxygen enhances stx-II mRNA expression and Stx production in E. coli O157:H7. Stress conditions such as acid adaptation and starvation enhance stx-II toxin mRNA levels but do not enhance subsequent Stx toxin production.

Adaptation, Physiological↗

Use of the glucose starvation-inducible glucose-regulated protein 78 promoter in suicide gene therapy of murine fibrosarcoma.

A new strategy in anticancer gene therapy uses stress-responsive cellular promoters that offer the advantage of enhanced gene expression in a variety of tumors. Although the feasibility of their selective expression has been demonstrated, functional evidence of their ability to activate therapeutic agents within the tumor environment leading to tumor eradication has not been established. Glucose deprivation, chronic anoxia, and acidic pH known to persist in poorly vascularized solid tumors strongly induce the transcription of the glucose-regulated protein 78 (grp78) gene, which encodes an Mr 78,000 stress-inducible protein. In this report, we tested directly the efficacy of the grp78 promoter in a retroviral system to drive the expression of the herpes simplex virus-thymidine kinase (HSVtk) suicide gene, using a murine fibrosarcoma model, in the context of their syngeneic, immunocompetent hosts. Our results showed that under glucose starvation conditions, the expression of HSVTK was enhanced in tumor cells where the HSVtk gene was driven by the internal grp78 promoter, in contrast to the Moloney murine leukemia virus long terminal repeat, where suppression was observed. We further demonstrated that in vivo, HSVTK expression was elevated to much higher levels inside tumors when driven by the internal grp78 promoter, resulting in complete eradication of sizable tumor mass, with no recurrence of tumor growth. Our study suggests that the glucose starvation-inducible grp78 promoter could be useful for enhanced expression of a variety of therapeutic agents within the solid tumor environment.

Animals↗

[A comparison of the yield of Vi and O antigens during the adaptation of Salmonella typhi strains to cultivation under starvation conditions].

S. typhi strains Ty(2)4446 and Vi-1S underwent multiple passages in f synthetic liquid starvation culture medium consisting of water with salts and glucose added. In the process of the adaptation of the cultures to these stress conditions (starvation stress) the increasing yield of biomass from passage to passage was observed. Differences in the accumulation of Vi- and O-antigens were noted in two strains under study. In the cultures of strain Ty(2)4446 an insignificant increase in the antigen content from passage to passage was observed, while in the cultures of strain Vi-1S an increase in the content of Vi- and O-antigens was 4- to 5-fold. With the adaptation of the culture the Vi-antigen to O-antigen ratio changed from 1:57 to 1:20 for strain Ty(2)4446 and from 1:2.7 tp 1:2.2 for strain Vi-1S. Strain Ty(2)4446 had an advantage over strain Vi-1S with respect to the synthesis of Vi-antigen. These data are indicative of the expediency of using not only strain Ty(2)4446, but also strain Vi-1S for the preparation of typhoid vaccine, especially the one based on Vi-antigen.

Adaptation, Physiological↗

[Ribosome stability of Escherichia coli cells in amino acid starvation].

The dissociation of ribosomes from two isogenic pairs of Escherichia coli strains was studied during exponential growth, under amino acid starvation and subsequent chloramphenicol treatment. There were no significant differences in Mg2+-dependent dissociation of ribosomes from exponentially growing rel+ and rel- minus strains. The differences in dissociation of the ribosomes from rel+ and rel- minus cells were observed only upon amino acid starvation of these cultures. The dissociation of ribosomes from starved rel+ cells was more complete. After chloramphenicol treatment isolated ribosomes were more resistant to dissociation into subunits. Alterations of dissociation of the ribosomes in vitro correlated both with the amount of polysomes and the level of RNA synthesis in cells. It is proposed that rRNA synthesis in bacteria depends on the ratio of programmed and deprogrammed ribosomes.

Aerobiosis↗

[Effect of Actoflor preparations on survival of Escherichia coli M-17 and Salmonella enteritidis under starvation conditions in mixed cultures].

The viability of E. coli M-17 and S. enteritidis under starvation conditions in mono- and mixed cultures was studied. E. coli M-17 showed greater capacity for survival in mixed cultures than in monocultures, while for S. enteritidis the contrary was true. Preparations "Actoflor" enhanced the antagonistic activity of E. coli M-17, ensuring its absolute selective advantage under starvation conditions in mixed cultures. The role of E. coli M-17 low-molecular exometabolites is discussed; they are probably an important factor in the antagonistic activity of these microorganisms.

Biological Factors↗

[Starvation of bacteria as a stress caused by substrate limitation].

The analysis of literature has made it possible to establish the priority of Russian research works made in the 1970-80s on the subject of starvation of bacteria caused by substrate limitation as well as research made in the 1990s concerning starvation of bacteria. This state is characterized by synthesis of additional proteins, so-called stress proteins, which not only ensure the survival of bacteria under the conditions of substrate limitation, but also protect them from a number of other stressors. In spite of the fact that genetic mechanisms regulating the synthesis of some stressor proteins have been revealed their significance for microbiological technology is not yet clear.

Bacterial Physiological Phenomena↗

Comparative studies on utilizing nitrogen capacity between two macroalgae Gracilaria tenuistipitata var. liui (rhodophyta) and Ulva pertusa (chlorophyta). I. Nitrogen storage under nitrogen enrichment and starvation.

This paper deals with the N storage of Gracilaria tenuistipitata var. liui and Ulva pertusa under ammonium enrichment and starvation. After 10 days of ammonium enrichment, ammonium NH4+, free amino acid (FAA), protein (pro), chlorophyll (Chl), phycoerythrin (PE) and total dissolved nitrogen (TDN) of the two macroalgae increased significantly. Total nitrogen (TN) increased significantly from 3.65% to 5.78% dry weight of G. tenuistipitata var. liui and 2.82% to 5.07% dw of U. pertusa, respectively. Protein and FAA were the most important N storage pools in the macroalgae. During N-starvation period, individual N pools of the two species were depleted at exponential rates. Each N pool in U. pertusa decreased more rapidly than in G. tenuistipitata, var. liui and the latter was able to sustain fast growth for more time (> 20 days) than U. pertusa. N demands for supporting growth were different between the two species, U. pertusa grew more rapidly and had higher N demands than G. tenuistipitata var. liui did.

Amino Acids↗