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PubMed1979

Effects of starvation and refeeding on lung mechanics and morphometry.

Rats receiving one fifth of their usual daily food consumption for 10 days showed a significant increase in static recoil pressure of the lung (Pst[L]) due to surface forces at low lung volumes during inflation; their tissue Pst (L) decreased significantly over the entire volume-pressure loop compared to that of control rats. After 1 week of refeeding, the surface Pst (L) returned almost completely to normal, but tissue Pst (L) remained abnormally low. In starved rats, air-space enlargement with minimal loss of interalveolar septa was associated with a significant increase in mean linear intercept and volume fraction of air spaces, and with a significant decrease in corrected internal surface area and surface fraction of air space. These alterations returned partially toward normal in the refed group. We conclude that starvation increases surface elastic forces, decreases tissue elasticity of lung, and leads to air-space enlargement; redeeding leads to restoration of surface forces without the return of tissue elasticity to normal and to less severe air-space enlargement.

Animals↗
PubMed1983

Changes in connective tissue composition of the lung in starvation and refeeding.

Adult male rats were starved by allowing them one fifth of their measured daily food consumption until they lost 40% of their initial body weights. Some of these rats were then refed until their initial body weights were reached. We measured the total content of the following in the lung tissue of fed, starved, and refed animals: (1) elastin, (2) hydroxyproline, and (3) protein. Body weight and lung dry and wet weights were significantly reduced in starved and similar in refed rats compared with fed animals. Total contents of crude connective tissue, hydroxyproline, elastin, and protein were significantly lower in starved than in fed rat lungs. After refeeding, hydroxyproline content returned completely to levels found in fed rats, but other components only partially returned to normal values. These results provide a biochemical counterpart for our previous observations on the effects of starvation and refeeding on lung mechanics and morphologic aspects. It appears that the emphysema like changes in the lungs of starved rats are at least partly related to the loss of connective tissue elements.

Animals↗
PubMed1987

Interaction of prenatal starvation and dexamethasone treatment on lung development in newborn guinea pigs.

Prenatal starvation causes pulmonary hypoplasia, retarded alveolarization, and reduced surfactant production in newborn guinea pigs. This study examined the potential benefit of simultaneous transplacental dexamethasone, which accelerates fetal lung maturation in other species. Pregnant guinea pigs were placed in 1 of 4 groups: Control (C), fed ad libitum until term (67 days) and given daily saline injections from Day 55 of gestation until term; Dexamethasone (D), fed as Group C but given daily injections of 2.0 mg dexamethasone/kg BW from Day 55 until term; Starved (S), given 50% rations from Day 45 until term and injected as Group C; Starved + Dexamethasone (SD), fed as Group S and injected as Group D. Controls and Group D did not differ in body or lung weight, DNA, protein, or lung volume (VL), but Group D lungs contained more lavageable and tissue surfactant, total alveolar surface area (Sa), and membrane diffusing capacity (DmO2) because of increased alveolar surface density. The S neonates weighed 38% less than controls, with proportional reductions in lung weight, DNA, protein, lavage and tissue phospholipids, VL, Sa septal tissue, capillary surface area (Sc), and DmO2. Compared with these S neonates, the SD neonates did not differ for BW, lung weight, DNA, protein, phospholipids, or VL, but their lungs contained significantly more Sa, Sc, epithelial and endothelial tissue volumes, and a higher alveolar surface density. These differences resulted in an average DmO2 for SD neonates that was indistinguishable from that of controls, and correlated with greater viability among the smallest SD animals compared with those in Group S.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1971

Human forearm metabolism during progressive starvation.

Forearm muscle metabolism was studied in eight obese subjects after an overnight, 3 and 24 day fast. Arterio-deep-venous differences of oxygen, carbon dioxide, glucose, lactate, pyruvate, free fatty acids, acetoacetate, and beta-hydroxybutyrate with simultaneous forearm blood flow were measured. Rates of metabolite utilization and production were thus estimated. Oxygen consumption and lactate and pyruvate production remained relatively constant at each fasting period. Glucose, initially the major substrate consumed, showed decreased consumption after 3 and 24 days of fasting. Acetoacetate and beta-hydroxybutyrate consumption after an overnight fast was low. At 3 days of fasting with increased arterial concentrations of acetoactate and beta-hydroxybutyrate, consumption of these substrates rose dramatically. At 24 days of fasting, despite further elevation of arterial levels of acetoacetate and beta-hydroxybutyrate, the utilization of acetoacetate did not increase further and if anything decreased, while five out of eight subjects released beta-hydroxybutyrate across the forearm. Acetoacetate was preferentially extracted over beta-hydroxybutyrate. At 24 days of starvation, free fatty acids were the principal fuels extracted by forearm muscle; at this time there was a decreased glucose and also ketone-body consumption by skeletal muscle.

Acetoacetates↗
PubMed1974

Nitrogen sparing induced by a mixture of essential amino acids given chiefly as their keto-analogues during prolonged starvation in obese subjects.

11 normal obese subjects were fasted for 33 days. In five, who served as controls, urine urea nitrogen excretion remained constant for 2 wk thereafter. The other six were given seven daily infusions containing 6-8 mmol each of the alpha-keto-analogues of valine, leucine, isoleucine, phenylalanine, and methionine (as sodium salts) plus 3-4 mmol each of the remaining essential amino acids (lysine, threonine, tryptophan, and histidine). Rapid amination of the infused ketoacids occurred, as indicated by significant increases in plasma concentrations of valine, leucine, isoleucine, alloisoleucine, phenylalanine, and methionine. Glutamine, glycine, serine, glutamate, and taurine fell significantly. Blood glucose, ketone bodies, plasma free fatty acids, and serum immunoreactive insulin concentrations were unaltered. Urine urea nitrogen fell from 1.46 to 0.89 g/day on the last day of infusions; 5 days later it was still lower (0.63 g/day) and in two subjects studied for 9 and 17 days postinfusion it remained below preinfusion control values. Urine ammonia, creatinine, and uric acid were unaltered. Nitrogen balance became less negative during and after infusions. The results indicate that this mixture of essential amino acids and their keto-analogues facilitates nitrogen sparing during prolonged starvation, in part by conversion of the ketoacids to amino acids and in part by altering mechanisms of nitrogen conservation. The latter effect persists after the ketoacids are metabolized.

Amino Acids↗
PubMed1976

Composition of weight lost during short-term weight reduction. Metabolic responses of obese subjects to starvation and low-calorie ketogenic and nonketogenic diets.

The effects of starvation, an 800-kcal mixed diet and an 800-kcal ketogenic (low carbohydrate-high fat) diet on the composition of weight lost were determined in each of six obese subjects during three 10-day periods. The energy-nitrogen balance method was used to quantify the three measurable components of weight loss; protein, fat, and water. On the 800-kcal ketogenic diet, subjects lost (mean +/- SE) 466.6 +/-51.3 g/day; on the isocaloric mixed diet, which provided carbohydrate and fat in conventional proportions, they lost 277.9+/- 32.1 g/day. Composition of weight lost (percentage) during the ketogenic diet was water 61.2, fat 35.0, protein 3.8. During the mixed diet, composition of loss was water 37.1, fat 59.5, protein 3.4...

Adult↗
PubMed1995

Bibliographical note on behavioral aspects: on the margin of the 50th anniversary of the Minnesota Starvation-Nutritional Rehabilitation experiment.

The principal technical aim of this note is to bring together bibliographic information on the papers dealing with the behavioral aspects of the study and published both before and, in particular, after the appearance in print of the two-volume treatise on The Biology of Human Starvation by Keys, et al. in 1950, which provides a systematic, comprehensive account. The communications fall into three categories: methods, results, and overviews. The section on results is concerned primarily with the effects on personality.

Anniversaries and Special Events↗
PubMed1979

Response to starvation before and after a jejuno-ileal bypass operation for morbid obesity.

A greater metabolic response developed during a seven day starvation in two morbidly obese patients three months after a 90 per cent jejuno-ileal bypass operation when compared with a similar fast before operation. There was a greater degree of ketosis, a decreased urinary urea excretion and an earlier utilization of ketone bodies. These changes suggest a metabolic adaptation of the body to the semistarvation state caused by the operation with a more rapid utilization of adipose tissue as a fuel and a sparing of lean body mass.

Adult↗
PubMedDate not supplied

Effect of glutamine-supplemented total parenteral nutrition on recovery of the small intestine after starvation atrophy.

Intestinal atrophy was induced in rats by infusion of 5% dextrose for 7 days with only oral water allowed. Compared with control animals fed standard rat chow (Purina Mills, St. Louis), the starved animals lost 30.5% of their initial body weight, 34.7% mucosal wet weight, 68.3% mucosal nitrogen content, 36.7% mucosal thickness, and 38.6% villous height and had variable losses of mucosal disaccharidase activities. Three groups of depleted rats were then refed with different regimens. One group was refed with standard Purina rodent chow (n = 15); a second group with a standard total parenteral nutrition (TPN) solution containing 16% glucose, 2.8% fat, and 4.25% standard amino acids (Travasol 8.5%, Baxter Healthcare Corporation, Deerfield, IL) (n = 15); and the third group with a TPN solution of 16% glucose, 2.8% fat, 2.75% standard amino acids, and 1.5% glutamine (n = 15). After 7 days of refeeding, rats were killed to determine the degree of intestinal recovery. Animals refed with standard TPN solution showed no significant recovery of intestinal mucosal weight, mucosal nitrogen content, villous height, mucosal thickness, or mucosal disaccharidase activities. Animals refed with glutamine-supplemented TPN solution demonstrated significant recovery of all parameters but not back to normal. Oral rodent chow completely restored intestinal anatomy and function. The addition of glutamine to TPN solutions significantly improved recovery of the intestine from starvation atrophy, and additional efforts to make it commercially available are indicated. This study again confirms the preferable use of a regular oral diet when clinically feasible and safe.

Animals↗
PubMed2003

Expression of Drosophila FOXO regulates growth and can phenocopy starvation.

BACKGROUND: Components of the insulin signaling pathway are important regulators of growth. The FOXO (forkhead box, sub-group "O") transcription factors regulate cellular processes under conditions of low levels of insulin signaling. Studies in mammalian cell culture show that activation of FOXO transcription factors causes cell death or cell cycle arrest. The Caenorhabditis elegans homologue of FOXO, Daf-16, is required for the formation of dauer larvae in response to nutritional stress. In addition, FOXO factors have been implicated in stress resistance and longevity. RESULTS: We have identified the Drosophila melanogaster homologue of FOXO (dFOXO), which is conserved in amino acid sequence compared with the mammalian FOXO homologues and Daf-16. Expression of dFOXO during early larval development causes inhibition of larval growth and alterations in feeding behavior. Inhibition of larval growth is reversible upon discontinuation of dFOXO expression. Expression of dFOXO during the third larval instar or at low levels during development leads to the generation of adults that are reduced in size. Analysis of the wings and eyes of these small flies indicates that the reduction in size is due to decreases in cell size and cell number. Overexpression of dFOXO in the developing eye leads to a characteristic phenotype with reductions in cell size and cell number. This phenotype can be rescued by co-expression of upstream insulin signaling components, dPI3K and dAkt, however, this rescue is not seen when FOXO is mutated to a constitutively active form. CONCLUSIONS: dFOXO is conserved in both sequence and regulatory mechanisms when compared with other FOXO homologues. The establishment of Drosophila as a model for the study of FOXO transcription factors should prove beneficial to determining the biological role of these signaling molecules. The alterations in larval development seen upon overexpression of dFOXO closely mimic the phenotypic effects of starvation, suggesting a role for dFOXO in the response to nutritional adversity. This work has implications in the understanding of cancer and insulin related disorders, such as diabetes and obesity.

Amino Acid Sequence↗
PubMed1977

The effect of maternal starvation on the metabolic response to cold of the newborn rabbit.

Acute starvation of the pregnant rabbit before delivery leads to lipid mobilization, the circulating concentrations of free fatty acids (FFA) increase, and more fatty acids cross the placenta and are stored as triglyceride in fetal tissues, particularly the liver and adipose tissue. Thus the newborns from these unfed does are born with larger fat stores than normal. In this investigation the responses of newborns of unfed and fed does were compared with respect to aspects of the metabolic responses to birth and subsequent cold exposure. It was found that at 2 hr of age the newborns of unfed does had higher circulating concentrations of FFA and triglycerides. The glucose and glycerol concentrations were similar in the two groups, but after 2 hr of cold exposure the newborns of fed does had much higher blood concentrations of both glucose and glycerol. In both, a large increase in FFA concentration was seen. The newborns of unfed and fed does had similar minimal metabolic rates, but the maximal rate of heat production was greater on average by 15% in the newborns of unfed does over the first 3 days of life. Maternal nutrition immediately before delivery has considerable effect on the circulating concentrations of metabolites and the responses to cold of the newborn.

Acute Disease↗
PubMed1979

Starvation diabetes in the rat: onset, recovery, and specificity of reduced responsiveness of pancreatic beta-cells.

A 24-h starvation markedly diminished the stimulant action of 8 mM glucose on insulin secretion from isolated perifused rat islets of Langerhans. The response to a supramaximal glucose stimulus (27.5 mM) remained normal, but prolonged fasting (48 or more) also reduced its efficacy. Refeeding of 24-h fasted animals resulted in complete restoration of glucose sensitivity within 24 h. The responses to glyceraldehyde (2 mM) and alpha-ketoisocaproate (8 mM) at concentrations which elicit approximately half-maximal stimulation were unaltered by a 24-h fast, while that to a half-maximally effective dose of mannose (15 mM) was decreased. Theophylline (5 mM) could not normalize the reduced secretory response to glucose seen in this state. The islets' ability to metabolize glucose, using various in vitro pretreatment protocols and different incubation times, was not affected by a 24-h fast. Mannose and glyceraldehyde metabolism were also unaltered. Prolonged fasting (48 h) reduced glucose metabolism by 25% at both 8 and 27.5 mM. The acute adaptive changes in islet sensitivity to moderate glucose and mannose concentrations during short term fasting (24 h) cannot be explained by an altered usage of the added hexoses.

Animals↗
PubMed1997

Decreased interleukin-2 production from cultured peripheral blood mononuclear cells in human acute starvation.

Depressed cell-mediated immunity and decreased insulin-like growth factor I (IGF-I) are observed in malnourished humans. To study the interaction among nutrition, IGF-I, and cytokines, healthy volunteers (six men and four women, aged 21-38 yr, weighing 93-124% of ideal body weight) were subjected to a 7-day fast (mineral water only). Fasting steadily decreased serum IGF-I from 247 +/- 29 (prefast) to 87 +/- 10 ng/mL (postfast; P < 0.0001), total T cells (CD3+) from 1499 +/- 68 to 1308 +/- 70 x 10(9) (P < 0.0001), and T helper cells (CD4+) from 997 +/- 62 to 856 +/- 55 x 10(9) (P < 0.001). Peripheral blood mononuclear cells were isolated and cultured in serum-free RPMI 1640 for 24 h. Fasting attenuated peripheral blood mononuclear cell production of interleukin-2 in response to various concentrations of phytohemagglutinin P [PHA-P; 347 +/- 48 (prefast) vs. 135 +/- 52 pg/mL (postfast) when challenged with 3 micrograms/mL PHA-P; P < 0.005 when comparing dose-response curves (1-100 micrograms/mL PHA-P)]. Although the approximately 3-fold suppression of interleukin-2 and IGF-I in subjects fasted for 1 week is not likely to affect immune function significantly, our results with this short term model of nutrient restriction provide insight into possible mechanisms for immune suppression in chronic starvation.

Acute Disease↗
PubMed1999

Starvation promotes Dictyostelium development by relieving PufA inhibition of PKA translation through the YakA kinase pathway.

When nutrients are depleted, Dictyostelium cells undergo cell cycle arrest and initiate a developmental program that ensures survival. The YakA protein kinase governs this transition by regulating the cell cycle, repressing growth-phase genes and inducing developmental genes. YakA mutants have a shortened cell cycle and do not initiate development. A suppressor of yakA that reverses most of the developmental defects of yakA- cells, but none of their growth defects was identified. The inactivated gene, pufA, encodes a member of the Puf protein family of translational regulators. Upon starvation, pufA- cells develop precociously and overexpress developmentally important proteins, including the catalytic subunit of cAMP-dependent protein kinase, PKA-C. Gel mobility-shift assays using a 200-base segment of PKA-C's mRNA as a probe reveals a complex with wild-type cell extracts, but not with pufA- cell extracts, suggesting the presence of a potential PufA recognition element in the PKA-C mRNA. PKA-C protein levels are low at the times of development when this complex is detectable, whereas when the complex is undetectable PKA-C levels are high. There is also an inverse relationship between PufA and PKA-C protein levels at all times of development in every mutant tested. Furthermore, expression of the putative PufA recognition elements in wild-type cells causes precocious aggregation and PKA-C overexpression, phenocopying a pufA mutation. Finally, YakA function is required for the decline of PufA protein and mRNA levels in the first 4 hours of development. We propose that PufA is a translational regulator that directly controls PKA-C synthesis and that YakA regulates the initiation of development by inhibiting the expression of PufA. Our work also suggests that Puf protein translational regulation evolved prior to the radiation of metazoan species.

Amino Acid Sequence↗
PubMed1986

Myofibrillar ATPase activity in the carp Cyprinus carpio: interactions between starvation and environmental temperature.

The myofibrillar ATPase activity of the epaxial white muscle was measured in carp Cyprinus carpio L. acclimated to 10 degrees C or 28 degrees C. As previously reported, cold acclimation was associated with an increase in the ATPase specific activity and a decrease in the thermostability. The water content of the white muscle was significantly higher in cold-acclimated fish than in warm-acclimated fish (P less than 0.002). Starvation for 10 weeks resulted in a significant increase in the white muscle water content of both warm- and cold-acclimated fish (P less than 0.002). When carp were starved, the ability of the myofibrillar ATPase to show thermal compensation disappeared. Previously acclimated fish, when starved, showed steady alterations of the myofibrillar ATPase activity to a level mid-way between the acclimated extremes. Refeeding resulted in a gradual return to the normal acclimated level.

Acclimatization↗
PubMed2001

Plasticity of chemotaxis revealed by paired presentation of a chemoattractant and starvation in the nematode Caenorhabditis elegans.

While the basic functioning of the nervous system of Caenorhabditis elegans has been extensively studied, its behavioural plasticities have not been fully explored because of the limited availability of assay systems. We report here a simple form of chemotaxis plasticity in this organism: when worms are starved on plates that contain NaCl, their chemotaxis towards NaCl falls dramatically. This conditioning requires both the presence of NaCl and the absence of a bacterial food source, indicating that it is not merely adaptation or habituation, but that it is likely to be a form of associative learning. While chemotaxis towards volatile chemoattractants does not change significantly after conditioning with NaCl, chemotaxis towards other water-soluble attractants does decrease. This suggests that an altered response of a cell or a group of cells specifically involved in chemotaxis towards water-soluble chemoattractants is responsible for the behavioural alteration. The decrease in chemotaxis occurred slowly over 3-4 h of conditioning and returned quickly to the original level when either of the conditioning stimuli, NaCl or starvation, was removed. The application of serotonin partially blocked this reduction in chemotaxis, consistent with the proposed function of this neurotransmitter in food signalling. Using this assay, we have isolated three mutants with reduced plasticity. This assay system expands the opportunities for studying the molecular and cellular mechanisms of behavioural plasticity in C. elegans.

Animals↗
PubMed2001

Behavioural, physiological and metabolic responses to long-term starvation and refeeding in a blind cave-dwelling (Proteus anguinus) and a surface-dwelling (Euproctus asper) salamander.

The effects of long-term starvation and subsequent refeeding on haematological variables, behaviour, rates of oxygen consumption and intermediary and energy metabolism were studied in morphologically similar surface- and cave-dwelling salamanders. To provide a hypothetical general model representing the responses of amphibians to food stress, a sequential energy strategy has been proposed, suggesting that four successive phases (termed stress, transition, adaptation and recovery) can be distinguished. The metabolic response to prolonged food deprivation was monophasic in the epigean Euproctus asper (Salamandridae), showing an immediate, linear and large decrease in all the energy reserves. In contrast, the hypogean Proteus anguinus (Proteidae) displayed successive periods of glucidic, lipidic and finally lipido-proteic-dominant catabolism during the course of food deprivation. The remarkable resistance to long-term fasting and the very quick recovery from nutritional stress of this cave organism may be explained partly by its ability to remain in an extremely prolonged state of protein sparing and temporary torpor. Proteus anguinus had reduced metabolic and activity rates (considerably lower than those of most surface-dwelling amphibians). These results are interpreted as adaptations to a subterranean existence in which poor and discontinuous food supplies and/or intermittent hypoxia may occur for long periods. Therefore, P. anguinus appears to be a good example of a low-energy-system vertebrate.

Adaptation, Physiological↗
PubMed1983

Studies on the pharmacological bases of fetal toxicity of drugs (IV). Effect of endotoxin and starvation on serum protein binding of salicylic acid in pregnant rats.

Our previous paper reported that the fetotoxic effects of aspirin (ASA) were enhanced by bacterial endotoxin (LPS), and the effects of ASA were attributed to its major metabolite, salicylic acid (SA), as indicated by high SA concentrations in fetus and placenta. In order to clarify the mechanisms of the enhancement by LPS, serum total protein, albumin and free fatty acid (FFA) levels and SA-binding capacity of serum protein were investigated in pregnant rats. The following results were obtained: 1) FFA levels increased steadily after day 16 of pregnancy, and SA-binding capacity of serum protein decreased gradually after day 18, as the pregnancy proceeded to full term. 2) LPS injection decreased total protein and albumin levels in normal and starved rats on day 15 of pregnancy. 3) Starvation and/or LPS injection potentiated the increase of FFA level and reduced significantly SA-binding capacity of serum protein in the rats on day 15 of pregnancy. 4) Serum protein showing low SA-binding capacity from LPS-treated rats recovered normal SA-binding capacity when FFA was removed from serum protein by charcoal treatment. These data suggested the decrease of the SA-protein binding in serum by the increased level of FFA, an inhibitor of the binding, and the decreased level of albumin as a possible mechanism for the potentiation of the fetotoxicities of ASA by LPS.

Animals↗