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Whole-body protein breakdown and 3-methylhistidine excretion during brief fasting, starvation, and intravenous repletion in man.

Simultaneous whole-body protein breakdown (using 15N-glycine) and urinary 3-methylhistidine (3MH) excretion rates were determined in six hospitalized normal volunteers after 10 days of starvation and a subsequent 10-day period of total parental nutrition (TPN). These data were contrasted to whole-body protein breakdown and urinary 3MH excretion in ten depleted (14.8% body weight loss) patients with benign intraabdominal disease studied in the basal (48 hours without nutrient intake) and intravenously refed states. The rates of whole-body protein breakdown were significantly reduced from basal (brief fasting or starvation) conditions in both normal volunteers (p less than 0.01) and depleted patients (p less than 0.01) during TPN. The rate of protein catabolism normalized for creatinine excretion in patients was higher than that observed in normal subjects during both basal (p less than 0.05) and intravenous feeding conditions. Daily urinary 3MH excretion was reduced during intravenous feeding in both starved normal volunteer (235 +/- 13 mumol/d to 197 +/- 9 mumol/d p less than 0.05) and in depleted patients (209 +/- 31 mumol/d to 140 +/- 35 mumol/d), and an apparent linear relationship between protein breakdown and urinary 3MH, normalized for creatinine excretion, was obtained in both volunteer and patient (r = 0.85) populations during fasting-refeeding. However, separate regression analysis of the protein breakdown and 3MH responses of both volunteer and patient groups under conditions of fasting, starvation, and refeeding revealed significant differences between volunteer and patient populations during intravenous refeeding (p less than 0.01). Further analysis of 3MH excretion in relationship to nitrogen balance during refeeding suggests a complex relationship between urinary 3MH excretion and whole-body protein metabolism that may be partly related to the degree of antecedent malnutrition.

Adult↗

The effect of starvation on brain carnitine concentration in neonatal rats.

BACKGROUND: We examined carnitine concentrations in fasted neonatal rat brain to evaluate the effect of starvation on fatty acid metabolism. METHODS: The free- and acylcarnitine concentrations in neonatal rat brain and heart were determined after a 72-hour starvation period from the 3rd to 6th postnatal day. They were also determined in rats at 3 and 6 days of age fed normally by the mother rats as controls. RESULTS: In the brain, the mean free carnitine concentration in the fasted group showed an increase similar to that in normal rats and there was no difference between the fasted and 6-day-old control rats. However, the mean acylcarnitine concentration was significantly higher in the fasted group than in the control group at both 3 and 6 days of age. Almost all of the increased acylcarnitine in the fasted group was short-chain acylcarnitine. In the heart, there was no difference in the mean free carnitine concentration between the fasted group and control group at 6 days of age. The 6-day-old rats in both the fasted and control groups showed higher levels compared to 3-day-old rats in the control group. The mean acylcarnitine concentration in the fasted group was not different from that in control group at 6 days of age, while the amount of short-chain acylcarnitine was less than that in the control group at 6 days of age. CONCLUSIONS: These findings suggest that in the brain, carnitine is accumulated as a result of redistribution during starvation, and is utilized for energy supply by fatty acid oxidation.

Aging↗

Starvation and endotoxin act independently and synergistically to coordinate hepatic glutamine transport.

OBJECTIVE: Because hepatic glutamine transport is markedly enhanced during critical illness, we tested the hypothesis that nutrient starvation and endotoxemia act coordinately to augment transport activity. DESIGN: Fed or starved (48 hours) rats received Escherichia coli endotoxin (LPS, 10 mg/kg of body weight, intraperitoneally) or saline before hepatocyte isolation for measurement of glutamine transport. MATERIALS AND METHODS: Hepatocytes were isolated from fed or fasted rats 4 hours after LPS treatment. [3H]glutamine uptake was measured and normalized to cellular protein. Data (mean +/- standard deviation, three separate determinations) were analyzed by Student's t test and analysis of variance. MAIN RESULTS: Starvation induced a 1.6-fold increase in glutamine transport, while LPS treatment of fed rats increased transport activity 2.6-fold. Treatment of fasted animals with LPS induced a sixfold increase in glutamine transport. Kinetically, this effect in endotoxemic starved rats was mediated by both an increase in System N Vmax and the induction of a high affinity System A amino acid carrier which transports glutamine. CONCLUSIONS: Starvation and endotoxemia regulate hepatocyte glutamine transport independently and synergistically. This hepatic response provides glutamine and other amino acids to support key metabolic pathways in the liver during critical illness.

Amino Acids↗

Perturbed bioelectrical properties of the mouse cecum following hepatectomy and starvation: the role of bacterial adherence.

Previous work in our laboratory has demonstrated that bacterial adherence alone to the intestinal epithelium, as occurs following catabolic stress, significantly perturbs the normal electrophysiology of the cecal mucosa. The aim of this study was to further characterize these effects in the mouse cecum following hepatectomy and short-term starvation, and to define the role of bacterial adherence in this process. Groups of mice underwent a surgical hepatectomy and were either fed or starved during the postoperative period. Groups of controls underwent sham operations and were either fed or starved postoperatively. Electrophysiologic studies in Ussing chambers at 48 hours were performed. Bacterial adherence to the mucosa was assessed by culture and histologic staining. To determine the role of bacteria in the altered electrophysiologic response, ciprofloxacin decontamination studies were performed. Only mice subjected to both hepatectomy and starvation developed bacterial adherence of sufficient magnitude (>10(5) cfu/gm) to alter mucosal electrophysiology (short-circuit current and basal potential difference). Ciprofloxacin decontamination completely abrogated this effect. Ion replacement studies suggested that active sodium transport was primarily responsible for the observed changes in mucosal electrophysiology. Bacterial-epithelial cell interactions may be responsible for altered mucosal ion transport observed following operative catabolic stress and short-term starvation.

Animals↗

Levels of variation in stress resistance in drosophila among strains, local populations, and geographic regions: patterns for desiccation, starvation, cold resistance, and associated traits.

Stress resistance traits in Drosophila often show clinal variation. Although these patterns suggest selection, there is generally no attempt to test how large differences at the geographical level are relative to levels of variation within and between local populations. Here we compare these levels in D. melanogaster from temperate Tasmania versus tropical northern Queensland by focusing on adult resistance to desiccation, cold and starvation stress, as well as associated traits (size, lipid content). For starvation and desiccation resistance, levels of variation were highest among strains from the same population. whereas there was little differentiation among local populations and a low level of differentiation at the geographic level. For adult cold resistance, there was local differentiation and strain variation but no geographic variation. For size (thorax length), geographic differentiation was higher despite some overlap among strains from the tropical and temperate locations. Finally, for lipid levels there was only evidence for variation among strains. The low level of differentiation among geographic locations for stress resistance was further verified with the characterization of isofemale strains from 18 locations along a coastal transect extending from Tasmania to northern Queensland. Crosses among some of the isofemale strains showed that results were not confounded by inbreeding effects. Strains derived from a cross between a tropical and temperate strain differed for all traits, and variation among strains for body size was higher than strain variation within the geographic regions. Unlike in previous studies, lipid content and starvation resistance were not correlated in any set of strains, but there was a correlation between cold resistance and lipid content. There was also a correlation between desiccation resistance and size but only in the geographic cross strains. These findings suggest a large amount of variation in stress resistance at the population level and inconsistent correlation patterns across experimental approaches.

Analysis of Variance↗

Triglyceride metabolism in acute starvation: the role of secretin and glucagon.

Plasma lipid and hormone levels have been measured during 72 hours total starvation in nine healthy subjects, to assess the relative importance of hormones and substrates in human triglyceride metabolism. Plasma free fatty acid and glycerol concentrations rose steadily on each day of starvation. Plasma triglyceride concentrations rose on the second and third days, from a control level of 649 +/- 67 mg/1 to a maximum of 1001 +/- 66 mg/1. Plasma cholesterol concentrations remained unchanged while glucose concentrations fell and insulin did not change. Plasma glucagon (C-GLI) levels doubled while secretin levels, reported previously, rose threefold. It is suggested that during acute starvation the rise in triglyceride concentration results from the increased availability of free fatty acids, and that elevated secretin and glucagon levels enhance lipolysis and hence provide substrates for triglyceride synthesis.

Adult↗

Effect of long-term starvation on acetate and ketone body metabolism in obese patients.

The turnover of ketone bodies and acetate was evaluated as well from the disappearance rate of (3-14C)acetoacetate or (1-14C)acetate respectively as from the conversion of FFA into these metabolites in normal weight and obese overnight-fasted and in obese long-term starved patients. The disappearance rate of (1-14C)oleate was the same in all three groups. Long-term starvation enhanced ketone body turn-over almost 10-fold, whereas the disappearance rate for ketone bodies decreased from 0.035 to 0.015 min-1. Under the same circumstances the turnover of acetate was about 1 mumol g-1 min-1 accounting for about 5% of FFA turnover. Long-term starvation decreased the conversion of (1-14C)oleate into triglycerides by almost 50% and increased the (2-C)-(4-C)/(1-C) ratio of radioactivity in ketone bodies. The reincorporation of radioactivity from the (1-C)position of (1-14C)oleate into the ( (2-C)-(n-C) ) position of FFA, which is a measure of the reutilization of acetyl-CoA for FFA synthesis decreased significantly during long-term starvation.

3-Hydroxybutyric Acid↗

Refeeding after starvation in the rat: comparative effects of lipids, proteins and carbohydrates on jejunal and ileal mucosal adaptation.

To compare the tropic effect of different dietary nutrients on mucosal adaptation in the jejunum and ileum, adult rats were submitted to a 96-h period of starvation and refed isocaloric liquid diets (1.5 kcal ml-1) containing either protein (casein), carbohydrate (starch) or lipids. In the jejunum, 4 days of starvation caused mucosal hypoplasia, villus and crypt shortening and a decrease in the total activity of disaccharidases with the exception of lactase which was markedly enhanced. In contrast, mucosal hypoplasia was incomplete in the ileum which exhibited an increase in crypt depth and in the specific and total activities of disaccharidases and of aminopeptidase. Compared with protein and carbohydrates, lipids exerted the strongest stimulatory effect for mucosal regeneration. In the jejunum as well as in the ileum, mucosal mass parameters, villus length, crypt depth and lactase activity did reverse towards their initial value within 1-3 days of refeeding lipids, even though the animals received only one-third of their normal daily caloric intake. Our results indicate that the pattern of response to fasting differs between the proximal and distal small intestine, and that the intestinal changes induced by starvation are rapidly reversed by refeeding small amounts of a diet rich in fat.

Animals↗

Influence of starvation, surface attachment and biofilm growth on the biocide susceptibility of the biodeteriogenic yeast Aureobasidium pullulans.

AIM: To investigate the effect of starvation, surface attachment and growth in a biofilm on the susceptibility of Aureobasidium pullulans to the biocides 2-n-octyl-4-isothiazolin-3-one (OIT) and sodium hypochlorite (NaOCl). METHODS AND RESULTS: Fluorescence loss from a green fluorescent protein (GFP)-transformed strain was used to monitor real-time loss in viability as previously described in situ in 96-well plates. Exponential phase, yeast-like (YL) cells were settled in the bottom of the wells as a low-density monolayer (LDM) and were susceptible to all biocide concentrations (25-100 mug ml(-1)). The exponential phase YL cells were either starved for 48 h in suspension or starved for 48 h as LDMs in the wells. Starvation in both cases led to a small reduction in susceptibility to the biocides. In contrast, 48-h biofilms grown in malt extract broth showed an apparent lack of susceptibility to 25 and 50 mug ml(-1) OIT and to 25-100 mug ml(-1) NaOCl. However, when the OIT concentration was increased to compensate for the higher cell density in the biofilm, the biofilms were found to be equally susceptible to the LDM. CONCLUSIONS: Starvation of A. pullulans YL cells either in suspension or as attached LDM resulted in a decrease in susceptibility to low concentrations of both OIT and NaOCl while the apparent reduced susceptibility of mature biofilms was due to the increase in biofilm cell density rather than true biofilm resistance per se. SIGNIFICANCE AND IMPACT OF THE STUDY: Monitoring fluorescence loss from the GFP-transformed strain of A. pullulans can be used as a fast and reliable method for monitoring cell death in real time as a response to biocide and antimicrobial challenge.

Biodegradation, Environmental↗

Starvation-induced alterations of ribosomal protein phosphorylation in Bombyx mori L. Evidence for different phosphorylation kinetics in free and membrane-bound ribosomes.

In the posterior silk gland of Bombyx mori, ribosomal protein S1, homologous to S6 in mammals, is partially phosphorylated in a normally fed animal. Before the first meal of the fifth larval instar, S1 is completely dephosphorylated. Likewise, starvation induces rapid dephosphorylation of the protein in both free and membrane-bound ribosomes. Upon refeeding after 48 h of starvation, S1 becomes phosphorylated again, first on membrane-bound ribosomes, then on free ribosomes, with a lag time of about 3 h. Following 48 h of refeeding, the most highly phosphorylated form of S1 predominates in both populations of ribosomes. These variations in phosphorylation are correlated with the level of protein synthesis in the posterior silk gland, 70% of the ribosomes occurring in polysomes upon feeding and only 30% upon starvation [Prudhomme, J.-C. & Couble, P. (1979) Biochimie (Paris) 61, 215-227]. After in vivo 32P labelling, the phosphopeptides of S1 from free and membrane-bound ribosomes were found to be identical and phosphoserine (only) was found in each S1. These results suggest the involvement of S1 phosphorylation in the regulation of protein synthesis at the translational level and the existence of at least two different pathways controlling this phosphorylation: one for the free ribosomes, the other for the membrane-bound ribosomes.

Animals↗

Energy metabolism and substrate oxidation in pigs during feeding, starvation and re-feeding.

Energy metabolism and substrate oxidation was measured in 12 growing pigs by means of indirect calorimetry and nutrient balances. The measurements were carried out during 5 days of feeding followed by 4 days of starvation and 5 days of re-feeding. During the feeding period, dietary carbohydrates were the main energy source, sufficient to cover energy requirements without oxidation of fat. Starvation reduced the total heat production and affected the oxidation pattern by reducing protein oxidation and shifting from carbohydrate to fat oxidation. On the second day of starvation, the main energy source was body fat and there was no oxidation of carbohydrate. On the second day of re-feeding, the heat production reached the same level as during the feeding period. Also, during the second day of re-feeding, the pattern of nutrient oxidation was similar to the feeding period with oxidation of carbohydrate providing 90% and oxidation of protein providing 10% of the total heat production. There was no fat oxidation. The results demonstrated that the growing pigs were able to re-establish oxidative patterns already 2 days after re-alimentation.

Adipose Tissue↗

Characterization of starvation-induced dispersion in Pseudomonas putida biofilms.

The biofilm lifestyle, where microbial cells are aggregated because of expression of cell-to-cell interconnecting compounds, is believed to be of paramount importance to microbes in the environment. Because microbes must be able to alternate between sessile and planktonic states, it is anticipated that they must be able to regulate their ability to form biofilm and to dissolve biofilm. We present an investigation of a biofilm dissolution process occurring in flow-chamber-grown Pseudomonas putida biofilms. Local starvation-induced biofilm dissolution appears to be an integrated part of P. putida biofilm development that causes characteristic structural rearrangements. Rapid global dissolution of entire P. putida biofilms was shown to occur in response to carbon starvation. Genetic analysis suggested that the adjacent P. putida genes PP0164 and PP0165 play a role in P. putida biofilm formation and dissolution. PP0164 encodes a putative periplasmic protein of previously unknown function, and PP0164 mutant bacteria are sticky, and unable to reduce their adhesiveness and dissolve their biofilm in response to carbon starvation. PP0165 encodes a putative transmembrane protein containing GGDEF and EAL domains, and PP0165 mutant bacteria are unable to increase their adhesiveness and form biofilm. We suggest that the PP0164 and PP0165 proteins are involved in the regulation of the adhesiveness of the bacteria; the PP0165 protein through c-di-GMP signalling, and the PP0164 protein as a transducer of the signal.

Bacterial Proteins↗

Short-term starvation decreases skeletal muscle protein synthesis rate in man.

The rate of protein synthesis in skeletal muscle was determined in the post-absorptive state and after 3 days of starvation in healthy volunteers. The flooding dose technique employing intravenous injection of (1-13C)leucine (0.05 g kg-1) was used and incorporation of isotope into muscle protein was measured by taking percutaneous biopsies at 0 and 90 min. Blood samples were taken during the incorporation period for assessment of the enrichment of the free amino acid precursor of protein synthesis. The median (25,75 quartiles) rate of muscle protein synthesis after an overnight fast was 2.03 (2.00,2.23) % days-1 when the precursor enrichment was obtained by measurement of the plasma alpha-ketoisocaproate, taken to be representative of muscle free leucine. Repeat measurements in the same subjects after 3 days of total starvation showed a decrease to 1.82 (1.57,2.05) % days-1. Rates calculated on the basis of the plasma leucine as precursor were 5% lower at both times. An interindividual variation in response to starvation was observed, but the median decrease of 13% in the rate of protein synthesis was statistically significant (P less than 0.01).

Adult↗

Liver and heart mitochondrial succinate dehydrogenase activity of newborn rats in anoxic hypoxia and starvation.

Succinate dehydrogenase activity was determined in the liver and heart of newborn rats after 3 and 48 hours' exposure to anoxic hypoxia (10% O2) and after 48 hours' starvation. Control determinations were made on newborn animals of corresponding ages, full term foetuses (21 days), infantile (1 and 2 weeks) and full grown animals. Hypoxia for 3 h had no influence on succinate dehydrogenase activity at all in either the heart or liver mitochondria of the newborn animals. After 48 h no difference was observed in the liver between the hypoxic animals and the starved controls of the same age, though starvation itself had resulted in a significant increase in activity, as much as 42%. When liver mitochondrial succinate dehydrogenase in normal mitochondria was activated by preincubation mitochondria with the substrate, the activity increase obtained was greater than that resulting from starvation. The increase in activity in the heart of the hypoxic or starved animals was not significant (less than 10%).

Age Factors↗

Regulation of insulin-like growth factor-I in starvation and injury.

Both starvation and sepsis are characterized by growth hormone (GH) insensitivity, which leads to a reduction in circulating insulin-like growth factor (IGF)-I. Because of the anabolic properties of this growth factor, its decline may contribute to the growth arrest and the catabolic reaction observed in starvation and sepsis. This review focuses on the mechanisms responsible for the reduction in circulating IGF-I and impairment of GH responsiveness that occur during starvation and sepsis. A clearer understanding of the complex nature of GH resistance should lead to the development of new therapeutic strategies aimed at restoring the beneficial effects of anabolic agents such as GH and IGF-I.

Energy Intake↗

Acute starvation protects mice against Listeria monocytogenes.

We investigated the effect of starvation on the course of Listeria monocytogenes infections in mice. Mice starved for 24, 48, or 72 h and then inoculated with a lethal dose of L. monocytogenes showed significantly less mortality than mice not starved (i.e., fed mice). The protective effect of 48 or 72 h of starvation began immediately after the starvation period and persisted for at least 48 h. Starved, infected mice had significantly fewer L. monocytogenes cells in their spleens 2, 3, and 4 days after infection than did fed mice. Neither changes in T-lymphocyte function nor serum factors appeared to be responsible for the protective effect. Delayed hypersensitivity responses to L. monocytogenes antigen were smaller in starved mice than in fed mice. Adoptive transfer of spleen cells from nonimmune starved mice did not protect against L. monocytogenes. Additional studies indicated that the serum of starved mice did not inhibit multiplication of L. monocytogenes in vitro, nor was it able to transfer protection against L. monocytogenes to normal mice. In contrast, peritoneal macrophages from starved mice inhibited deoxyribonucleic acid synthesis of P815 tumor cells compared with macrophages from control mice. Therefore, the resistance of starved mice to L. monocytogenes is most likely due to nonspecific factors, one of which may be activation of macrophages.

Animals↗

Diarrhoea of famine and malnutrition--investigations using a rat model. 2--Ileal hypersecretion induced by starvation.

The effects of progressive starvation for up to three days on the basal and secretagogue stimulated secretory functions of the rat ileum were investigated in vitro and in vivo. The secretagogues used included agents acting via cyclic AMP (dibutyryl cyclic AMP, theophylline, forskolin, and PGE2) and those acting via Ca++ (acetylcholine, bethanecol, carbachol, 5-hydroxytryptamine, and A23187). Starving rats for 24 h (day 1) had no effect on the basal electrogenic secretion (measured as the short circuit current, Isc muamps/cm2) or on the stimulated maximum electrogenic secretion (measured as the delta Isc where delta Isc = maxIsc-basal Isc). By day 2 of starvation, however, both the basal Isc and the delta Isc induced by all the secretagogues were significantly greater than in the fed and increased even more on day 3. Replacement of all the chloride ions and inhibition by furosemide indicated that the enhanced secretion was due mainly to chloride ions. Cholinergic stimulation was blocked by atropine, indicating the stimulation was via muscarinic receptors while cholinergic dose - delta Isc response curves for fed and starved ilea showed significantly increased maximum electrogenic secretory response in the latter but no evidence of any change in the affinity (ED50) of the receptors mediating the response. The basal secretion and the secretory response to acetylcholine in both fed and starved ilea was unaffected by tetrodotoxin, revealing that the enhanced secretory response could be expressed via the muscarinic receptors on the enterocytes without the enteric neural network. Measurement of ileal fluid movement in vivo showed that in fed and day 1 starved rats the basal, unstimulated 'tone' of the ileum was absorptive. On day 2, however, the basal 'tone' had reversed to one of secretion which increased further on day 3. Stimulation of fluid secretion in vivo by bethanecol, carbachol, or PGE2 induced larger increases in the starved ilea by day 2 which increased even further on day 3. Lumenal chloride and bicarbonate concentrations were greater in the starved ileal fluid than in the fed. The studies in rat ileum confirm and extend those on rat jejunum and indicate that starvation creates a hypersensitive small bowel that responds to secretagogues and cholinergic neurotransmitters with a greatly enhanced secretory response.

Acetylcholine↗

The implications of starvation induced psychological changes for the ethical treatment of hunger strikers.

OBJECTIVE: To evaluate existing ethical guidelines for the treatment of hunger strikers in light of findings on psychological changes that accompany the cessation of food intake. DESIGN: Electronic databases were searched for (a) editorials and ethical proclamations on hunger strikers and their treatment; (b) studies of voluntary and involuntary starvation, and (c) legal cases pertaining to hunger striking. Additional studies were gathered in a snowball fashion from the published material cited in these databases. Material was included if it (a) provided ethical or legal guidelines; (b) shed light on psychological changes accompanying starvation, or (c) illustrated the practice of hunger striking. Authors' observations, opinions, and conclusions were noted. CONCLUSIONS: Although the heterogeneous nature of the sources precluded statistical analysis, starvation appears to be accompanied by marked psychological changes. Some changes clearly impair competence, in which case physicians are advised to follow advance directives obtained early in the hunger strike. More problematic are increases in impulsivity and aggressivity, changes which, while not impairing competence, enhance the likelihood that patients will starve themselves to death.

Humans↗