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At least 811 records · Page 45Linked to original sources
PubMed1986

Starvation-induced changes in metabolic rate, blood flow, and regional energy expenditure in rats.

Starvation results in an energy-conserving reduction in metabolic rate that has features of an adaptive response. Tissue and organ sites of this response were investigated by examining the effects of starvation for 5 d on tissue blood flow (microsphere method) and regional arteriovenous O2 differences ((a-v)O2) in conscious rats resting quietly at 28 degrees C. Comparison was with fed and overnight-fasted animals. Whole body resting metabolic rates (MR), colonic temperatures (Tc), and tissue weights were also determined. Quantitative changes in energy expenditure (as O2 consumption) were obtained for two regions: the portal-drained viscera (PDV) and the hindquarters (HQ). Fasting overnight resulted in increased blood flow to white adipose tissue (WAT) and decreased flow to the brain, PDV, testes, and skin; however, MR, Tc, the two regional ((a-v)O2, and the weights of most tissues were not significantly altered. In comparison with overnight fasting, starvation for 5 d resulted in a 13% reduction in body weight, weight loss in many tissues and organs, a 26% reduction in MR, a decline of 0.5 degree C in Tc, decreased (a-v)O2 across both the PDV and HQ, reduced cardiac output, and decreased blood flow to the heart, PDV, skin, WAT, leg muscle, HQ, and the musculoskeletal body as a whole. Utilization of O2 by the PDV and HQ (flow X (a-v)O2) declined by amounts that accounted for 22 and 18%, respectively, of the reduction in MR. The reductions in cardiac output (18%) and heart blood flow (36%) indicate that the heart also made a contribution to energy conservation (roughly estimated as 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Activation of a selective pathway of lysosomal proteolysis in rat liver by prolonged starvation.

Lysosomal uptake and degradation of polypeptides such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribonuclease A (RNase A), and RNase S-peptide (residues 1-20 of RNase A) are progressively activated in rat liver by starvation before isolation of lysosomes. This pathway of proteolysis is selective, since it is stimulated by the heat shock cognate protein of 73 kDa (HSC73) and ATP-MgCl2, and lysosomal uptake of RNase A could be competed by GAPDH but not by ovalbumin. A portion of intracellular HSC73 is associated with certain lysosomes, and the amount of lysosomal HSC73 increases by 5- to 10-fold during prolonged starvation. The lysosome-associated HSC73 is primarily within the lysosomal lumen. Double immunogold labeling of lysosomes incubated in vitro with RNase A detects this protein substrate as well as HSC73 within lysosomes. More than two-thirds of the labeled lysosomes contain both RNase A and HSC73. The possible physiological significance of the activation of this selective pathway of lysosomal proteolysis in long-term starvation is discussed.

Animals↗
PubMed2002

Cardiac gene expression profile and lipid accumulation in response to starvation.

Starvation induces many biochemical and histological changes in the heart; however, the molecular events underlying these changes have not been fully elucidated. To explore the molecular response of the heart to starvation, microarray analysis was performed together with biochemical and histological investigations. Serum free fatty acids increased twofold in both 16- and 48-h-fasted mice, and cardiac triglyceride content increased threefold and sixfold in 16- and 48-h-fasted mice, respectively. Electron microscopy showed numerous lipid droplets in hearts of 48-h-fasted mice, whereas fewer numbers of droplets were seen in hearts from 16-h-fasted mice. Expression of 11,000 cardiac genes was screened by microarrays. More than 50 and 150 known genes were detected by differential expression analysis after 16- and 48-h-fasts, respectively. Genes for fatty acid oxidation and gluconeogenesis were increased, and genes for glycolysis were decreased. Many other genes for metabolism, signaling/cell cycle, cytoskeleton, and tissue antigens were affected by fasting. These data provide a broad perspective of the molecular events occurring physiologically in the heart in response to starvation.

Animals↗
PubMed1981

Effects of starvation and obesity on somatostatin, insulin, and glucagon release from an isolated perfused organ system.

We have studied the effects of starvation and of obesity on somatostatin, insulin, and glucagon release from an isolated perfused organ system in fed and 3- and 5-day fasted Holtzman rats and in obese (fa/fa) and lean (Fa/?) Zucker rats. Fasting for 3 days significantly decreased basal (-71%) and amino acid-stimulated (-62%) somatostatin output. After 5 days of starvation, there was a significant increase over the 3-day level in somatostatin output stimulated by amino acid plus glucose (+540%) and by amino acids plus tolbutamide (+238%). Three and five days of starvation severely depressed insulin output while having no statistically significant effects on glucagon secretion. Somatostatin output from obese Zucker rats was significantly greater than that from lean controls in response to amino acids (41.2 +/- 13.2 vs. 16.3 +/- 10.3 ng/25 min, P less than 0.05). Insulin output was greatly increased from obese compared to lean Zucker rats, whereas there were no statistically significant differences in glucagon output. These data show that fasting decreases and obesity increases both somatostatin and insulin release. They suggest that altered stimulation by nutrients was primarily responsible for changes in somatostatin and insulin release observed in starving and obese rats.

Amino Acids↗
PubMed1984

Sites of protein conservation and loss during starvation: influence of adiposity.

Previous studies have established that older (16 wk) and more obese rats conserve body protein during prolonged starvation. This adaptation is due in part to a curtailment of muscle proteolysis. To determine whether this response occurs also in younger rats and whether protein is conserved at sites other than muscle, studies were conducted in young 6-wk-old rats previously fed either a chow or a high-fat diet before starvation. Fat feeding caused a marked increase in adipose mass and prolonged survival. Whereas chow-fed rats survived the fast for approximately 5 days, fat-fed rats lived for 10 days and diminished their excretion of nitrogen for at least 6 days, indicative of protein conservation. Despite the ability of fat-fed rats to survive the fast longer, protein was conserved in only a few organs. The timing and magnitude of protein loss from liver, kidney, intestine, and lung was similar to that in chow-fed rats, and little protein was lost during the fast from brain, stomach, skin, and soleus muscle in either group. In fat-fed rats, cardiac and skeletal muscle were the principle tissues in which protein was conserved, and this adaptation was lost when body fat stores were nearing exhaustion. In both groups nitrogen excreted in the urine early in the fast was derived mainly from protein lost from muscle, liver, and to a lesser extent intestine. Later in the fast, the principal source was muscle. These findings indicate that during starvation in the rat the conservation of protein occurs principally in skeletal and cardiac muscle. They also suggest that the ability of the rat to conserve protein is dependent on the size of its lipid stores.

Adipose Tissue↗
PubMed1986

Extremity amino acid metabolism during starvation and intravenous refeeding in humans.

This study was designed to evaluate peripheral tissue amino acid metabolism in normal subjects who underwent starvation followed by intravenous administration of a nutritional repletion regimen with varying nonprotein caloric sources. Extremity amino acid (AA), arteriovenous differences, and blood flow were measured across forearm and/or leg of 12 healthy male subjects. Plasma AA flux [(arterial concentration - venous concentration) X flow X (1 - hematocrit); ml X min-1 X 100 ml tissue-1] was determined postabsorptively (PA), after 10 days of starvation (ST) and on the 10th day of intravenous feeding (IVF). There was a significant (P less than 0.05) decrease in efflux of total amino acids during the starvation study (-345 +/- 74) compared with the PA study (-1,463 +/- 263). Peripheral tissue AA uptake increased significantly (P less than 0.05) after 10 days of IVF (+276 +/- 79) compared with both PA and ST studies. There were no significant differences in extremity AA flux between those subjects who received 100% dextrose and those receiving 50% dextrose-50% lipid as a nonprotein caloric source. Linear relationships of AA infusion rate (IR) to AA flux (r = 0.845, P less than 0.001) and AA IR to [AA]art IVF (r = 0.842, p less than 0.001) were observed during IVF. Results of this study suggest that extremity flux determinations during IVF cannot be interpreted without correction for AA availability as reflected by AA infusion rate.

Amino Acids↗
PubMed1995

Blood-brain barrier permeability of glucose and ketone bodies during short-term starvation in humans.

The blood-brain barrier (BBB) permeability for glucose and beta-hydroxybutyrate (beta-OHB) was studied by the intravenous double-indicator method in nine healthy subjects before and after 3.5 days of starvation. In fasting, mean arterial plasma glucose decreased and arterial concentration of beta-OHB increased, whereas cerebral blood flow remained unchanged. The permeability-surface area product for BBB glucose transport from blood to brain (PS1) increased by 55 +/- 31%, whereas no significant change in the permeability from brain back to blood (PS2) was found. PS1 for beta-OHB remained constant during starvation. The expected increase in PS1 due to the lower plasma glucose concentration was calculated to be 22% using previous estimates of maximal transport velocity and Michaelis-Menten affinity constant for glucose transport. The determined increase was thus 33% higher than the expected increase and can only be partially explained by the decrease in plasma glucose. It is concluded that a modest upregulation of glucose transport across the BBB takes place after starvation. Brain transport of beta-OHB did not decrease as expected from the largely increased beta-OHB arterial level. This might be interpreted as an increase in brain transport of beta-OHB, which could be caused by induction mechanisms, but the large nonsaturable component of beta-OHB transport makes such a conclusion difficult. However, beta-OHB blood concentration and beta-OHB influx into the brain increased by > 10 times. This implies that the influx of ketone bodies into the brain is largely determined by the amount of ketones present in the blood, and any condition in which ketonemia occurs will lead to an increased ketone influx.

Adult↗
PubMed1986

Ileal hyperplastic response to starvation in the rat.

The ability to respond to changes in the external and internal environments is a fundamental characteristic of intestinal structure and function. We compared the responses of the rat proximal and distal small intestine to the stresses of fasting and refeeding in the rat. In the duodenum, 3 days of starvation caused villus and crypt hypoplasia, reduced incorporation of [3H]thymidine into crypt cells, decreased cell migration rate on the villus, and lowered specific and total activities of several cellular enzymes. These changes were reversed by 1 day of refeeding. In contrast, mucosal hypoplasia did not occur in the ileum during fasting, and the specific activities of the disaccharidases were increased after 3 days of starvation. However, ileal [3H]thymidine incorporation, thymidine kinase activity, and ornithine decarboxylase activity decreased during starvation. These effects were also reversed by refeeding. The results of these studies illustrate differing responses for the proximal and distal small intestine and suggest the presence of distinctly differing mechanisms for the control of their mucosal mass and enzyme activities.

Adenosine Deaminase↗
PubMed1975

Hypercholesterolemia of total starvation: its mechanism via tissue mobilization of cholesterol.

After the establishment of a relatively linear decay curve for plasma [4-14C]cholesterol, rabbits were starved for 26-32 days. The plasma cholesterol concentration increased 400% during starvation. Concurrently, the plasma triglyceride level declined by 50%. While the plasma cholesterol was rising, the cholesterol specific radioactivity of the plasma remained unchanged in starved animals, but in control animals the plasma cholesterol specific radioactivity declined substantially. The cholesterol content of the liver and adipose tissue increased with starvation. The cholesterol specific radioactivities relative to plasma for adipose tissue were lower in the starved animals versus controls. These results support the hypothesis that cholesterol stored in the lipid droplet of the adipose tissue cell is released into plasma and is the chief source of the hypercholesterolemia observed during complete caloric starvation. Cholesterol metabolism in the starved animal can be depicted as a virtually closed system in both the input from biosynthesis and diet being low or zero and the output likewise being close to zero.

Adipose Tissue↗
PubMed1990

Enhanced thermogenic response to epinephrine after 48-h starvation in humans.

The effects of 48-h starvation on the physiological responses to a 30-min infusion of epinephrine at 25 ng.min-1.kg body wt-1 were studied in 11 normal-weight healthy young subjects. Starvation led to considerable alterations in basal metabolism including a significant (mean 3.6%) increase in resting metabolic rate. During the infusions, plasma epinephrine concentration rose less in the starved state (+1.47 nmol/l) than in the normally fed state (+1.73 nmol/l) (SE 0.06 nmol/l; P less than 0.05). The maximum increments (mean +/- SE) in heart rate induced by epinephrine were 11.9 +/- 1.3 beats/min in the normally fed state and 20.1 +/- 2.0 beats/min in the starved state (P less than 0.001); the corresponding mean increments in blood glycerol concentration were 0.07 and 0.14 mmol/l (SE 0.01 mmol/l; P less than 0.01). The increase in the metabolic rate above base line during the final 10 min of the epinephrine infusion was 0.58 +/- 0.18 kJ/min in the normally fed state and 0.78 +/- 0.14 kJ/min in the starved state (P less than 0.01). The chronotropic, lipolytic, and thermogenic effects of infused epinephrine were therefore enhanced by prior starvation, despite the lower plasma epinephrine levels.

3-Hydroxybutyric Acid↗
PubMed2004

Transcriptional profile of a myotube starvation model of atrophy.

Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

Animals↗
PubMed1988

Effects of starvation on the parathyroid glands in golden hamsters of different ages, with special reference to the frequency of lipid droplets.

The frequency of lipid droplets in the parathyroid glands of young, adult and senile golden hamsters after starvation was investigated. In the parathyroid glands of the young and senile golden hamsters, the number of lipid droplets increased to reach a peak by 2 days, then decreased slowly by 5 days after starvation, and decreased rapidly after refeeding. In the glands of adult animals it increased to reach a peak by 5 days after starvation and decreased rapidly after refeeding. These findings suggest that in the fasting condition there is a relationship between the number of lipid droplets and aging.

Aging↗
PubMed1981

Effect of starvation of the synthesis rate of albumin in vivo and its relation to the concentrations of amino acids in the peripheral blood, the portal circulation and in the liver cytosolic fraction.

The synthesis rate of albumin was measured in vivo by the 14C-carbonate method in fed control rabbits, in animals after a short-term fast (24-36h), and after starvation for 8 days. The albumin synthesis rate was significantly lower in animals after a short-term fast in comparison to the fed control group. A starvation for a longer period did not further decrease the synthesis rate of albumin. The serum concentrations of essential amino acids from the systemic circulation and from the portal blood after a short-term fast did not differ significantly nor were they higher in comparison to those of fed rabbits. Despite the increased serum levels of the most essential amino acids in the systemic venous blood after long-term starvation, there were no or little changes in concentrations of amino acids in portal blood and liver cytosolic fraction from fasted animals as compared to those of the fed group. These findings suggest that the reduction of albumin synthesis in fasting state is not primarily due to a reduction in the direct availability of these amino acids for albumin synthesis in the liver.

Albumins↗
PubMed1996

Age-related response of the small intestine to severe starvation and refeeding in rats.

The impact of severe starvation and refeeding on the intestinal mucosa of rats of different ages has been studied in a diet-controlled model. Structural and functional alterations of the small intestinal mucosa were assessed by standard parameters including mucosal protein, DNA content as well as maltase, sucrase and leucine aminopeptidase enzymatic activities. Decreases in mucosal mass, DNA, protein and leucine aminopeptidase activity in both the jejunum and ileum caused by starvation, diminished with age. The depression of disaccharidase activities increased with age in the jejunum but not in the ileum. Except for jejunal protein and leucine aminopeptidase activity, the recovery from starvation, after refeeding, was complete for the other parameters studied, regardless of age.

Aging↗
PubMed1990

Effects of starvation and difluoromethylornithine (DFMO) on diamine oxidase activity in rat ileum.

Starvation and difluoromethylornithine (DFMO) administration have profound affects on intestinal proliferation, ornithine decarboxylase activity, and tissue polyamine levels. Diamine oxidase activity may play a role in the regulation of proliferation, and the activity of this enzyme may be influenced by ornithine decarboxylase activity. To determine if diamine oxidase is influenced by starvation and DFM administration, ileal diamine oxidase activities were determined on mucosal homogenates from five groups of rats: fed control, starved for 48 h, fed group receiving DFMO, a starved/refed group, and a starved/refed group receiving DMFO. The homogenates from starved rats were found to have decreased ornithine decarboxylase activity and increased diamine oxidase activity when compared to control values. The homogenates from the DFMO group also were found to have decreased ODC activity however, mucosal diamine oxidase activity was also decreased. Refeeding produced a dramatic increase in ornithine decarboxylase activity and a minimal change in diamine oxidase activity. The preservation of diamine oxidase activity during starvation implies a need for the enzyme not related to mucosal proliferation or digestion. However, in the fed state, diamine oxidase activity may be more dependent on ornithine decarboxylase activity or its reaction product putrescine.

Amine Oxidase (Copper-Containing)↗
PubMed1978

Source of fetal-stored lipids during maternal starvation in rabbits.

The effect of 48 h maternal starvation on the composition of fetal rabbit brown and white adipose tissue was examined. Compared with fed control rabbits, adipose tissue triglyceride fatty acids took on a composition more like that of maternal plasma free fatty acids (FFA), whose concentration more than doubled after 48 h starvation. It is concluded that maternal FFA contribution to the fetal lipids increases during starvation and certain fetal acids, in particular linoleic acid, may in the fed state be derived from maternal lipids other than the FFA.

Adipose Tissue↗
PubMed1988

Combined pregnancy and starvation effects on rat tissue iron, zinc and copper contents.

The essential metal copper, zinc and iron content in starved virgin and pregnant rat tissue has been studied. The copper content of the whole rat, which was actually increased in pregnant rats, decreased in starved pregnant rats. The differences were significant in 19-day pregnant rats. The total copper content of the conceptus was not affected by starvation. Iron distribution and net tissue content showed the same pattern as that of copper. With regard to zinc, however, there was a decrease of its content associated with starvation in rat tissue. This decrease was statistically significant on the 21st day of gestation both in the mother and in fetuses, which marks a difference compared with the copper-iron pattern. It must be pointed out, however, that--with the significant exception of zinc--the maternal stores of the metals are enough to supply the fetus during starvation despite significant reductions in the maternal reserves.

Animals↗
PubMed1972

Amino acid metabolism during starvation in human pregnancy.

To evaluate the factors regulating gluconeogenesis in pregnancy, plasma amino acid levels were determined during the course of an 84-90 hr fast in physically healthy women studied during wk 16-22 of gestation (before undergoing therapeutic abortion), and in nonpregnant controls. The effect of pregnancy on the glycemic response to exogenous alanine administration during starvation was also investigated. In the nonpregnant group fasting resulted in a 2- to 3-fold increase in the levels of plasma valine, leucine, isoleucine, and alpha-aminobutyrate, while the concentration of alanine and glycine fell. In the pregnant group, the levels of most amino acids were significantly reduced in the postabsorptive state. With starvation, the plasma concentration of alanine fell more rapidly in the pregnant group and was significantly below that of the nonpregnant subjects for the first 60 hr of the fast. In contrast, a significant elevation in plasma glycine, serine, and threonine was observed in the pregnant group after 84 hr of fasting, whereas similar increments were not demonstrable until after 10 days of fasting in previously studied nonpregnant obese subjects. Paralleling the changes in maternal plasma, amniotic fluid levels of valine, leucine, and isoleucine increased while that of alanine fell during the fast. Although the plasma glucose concentration was lower in the pregnant group at termination of the fast, intravenous alanine administration (0.15 g/kg), resulted in a prompt, comparable increase (20-25 mg/100 ml) in plasma glucose in both groups of subjects. It is concluded that (a) pregnancy accelerates and exaggerates the hypoalaninemic and hyperglycinemic effects of starvation; (b) lack of key endogenous substrate rather than altered intrahepatic processes may limit hepatic gluconeogenesis in pregnancy and contribute to gestational hypoglycemia; (c) maternal caloric deprivation profoundly alters the levels of amino acids in amniotic fluid.

Adolescent↗