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[Energy metabolism in fasting and subsequent refeeding].

A metabolism trial with six adult sows was conducted to study the effect of fasting and realimentation on heat production, energy retention, and utilization of energy. Complete balance measurements by indirect calorimetry (CN-method, RQ-method) were carried out from the 8th to the 10th day of fasting, and thereafter from the 1st to the 7th day and from the 33rd to the 36th day of the realimentation phase. Previous to fasting and during the time of refeeding the energy supply was adapted to maintenance requirement. Heat production rose by 20% after refeeding the animals. This heat increment corresponded to 2.2 MJ/kg feed dry matter, or 12% of the energy intake, respectively. The stimulation of heat production induced by refeeding occurred spontaneously within one day. After the first day of refeeding a plateau was reached, which in the course of the steady energy supply was still present even after the 5th week of realimentation. Residual effects of fasting in the mode of a compensatory heat production were not observed. Therefore, a constant utilization of efficiency of metabolizable energy for maintenance was estimated at 82%. The change of body energy during the entire experimental period resulted in a loss of 198 MJ corresponding to about 5% of the body weight.

Animals↗

The effects of starvation and refeeding on intestinal cell proliferation in the mouse.

The effects of starvation and refeeding on intestinal cell proliferation were studied in four sites of the mouse intestine. Control mice were studied at different times of day in order to compensate for any circadian variations in proliferation. A circadian rhythm in crypt cell production rate was observed in all the sites of the small intestine and colon, and this rhythm appeared to be entrained to the food intake. The fractional crypt cell production rate decreased in all sites of the intestine after 24 h starvation, and remained low until 9 h after refeeding, when there was a marked increase in the crypt cell production rate of all the small intestinal sites, especially the proximal sites. There was little change in colonic crypt cell production rate until 12 h after refeeding, when there was a large increase in cell production. The crypt cell production rate of all sites then returned to control values for the remainder of the investigation. Crypt cell number decreased after refeeding and villus cell number increased, however a similar effect was observed in the control animals, nevertheless the changes in villus cell population of the refed mice occurred before any increase in crypt cell production, suggesting that cell migration from crypt to villi is not immediately dependent on cell proliferation.

Animals↗

Effects of pre- and postnatal protein deprivation and postnatal refeeding on myenteric neurons of the rat large intestine: a quantitative morphological study.

We investigated the effect of protein deprivation and refeeding on weight gain, the size of the colon, and the numbers and sizes of enteric neurons. Neurons were located by reduced nicotinamide adenine dinucleotide (NADH) diaphorase staining. Protein deprivation of the mother throughout pregnancy, and the mother and unweaned rat pups in the first 21 postnatal days, reduced the weights of pups to about 50% of control. The size of the colon was also reduced, by about 40%. Despite this, total numbers of neurons in the colon were not reduced. However, there was a small, but significant, 15% reduction in the areas of neuron profiles. After 21 days the remaining pups were removed from the mothers, and either maintained on the control diet, maintained on the protein-deprived diet, or changed from the protein-deprived diet to a normal diet (refed group). These rats were examined after a further 21 days. Refeeding restored body weight to 20% below control, restored colon size, and restored nerve cell size. After a total of 42 days of protein deprivation, nerve cell numbers were not significantly different from control. In undernourished rats at 21 and 42 days, neurons were less well stained than control for NADH diaphorase. Refeeding between 21 and 42 days restored the normal appearance of the neurons. It is concluded that enteric neurons are protected from loss even when there is a substantial reduction in body weight and organ size caused by protein deprivation. The neurons become smaller, but recover size after refeeding.

Animals↗

Changes in resting energy expenditure and body composition in anorexia nervosa patients during refeeding.

Accurate prediction of the energy level necessary to promote weight restoration in patients with anorexia nervosa would be clinically useful. Resting energy expenditure (REE), respiratory quotient, and body composition were measured in 10 nonmedicated women with anorexia nervosa during a vigorous refeeding protocol. REE was measured three times per week by open-circuit indirect calorimetry after an overnight fast. Subjects ranged in age from 19 to 38 years and weighed 39.9 +/- 4.3 kg (mean +/- standard deviation) at admission. The refeeding protocol was as follows: phase 1, 1,200 kcal/day for 1 week (baseline); phase 2, an increase of 300 kcal/day for 1 week; phase 3, 3,600 kcal/day until target weight was reached; phase 4, 1,800 to 2,800 kcal/day (stabilization). REE was 30.0 +/- 6.4, 33.5 +/- 6.7, 37.3 +/- 6.6 and 34.5 +/- 4.4 kcal/kg body weight during phases 1, 2, 3, and 4, respectively. The Harris-Benedict equation overestimated phase 1 24-hour REE by a mean of 14% and underestimated REE in phases 2, 3, and 4 by a mean of 8%, 24%, and 23%, respectively. Skinfold measurements revealed percent body fat to be 12 +/- 4% at admission and 19 +/- 5% at discharge, with a mean of 48% of the weight gained during refeeding attributable to increased body fat. These findings indicate that refeeding in anorexia nervosa is associated with increased REE, which cannot be explained by increased body mass, and that caloric requirements for weight restoration in patients with anorexia nervosa are best determined by monitoring individual response.

Adipose Tissue↗

Hexose transport after glucose refeeding of glucose-starved human fibroblasts: 1. The effects of tunicamycin and cycloheximide. 2. Insulin binding and action.

Hexose transport in glucose-starved human fibroblasts was readily reversed by glucose refeeding. This hexose transport reversal was not inhibited by tunicamycin (1.5 microgram/ml) but was blocked by cycloheximide (20 micrograms/ml). The ability of insulin (100 mU/ml) to stimulate hexose transport was returned by glucose refeeding and this was not affected by tunicamycin. Cycloheximide which blocked the glucose refeeding effect on hexose transport, decreased the ability of insulin to stimulate hexose transport. Specific 125I-insulin binding was increased by glucose refeeding of glucose-starved cells and this change in binding was inhibited by tunicamycin and cycloheximide. Thus, it appears that under the conditions employed in human fibroblasts, the ability of insulin to stimulate hexose transport is differentially regulated more by factors affecting basal hexose transport than by those affecting changes in insulin binding.

Biological Transport↗

The increases in the rates of synthesis of ribosomal proteins and ribosomal RNA during refeeding of starved Tetrahymena cells are not dependent on DNA replication.

We have analysed the effects of an inhibition of DNA replication by hydroxyurea on the synthesis of ribosomal proteins (r-proteins) and ribosomal RNA (rRNA) in Tetrahymena cells resuming growth after long-term starvation. The coordinate regulation of the synthesis of individual r-proteins and their increased rate of synthesis during refeeding are not impaired by inhibition of DNA replication. Moreover, the presence of hydroxyurea does not prevent an increase in the rate of synthesis of rRNA around 70-80 min after refeeding. Previously, this increase was claimed to be gene dose-dependent. Up to 180 min after refeeding, the synthesis of r-proteins appears to be closely coupled with that of rRNA and proceed in stoichiometric balance, irrespective of whether hydroxyurea is present or not. After 180 min of refeeding in the presence of hydroxyurea, this stoichiometric balance breaks down, and the rate of synthesis of r-proteins clearly exceeds that of the rRNA synthesis.

Animals↗

Protein synthesis in skeletal muscle of rats following starvation and refeeding.

Determination of protein synthesis in individual tissues is important to understand the changes in protein metabolism during catabolic states. Three methods based on different underlying assumptions were compared in assessing muscle protein synthesis during nutritional manipulation. Rats were nonstarved, starved for 1 or 3 days, or refed for 2 days after 3 days of starvation. The extensor digitorum longus (EDL) muscles from the two hindlegs were used for analysis. In one EDL muscle the concentration and size distribution of ribosomes as well as the incorporation of [14C]leucine into protein in a cell-free system were determined. The other EDL muscle was incubated as such and the incorporation of [14C]phenylalanine into protein was measured. The total ribosome concentration per milligram of DNA decreased to 65% on the third day of starvation and remained low after refeeding. The amount of polyribosomes in the percentage of total ribosomes fell to 90% on the first day of starvation, regained the initial level on the third day, and reached 110% upon refeeding. During refeeding amino acid incorporation into protein in a cell-free system decreased to 40% and that in intact muscle to 64% of the prestarvation level. Upon refeeding, the activity increased to or above the original values. The use of several different techniques in parallel to assess protein synthesis in skeletal muscle is recommended since it gives information about the factors involved in regulation of the translational process in intact mammalian tissues.

Animals↗

Refeeding after the late increase in nitrogen excretion during prolonged fasting in the rat.

Recovery of body mass, food intake and body composition was studied in the laboratory rat after the late increase in nitrogen excretion that characterizes prolonged fasting in mammals and birds. The rats lost 43% of their body mass during 13 days of food deprivation. They all regained their prefasting body mass within a shorter period of 11 days of refeeding. These results confirm that the late increase in nitrogen excretion in rats, as in spontaneously fasting birds, is reversible and is a part of the physiological adaptations to long-term food deprivation. Water intake of the rats continuously decreased during fasting, and the animals virtually stopped drinking as protein utilization increased. On refeeding, changes in water intake paralleled those in food intake. The refed rats progressively increased their daily food intake, that was always higher than the prefasting value (8.0-10.4 vs. 6.7% of body mass). The comparison of organ weights between fed and ad lib refed rats of similar body weight indicates that muscle mass was regained earlier than body fat during refeeding. The laboratory rat therefore appears to be a good experimental model to investigate the metabolic and behavioural changes that occur during spontaneous anorexia and refeeding in wild animals.

Animals↗

Ornithine decarboxylase activity in mouse tumour tissue in response to refeeding and diet components.

Ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase activity (SAMD) were measured in tumour tissue in mice during periods of starvation (24 h) and refeeding. Starvation led to a 60% reduction in tumour ODC activity. Refeeding normalised the activity within 4 h. Restitution in ODC activity, representing de novo enzyme synthesis, preceded DNA resynthesis. SAMD activity continued to fall along the increase in ODC activity during refeeding, while difluoro-methyl-ornithine (DFMO) caused a compensatory increase in SAMD activity as expected. A fall and regain in ODC activity was associated with inhibition and regrowth of the tumour. Starvation-refeeding was not related to any decrease in tumour polyamine concentrations, while systemic DFMO blockade was. Glucose stimulated ODC when refed orally, but not when given systemically. Tumour ODC activity was not decreased in refed mice by anti-insulin, a procedure that antagonised insulin's bioactivity. Exogenous insulin did not stimulate tumour ODC activity. Our results suggest that gastrointestinal metabolism of carbohydrates stimulates the release of a factor, which initiates both ODC activity and DNA synthesis in tumour cells. This factor was not insulin.

Adenosylmethionine Decarboxylase↗

The effects of starvation and refeeding on egg laying and the synthetic activity of the albumen gland in Bulinus truncatus, a snail vector of urinary schistosomiasis.

1. The effects of starvation (for 1, 2, 3, 6, 9 and 12 days, respectively) and refeeding (12 days starvation and 1, 2 and 3 days refeeding, respectively) on egg laying and albumen gland activity in the freshwater snail, Bulinus truncatus were studied. 2. The egg laying of starving snails rapidly decreased and ceased by day 6 of starvation. Egg laying was restored 24 hr after refeeding. The recorded decrease in albumen gland wet weight was proportional to the starvation periods. The DNA contents of the glands of the different experimental groups was not statistically different from the controls. 3. Albumen gland synthetic activity expressed as 14C-glucose incorporation into galactogen/microgram DNA and 3H-amino acids into total protein was determined. The glands showed an abrupt decrease in synthetic activity after 1 day of starvation and gradually decreased further until days 9-12. The decrease in activity of the glands was more rapid than that of egg laying. Upon refeeding, the activity of the glands recovered rapidly, simultaneous with the increase in wet weight and egg laying. 4. In conclusion, there is a correlation between egg laying and the in vitro activity of albumen glands. The results show a short-term effect of starvation on the fecundity of the snails. Such studies could be useful in field studies as well as snail control by applying molluscicides under optimal conditions.

Animals↗

Fasting and refeeding affect the expression of the Inhibitor of DNA Binding (ID) genes in rainbow trout (Oncorhynchus mykiss) muscle.

The Inhibitor of DNA Binding/Differentiation (ID) proteins are a family of dominant negative regulators of the basic helix-loop-helix (bHLH) transcription factors, shown in mammals to delay cell differentiation and prolong proliferation. In the current study we used real-time PCR to investigate the effects of fasting and refeeding on the expression of ID genes in rainbow trout muscle. Fry shortly following yolk-sac absorption (approximately 250 mg) were used in a pair of experiments. In the first experiment, the treatment groups included fish fed or fasted throughout the duration of the experiment, and fish fasted for 14 days followed by feeding for the remainder of the experiment. The second experiment consisted of the same treatment groups; however the fish were only fasted for 7 days prior to refeeding. In both experiments, ID gene expression in the muscle of fasted fish was significantly lower than the fed samples after 7 days. Refeeding for 3 or 7 days returned the ID expression to levels similar to the fed fish. The reduction of ID expression during a fast and the subsequent return to fed levels with refeeding suggests the ID proteins participate in the regulation of muscle growth in the rainbow trout.

Animals↗

Changes in heart rate with refeeding in anorexia nervosa: a pilot study.

OBJECTIVE: To find differences in heart rate before and after refeeding and to identify which parameters of autonomic activity and endocrine function are associated with these differences. METHODS: Before and after the start of refeeding, body weight, RR interval (RRI), heart rate variability, endocrine function, and energy expenditure were measured in nine female anorexia nervosa patients. RESULTS: After short-term refeeding, mean daytime heart rate rose from 54.9 to 69.4 bpm (P<.05). The changes in sympathetic activity were correlated negatively with the changes in RRI (r=-.933, P<.001). Urine C-peptide, IGF-1, and fT3 increased significantly, and norepinephrine tended to increase. CONCLUSION: We demonstrated that autonomic nervous activity was relevant to changes in heart rate during refeeding, and it is speculated that the increases in insulin secretion, thyroid function, and IGF-1 were responsible for the mechanisms.

Adolescent↗

Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa.

Normal or high levels of cholesterol have been measured in patients with anorexia nervosa (AN). Given that cholesterol intake in AN is usually very low, the reasons for this anomaly are not clearly understood. We studied lipid and lipoprotein profiles and endogenous cholesterol synthesis, estimated by serum lathosterol, in a population of 14 girls with AN, before and during a period of 30 days refeeding. The initial body mass index (BMI) of the patients was 13.41+/-1.62 kg/m(2). No changes were observed during refeeding in endocrine parameters (ACTH, cortisol and estradiol). At Day 0 the lipids data measured here showed normal levels of triglycerides, and total cholesterol at the upper limits of the normal range (5.44+/-1 mmol/l). At this time, total and LDL cholesterol were negatively correlated with transthyretin and BMI. Serum lathosterol (a precursor in cholesterol synthesis pathway) increased significantly (5.99+/-1.75 (Day 0) vs. 8.39+/-2.96 (Day 30); P=0.02) while there was a significant decrease in apo B (0.79+/-0.33 (Day 0) vs. 0. 60+/-0.17 g/l (Day 30), P=0.02) with refeeding. Thus, patients with initial high cholesterol levels have the worst nutritional status and high cholesterol levels are not related to a de novo synthesis. This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for this apparently paradoxical evolution with increase of cholesterol synthesis and decrease of apo B during renutrition.

Adolescent↗

Changes in body composition during refeeding of patients with anorexia nervosa.

Changes in body composition were studied in 13 girls with anorexia nervosa before and during 2 months of refeeding. Fat body mass and fat-free body mass were derived from skin-fold measurements. Total body potassium was measured by whole body counter, and intracellular water was calculated from it. Extracellular water was measured as the bromide space after oral bromide administration. A gradual increase was noted in weight, fat body mass, fat-free body mass, and total body potassium during refeeding. Extracellular water was expanded on admission and increased in all patients in the first weeks of treatment; later it fell to normal. Most of the changes in fat-free body mass over the first weeks of refeeding could be accounted for by an expansion in extracellular water. Particular care must therefore be taken with fluid balance during the first few weeks of refeeding.

Adipose Tissue↗

Alterations in the enzyme activity and protein contents of protein disulfide isomerase in rat tissues during fasting and refeeding.

Protein disulfide isomerase (PDI) is an enzyme that participates in the formation of disulfide bonds. It is also known to be the subunits of some enzymes and the membrane-associated thyroid hormone-binding protein. In this study, we measured the quantitative distribution of PDI protein in rat tissues and examined the relationship between protein level and enzyme activity in PDI during fasting and refeeding. Western blotting with specific anti-PDI antiserum detected the PDI protein band of 55 kd. Among several tissues, liver contained the largest amount of PDI protein, followed by kidney and fat, in which one-third to one-fourth of the hepatic PDI protein existed. The PDI protein band was also detected in heart and muscle. Fasting for 3 days decreased PDI protein levels in rat liver by 40%; control levels were recovered after 3 days of refeeding. The same change was observed in kidney. PDI activity, measured by the scrambled ribonuclease method, did not show the parallel alteration to PDI protein level in liver and kidney. Isomerase activity decreased to 50% of control values during fasting, but did not recover by refeeding. Thyroidal status did not affect either PDI protein level or isomerase activity. These findings show that fasting and refeeding affect PDI protein and enzyme activity, and that PDI protein level does not always reflect PDI activity.

Animals↗

Protein depletion and refeeding change the proportion of mouse liver glutathione S-transferase subunits.

The effect of protein depletion followed by refeeding with a normal diet on the content of mouse liver cytosolic proteins was studied. By peptide-mass fingerprinting and N-terminal sequencing, three polypeptides whose contents changed with dietary protein level were identified as glutathione S-transferases (GST) Yb1, Yc and Yf subunits. Five days of depletion caused the increase of Yb1 and Yf (21.6% and 78.5%, respectively) and the decrease of Yc (31.2%). After two days of refeeding, Yb1 and Yc were practically restored, while the neoplastic marker Yf remained higher (63.4%). None of the nutritional conditions tested induced new GSTs. While protein depletion-refeeding altered the ratios between the constitutive GST subunits, total liver GST content and activity were unaffected by depletion and slightly increased by refeeding. The increased amounts of Yb1 and Yf, and the maintenance of total GST content, indicate that during protein depletion, the GST subunits levels are controlled by mechanisms different from the majority of cytosolic proteins.

Amino Acid Sequence↗

Changes in thyroid hormone levels in chicken liver during fasting and refeeding.

In chickens, fasting results in increased plasma thyroxine (T(4)) levels and decreased plasma 3,5,3'-triiodothyronine (T(3)) levels. Refeeding, in turn, restores normal plasma T(3) and T(4) levels. The liver is an important tissue for the regulation of circulating thyroid hormone levels. Previous studies demonstrated that the increase in hepatic type III deiodinase in fasted chickens plays a role in the decrease of plasma T(3). Another factor that could be important is the level of T(4) and T(3) uptake by the liver. In mammals, caloric restriction is known to diminish transport of T(4) and T(3) into tissues. The present study examines whether this is also the case in chicken. Four-week-old chickens were subjected to a 24-h starvation period followed by refeeding. Blood and liver samples were collected at the start of refeeding and at different times of refeeding. Thyroid hormone levels were measured directly in plasma and in tissues following extraction. The results demonstrate that intrahepatic T(4) levels are increased and T(3) levels are decreased in fasted compared to ad libitum fed chickens. The parallel changes in plasma and hepatic T(3) and T(4) content demonstrate that T(4) availability in liver tissue is not diminished during fasting, suggesting that in chicken thyroid hormone uptake by the liver is not affected by nutritional status.

Animals↗

Lipogenesis in rat tissues following carbohydrate refeeding: spleen lipogenesis is modulated by insulin.

Intraperitoneal administration of [1,2-14C]-acetate to Wistar rats was used to assess tissue lipogenic rates after estimating the incorporation of the label into the tissular lipid fractions. Refeeding the animals with glucose (after an overnight fast) induced an increase in white adipose tissue (4.5 fold), liver (4.1 fold), small intestine (1.9 fold), carcass (2.9 fold) and spleen (3.7 fold) lipogenesis (expressed as the radioactivity present in the lipid fraction corrected by the plasma circulating radioactivity). No changes were found following refeeding in either brain or brown adipose tissue. Administration of mannoheptulose (an inhibitor of insulin secretion) to refed rats completely abolished the increased lipogenesis in white adipose tissue, liver, carcass, spleen and small intestine, thus suggesting that insulin secretion is involved in this phenomenon. This is the first report showing that spleen lipogenesis may be modulated by refeeding via insulin secretion and suggests an important role of this organ on the in vivo lipogenic response of the organism after carbohydrate refeeding.

Acetates↗