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PubMed1992

The effects of fasting and refeeding on liver glycogen synthase and phosphorylase in obese and lean mice.

The responses of hepatic glycogen synthase and phosphorylase to fasting and refeeding were assessed as part of an investigation into possible sites of insulin resistance in gold thioglucose (GTG) obese mice. The active forms glycogen synthase and phosphorylase (synthase I and phosphorylase a) and the total activity of these enzymes were estimated in lean and GTG mice over 48 h of food deprivation, and for 120 min after glucose gavage (1 g/kg wt). In lean mice there was a maximal reduction in hepatic glycogen content after 12 h of starvation and the activity of phosphorylase a decreased from 23.8 +/- 1.9 to 6.8 +/- 0.7 mumol/g protein/min. These changes were accompanied by an increase in the activity of synthase I (from 0.14 +/- 0.01 to 0.46 +/- 0.04 mumol/g protein/min). In obese mice, similar changes in enzyme activity occurred after 48 h of starvation. These changes were accompanied by a significant reduction in the hyperinsulinemia and hyperglycemia of the GTG mice. After glucose gavage in both lean and obese mice, the activity of synthase I further increased over the first 30 min and declined thereafter. The activity of phosphorylase a increased progressively after refeeding. Results from this study suggest that despite increased hepatic glycogen deposition, the responses of glycogen synthase and phosphorylase, in livers of obese mice, to fasting and refeeding are similar to those of control mice even in the presence of insulin resistance.

Animals↗

PubMed1987

Calcitonin and hepatic fatty acid synthesis: effect of thyroparathyroidectomy on the elevation of ATP citrate lyase activity by refeeding of starved rats.

The effect of thyroparathyroidectomy (TPTX) on ATP citrate lyase regulation, a rate-limiting enzyme of fatty acid synthesis in hepatic cytosol, was investigated in rats refed after a 24 h fast. ATP citrate lyase activity in the hepatic cytosol was increased 2-fold by refeeding. This increase was suppressed about 50% by TPTX. The suppression of the enzyme activity by TPTX was completely restored by administration of calcitonin (CT; 80 MRC mU/100 g body weight). This hormonal effect was also observed at 20 MRC mU/100 g dose of CT. CT administration to refeeding-TPTX rats produced a significant increase in the calcium content of the liver tissue and the cytosol. The cytosolic ATP citrate lyase activity increase with CT administration was completely blocked by treatment of cytosol with EGTA (10 microM). This inhibition was clearly reversed by addition of calcium ion (1.25-5.0 microM). In addition, CT-induced rise in enzyme activity was markedly reduced by the presence of W-7 (5 and 50 microM), a calmodulin inhibitor, in the enzyme assay system. The present results suggest that CT plays a role in the elevation of hepatic ATP citrate lyase activity brought about by refeeding of fasted rats, and that this hormonal regulation might depend on Ca2+-calmodulin.

ATP Citrate (pro-S)-Lyase↗

PubMed2005

The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition.

The liver plays a central role in the control of blood glucose homeostasis by maintaining a balance between glucose production and utilization. The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor. Hepatic FXR expression is regulated by glucose and insulin. Here we identify a role for FXR in the control of hepatic carbohydrate metabolism. When submitted to a controlled fasting-refeeding schedule, FXR(-/-) mice displayed an accelerated response to high carbohydrate refeeding with an accelerated induction of glycolytic and lipogenic genes and a more pronounced repression of gluconeogenic genes. Plasma insulin and glucose levels were lower in FXR(-/-) mice upon refeeding the high-carbohydrate diet. These alterations were paralleled by decreased hepatic glycogen content. Hepatic insulin sensitivity was unchanged in FXR(-/-) mice. Treatment of isolated primary hepatocytes with a synthetic FXR agonist attenuated glucose-induced mRNA expression as well as promoter activity of L-type pyruvate kinase, acetyl-CoA carboxylase 1, and Spot14. Moreover, activated FXR interfered negatively with the carbohydrate response elements regions. These results identify a novel role for FXR as a modulator of hepatic carbohydrate metabolism.

Animals↗

PubMed1991

Effect of refeeding diets containing cottonseed flour with traces of gossypol on rat liver and testis.

The aim of the present work was to show that cottonseed flour introduced into rehabilitation diets is not nutritionally harmful. The cottonseed flour obtained from glandless seeds contains traces of gossypol. As gossypol is known to have pathological hepatic and testicular actions, the effects on hepatic variables and on the histological appearance of liver and testis of diets containing cottonseed flour were compared with those without cottonseed flour. Seventy growing male Wistar rats were divided into two groups. The control group (C) received a balanced diet (200 g casein + 3 g methionine/kg) for 78 d and the experimental group was fed on a low-protein diet (20 g casein + 3 g methionine/kg) for 29 d. After the period of protein deprivation, the depleted rats were divided into four groups and each group was refed with a different diet, for 49 d: a balanced diet (200 g casein + 3 g methionine/kg; rC), maize-soya-bean flour-milk (60:30:5, by wt; MSM), maize-cottonseed flour-milk (60:30:5, by wt; MCM) or rice-cottonseed flour-milk (60:30:5, by wt; RCM). Each diet was supplemented with a vitamin mixture (10 g/kg) and a salt mixture (40 g/kg). In the liver, protein, total lipid, fatty acid composition and nucleic acid contents were determined after 29 d of protein deprivation and after 2, 14, 29, 49 d of refeeding. The refeeding of rats with either diet MSM or RCM promoted a higher growth than that with diet MCM or diet rC. In all groups, a progressive decrease in relative liver weights with age was observed. The highest values were obtained with diets rC and MSM. After 49 d of refeeding, the lowest values for lipid, DNA and protein:RNA and the highest values for RNA and RNA:DNA were obtained with the cottonseed diets (MCM and RCM). Rats fed on the cottonseed-flour diets for a 49 d period after severe protein malnutrition showed no change in size or shape of their hepatocytes compared with those obtained with the control casein diet, and all stages of spermatogenesis occurred normally and spermatozoa were accurately formed. Therefore, our findings show that a low level of gossypol administrated during 49 d, even to an organism weakened by protein malnutrition, does not affect hepatic variables and the histological appearance of liver and testis.

Animal Feed↗

PubMed1996

Effects of fasting and refeeding on structures of the intestinal villi and epithelial cells in White Leghorn hens.

1. The fine structural alterations of villi and epithelial cells in each part of the small intestine were investigated in layer-type hens fasted for 12 h to 20 d or refed for one day after each fasting period. 2. Within the first 24-h-fasting, villi of the duodenum showed a remarkable reduction in height and those of the jejunum revealed a gradual decrease; such a significant reduction of the villus height was not obtained in the ileum. After 36-h-fasting, villus height in each part gradually decreased with days of fasting. 3. All intestinal villus heights increased after only 1-d-refeeding of various kinds of diets following 3-, 10-, or 20-d-fasting. The duodenum especially rapidly recovered even after long-term fasting of 20 d but the ileum showed very slow recovery, suggesting that the ileum seems to be inactive in absorptive function. 4. These variable alterations of villus height in the proximal intestine suggest that the higher intestinal absorptive ability is under the normal feeding, the more rapidly villus height is influenced by nutritional conditions. 5. Cell area and cell mitosis decreased after fasting, the latter showing a marked reduction. However, in spite of a remarkable decrease of cell mitosis in the proximal intestine after fasting, refeeding activated cell renewal and it soon reached control levels, demonstrating that the villus height mainly varied with the numbers of epithelial cells. 6. In the epithelial cells of the proximal intestine in chickens fasted for 20 d, large lysosomal autophagous vacuoles including mitochondria and dense bodies were observed. These were reduced in size by refeeding for only one day, suggesting that fasting may cause intracellular digestion through lysosomal autophagy. 7. These results lead to the conclusion that long-term for force moulting is possible, that a high protein and high energy diet can be fed immediately after fasting and that a cell undergoing lysosomal autophagy in normal chickens indicates undernutrition.

Animals↗

PubMed2004

Effects of fasting and refeeding on jejunal morphology and cellular activity in rats in relation to depletion of body stores.

BACKGROUND: Intestinal mucosa atrophy following a period of starvation characterized by the mobilization of fat stores for energy expenditure (phase II) worsen after a long fast marked by an increase in protein catabolism (phase III). However, the morphology of the jejunum is completely restored after 3 days of refeeding. The aim of this study was to determine the mechanisms involved in the rapid jejunal restoration following the critical phase III. METHODS: Jejunal structure was observed through conventional and environmental scanning electron microscopy, whilst cellular dynamics were studied using classical optic microscopy tools and immunohistochemistry. RESULTS: Mucosal structural atrophy during fasting proved to worsen over the two phases. During phase II, apoptosis is still present at the tip of the villi, the number of mitosis in crypts showed a 30% decrease and a transient drop in cell migration is observed. During phase III, however, an 85% rise in mitosis was noticed along with an increase in cell migration and the disappearance of apoptotic cells at the villus tips. This increased cell renewal continues after food ingestion. CONCLUSIONS: Starved rats appeared to be in a phase of energy sparing in phase II, with depressed cellular events in the intestinal mucosa. In phase III, however, the preservation of functional cells and the early increase in crypt cell proliferation should prepare the mucosa to refeeding and could explain why jejunal repairs are complete after 3 days of refeeding following either phase II or phase III.

Animals↗

PubMed2006

Severe refeeding hypophosphatemia in a CAPD patient: a case report.

Refeeding syndrome is defined as severe electrolyte and fluid shifts associated with metabolic abnormalities in malnourished, refeeding patients. Hypophosphatemia is its predominant concern, though its occurrence is unusual in uremic patients due to the concomitant hyperphosphatemia. This case study reports a 56-year-old woman on continuous ambulatory peritoneal dialysis (CAPD) therapy who was admitted for peritonitis. Ileus and diarrhea developed during admission; enteral feeding was given initially and then shifted to total parenteral nutrition (TPN) because of poor digestion. A lower concentration of phosphate was administered in the TPN formula initially due to high initial serum phosphate level. However, severe hypophosphatemia (0.3 mg/dL) developed on the second day after TPN supplementation. Continuous intravenous phosphate (total 6 mmol of phosphate) was supplied immediately. Unfortunately, the sudden onset of conscious loss and cardiac arrest happened on the third day of TPN. It should be emphasized that severe refeeding hypophosphatemia can also develop early in uremic patients with hyperphosphatemia.

Enteral Nutrition↗

PubMedDate not supplied

Basal metabolic rate in anorexia nervosa patients: using appropriate predictive equations during the refeeding process.

BACKGROUND: The refeeding process is a particularly dangerous time for some anorexia nervosa (AN) patients. Great physiologicatress can occur from imposing a large caloric intake on a body dealing with the effects of long-term starvation. Accurate predictive equations of basal metabolic rate (BMR) are needed to ensure AN patients gain weight at a safe rate. METHODS: Patients with AN undergoing strictly controlled nutritional rehabilitation on an inpatient unit were examined for changes in BMR via indirect calorimetry. Seven female patients were assessed shortly after inpatient admission. Follow-up measures of weight and BMR were obtained after three weeks of refeeding treatment comprised of approximately 3500 kcal/day. RESULTS: Body mass index (BMI) increased in all subjects from a median 13.7 kg/m2 at baseline to 15.2 kg/m2. BMR also increased from a median of 1000 kcal/day to 1220 kcal/day. The Owens and Mifflin equations were moderately accurate (within 10%) of predicted BMR at baseline and 3-week follow-up, and the Harris-Benedict equation was very accurate (within 2%) at 3-week follow-up only. CONCLUSIONS: These results may guide nutritional therapies for AN by demonstrating the suppression of metabolism induced by calorie restriction as well as its relatively prompt rebound to expected values with weight gain. Derivation of accurate predictive equations for use during the early refeeding period is needed.

Adult↗

PubMed1977

Effect of repeated food restriction-refeeding on growth rate and weight.

The effect of repeated food restriction-refeeding was investigated in male Wistar rats. After the first food restriction, rats grew faster than did ad libitum-fed animals. The extent of compensatory growth was less with each subsequent restriction-release episode. Food intake determinations gave similar results: the extent of overeating decreased with each successive restriction. Studies on the effects of the first restriction-refeeding at various sizes (ages) indicate that a considerable portion of the decrease in compensatory growth with increasing number of food restriction-refeeding is due to increasing size (age). However, some of the decreased response can be directly attributed to the repetition of food restriction.

Adaptation, Physiological↗

PubMed1982

Refeeding after fasting in the rat: effects on body composition and food efficiency.

Adult male Sprague-Dawley rats were fasted for 65 h and then refed ad libitum for 8 days, during which time body weight and body composition returned to the levels of nonfasting controls. During refeeding, after a decrease on the lst day, daily food intake was moderately increased above control levels. This compensatory increase after the fast brought the total consumption for the whole period to the same level as for the controls. Thus, a greater body weight increase per gram food consumed ("food efficiency") was achieved during the refeeding period. Starvation-induced energy conservation processes thus seemed to persist during refeeding. This mechanism(s) might participate in causing weight gain after reduction as a treatment for obesity.

Adipose Tissue↗

PubMed1990

Adaptive changes in energy expenditure during refeeding following low-calorie intake: evidence for a specific metabolic component favoring fat storage.

Studies in this report investigate the existence and quantitative contribution of a metabolic component to an apparently elevated efficiency of energy utilization during refeeding following low-calorie consumption. Energy balance during a 25-d refeeding period was assessed in rats that had been food restricted (at 50% of normal intake) for either 30 or 10 d. Relative to weight-matched controls (with comparable lean tissue mass and similar food intake), refeeding following both periods of low food consumption (30 or 10 d) was associated with a 10% reduction in energy expenditure (p less than 0.001). Analysis of body composition revealed that virtually all the energy saved as a result of this metabolic (as opposed to tissue mass) adaptation was deposited as fat rather than protein. After the energy cost for depositing the extra fat is accounted for, the metabolic component represents a net 15% lower energy expenditure when normal food intake is resumed. These adaptive changes in energy expenditure may thus constitute an important mechanism for the rapid replenishment of energy stores in preparation for recurring food shortages and may also underlie the ease with which the obese condition is rapidly reachieved after weight loss.

Adaptation, Biological↗

PubMed1991

Intracellular potassium and membrane potential in rat muscles during malnutrition and subsequent refeeding.

Nutrition alters total body potassium (TBK) and muscle potassium but little is known about in vivo intracellular K+. We measured free intracellular potassium-ion activity (aKi+), membrane potential (Em), and total potassium (Kt) and calculated intracellular potassium concentration [K+]i in predominantly slow- (soleus) and fast- (extensor digitorum longus) twitch muscles in rats undergoing underfeeding and subsequent refeeding. After underfeeding, aKi+ and Em decreased (P less than 0.025 and P less than 0.006, respectively) only in soleus muscle with restoration after refeeding, whereas [K+]i decreased in both muscles (P less than 0.005) and remained low after refeeding. K+ supplementation did not significantly change these indices or the ratio of free to total intracellular potassium (gamma Ki+). The data show that aKi+ behaves differently from [K+]i during malnutrition and that changes in aKi+ occur especially in slow-twitch fibers, suggesting that previously observed changes in TBK and muscle function are the result of fundamental alterations in muscle-cell energetics and membrane functions, not just mass.

Animals↗

PubMed1997

Effect of hypoenergetic feeding and high-carbohydrate refeeding on muscle tetanic tension, relaxation rate, and fatigue in slow- and fast-twitch muscles in rats.

Studies using nuclear magnetic resonance have shown that undernutrition affects muscle performance and energetics. It is unclear to what extent underfeeding and refeeding influence the availability of muscle glycogen, net glycogenolysis, skeletal muscle wasting, and recovery. We hypothesized that muscle performance is independent of muscle size and weight, is specific to muscle type, and is unrelated to muscle glycogen concentrations. Slow- and fast-twitch muscles were studied in three groups of adult male Wistar rats: well-fed controls, hypoenergetically fed (Hypo) rats, and rats refed for 4 d after the hypoenergetic diet. Glycogen concentrations and net glycogenolysis; serum glucose, insulin, and protein concentrations; and muscle weight, protein, and cross-sectional area were studied relative to the performance of both types of muscles. Our study controlled for muscle size, weight, and type and electrolyte-micronutrient deficiency. Undernutrition affected muscle performance in five ways. First, compared with controls, fatigue increased only in the soleus muscles of Hypo rats yet the maximal relaxation rate (MRR) decreased in both the soleus and extensor digitorum longus (EDL) muscles. Second, muscle glycogen concentrations did not significantly correlate with fatigue in either the soleus or the EDL although net glycogenolysis was significantly correlated with fatigue in the soleus (r = -0.64; P > 0.01 < 0.05). Third, lower glycogen concentrations did not hinder net glycogenolysis in the EDL of Hypo rats or the soleus of refed rats. Fourth, muscle weight, size, and protein were dissociated from function. Fifth, refeeding did not restore muscle endurance; however, the MRR of the soleus normalized. In conclusion, glycogen values and muscle performance did not correlate but net glycogenolysis correlated with fatigue in the soleus. Also, there was a dissociation between muscle weight, size, and protein and muscle function during hypoenergetic feeding and refeeding.

Animals↗

PubMed1978

Starvation and refeeding in rats: effect on organismic respiration, cytoplasmic constituents of liver, and succinic dehydrogenase activity in liver, kidney, and heart.

An analysis of starvation and starvation followed by refeeding was undertaken to characterize some organismic, organ, and mitochondrial responses to these two circumstances. Body weight, organismic respiration as well as weight protein and succinic dehydrogenase activity for liver, kidney, and heart were determined over the course of 6 days of starvation and 5 days refeeding for adult male rats. Assays of marker enzyme activities for mitochondria (cytochrome oxidase), lysosomes (acid phosphatase), endoplasmic reticulum (glucose-6-phosphatase), and plasma membranes (5'-nucleotidase) were conducted for liver in addition to quantitations of mitochondrial protein. All enzyme determinations were done on whole tissue homogenates and reported as total organ activity. Liver mitochondria were harvested quantitatively directly from whole liver homogenates by zonal centrifugation for determination of mitochondrial protein. Starvation resulted in a major loss of body weight, organ weight, and organ protein; liver greater than kidney greater than heart. These changes were accompanied by a major reduction in organ succinic dehydrogenase activity; liver greater than kidney. In heart, succinic dehydrogenase was doubled in activity at day 2 of starvation and subsequently diminished to values not significantly lower than controls. In liver, mitochondrial mass (protein) was severely diminished. From analysis of marker enzyme activities, it appeared that lysosomes, endoplasmic reticulum, and plasma membrane were also decreased. Refeeding restored the greatest part of these losses within 5 days.

Animals↗

PubMed1978

Age-related changes in ribosomal profiles and in vitro protein synthesis in skeletal muscle during fasting and subsequent refeeding of rats.

Age-dependent changes in ribosomal profiles and in in vitro protein synthesis in skeletal muscle (gastrocnemius muscle) were studied in rats subjected to fasting and subsequent refeeding. Male rats of 4, 7, and 21 weeks of age were used. Incorporation of 14C-leucine into protein in vitro using skeletal muscle ribosomes from fed rats decreased with the age of the animals. Sucrose density gradient analyses of ribosomal profiles revealed that the changes in protein synthesis were accompanied by progressive declines in the concentrations of polyribosomes and total RNA in skeletal muscle. After fasting for 1 or 2 days, protein synthesis in muscle of young rats dropped markedly and this change could be attributed to the fall in the concentrations of polyribosomes. Also, the concentration and total RNA in the muscles of the young rats decreased. During refeeding of rats after fasting for 2 days, the incorporation of 14C-amino acids into protein recovered more efficiently using ribosomes of skeletal muscle of young animals compared with using those of older animals. This rapid increase in the protein synthesizing activity of skeletal muscle may be related to the efficient recovery of the ribosomes toward heavier aggregates. The results indicate that young animals adapt more efficiently to fasting and refeeding than do older animals.

Aging↗

PubMed1981

Tissue glutathione as a cyst(e)ine reservoir during fasting and refeeding of rats.

Previous reports suggest that liver glutathione serves as a cyst(e)ine reservoir in both starved rats and rats fed a cyst(e)ine-deficient diet. We investigated whether glutathione concentrations in other tissues also decrease and whether component amino acids of glutathione increase under such conditions. Tissue glutathione and free amino acid concentrations were measured in six groups of growing rats (120-150 g; four animals/group) during fasting and refeeding regimens. All animals were fed a rat stock diet ad libitum for 5 days. Two groups were than fasted for 24 or 48 hours, respectively. Other groups were fasted for 48 hours and then refed for 10, 24 or 48 hours respectively the stock diet. Significant changes (P less than or equal to 0.05) in liver and intestine glutathione concentrations were noted with 24 and 48-hour fasting, and a 24-hour refeeding was necessary to return concentrations to prefasting values. Muscle glutathione concentrations decreased slightly with fasting, but remained low with refeeding. Erythrocyte glutathione concentrations were independent of dietary treatment. Liver cysteine and glycine concentrations increased after 24 hours' fasting, but glutamate levels were not affected. The data indicate that liver and intestine glutathione serve as cyst(e)ine reservoirs during fasting. Since erythrocyte and muscle glutathione levels did not decrease, levels in these tissues cannot be used to measure cyst(e)ine status in premature infants fed parenterally.

Animals↗

PubMed1983

The influence of starvation and refeeding on the lipoprotein lipase activity of skeletal muscle and adipose tissue of lean and obese Zucker rats.

Lipoprotein lipase (LPL) activities of skeletal muscles, heart and adipose tissue were investigated during feeding, prolonged food restriction, and refeeding. The influence of the duration of starvation on adipose tissue LPL activity was to cause it to decrease throughout starvation, whereas heart LPL activity increased during the first 24 hours of fasting and then declined for the remainder of the fast. Starvation of 10-week-old female, lean and obese rats to 80% of initial body weight required 5 and 9 days, respectively. In fed controls, no differences between phenotypes were found for any tissue in the LPL activities expressed per gram tissue. However, obese rats exhibited significantly smaller muscle mass and a resulting 29% lower total skeletal muscle LPL activity. No phenotype differences were detected for tissue LPL activities during starvation or refeeding. During caloric restriction, the LPL activities were reduced in heart (-18%) and adipose (-52%) tissues, but skeletal muscle was unchanged except for the slow-twitch, oxidative soleus muscle, which was increased approximately two-fold. After refeeding to initial body weight, the LPL activity of heart returned to normal, but adipose tissue was dramatically increased (+300%) for both lean and obese Zucker rats. These data suggest that reduced skeletal muscle mass with normal LPL activity per gram tissue may contribute to an increased availability of plasma triglyceride fatty acids to adipose tissue of the genetically obese rat.

Adipose Tissue↗

PubMed1983

Novel regulation of lipoprotein lipase activity in rat brown adipose tissue: effects of fasting and caloric restriction during refeeding.

We studied the effects of a 3-day fast and 20 days of refeeding on lipoprotein lipase activity (LPL) in the interscapular brown adipose tissue (BAT) of sexually mature male rats. Rats were refed either ad libitum or restricted quantities (75 or 50% of normal ad libitum food intake). BAT-LPL, expressed on a per depot basis, decreased with fasting and returned to control values by day 3 of refeeding ad libitum. In contrast, refeeding restricted quantities for 5 to 20 days limited regain of body weight and increased BAT-LPL significantly above the values observed in rats refed ad libitum. These adaptations in BAT-LPL activity differ markedly from those observed in rat white adipose tissue or heart muscle and may serve to increase the supply of fatty acids from circulating lipoproteins for BAT metabolic needs and maintenance of thermogenesis during undernutrition.

Adipose Tissue, Brown↗