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Proliferative activity in the proximal and distal colon of the rat after fasting and refeeding.

Several methods were used to assess proliferation of colonocytes in the proximal and distal colon of the rat after fasting and refeeding. Those applied in vivo included metaphase arrest, labelling with bromodeoxyuridine and uptake of tritiated thymidine. The latter two techniques were also applied after isolation of colonocytes in vitro. Methods applied in vivo showed similar proliferation in the proximal and distal colon after fasting and enhanced proliferation in both regions after refeeding. However, the degree of enhancement was greater in the distal colon than in the proximal colon. In vitro, proliferation was enhanced in both the proximal and distal colon after refeeding but the degree of variability was greater than after assessment in vivo. Methods applied in vivo are preferred for assessment of proliferative activity in the rat colon, and major changes in proliferation in both proximal and distal colon can be induced by fasting-refeeding.

Animals↗

Changes in bioimpedance analysis after stable refeeding of undernourished anorexic patients.

OBJECTIVE: To evaluate bioimpedance analysis (BIA) parameters in patients with anorexia nervosa when undernourished and then after stable refeeding. DESIGN: Follow-up study. SUBJECTS: Thirteen patients with anorexia nervosa who were studied when undernourished (body weight (Wt): 36.9+/-5.6kg, body mass index (BMI): 14.8+/-1.8kg/m2) and after stable refeeding (Wt: 52.9+/-7.1kg, BMI: 21.2+/-2.3 kg/m2) compared to 25 well-nourished control women (Wt: 53.7+/-4.9 kg, BMI: 21.1+/-1.3 kg/m2). MEASUREMENTS: Impedance and phase angle were determined for the whole body (13 patients) and separately for arms and legs (10 patients). RESULTS: Bioimpedance index (height2/impedance) and phase angle were lower in the undernourished group. Whole-body impedance declined (median, min-max) by 45, 1-151 Ohm after refeeding; the variations of bioimpedance index (BI-Index) were weakly correlated (P < 0.10) with BMI changes. Limb phase angles increased with refeeding, but only changes in whole-body phase angle were correlated (P < 0.025) with the corresponding variations of Wt or BMI. CONCLUSION: Whole-body phase angle increased after weight recovery of anorexic patients, suggesting the occurence of modifications in the extracellular-to-intracellular water ratio. These changes were proportional to the increase in BMI and Wt.

Adolescent↗

The effect of starvation and refeeding on lipogenic enzymes in mammary glands and livers of lactating rats.

Lactating rats were starved for 48 h and refed a high-carbohydrate diet for a further 48 h. Starvation stops milk secretion, which resumes shortly after refeeding. Three lipogenic enzymes, fatty acid synthase, glucose 6-phosphate dehydrogenase (EC 1.1.1.49) and 'malic' enzyme (EC 1.1.1.40) all decrease in the mammary gland during starvation and are restored to the pre-starvation levels 48 h after refeeding. The same enzymes in liver also decrease during starvation, but increase to values significantly higher than those for the normal fed rats after refeeding the high-carbohydrate diet. For the fatty acid synthase these values were four times the pre-starvation values. Serum insulin and prolactin concentrations also increased upon refeeding the high-carbohydrate diet.

Animals↗

Refeeding syndrome: effective and safe treatment with Phosphates Polyfusor.

BACKGROUND: Severe hypophosphataemia associated with refeeding syndrome requires treatment with intravenous phosphate to prevent potentially life-threatening complications. However, evidence for replacement regimens is limited and current regimens are complex and replace phosphate inadequately. AIM: To assess the effectiveness and safety of 50 mmol intravenous phosphate infusion, given as a 'Phosphates Polyfusor', for the treatment of severe hypophosphataemia in refeeding syndrome. METHODS: Patients with refeeding syndrome and normal renal function received a Phosphates Polyfusor infusion for the treatment of severe hypophosphataemia (< 0.50 mmol/L). The outcome measures were serial serum phosphate, creatinine and calcium concentrations for 4 days following phosphate infusion and adverse events. RESULTS: Over 2 years, 30 patients were treated. Following treatment, 37% of cases had a normal serum phosphate concentration and 73% had a serum phosphate concentration of > 0.5 mmol/L within 24 h. Ten patients required more than one Phosphates Polyfusor infusion. Within 72 h, 93% of cases had achieved a serum phosphate concentration of > or = 0.50 mmol/L. No patient developed renal failure. Three episodes of transient mild hyperphosphataemia were recorded. Four patients developed mild hypocalcaemia. CONCLUSIONS: This is the largest published series of the use of intravenous phosphate for the treatment of severe hypophosphataemia (< 0.50 mmol/L), and is the most effective regimen described. All patients had refeeding syndrome and were managed on general wards.

Feeding Methods↗

Increase of lipogenic enzyme mRNA levels in rat white adipose tissue after multiple cycles of starvation-refeeding.

Recently, we have found that despite the significant reduction of body weight after multiple starvation-refeeding cycles, white adipose tissue (WAT) exhibits surprisingly high rates of lipogenesis and lipogenic enzyme activities. The purpose of this study was to determine the response of WAT lipogenic enzyme mRNAs of rats subjected to multiple cycles of 3 days fasting and 3 days of refeeding. Despite the body weight reduction, significant increase of lipogenic enzymes (ie, fatty acid synthase [FAS], acetyl-coenzyme A [CoA] carboxylase [ACC], adenosine triphosphate (ATP)-citrate lyase [ACL], NADP-linked malic enzyme [ME], and glucose 6-phosphate dehydrogenase [G6PDH]) mRNAs in WAT was found after multiple cycles of starvation-refeeding of rats on standard laboratory diet. These findings, together with the results published recently, indicate that multiple cycles of starvation-refeeding cause the increased lipogenesis in WAT by upregulation of the lipogenic enzymes gene expression.

Adipose Tissue↗

Metabolic control of phosphorylase conversion in muscle. Effect of fasting and refeeding on the response of rat diaphragm glycogen phosphorylase, cyclic AMP Dependent protein kinase, and phosphorylase b kinase to adrenergic stimulation.

The influence of fasting and refeeding on the response to adrenergic stimulation of several enzymes involved in glycogen metabolism has been investigated in the isolated, intact rat diaphragm. The in vitro response of the phosphorylase system to terbutaline was found to decrease markedly following fasting. A pronounced increase in this response was seen upon refeeding. This increased responsiveness was normalized by incubation of isolated tissues with palmitate (1.5 mM). Plasma free fatty acid concentration was increased in fasted rats compared to the value found in refed animals. The effect of terbutaline on cyclic AMP concentration and protein kinase activity was not significantly influenced by fasting and refeeding while fasting decreased the effect of terbutaline upon phosphorylase b kinase. Diaphragm glycogen levels were reduced by more than 50% in rats fasted for 24 hours and were significantly increased upon refeeding compared to fed rats. The results indicate that the nutritional state can modulate the sensitivity of the interconverting system for phosphorylase. It is suggested that this modulation might depend upon fatty acid metabolism.

Animals↗

Serum leptin monitoring in anorectic patients during refeeding therapy.

Circulating concentrations of leptin are exceedingly low in severe malnutrition as seen in the acute state of anorexia nervosa (AN). During refeeding therapy plasma leptin levels increase to normal and in some cases peak at values in excess of the BMI of matched controls even before a normal body weight has been achieved. Peak leptin levels are possibly the cause of an increased energy expenditure during this stage of the disorder and might predispose to renewed weight loss (rebound phenomenon). In this study we investigated the role of leptin fluctuations as a prognostic factor of therapeutic success in AN. In 11 anorectic female patients serum leptin levels, BMI and body fat percentage were evaluated in four-week intervals during a conventional refeeding program over three months (group 1). The results of the first two measurements were used to determine a range of increases in leptin levels in relation to increases in BMI. The values between the 25th and 75th percentiles determined the reference range. In a second group of 9 anorectic female patients serum leptin levels, BMI, body fat percentage and the increase in the leptin level in relation to the BMI of each subject were investigated for three months every two weeks. These patients were also treated according to the same conventional refeeding program, but the caloric intake was reduced or increased (+/-250 kcal/d) if the increase in the leptin level, in relation to the increase in the BMI, had exceeded or fallen short of the reference range. During the refeeding therapy every subject of each group experienced increases in serum leptin levels, BMI and body fat percentage. Six subjects of group 1 and six subjects of the second group had an increase in leptin levels in relation to the increase of the BMI out of the reference range at least once. To investigate the therapeutic outcome of leptin monitoring and the following alteration of caloric intake, weight gain of the patients of both groups during the whole treatment was compared. No significant difference was found. Our results probably do not support the findings that high leptin levels predispose to a renewed loss of weight. The outcome in our patients whose caloric intake was modified due to their serum leptin levels was not significantly improved.

Adipose Tissue↗

Changes in the concentrations of the minor constituents of goat's milk during starvation and on refeeding of the lactating animal and their relationship to mammary gland metabolism.

1. Changes in the concentrations of the minor constituents of goat's milk were observed during 48 h starvation and on refeeding. 2. The concentrations of hexose phosphate and UDP-hexoses increased during starvation and decreased on refeeding. 3. The concentrations of phosphoenolpyruvate and glycerate 3-phosphate decreased during starvation and increased on refeeding. 4. Isocitrate:2-oxoglutarate increased during starvation and decreased on refeeding. 5. Changes in the minor constituents of milk can be explained in terms of the metabolic changes occurring in the mammary gland during starvation. It is proposed that changes in the concentrations of these metabolites in milk reflect changes in their concentrations in the cytosol or Golgi vesicles of the mammary gland.

Animals↗

Changes in insulin-receptor mRNA levels in skeletal muscle and brown adipose tissue of weanling rats during fasting and refeeding.

Tissue-specific alterations in insulin sensitivity occur in response to fasting and refeeding, as part of the integrated adaptive mechanisms employed to adjust to major changes in nutritional status. In the present study the effects of fasting and refeeding on insulin-receptor, actin and myosin mRNA levels in skeletal muscle, and insulin-receptor and uncoupling-protein mRNA in brown adipose tissue of rats have been examined. Insulin-receptor mRNA levels increased markedly in both skeletal muscle and brown adipose tissue after a 40 h fast, the increase being greater in brown fat (8-fold) than in muscle (2-fold). On refeeding for 4 h, the insulin-receptor mRNA level in both tissues declined rapidly to control levels. An increase in insulin-receptor mRNA level was also observed in brown adipose tissue after a 16 h fast, although not in skeletal muscle. In contrast to the insulin-receptor mRNA, the level of the mRNA for the mitochondrial uncoupling protein declined markedly in brown adipose tissue during a 40 h fast. These results indicate that insulin-receptor mRNA levels are modulated in response to the alterations in nutritional status that occur during fasting and refeeding; this may reflect a nutritional influence on transcription of the receptor-protein gene.

Actins↗

Refeeding after a fast in rats: effects on small intestinal enzymes.

The effect of resuming food intake after a period of starvation (refeeding) on the specific activities of selected rat intestinal enzymes was determined. The rate of weight gain was higher in refed animals than in control animals, without a difference in food intake. Fasting caused intestinal atrophy which reversed rapidly on refeeding. Fasting decreased the specific activities of sucrase, maltase, and galactokinase, but did not affect the specific activities of hexokinase, pyruvate kinase, or crypt thymidine kinase. Sucrase, maltase, hexokinase, pyruvate kinase, and thymidine kinase specific activities all rose above control values during refeeding. The overshoot in intestinal enzyme specific activities may help promote the rapid weight gain observed in refed rats and is an integral part of the total adaptation to fasting and refeeding.

Animals↗

Energy depot replenishment in rats during refeeding after fasting: effect of exercise.

The effect of progressive moderate exercise on body weight gain, visceral and muscle protein stores, and thyroid hormone levels during an 8-day refeeding period after 65 h of starvation was studied in 2-month-old male Sprague-Dawley rats. Twenty-four animals were divided into three groups and acclimated for 5 days while being fed with ordinary Purina Chow. After the fasting phase, a group of rats was killed in order to provide base-line information concerning fasting-induced changes in body composition; a sedentary group was fed Purina Chow ad libitum; and a treadmill-exercised group was pair fed with the sedentary rats. During the refeeding phase, the exercised animals regained significantly less weight than the sedentary animals (p less than 0.001), but the two groups did not differ significantly with respect to visceral, muscle, eviscerated carcass, and skin protein. Total body fat content was lower in the exercised than the sedentary group. The thyroid hormone levels were not significantly different for the two refed groups. These results indicate that exercise during refeeding may alter the pattern of body weight gain during refeeding after fasting such that the replenishment of adipose tissue stores is reduced without compromising the restoration and growth of lean tissue.

Adipose Tissue↗

Gastrointestinal and cardiac response to refeeding after low-calorie semistarvation.

A recent development in the treatment of obesity is the widespread use of very-low-calorie diets. This study assessed the response to refeeding (RF) after semistarvation (SS) in a rat model. Male Sprague-Dawley rats (440 g) were semistarved for 21 d, receiving a nutritionally complete defined formula diet at 23% of calories of control (C) rats fed ad libitum, and subsequently refed over 21 d (SS----RF). Organ weight, contents of protein and DNA, and the protein-DNA ratio were determined for the liver, pancreas, small intestine, and heart. Compared with C animals, SS----RF animals showed variable repletion of tissue protein but not of tissue DNA. The higher protein-DNA ratio shown in these organ systems suggests a cellular hypertrophic adaptive response to refeeding. A persistent reduced number of cells in ratio to protein concentration is evident despite refeeding over 21 d. Very-low-calorie diets as well as refeeding influence nitrogen economy of selected organ systems.

Adaptation, Physiological↗

Specific and nonspecific immune responses to fasting and refeeding differ in healthy young adult and elderly persons.

BACKGROUND: Undernutrition is a main cause of immunodeficiency. Many confounding factors limit the interpretation of immune function in hospitalized elderly patients. OBJECTIVE: We compared the effects of short-term fasting and refeeding on lymphocyte subset distribution and neutrophil function in healthy subjects. DESIGN: Seven young adult (x +/- SE age: 24 +/- 2 y) and 8 elderly (71 +/- 3 y) subjects were fed standardized diets (1.6 x predicted resting energy expenditure; 16% protein) for 7 d. They then fasted for 36 h and were refed for 4 h (42 kJ/kg). Lymphocyte subsets were quantified by using fluorochrome-conjugated monoclonal antibodies. Neutrophil chemotactic migration was evaluated by using a 2-compartment chamber. Neutrophil reactive oxygen species production was measured by using a luminol-amplified chemiluminescence assay and oxidation of 2'7'-dichlorofluorescein diacetate. RESULTS: Baseline total and cytotoxic T lymphocyte subpopulations were lower in elderly than in adult subjects (P < 0.01). Nutritional state had a significant effect (P < 0.05) on total, helper, and cytotoxic T and B lymphocyte counts in all subjects, and the response of lymphocyte subpopulations to nutritional fluctuations was significantly affected by age. The chemotactic index was lowered by fasting in both groups (P < 0.05 compared with basal values). After refeeding, neutrophil migration was restored in adult but not elderly subjects. The superoxide anion production rate increased with fasting and reverted to prefasting values with refeeding in both groups (P < 0.05). Fasting induced a significant decrease in hydrogen peroxide production in stimulated neutrophils that was reversed by refeeding in adult but not elderly subjects. CONCLUSION: The lack of response of lymphocyte subpopulation counts and neutrophil function to nutritional changes may help to explain the proneness of elderly persons to infection.

Adult↗

Effect of malnutrition and short-term refeeding on peripheral blood mononuclear cell mitochondrial complex I activity in humans.

BACKGROUND: Previous investigations in rats have shown that the first enzyme of the mitochondrial electron transport chain (complex I) is altered in peripheral blood mononuclear cells (PBMCs) and muscle by dietary manipulations. OBJECTIVE: We hypothesized that similar changes would occur in human PBMCs as a result of dietary malnutrition and short-term refeeding irrespective of the presence or absence of active inflammatory bowel disease (IBD). DESIGN: Fourteen malnourished patients with active IBD, 13 malnourished patients without IBD, and 42 healthy subjects were investigated. Complex I activity, body mass index, body composition, energy and protein intakes, and resting energy expenditure were measured. Five patients without IBD and 6 patients with IBD were investigated after 7 d of refeeding. RESULTS: In patients without IBD, weight loss was mainly due to a loss of fat mass. In contrast, weight loss in IBD patients was due to a loss of both fat-free mass and fat mass. Complex I activity was reduced to the same degree in both groups of patients and was significantly lower than that observed in healthy subjects. In both groups of patients, complex I activity correlated significantly with body weight, body mass index, percentage weight loss, and fat mass. Complex I activity increased significantly after 1 wk of refeeding in both groups of patients before observed changes of measured nutritional assessment indexes. CONCLUSION: Our study showed that mitochondrial complex I activity measured in PBMCs seems to be a specific marker of dietary malnutrition and responds rapidly to refeeding.

Adult↗

Factors associated with the increase in resting energy expenditure during refeeding in malnourished anorexia nervosa patients.

BACKGROUND: In malnourished anorexia nervosa (AN) patients, body-weight gain during refeeding is slowed by an increase in resting energy expenditure (REE). OBJECTIVE: The objective of the study was to identify factors associated with the increase in REE during refeeding. DESIGN: Before and 8, 30, and 45 d after the beginning of refeeding, REE was studied by indirect calorimetry in 87 female AN patients [x +/- SD age: 23.4 +/- 7.9 y; body mass index (in kg/m2) 13.2 +/- 1.3]. Energy intake, body composition (by bioelectrical impedance analysis), physical activity, smoking behavior, abdominal pain, anxiety, depressive mood, serum thyrotropin and thyroid hormone, and urinary catecholamines were measured. REE was also evaluated in 18 patients after 1 y of recovery. RESULTS: By day 8, REE increased from 3.84 +/- 0.6 to 4.36 +/- 0.59 MJ/d (P < 0.01). This increase (13.4%) was significantly (P <0.01) greater than that expected on the basis of the increase in fat-free mass (FFM; 1.6%). Thereafter, the ratio of REE to FFM remained high and, in multivariate analysis, was significantly related to 4 factors: energy intake (P <0.01), anxiety (P <0.01), abdominal pain (P <0.05), and depressive mood (P <0.05). The ratio also increased significantly with physical activity (P <0.01) and cigarette smoking (P <0.02). This rise in REE leveled off after recovery from AN. CONCLUSION: In AN patients, the rise in REE observed during refeeding was independently linked to anxiety level, abdominal pain, physical activity, and cigarette smoking, and it contributed to resistance to weight gain.

Abdominal Pain↗

The effects of starvation and refeeding on muscle protein synthesis and catabolism in the young rat.

We studied the effects of acute starvation and refeeding on muscle protein synthesis and degradation in young rats. As measures of synthesis, we determined muscle RNA concentration and the rate of incorporation of [14C]leucine into skeletal muscle protein (Sm). As an estimate of nitrogen retention we measured urea production (UrP). Starvation reduced these variables significantly. One refeeding period returned Sm to control values, only partially restored RNA concentration, and increased UrP. We determined the urinary excretion rate of 3-methylhistidine (3-MH) as a measure of the rate of myofibrillar protein degradation. Excretion of 3-MH was lowest in control and highest in starved rats. Refeeding decreased 3-MH excretion to a level midway between control and starved animals. Growth was attended by high rates of synthesis and low rates of degradation. Starvation depressed synthesis and increased degradation. With refeeding, synthesis increased and degradation decreased, compared with the starved state.

Animals↗

Metabolic responsiveness of different size adipocytes to fasting and refeeding in the pig.

The effects of fasting (F) and fasting-refeeding (FR) on [U-14C]glucose and [1-14C]palmitate metabolism were examined in pig middle subcutaneous (MSQ) adipocytes fractionated into 20--63, 63--102 and 102--153 microns diameter ranges. Fasting caused a similar decrease in de novo glyceride fatty acid (GFA) and glyceride-glycerol (GG) synthesis from glucose among adipocytes of different size. After refeeding for 2 days, glucose metabolism significantly increased in all fractions, however, the increase did not reach non-fasting levels. There was a disparate increase in glucose metabolism among adipocyte fractions after refeeding. Adipocytes 102--153 microns in diameter had a larger increase in glucose metabolism than smaller adipocytes. Fasting suppressed palmitate esterification rates in 20--63 and 63--102 microns fractions. Esterification by adipocyted 102--153 microns in diameter was not diminished after fasting. An "overshoot" in esterification by adipocytes 63--102 and 102--153 microns in diameter relative to control adipocytes was observed after refeeding; no "overshoot" occurred in 20--63 microns adipocytes. These results indicate that adipocytes of different size have markedly different capacities for substrate utilization after F or FR as well as different metabolic adaptations to F or FR.

Adipose Tissue↗

Effect of starvation and refeeding on activity of a Ca2+-dependent protease in rat skeletal muscle.

The effects of starving, refeeding, and restarving rats for different periods on content of sarcoplasmic and contractile proteins and on activity of the Ca2+-dependent proteinase (CAF) in skeletal muscle was determined. Groups of five to six male rats, 8 to 11 weeks old, were starved up to 8 days, refed up to 6 days, and in two experiments, restarved up to 10 days. CAF activity was assayed in P 0-45 crude CAF fractions prepared so as to remove a protein inhibitor of CAF; the assays were demonstrated to be specific for CAF. Sarcoplasmic protein content of rat skeletal muscle changed little until after 6 days of restarvation when it decreased to 68-89% of control level (P less than 0.05). Contractile protein content decreased to 65% of control level (P less than 0.01) after 8 days of starvation, remained at this level for 4 days of refeeding, then increased to approximately 80% of control level after 6 days of refeeding, remained at this level for 2 days of restarvation, and then decreased to approximately 65% of control level (P less than 0.01) after 6 and 8 days of restarvation. Muscle CAF activity did not change during the first 8 days of starvation but increased to 113% above control level (P less than 0.01) after 6 days refeeding and then decreased to only 29% of control level (P less than 0.01) after 8 days of restarvation. These changes in muscle CAF activity are consistent with the proposed role for CAF in initiating metabolic turnover of contractile proteins, but because actual measurements of myofibrillar protein were not made and because in vivo CAF activity is difficult to assess, they do not prove this role for CAF nor do they exclude participation of other proteinases.

Animals↗