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Stimulation of gastric prostaglandin synthesis by refeeding in the rat. Role in protection of gastric mucosa from damage.

The purpose of the present study was to determine whether feeding stimulates prostaglandin (PG) synthesis in the gastric mucosa and whether this might play a role in the defensive mechanism of the gastric mucosa. The effect of refeeding on the formation of gastric lesions induced by nonsteroidal antiinflammatory drugs and on the generation of prostaglandin in the gastric mucosa was investigated. In the fasted rat aspirin and indomethacin produced many lesions in the corpus, but few or no lesions in the antrum. Refeeding of chow pellets before aspirin or indomethacin significantly decreased the corpus lesions, but provoked lesions in the antrum. When each drug was given before the refeeding, the protection against corpus lesions by refeeding was reduced and the lesions in the antrum were significantly increased. Mucosal generation of 6-keto-PGF 1 alpha (a stable metabolite of PGI2) and PGF2 alpha was measured ex vivo by the method of Whittle. The generation of 6-keto-PGF1 alpha and PGF2 alpha in the fasted rat deprived of food for 24 hr was 1761 +/- 170 and 217 +/- 7 ng/min/g tissue in the corpus mucosa, and 2958 +/- 217 and 453 +/- 33 ng/min/g tissue in the antral mucosa, respectively. Refeeding of chow pellets significantly increased the generation of both prostaglandins in the antral mucosa and of PGF2 alpha in the corpus mucosa, but did not affect the generation of PGI2 in the corpus mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Downregulation of skeletal muscle UCP-3 gene expression during refeeding is prevented by cold exposure.

We wished to gain insights into the role of skeletal muscle uncoupling protein-3 (UCP-3) in the elevated efficiency of fat recovery during refeeding after starvation. Previous observations have revealed that muscle UCP-3 expression is downregulated in rats during refeeding at 22 degrees C. Therefore, we investigated whether this also occurs during refeeding at thermoneutrality (29 C) or in the cold (6 C), since at these environmental temperatures the refed animals also show diminished thermogenesis and a higher rate of fat deposition than controls. The UCP-3 mRNA level in the skeletal muscles studied (soleus, gastrocnemius and tibialis anterior) was significantly lower in the refed group than in controls at thermoneutrality, but there were no such differences between these two groups in the cold. This effect of cold, namely abolishing refeeding-induced downregulation of skeletal muscle UCP, is specific to UCP-3 since the gene expression of skeletal muscle UCP-2 remained significantly lower in the refed than in the controls both at thermoneutrality and in the cold. These findings during refeeding in the cold therefore dissociate UCP-3 gene regulation from the adaptive reduction in thermogenesis that accelerates fat deposition during weight recovery. They also reveal differential responses of UCP-3 and UCP-2, whose significance is discussed in the light of our previously proposed hypothesis, which centers upon a role for these UCP homologues in the regulation of lipids as a fuel substrate.

Animal Feed↗

Fat-free mass change to weight change ratio during refeeding following lung transplantation.

Malnutrition occurs frequently prior to lung transplantation (LTR), but patients gain weight after LTR. The study aimed to determine the ratio changes of fat-free mass (deltaFFM): changes of body weight (deltaBW) during refeeding. A total of 37 LTR patients were measured for weight and FFM and body fat by bioimpedance analysis at 1 month post-LTR, then annually for 3 years. Linear regressions determined the ratio deltaFFM:deltaBW during refeeding. DeltaFFM was: year- 1=1.822+0.389* deltaBW, r(2)=0.397; yr-2=0.611+0.246* deltaBW, r(2)=0.441; yr-3=-0.17+0.208 * deltaBW, r(2)=0.319. Refeeding during year-1 in thin subjects resulted in a ratio deltaFFM:deltaBW of 0.389, whereas the change in ratio deltaFFM:deltaBW during year- 2 and 3 was 0.246 and 0.208, respectively. Refeeding resulted in a larger ratio deltaFFM:deltaBW in thin subjects versus normal and overweight subjects. Thus, refeeding in underweight LTR patients is geared to normalizing depleted FFM, whereas later FFM gains were similar to FFM gains in normal and overweight subjects.

Adipose Tissue↗

Heterogeneity of glycogen synthesis upon refeeding following starvation.

1. Starvation of rats for 40 hr decreased the body weight, liver weight and blood glucose concentration. The hepatic and skeletal muscle glycogen concentrations were decreased by 95% (from 410 mumol/g tissue to 16 mumol/g tissue) and 55% (from 40 mumol/g tissue to 18.5 mumol/g tissue), respectively. 2. Fine structural analysis of glycogen purified from the liver and skeletal muscle of starved rats suggested that the glycogenolysis included a lysosomal component, in addition to the conventional phosphorolytic pathway. In support of this the hepatic acid alpha-glucosidase activity increased 1.8-fold following starvation. 3. Refeeding resulted in liver glycogen synthesis at a linear rate of 40 mumol/g tissue per hr over the first 13 hr of refeeding. The hepatic glycogen store were replenished by 8 hr of refeeding, but synthesis continued and the hepatic glycogen content peaked at 24 hr (approximately 670 mumol/g tissue). 4. Refeeding resulted in skeletal muscle glycogen synthesis at an initial rate of 40 mumol/g tissue per hr. The muscle glycogen store was replenished by 30 min of refeeding, but synthesis continued and the glycogen content peaked at 13 hr (approximately 50 mumol/g tissue). 5. Both liver and skeletal muscle glycogen synthesis were inhomogeneous with respect to molecular size; high molecular weight glycogen was initially synthesised at a faster rate than low molecular weight glycogen. These observations support suggestions that there is more than a single site of glycogen synthesis.

Animals↗

The mechanism of adaptive hyperlipogenesis: insulin receptor binding and glucokinase activity in rat liver during fasting and refeeding.

In the present study, rats were fasted for 3 days and subsequently refed for 1, 3, or 5 days. Measurements of insulin binding to its receptors on liver plasma membranes were carried out in conjunction with measurements of the activity of an insulin-regulated enzyme from liver cytosol, glucokinase. In response to the 3-day fast (chronic hypoinsulinemia), the insulin receptor number almost tripled, whereas the glucokinase activity was halved. The insulin receptor number slowly fell to control values during the 5 days of refeeding. In contrast, glucokinase activity rose to levels 2.5 times higher than control (5 times higher than the fasting values) after 1 day of refeeding. Altough the activity fell off somewhat during refeeding it was still dobule control values after 5 days refeeding. It was concluded that in the fasted rat there was a dissociation between insulin receptor concentration and the activity of the insulin-regulated enzyme glucokinase. However, the fasting-induced increase in receptor concentration appeared to play a permissive role in the rapid overshoot of glucokinase activity observed in the early stages of refeeding. Such a scheme would explain the metabolic changes occurring in the fasted-refed rat.

Animals↗

Orotic acid excretion during starvation and refeeding in normal men.

The effects of acute food deprivation and subsequent refeeding on urinary orotic acid excretion were examined in nine healthy adult male subjects. During inpatient metabolic ward conditions, the volunteers were fed a nutritionally complete, pyrimidine- and purine-free diet for three days and subsequently underwent a ten-day fast followed by a ten-day period of refeeding by total parenteral nutrition. Mean daily excretion of 4.33 +/- 0.23 mg (2.77 +/- 0.12 mg/g creatinine) of orotic acid during the enterally fed state was significantly reduced (mean 46 +/- 5%) in all subjects during starvation. This reduction in the excretion of orotic acid during starvation is more likely related to a lowered rate of production and utilization. The starvation adaptation of orotate excretion occurred more rapidly than did the decrease in urinary nitrogen loss. All subjects showed an increase (mean 48 +/- 14%) in the excretion of orotic acid during the first day of refeeding which continued throughout the refeeding phase. A significant positive correlation was shown between the daily orotic acid excretion and nitrogen intake (r = 0.98) or protein balance (r = 0.83). The response to refeeding of acutely malnourished normal male is an increase in orotic acid excretion with a decrease in whole body protein catabolism.

Adult↗

Superoxide production during refeeding in patients with anorexia nervosa.

The effect of undernutrition and refeeding on superoxide production by polymorphonuclear cells (PMN) was studied in 11 girls suffering from anorexia nervosa (AN) and 17 age-matched, normal, healthy, control subjects. Superoxide anion production by PMNs from undernourished AN patients was comparable to normal, while a significant decrease in this function was observed during the initial period of refeeding. After a more extended period of refeeding, superoxide production by PMNs from AN patients increased and gradually returned toward normal values. Superoxide production correlated with length of the refeeding period (RF), weight as a percentage of ideal weight for height (W/H%), and rate of weight gain (WG). These results imply that a variety of physiological parameters, including susceptibility to infection, may be altered by refeeding undernourished patients.

Adolescent↗

Effect of food deprivation and refeeding on the concentration of vasopressin and oxytocin in discrete hypothalamic sites.

Recent evidence has implicated hypothalamic peptides, such as arginine vasopressin (AVP) and oxytocin (OT) in the control of feeding behavior. In this study, we investigated the impact of food deprivation (48 h) and subsequent refeeding (6 h) on the concentration of AVP and OT in discrete hypothalamic areas, as well as in the neurohypophysis. We also estimated in these rats certain peripheral measures, including hydroelectrolytic parameters, plasma and urine AVP, and plasma corticosterone. The results of this study revealed that food deprivation for 48 h produced little change in OT concentration in the various hypothalamic nuclei studied, including the paraventricular and supraoptic nuclei, with the exception of the median eminence (ME), where a significant decline (-36%; p < 0.05) was detected. This effect was not significantly reversed by 6 h of refeeding. With respect to AVP concentration, food deprivation caused a reliable decline exclusively in the parvocellular subdivision of the paraventricular nucleus (pPVN; -45%; p < 0.01) and in the supraoptic nucleus (SON; -45%; p < 0.01). No change in AVP was detected in the ME or in most other hypothalamic nuclei examined. Refeeding for 6 h actually potentiated the effect of food deprivation, decreasing further from baseline the content of AVP in the pPVN and SON. The only other hypothalamic area to exhibit a change in AVP content was the ventromedial nucleus, where AVP level increased (p < 0.001) after deprivation and declined to normal after 6 h of refeeding. The content of AVP and OT in the neurohypophysis was unaffected by food deprivation and subsequent refeeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Radionuclide ventriculography in severely underweight anorexia nervosa patients before and during refeeding therapy.

Congestive heart failure is a well-recognized complication of refeeding therapy in underweight patients with anorexia nervosa but there are few data describing cardiac function during the critical refeeding period. This prospective study examined left ventricular function with conventional electrocardiographic-gated radionuclide ventriculography (RVG) in severely underweight anorexia nervosa patients both before and during refeeding therapy. Eight patients underwent rest and exercise RVG at admission and after regaining approximately 5% to 10% of their ideal body weight. With the admission study serving as a control, the left ventricular ejection fraction and regional wall motion analysis were analyzed before and after refeeding and weight gain. Resting left ventricular ejection fractions were not significantly different between the first and second RVGs (64 +/- 11% vs. 62 +/- 8%, respectively; P greater than .05). Likewise, the left ventricular ejection fraction with maximal exercise did not significantly differ when comparing the first or the second RVG (74 +/- 10% vs. 72 +/- 8%, P greater than .05). During the baseline RVG, the left ventricular ejection fraction increased from 64 +/- 11% (rest) to 74 +/- 10% (maximal exercise) (P less than .001). During the second RVG, the ejection fraction increased from 62 +/- 8% (rest) to 72 +/- 8% (maximal exercise) (P = .003). However, the left ventricular exercise ejection fraction in the second RVG in one patient increased only by one absolute percentage point. Four of the eight patients had regional wall motion abnormalities detected during resting and/or exercise RVG. Abnormal cardiac function occurs in asymptomatic patients with anorexia nervosa undergoing refeeding therapy.

Adolescent↗

Rehabilitation of microsomal enzymes in malnourished rats: comparison of parenteral versus oral refeeding.

Protein malnutrition decreases the activity of drug-metabolizing liver microsomal enzymes. In the first part of our study, we evaluated those enzymes during malnutrition and refeeding. Then we compared the effects of different nutritional patterns on these parameters. During malnutrition (M), rats were fed a 5% casein diet. During refeeding, they were randomized in 3 groups: oral refeeding (20% casein diet: A), continuous total parenteral nutrition (TPN: B) and oral energy refeeding (glucose + lipids) + continuous amino-acid infusion (C). Rats were sacrificed before and at various times during malnutrition and refeeding (2 to 28 days). There was no difference in caloric intake between the 3 groups. Nitrogen balance was not different in A and B. It was lower in C, though nitrogen intake was not different. Body and liver weights were not different between the 3 groups. Microsomal proteins and cytochrome P-450 were improved in A and B but not in C compared to M. Our results suggest that TPN (but not continuous amino-acids infusion + oral energy intake) is as effective as oral nutrition on rehabilitation of microsomal enzymes in malnourished rats.

Journal Article↗

Fasting-refeeding regimes induce compensatory growth and muscle transcriptomic remodeling in juvenile Qihe gibel carp (Carassius gibelio var. Qihe).

Compensatory growth, an important adaptive response in fish, holds considerable potential for improving feeding efficiency in aquaculture. To identify an optimal fasting-refeeding strategy for juvenile Qihe gibel carp (Carassius gibelio var. Qihe) and to clarify the mechanisms underlying the compensatory growth, we divided two-month-old fish into four groups, namely S0 group (continuous feeding for 28&#xa0;days), S2 group (4&#xa0;cycles of 2-day fasting followed by 5-day refeeding), S4 group (fasting for 4&#xa0;days followed by refeeding for 24&#xa0;days), and S8 group (fasting for 8&#xa0;days followed by refeeding for 20&#xa0;days), then growth performance, muscle tissue morphology, biochemical responses, and muscle transcriptomic profiles under different feeding regimes were investigated. After a 28-day aquaculture experiment, fish in the S4 group exhibited significantly greater body length and weight than those in the S0, S2, and S8 groups, indicating over-compensatory growth. Histological analysis further showed that muscle growth in the S4 group was mainly associated with myofiber hyperplasia. Different feeding regimes also induced distinct changes in hepatic antioxidant and metabolic enzyme activities, as well as intestinal digestive enzyme activities. Transcriptome analysis revealed that the forkhead box O (FoxO) signaling pathway was significantly enriched during compensatory growth. Key genes, including serum/glucocorticoid regulated kinase 1 (sgk1) and insulin receptor substrate 1 (irs1), were predicted to play important roles in this process. Overall, these results indicate that fasting for 4&#xa0;days followed by refeeding for 24&#xa0;days (the S4 regime) is the optimal strategy for inducing compensatory growth in juvenile Qihe gibel carp. This study provides new insights into the morphological, physiological, and molecular basis of compensatory growth and offers a scientific foundation for developing efficient and sustainable feeding strategies for this species.

Animals↗

Participation of beta-adrenergic activity in modulation of GLUT4 expression during fasting and refeeding in rats.

Through in vitro studies, several factors have been reported as modulators of GLUT4 gene expression. However, the role(s) of each potential GLUT4 modulator is not completely understood in the in vivo setting. The present study has investigated the hypothesis that beta-adrenergic stimulation participates in modulation of GLUT4 expression during fasting and refeeding. As such, GLUT4 messenger RNA (mRNA) and protein were investigated in insulin-sensitive tissues during a 48-hour fast. In addition, the effects of 8-hour refeeding on GLUT4 mRNA in the gastrocnemius muscle and interscapular brown adipose tissue (BAT) were investigated. Whether beta-adrenoceptor blockade by propranolol (20 mg/kg) treatment influenced the responsiveness to fasting/refeeding was also investigated. The results show that fasting repressed GLUT4 gene and protein expression in BAT, white adipose tissue, and soleus muscle, but had no effect on the gastrocnemius muscle. Refeeding induced a rapid overexpression of GLUT4 mRNA in both gastrocnemius (approximately 25%, P < .05) and BAT (approximately 200%, P < .001). Propranolol treatment induced an increase (approximately 60%, P < .05) in GLUT4 mRNA at the end of the fasting period. In contrast, propranolol treatment attenuated GLUT4 mRNA induction after refeeding; the latter may be due to attenuation of postprandial insulin levels. These results suggest that sympathetic activity is important for the repression of GLUT4 gene expression during fasting. In contrast, sympathetic control of the GLUT4 gene seems to be overbalanced by metabolic/hormonal modulators during refeeding stage. Taken together, the results suggest that feeding behavior influences GLUT4 gene expression pattern through changes in sympathetic activity, especially during long-term starvation periods.

Adipose Tissue, Brown↗

Phase shifts to refeeding in the Syrian hamster mediated by running activity.

Circadian rhythms in hamsters can be entrained by restricted daily feeding schedules. Phase control may be exerted by feeding per se, or by wheel running in anticipation of food access. Phase modulation by feeding was examined here by depriving hamsters of food for 9-24 h and refeeding at 1 of 7 different zeitgeber times on the first day of constant dim light. Significant group mean phase-advance shifts were observed only following 24 h and 17 h deprivations ending in the mid-subjective day, 7 h before the usual time of lights off (mean shifts 28 min and 66 min, respectively). The largest phase shifts were associated with wheel running during the first 6 h of refeeding. When running wheels were locked during this time in an additional group, no phase shifts were observed. A trend for small phase delays was evident for 14 h deprivations ending at the beginning of the subjective night, but no significant group mean or individual shifts were observed at other refeeding times. Refeeding after food deprivation, thus, appears to have minimal effects on circadian phase in hamsters; wheel running associated with refeeding may account for occasional shifts observed.

Animals↗

Response of leptin mRNA to 24-h food deprivation and refeeding is influenced by age in rats.

To obtain an insight into the influence of aging on leptin gene expression, the responses of leptin mRNA in retroperitoneal and epididymal adipose tissues and plasma leptin concentrations to 24-h food deprivation and refeeding were examined in 2-, 10- and 24-month-old normal rats. The basal level of leptin gene expression in retroperitoneal adipose tissue was significantly higher in 10- and 24-month-old rats than that in 2-month-old rats, while the level in epididymal adipose tissue was highest in 10-month-old rats for all three age groups. The basal concentrations of plasma leptin was significantly higher in 10- and 24-month-old rats than those in 2-month-old rats. The 24-h food deprivation was followed by a significant reduction in leptin mRNA expression in both retorperitoneal and epididymal adipose tissues for all three age groups. The leptin gene expression was restored to control levels 24 h following refeeding in the 2- and 10-month-old rats, but failed to be restored in the 24-month-old rats. In addition, the time course of recovery for leptin mRNA expression by refeeding to the control levels differed between the retroperitoneal and the epididymal adipose tissue in 2- and 10-month-old rats. The concentrations of plasma leptin 24 h following refeeding were compatible with the leptin mRNA levels in adipose tissues in three age groups. These results suggest that the expression of the leptin gene in response to food-deprivation and refeeding is influenced by an animal's age and that this expression is different for different regions of white adipose tissue.

Adipose Tissue↗

Effects of food deprivation and refeeding on neuropeptide Y (NPY) mRNA levels in goldfish.

In mammals, NPY is a key factor in the regulation of feeding behavior. In the present study, the effects of refeeding for 1-3 h in 72-75-h food deprived (FD) goldfish on the levels of NPY mRNA in telencephalon-preoptic (TEL-POA), hypothalamus (HYP) and optic tectum-thalamus (OT-THAL) were examined, using Northern blot analysis. Goldfish FD for 72 h exhibited a significant increase in NPY mRNA levels in all brain regions. At 1 h after 72-h FD (73-h FD), NPY mRNA was significantly increased in TEL-POA and OT-THAL, but remained the same as 72-h FD fish in HYP. At 3 h after 72-h FD (75 h), all brain regions exhibited a significant increase in NPY mRNA levels. However, subsequent refeeding for 1-3 h rapidly and completely reversed the effects of FD in all brain regions, reaching fed levels within 1-3 h of refeeding. Serum GH levels were highest in 72-h FD fish, but decreased significantly over 1-3 h after 72-h FD; whereas, refeeding reversed the increase in serum GH levels only at 3 h after refeeding. Taken together, these results further support that NPY is a physiological brain transducer involved in the regulation of daily appetite and feeding in goldfish.

Animals↗

The effect of repeated episodes of dietary restriction and refeeding on systolic blood pressure and food intake in exercise-trained normotensive rats.

OBJECTIVE: To explore the effects of weight cycling and exercise on blood pressure and macronutrient intake in Sprague-Dawley rats. RESEARCH METHODS AND PROCEDURES: Female Sprague-Dawley rats (n = 62; 5 months old) were assigned to an ad libitum (Con) or weight-cycled (Cyc) group. They were either sedentary (Con-Sed and Cyc-Sed) or exercise-trained (Con-Ex and Cyc-Ex) on a motorized treadmill (20 m/minute; 60 minutes/day; 6 days/week). The Cyc groups underwent 2 cycles of 3 weeks of 60% food restriction followed by 5 weeks of ad libitum refeeding using a macronutrient self-selection diet. Body mass and food intake were analyzed weekly. Systolic blood pressure (SBP) was measured at baseline and during the first and fifth weeks of each refeeding. RESULTS: For both cycling periods, SBP was elevated in Cyc vs. Con groups at Week 1 of refeeding, but was similar among groups by Week 5 of refeeding. Both Con groups had greater total energy intake than the Cyc groups for both cycling periods (Cycle 1: 2882.2 +/- 75.1, Con-Sed; 2916.1 +/- 67.1, Con-Ex; 2692.2 +/- 58.7, Cyc-Sed; and 2780.5 +/- 52.4 kcal, Cyc-Ex) (Cycle 2: 2815.8 +/- 75.1, Con-Sed; 2938.8 +/- 49.4, Con-Ex; 2577.1 +/- 60.5, Cyc-Sed; and 2643.5 +/- 65.9 kcal, Cyc-Ex). Relative fat intake (percentage of total kcal/week) was significantly less for Con-Ex and Cyc-Ex than Con-Sed and Cyc-Sed throughout both refeeding periods. DISCUSSION: Weight cycling failed to produce significant sustained effects on SBP, body mass, or food intake. Exercise training, irrespective of diet, lowered dietary fat intake.

Animals↗

Epithelial cell proliferation and intestinal absorptive function during starvation and refeeding in the rat.

1. Intestinal epithelial cell production and intestinal absorption were measured in fed, starved and refed rats. 2. Four days' starvation significantly decreased the crypt cell production rate (CCPR), absorption, small intestinal length and crypt cell population. 3. There was an immediate increase in absorption 1 day after refeeding, which preceded a slower increase in CCPR. The absorption rate then decreased progressively after refeeding, and was significantly lower than control levels 1 week after refeeding. The CCPR, however, increased more gradually, reaching control levels after 2 days and then 'overshooting' control values. 4. There was no significant change in the crypt cell population immediately after refeeding; thus we propose that the initial increase in absorption on refeeding is either due to an accelerated maturation rate of the enterocytes or to the migration of enterocytes from the base of the villus to the functional zone. 5. The rapid recruitment of absorptive function appeared to be a 'one-off' event, the villus compartment then having to wait for increased cell production in the crypts to repopulate the villi.

Animals↗

Refeeding syndrome with enteral nutrition in children: a case report, literature review and clinical guidelines.

Refeeding syndrome is a potentially fatal complication of the nutritional management of severely malnourished patients. The syndrome almost always develops during the early stages of refeeding. It can be associated with a severe derangement in electrolyte and fluid balance, and result in significant morbidity and mortality. It is most often reported in adults receiving total parenteral nutrition (TPN), although refeeding with enteral feeds can also precipitate this syndrome. We report what we believe to be the first case of refeeding syndrome in an adolescent with newly diagnosed Crohn's disease. This developed within a few days of starting exclusive polymeric enteral nutrition. A systematic literature review revealed 27 children who developed refeeding syndrome after oral/enteral feeding. Of these, nine died as a direct result of complications of this syndrome. We discuss the implications of this syndrome on clinical practice and propose evidence-based guidelines for its management.

Adolescent↗