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Visual and metabolic stimuli cause adrenocortical suppression in fasted chickens during refeeding.

Concentrations of corticosterone were determined in the plasma of fasted domestic fowl before and at intervals after refeeding. The deprivation of food markedly increased (p less than 0.001) the level of plasma corticosterone. When refed ad libitum the corticosterone concentration declined (by 70%) within 45 min to the level in fed birds and remained at this concentration thereafter. A similar depression in the corticosterone concentration was observed when fasted birds were merely given the sight of the same diet, although the concentration returned to the fasting level within 60 min of food presentation. Refeeding diets with different metabolic energy contents demonstrated that the duration of the feeding-induced adrenocortical suppression was energy related. In fasted birds the presentation of an inert cellulose diet caused a temporary decline in the corticosterone level. In the absence of visual stimuli the administration (by force feeding) of the inert diet had no effect on the corticosterone concentration, whereas force feeding of metabolizable diets still induced adrenocortical suppression. These results demonstrate that adrenocortical suppression occurs in fasted refed birds and both visual and metabolic stimuli are involved in this response.

Adrenal Cortex↗

[Nutritional status of the rat in refeeding following massive mobilization of DDT by fasting].

Rats were subjected to fasting-induced mobilization of a quantity of DDT equivalent to 45% of the LD50. They were then fed for 1 week for a nutritional and toxicological study. Mobilization of DDT by starvation had no apparent effect on the activity of the various enzymes or the weight of the organs measured at the end of the refeeding period. The animals which had received DDT pretreatment showed higher protein efficiency than the control animals. Only the level of body lipids was lower in the animals pretreated with DDT, although the quantities of lipids stored during the study period were identical in both groups of animals. Overall, the results show that the nutritional state of the two groups of animals was very similar at the end of the refeeding period.

Animals↗

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

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

Aging↗

The effects of refeeding on peripheral and respiratory muscle function in malnourished chronic obstructive pulmonary disease patients.

We carried out a prospective randomized controlled trial to investigate the effects of short-term refeeding (16 days) in 10 malnourished inpatients with chronic obstructive pulmonary disease (COPD). Six patients were randomized to receive sufficient nasoenterically administered calories to provide a total caloric intake equal to 1,000 kcal above their usual intake. The other four patients were sham fed, receiving only 100 kcal more. Measurements of nutritional status, respiratory muscle strength and endurance, adductor pollicis function, and pulmonary function were performed initially and at study end. The refed group gained significantly more weight and showed significant increases in maximal expiratory pressure and mean sustained inspiratory pressure. There were no significant changes in the maximal inspiratory pressure or in adductor pollicis function. In malnourished inpatients with COPD, short-term refeeding leads to improvement in respiratory muscle endurance and in some parameters of respiratory muscle strength in the absence of demonstrable changes in peripheral muscle function.

Aged↗

Changes in connective tissue composition of the lung in starvation and refeeding.

Adult male rats were starved by allowing them one fifth of their measured daily food consumption until they lost 40% of their initial body weights. Some of these rats were then refed until their initial body weights were reached. We measured the total content of the following in the lung tissue of fed, starved, and refed animals: (1) elastin, (2) hydroxyproline, and (3) protein. Body weight and lung dry and wet weights were significantly reduced in starved and similar in refed rats compared with fed animals. Total contents of crude connective tissue, hydroxyproline, elastin, and protein were significantly lower in starved than in fed rat lungs. After refeeding, hydroxyproline content returned completely to levels found in fed rats, but other components only partially returned to normal values. These results provide a biochemical counterpart for our previous observations on the effects of starvation and refeeding on lung mechanics and morphologic aspects. It appears that the emphysema like changes in the lungs of starved rats are at least partly related to the loss of connective tissue elements.

Animals↗

Glucose-induced alkalosis in fasting subjects. Relationship to renal bicarbonate reabsorption during fasting and refeeding.

This study documents the development of alkalosis in patients returning to caloric intake after a period of starvation and investigates the mechanisms responsible for this metabolic alteration. We studied the acid-base status, bicarbonate reabsorption, acid excretion, and sodium metabolism during fasting and glucose refeeding in 19 patients receiving sodium supplements. Metabolic alkalosis developed promptly in all of the subjects who terminated an 18 day fast with 300 g of glucose daily for 4 days. Tubular maximum reabsorptive capacity for bicarbonate and renal bicarbonate threshold determinations were performed at varying intervals in six and seven subjects, respectively, who had fasted for 3-18 days. The results demonstrated that bicarbonate reabsorptive capacity was normal or low during early fasting, markedly elevated during the 2nd wk; and moderately elevated during the 3rd wk of fasting. Glucose administration at all stages of fasting caused a further increase in bicarbonate threshold. Sodium balance during fasting with sodium supplements was found to follow a triphasic pattern, with the occurrence of a natriuresis during the 1st wk followed by a period of sodium retention after which neutral daily sodium balance was reestablished. Correlation of bicarbonate reabsorption with sodium homeostasis indicated a slight decrease in renal bicarbonate threshold during the natriuretic phase, a marked increase in bicarbonate reabsorption during the period of sodium retention, and a continued moderate elevation of threshold after sodium balance was reestablished. This relationship was interpreted to indicate that changes in bicarbonate reabsorption during fasting and refeeding may be secondary to alterations in the renal reabsorption of sodium.

Absorption↗

Effect of fasting, hypocaloric feeding, and refeeding on the energetics of stimulated rat muscle as assessed by nuclear magnetic resonance spectroscopy.

A previous study suggested that muscles from hypocalorically fed rats were limited in their ability to rephosphorylate ADP. During muscle contraction hydrolysis of ATP results in an increase in phosphorus, free ADP, delta GATP, and a reduction in phosphocreatine levels that is reversed during rest by rephosphorylation of ADP to ATP and the resynthesis of phosphocreatine by ATP. We therefore hypothesized that these changes would be restored more slowly during postcontraction rest in hypocalorically fed rats as compared with controls. We compared controls fed ad lib to 2-d fasted and hypocalorically fed rats, losing 20% of their weight. We also compared hypocalorically fed rats that had been refed ad lib for 7 d with age-matched controls fed ad lib. The results showed that ATP, muscle pH, and total muscle creatine levels were not different in all groups. The raised phosphorus and delta GATP levels and lower phosphocreatine/phosphorus ratio at the end of contraction changed more slowly during rest in the hypocaloric rats. These abnormalities were partially corrected by refeeding. The data taken as a whole support the concept of impaired rephosphorylation of ADP in malnourished muscle that is not completely restored by refeeding in stimulated muscle.

Adenosine Diphosphate↗

Regulation of SREBP-1 expression and transcriptional action on HKII and FAS genes during fasting and refeeding in rat tissues.

The sterol regulatory element binding protein 1 (SREBP-1) is regarded as a major factor involved in the nutritional regulation of lipogenesis. The aim of the present work was to demonstrate its involvement in the response of key genes of glucose and lipid metabolism in liver, adipose tissue, and skeletal muscle during fasting and refeeding. The regulation of hexokinase-2 (HKII) was investigated as a marker of the glucose metabolic pathway and that of FAS was investigated as a marker of the lipogenic pathway. The in vivo association of SREBP-1 with the promoter regions of these genes was determined in the different tissues using chromatin immunoprecipitation assays. Fasting decreased, and refeeding restored, FAS and HKII mRNA and protein levels in each tissue. The concomitant measurement of SREBP-1a and SREBP-1c mRNA levels, of mature SREBP-1 protein abundance in nuclear extracts, and of SREBP-1 interaction with target promoters led to the conclusion that SREBP-1 plays a major role in the response of FAS and HKII genes to nutritional regulation in rodents. These data elucidate the important role of SREBP-1 not only in the regulation of lipid metabolism but also of glucose metabolism and energy homeostasis.

Adipose Tissue↗

Iron therapy and refeeding in experimentally malnourished rats.

1. Rats suffering from protein-energy malnutrition were found to have low serum iron, low PCV, and low hemoglobin concentrations. 2. Oral iron supplement during the refeeding of these animals caused various types of infection, the severity of which was related to the dose given. 3. A close association between high serum iron, low serum transferrin, and high incidence of bacterial infection was found. 4. A high protein diet without any oral iron supplement was found to raise the PCV and hemoglobin concentration to the same levels as a high protein diet containing 65 mg iron/kg body wt/day, although this dose of iron was sufficient to produce infection in the malnourished rats during refeeding. Speculation Iron supplementation during the treatment of children with protein-energy malnutrition may predispose to bacterial infection, the severity of which depends on the dose of iron given.

Animals↗

Sensitization to cow's milk proteins during refeeding of guinea pigs recovering from polydeficient malnutrition.

We have previously shown that milk sensitization aggravates intestinal dysfunction in the malnourished guinea pigs, suggesting that it may also impair the recovery from malnutrition. To test this hypothesis, the growing guinea pigs were malnourished by feeding only maize for 7 d and then were refed for 21 d with a balanced diet containing either intact or hydrolyzed cow's milk proteins. The control animals received the hydrolyzed milk protein diet for 28 d. After an initial period of total inhibition of growth owing to maize, guinea pigs gained weight regularly, with both balanced diets, and there was no evidence of mucosal damage at the end of the refeeding period. However, refeeding with intact milk proteins induced milk sensitization, which was demonstrated on the systemic level by the presence of anti-beta-lactoglobulin IgG1 antibodies, and on the local level by the intestinal anaphylaxis measured by the increase in short circuit current induced by beta-lactoglobulin (16.4 +/- 2.6 microA/cm2) in jejunal segments mounted in Ussing chambers. Such an immune sensitization was associated with impaired intestinal permeability, as both the ionic conductance (21.0 +/- 1.6 versus 14.6 +/- 0.7 mS/cm2) and the transepithelial fluxes of horseradish peroxidase (537 +/- 203 versus 152 +/- 28 ng/h x cm2) were significantly increased in guinea pigs refed with the intact milk proteins compared with controls. In contrast, there was no difference in intestinal permeability between controls and guinea pigs refed with the hydrolyzed milk protein diet. These data show that sensitization to cow's milk proteins can develop in guinea pigs recovering from severe malnutrition and may impair full intestinal repair.

Anaphylaxis↗

Effects of fasting and refeeding of insulin receptors and glucose metabolism in rat adipocytes.

To investigate the mechanism of insulin insensitivity during fasting and hyperresponsiveness to insulin after refeeding, insulin binding, 2-deoxyglucose uptake and glucose oxidation were measured in adipocytes from three groups of rats: control, 48 h fasted, and 48 h refed after 48 h fasting. In 48 h fasted rats, fat cell diameters were decreased to five-sixths of that of the controls and plasma insulin levels were decrease to less than half of the controls; however, after 48 h refeeding, these parameters were restored to normal. In adipocytes from fasted rats, insulin binding was increased but insulin-stimulated 2-deoxyglucose uptake glucose oxidation were significantly decreased as compared to that of the controls. In adipocytes of refed rats, insulin bindings was slightly increased as compared to the controls, accompanied by a slightly decreased 2-deoxyglucose uptake and completely restored glucose oxidation. Conclusions from these studies are that both disorders in coupling of insulin-receptor complexes to glucose transport systems and intracellular glucose metabolism play major roles in the insulin insensitivity of adipocytes from fasted rats, whereas, in adipocytes from refed rats, intracellular glucose metabolism, rather than glucose transport, is mainly involved in restoring insulin sensitivity.

Adipose Tissue↗

Increased follicular heterogeneity in experimental colloid goiter produced by refeeding iodine excess after thyroid hyperplasia.

Delayed morphological changes induced in mouse hyperplastic thyroid by refeeding iodine were analyzed by light and electron microscopy, stereology, and autoradiography. Thyroid hyperplasia was induced by a low iodine diet supplemented with 0.25% propylthiouracil for 10 days. Involution was obtained by discontinuing the propylthiouracil and returning either to a moderate iodine diet [(MID) 1 microgram I/day] or to an iodine-rich diet [(HID) 10 micrograms I/day] for 40 days. In other experiments, three cycles of hyperplasia (8 days) and subsequent involution (8 days) with MID or HID were brought about. Control animals were fed MID or HID. All animals were killed when 12-14 weeks old after injection of 10-50 microCi 125I. Double labeling, with repeated injections of [3H]thymidine from day 0 to day 7 of involution followed by 125I injection 4 h before killing, was also performed. When involutions were performed with MID, most morphological variables returned to control values. However, when involution was brought about with HID, the glandular weight, the number of follicles, and the relative volume of follicular lumina remained larger than in controls. Moreover, the 125I-labeling pattern of the follicles was altered. The proportions of unlabeled, and unevenly or partly labeled, follicles, which were fewer than 5% in control groups, represented 25-35% of all follicles after involution with HID, whereas they were unchanged with MID. In unlabeled follicles the epithelium was flattened, with a reduced number of microvilli. Partly labeled follicles were of two types. In some follicles a persistent ring reaction was observed, suggesting an abnormally slow mixing of thyroglobulin. In others, the 125I labeling was restricted to areas adjacent to the apex of a reduced number of cells, suggesting that some cells were iodinating thyroglobulin, whereas others were not. There was no relationship between the follicular 125I labeling and the frequency of [3H]thymidine-labeled cells. These results indicate that refeeding iodine excess after hyperplasia leads to the formation of a colloid goiter with new follicles, and to an increased heterogeneity of iodine metabolism among follicles and among cells.

Animals↗

The role of the growth hormone/insulin-like growth factor I axis in stimulation of protein synthesis in skeletal muscles following oral refeeding.

The mechanisms behind stimulation of protein synthesis in skeletal muscles following oral feeding are not well understood. Previous research has not confirmed that insulin is a major factor behind this stimulation. In the present study we have used genetically altered mice, with either a lack of GH secretion due to a mutational gene inactivation [GH (-/-) dwarf, DW/JOrlBom-dw] or mice with a homozygous site-specific insertion mutation in the insulin-like growth factor-1 gene [IGF-I (m/m)], leading to a deficient IGF-I production. These gene knock-outs were used in comparison to their normal wild types for evaluation of the role that the GH/IGF-I axis may have in activation of nutritionally induced stimulation of protein synthesis in skeletal muscles during oral refeeding. Weight stable adult C57B16 mice served as an additional normal control group. Protein synthesis was measured by a modified flooding dose technique with radioactive L-[14C-U]phenylalanine incorporation into acid precipitated muscle proteins. Fractional protein synthesis in skeletal muscles after an overnight fast was comparable among C57B16 (0.076 +/- 0.009%/h), wild-type IGF-I(+/+) (0.061 +/- 0.008) and IGF-I(m/m) deficient mice (0.068 +/- 0.006%/h), whereas GH(-/-) incompetent mice had a lower fractional synthesis rate compared with GH(+/+) competent mice (0.045 +/- 0.006 vs. 0.068 +/- 0.007, P < 0.05). Refeeding with standard chow diet stimulated protein synthesis in muscles by more than 60% in all animal groups. This response was independent of circulating GH, total IGF-I concentrations in blood, as well as up-regulation of locally produced IGF-I messenger RNA (mRNA) in skeletal muscles.

Animal Feed↗

Serum concentrations of insulin-like growth factor II are not changed by short-term fasting and refeeding.

To determine the factors that regulate insulin-like growth factor II (IGF-II), we raised polyclonal antibodies to this peptide and developed a RIA that measures IGF-II in serum or plasma samples after extraction of IGF-binding proteins by C18 cartridge chromatography. The IGF-II antiserum was highly specific, exhibiting no cross-reactivity with IGF-I or insulin at the highest concentrations tested (10(-6) mol/L). As little as 0.43 micrograms/L IGF-II was detectable, and 50% displacement of tracer occurred at 1.7 microgram/L. The serum IGF-II concentrations of normal adults [mean, 634 +/- 170 (+/- SD) micrograms/L], patients with acromegaly (570 +/- 146 micrograms/L), and patients with hypopituitarism (156 +/- 58 micrograms/L) were similar to those reported by others. In eight obese subjects injected with GH (0.1 mg/kg ideal BW, im, every 48 h for 16 days), serum IGF-II concentrations did not rise significantly, whereas IGF-I concentrations increased 67%. Sixteen normal subjects, within 15% of ideal body weight, were fasted for 5 days on two to four occasions and refed diets of differing protein and calorie contents. Their mean serum IGF-II concentration before fasting (691 +/- 26 micrograms/L) was not significantly different from that after fasting (674 +/- 21 micrograms/L) or after refeeding (641 +/- 20 micrograms/L). In contrast, their mean IGF-I concentration decreased 42% with fasting and rose with refeeding. Unlike IGF-I, serum IGF-II concentrations do not appear to be regulated by short term changes in nutritional status. It is clear from this study and others that IGF-II and IGF-I are regulated differently despite their structural homology and the similarity of their actions in vitro.

Adult↗

Plamsa leptin response to acute fasting and refeeding in untreated women with bulimia nervosa.

Leptin is known to regulate body weight, energy balance, and reproduction. Therefore, investigation of its physiology is of obvious interest in bulimia nervosa (BN), an eating disorder characterized by body weight-related psychopathology, acute changes in the energy balance, and reproductive alterations. To date, the few studies that have assessed leptin production in BN have had several limitations, including the measurement of blood leptin levels in treated patients and the lack of normal weight healthy controls, so that the information they provide is not conclusive. As the investigation of leptin dynamics is likely to be more informative, we decided to assess leptin response to acute fasting and refeeding in both untreated patients with BN and healthy controls. Twelve women meeting the diagnostic criteria for BN of the Diagnostic and Statistical Manual of Mental Disorders, and 10 healthy women of the same age range participated in a 3-day study. At 1800 h on day 1, they received a meal of 1088 Cal, with 53% carbohydrates, 17% protein, and 30% fat. Then, they fasted until 1800 h on day 2, when they received the same meal. On day 3, they received a standard hospital diet of 2600 Cal, divided into 3 meals, with the same percentages of nutrients as described above. Blood samples were collected at different time points for plasma leptin, glucose, and insulin measurements. In bulimic patients, plasma leptin values were significantly lower than in healthy women (P < 0.0001) and were positively related to body weight, expressed as body mass index (r = 0.86; P < 0.0001). The leptin response to the fasting/refeeding paradigm significantly differed between patients and controls (time x group interaction, P < 0.0001). In fact, in healthy subjects, acute fasting induced a 58% decline in the plasma leptin concentration, whereas such a decrease was only 7% in bulimic women (P < 0.001). After acute refeeding, plasma leptin increased in both groups, although in the patients it did not reach the absolute values observed in normal controls. No significant difference was observed between bulimics and controls in plasma insulin response to the fasting/refeeding paradigm, whereas an abnormal increase in blood glucose levels was observed in the patients after the first meal following acute fasting. We conclude that in untreated women with BN, leptin, despite its very low plasma values, still holds its function as a sensor of body weight changes, but loses its role of signaling acute changes in energy balance.

Adult↗

Simultaneous observation of the GnRH pulse generator activity and plasma concentrations of metabolites and insulin during fasting and subsequent refeeding periods in Shiba goats.

The time course of GnRH pulse generator activity and plasma concentrations of energy substrates and insulin were simultaneously observed in female goats during 4-day fasting and subsequent refeeding in the presence or absence of estrogen for a better understanding of the mechanism of energetic control of gonadotropin secretion in ruminants. The GnRH pulse generator activity was electrophysiologically assessed with the intervals of characteristic increases in multiple-unit activity (MUA volleys) in the mediobasal hypothalamus. In estradiol-treated ovariectomized (OVX+E2) goats, the MUA volley intervals increased as fasting progressed. Plasma concentrations of non-esterified fatty acid and ketone body increased, while those of acetic acid and insulin decreased during fasting. The MUA volley intervals and plasma concentrations of those metabolites and insulin were restored to pre-fasting levels after subsequent refeeding. In ovariectomized (OVX) goats, changes in plasma metabolites and insulin concentrations were similar to those in OVX+E2 goats, but the MUA volley intervals were not altered. The present results demonstrated that fasting suppressed GnRH pulse generator activity in an estrogen-dependent manner. Changes in plasma concentrations of energy substrates and insulin during fasting were associated with the GnRH pulse generator activity in the presence of estrogen, but not in the absence of the steroid in female goats.

Acetic Acid↗

Changes in gut gross morphology of traíra, Hoplias malabaricus (Teleostei, Erythrinidae) during long-term starvation and after refeeding.

Adult traíra (Hoplias malabaricus) were submitted to different periods of food deprivation (from 30 to 240 days) and refed for 30 days after 90 and 240 days of starvation. Stomach length remained constant during all the experimental period. However, the intestine length was significantly reduced after 30 days of food deprivation. Normal length was not recovered after refeeding. The number of pyloric caeca did not change significantly. Conversely, caeca thickness decreased after 150 days of starvation and their length decreased after 180 days. After refeeding, however, the pyloric caeca recovered original thickness. In fish refed after 240 days of starvation the length of these structures seemed to present compensatory growth, becoming longer than in the control group.

Animal Feed↗

Effects of fasting and refeeding on some metabolic characteristics of rat brown adipose tissue.

To investigate the effects of fasting and refeeding on rat interscapular brown adipose tissue (BAT), we determined in vitro oxygen consumption, in vitro lipolysis, DNA content and composition of fatty acid (FA). Fasting decreased the weights of body and BAT, and the DNA content of BAT. Fasting reduced both basal oxygen consumption and basal lipolysis of BAT. Fasting also suppressed the noradrenaline- and glucagon-induced increases in both oxygen consumption and lipolysis of BAT. In both triglyceride and phospholipid FA of BAT the extent of unsaturation was increased by fasting. Refeeding restored all of these parameters to the control level. These observations indicate that fasting reduces both oxygen consumption and lipolysis of BAT, resulting in reduced thermogenesis, while fasting could stimulate BAT in certain phases of its function as observed in FA composition.

Adipose Tissue, Brown↗