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Response of heterogenous rat liver lysosome populations to starvation and refeeding.

Starvation-induced alterations in liver lysosomes and their recovery pattern following refeeding were investigated. Fasting of adult rats for five days caused an increase in 'free' activities of acid hydrolyses in liver homogenates and loss in sedimentation of one of the heterogenous populations of lysosomes that could be isolated by differential centrifugation. Isopycnic sucrose gradient centrifugation revealed a decrease in the median and modal equilibration densities of all the forms of lysosomes in response to the dietary deprivation. Further, starvation also evoked a distinct bimodal distribution in a population that was rich in acid phosphatases, beta-galactosidase and N-acetyl-beta-glucosaminidase. Realimentation of starved animals for 10 days was found to restore the enzyme levels and the sedimentation characteristics to normal profiles.

Acetylglucosaminidase↗

Refeeding attenuates bombesin-induced hypothermia in the rat.

The tetradecapeptide bombesin is a potent agent in producing hypothermia when injected centrally. Bombesin-induced hypothermia at normal ambient temperature occurs under conditions of food deprivation or insulin-induced hypoglycemia. This experiment examined the effect of refeeding on the duration of bombesin-induced hypothermia. Rats (n = 7) received microinfusions of bombesin (0.1 microgram/1.0 microliter) into the preoptic area under separate conditions of food deprivation (18 h) and insulin pretreatment (10 U/kg, IM). Core body temperature was evaluated over a period of 4 h with or without food available during testing. Hypothermia was observed under all conditions during the first 2 h. Food-deprived and insulin-pretreated rats not permitted access to food remained hypothermic until at least 4 h following bombesin. These results are discussed in terms of the possible role of glucose availability in the production and duration of bombesin-induced hypothermia.

Animals↗

Effects of fasting and refeeding on vasoactive intestinal peptide binding to rat blood mononuclear cells.

The effect of acute and chronic starvation on vasoactive intestinal peptide (VIP) binding to rat blood mononuclear cells was studied. A short-term (1 day) fasting period did not induce significant changes in VIP binding. Longer periods of fasting (3 and 5 days) elicited an increase in VIP binding. This increase was due to an increase in affinity of both the high and the low affinity binding sites rather than to changes in binding capacity. Refeeding of fasted animals resulted in a decrease in VIP binding, reaching similar values to those of the control groups.

Animals↗

Differences in mRNA expression of adipocyte-derived factors in response to fasting, refeeding and leptin.

The present study examines whether and to what extent the profiles of adipose-derived factors are altered in epididymal and subcutaneous adipose tissues of long-term fasted/refed and of fasted rats treated by recombinant leptin. Fasting was characterized by three successive metabolic phases. Minor differences in the time-course and magnitude of response were detected between the two adipose sites. Leptin, adiponectin, resistin, adiponutrin, and insulin-like growth factor-1 (IGF-1) gene expressions differentially decreased according to the fasting duration. mRNA levels reached a minimum in late fasting for these secreted factors, being decreased by 60-90% for adiponectin, resistin, and IGF-1, 95-98% for leptin and by 100% for adiponutrin. Refeeding partially or totally restored their mRNA expression in epididymal adipose. Expression levels of apolipoprotein E (ApoE), angiotensinogen (AGT), adipsin and macrophage migration inhibitory factor (MIF) were either unchanged or slightly affected. In leptin-treated rats, leptin mRNA concentrations were significantly decreased in phase 2 of fasting (by 85%) from levels in control phosphate-buffered saline (PBS)-treated rats in both tissues. Leptin treatment also decreased resistin mRNA levels (by 78% in P2L and 63% in P3L relative to control groups) in subcutaneous adipose. These data suggest that adiponectin, resistin, adiponutrin, and IGF-1 could be involved in overall energy homeostasis during prolonged fasting, as leptin is. The mechanisms that underlie the expressions of these adipose-secreted factors remain to be determined.

Adiponectin↗

The effects of fasting and refeeding on biochemical parameters in the red-legged partridge (Alectoris rufa).

Every year, about three million farm-reared red-legged partridges are released in Spain for hunting purposes, most of them for restocking where the success is very low. Some factors such as the sudden shift from abundant commercial energy-rich diet to natural food and absence of experience at looking for natural food resources could cause a rapid physical deterioration, being more vulnerable to predation and disease. To determine fasting capacity in red-legged partridges, we fasted 32 birds during 4 days and then we refed them, collecting blood samples and body masses during the experiment. Red-legged partridges entered in the third critic phase of fasting, in which body proteins became the main energetic source, after 48 h of fasting. The fasting period caused an average loss of 17% of their initial body mass and only attained a 93.6% of their initial body mass after 24 days of refeeding. The limited capacity to resist fasting in the red-legged partridge could be one of the reasons for the low success in restocking, mainly in those where neither supplementary feeding nor acclimation period is allowed for birds before they are finally released.

Adaptation, Physiological↗

Changes in cytokine production and impaired hematopoiesis in patients with anorexia nervosa: the effect of refeeding.

The changes in cytokines and hormones involved in hematopoiesis were studied in the serum of 7 girls with anorexia nervosa, 15-24 yr old, on admission and after 5% and 10% weight gain. Hematopoiesis was studied by in-vitro culturing of circulating granulocyte-macrophage colony forming cells and erythroid burst forming cells. Nutritional status was studied by anthropometric measurements and resting energy expenditure. On admission, granulocyte-macrophage colony forming cells and erythroid burst forming cells were significantly lower than in age-matched controls and increased significantly along weight gain. Blood leptin and erythropoietin levels increased significantly with weight gain. TNF-alpha levels tended to decrease while IL-1beta levels were lower than in the controls on admission (p <0.05) and did not change significantly during weight gain. IL-3, GM-CSF and IL-6 were undetected on admission or along weight gain. The changes in granulocyte-macrophage colony forming cells and erythroid burst forming cells positively correlated with changes in resting energy expenditure and fat free mass. These results may suggest that undernutrition affects hematopoiesis as indicated by the reduction of hematopoietic progenitor cells before treatment and the significant increase with weight gain. The changes in the levels of hormones and cytokines known to be involved in hematopoiesis along refeeding may suggest a role for these factors in anorexia nervosa.

Adolescent↗

cDNA encoding sequences for myostatin and FGF6 in sea bass (Dicentrarchus labrax, L.) and the effect of fasting and refeeding on their abundance levels.

Fish have the ability to compensate for set-backs in growth as a result of fasting. When food levels are restored, growth in these fish can increase over and above normal rates. This phenomenon, known as "compensatory growth", has been studied with respect to enhancing food conversion efficiency. However, the mechanisms by which food intake activates an increase in somatic growth, and especially in muscle growth, are not well understood. In this study, we report first on the isolation of two complete cDNAs sequences encoding sea bass (Dicentrarchus labrax) myostatin and fibroblast growth factor 6 (FGF6), which have been shown to be major genetic determinants of skeletal muscle growth. The open reading frames of myostatin (376 amino acids) and FGF6 (209 amino acids) showed 97-63% and 87-62% sequence identity with other vertebrate myostatins and FGF6s, respectively. We also report on the expression profile of myostatin and FGF6 in sea bass skeletal muscle in response to different feeding regimens, as quantified by real-time RT-PCR. Nutritional status significantly influenced the myostatin expression levels in muscle, inducing an up-regulation during fasting and a down-regulation during the recovery from fasting, whereas the muscular FGF6 mRNA levels were not significantly affected by the feeding status of the animals. These findings suggest that myostatin has an inhibitory role in muscle growth in response to different feeding regimens, whereas FGF6 is not involved in the muscle compensatory growth induced by refeeding.

Amino Acid Sequence↗

Lipopolysaccharide (LPS)- and muramyl dipeptide (MDP)-induced anorexia during refeeding following acute fasting: characterization of brain cytokine and neuropeptide systems mRNAs.

We investigated the effectiveness of lipopolysaccharide (LPS) and muramyl dipeptide (MDP) administered into the brain to induce anorexia in acutely fasted Wistar rats allowed to refeed. We also assayed for changes in mRNA levels of IL-1 system components, TNF-alpha, TGF-beta1, glycoprotein 130 (gp 130), leptin receptor (OB-R), pro-opiomelanocortin (POMC), neuropeptide Y (NPY), glucocorticoid receptor (GR), and CRF receptor (CRF-R) in selected brain regions. The data show that LPS and MDP induced anorexia differentially during refeeding. LPS-induced anorexia was of a stronger magnitude and duration than that of MDP. RNase protection assays showed that LPS and MDP significantly increased the expression of IL-1beta, IL-1 receptor type I, and TNF-alpha mRNAs in the cerebellum, hippocampus, and hypothalamus; LPS was more potent in all cases. MDP treatment, on the other hand, induced a stronger increase in hypothalamic levels of IL-1 receptor antagonist (IL-1Ra) and TGF-beta1 mRNAs relative to LPS. In addition, competitive RT-PCR analysis showed that LPS induced an eleven-fold increase in IL-1alpha mRNA in the hypothalamus relative to vehicle. These findings suggest that LPS and MDP mediate anorexia through different cytokine mechanisms. A stronger up-regulation of anti-inflammatory cytokines (IL-1Ra and TGF-beta1) mRNA expression by MDP may be involved in the weaker MDP-induced anorexia relative to LPS. No significant changes were observed in the peptide components examined except for an up-regulation in cerebellar gp 130 mRNA and down-regulation of hypothalamic GR mRNA expression in response to LPS or MDP. This study shows that LPS and MDP induce anorexia in fasted rats allowed to refeed, and suggests an important role for endogenous cytokine-cytokine interactions.

Acetylmuramyl-Alanyl-Isoglutamine↗

Refeeding-malaria and hyperferraemia.

During the Central African (Sahelian) drought, attacks of falciparum malaria were common in patients and their relatives shortly after their arrival in a hospital in Eastern Niger. A prospective study of 72 adult patients not admitted for malaria and 109 accompanying relatives was undertaken to investigate this observation. 23 attacks occurred in patients and 51 in relatives, with a peak frequency five days after arrival. On arrival, parasitaemia was low but reached a maximum by five days. Serum-iron and percentage saturation of transferrin were moderately increased initially, rose dramatically within forty-eight hours with near maximum saturation, and were falling by the fifth day. It is suggested that the early hyperferraemia, apparently related to refeeding, led to rapid multiplication of existing parasites and attacks of malaria. The results of experimental malarial infection of Wistar rats, half of which had been given intramuscular iron, supported this hypothesis.

Adult↗

Starvation suppression and refeeding activation of infection. An ecological necessity?

The hypothesis is advanced that starvation suppresses and refeeding activates certain infections as an essential part of an ecological balance between man, his animals, and his environment. During famine, then, man fails to thrive, but his ultimate extinction is prevented in part by the parallel decline in fecundity of his "micropredators". In times of plenty the parallel increase in the same predators is a check against his excessive multiplication.

Adult↗

Age-associated changes in the serum level of apolipoproteins A-I and A-IV and the gene expression as revealed by fasting and refeeding in mice.

Alterations of serum apolipoproteins A-I (apo A-I) and A-IV and their mRNAs in young and old mice by fasting and refeeding were investigated by polyacrylamide gel elecrophoresis and Northern blot, respectively. After fasting for three days, serum apo A-I concentration in young mice (6-9 month-old) was increased about 1.5 fold while that of old animals (25-34 month-old) did not change significantly. Apo A-I mRNA was increased about 3-fold and 1.7-fold in the liver and small intestine of the young mice, respectively. The increase in old animals was not more than 1.5-fold in both tissues. The serum apo A-IV was elevated 2-fold and its mRNA was markedly (ca. 50-fold) induced in the liver of fasted young mice, whereas the increase of the mRNA was less than 2-fold in the small intestine. In contrast, induced levels of the protein in serum and its mRNA in both tissues were much less in old mice. In view of the roles of apo A-I and A-IV in triglyceride mobilization and reverse cholesterol transport, the present findings suggest that the reduced induction of the mRNAs for these apolipoproteins in the liver by prolonged fasting and possibly under normal feeding conditions can be an important factor in the impaired immobilization of lipid in old animals, and may, in turn, have implication in age-related diseases such as coronary, cerebral and other vascular disorders.

Aging↗

Effects of underfeeding and refeeding on offals weight in the Barbary ewes.

The influence of long-term (161 days) underfeeding and refeeding (154 days) on the weight of offal components, and digestive content, was studied in 26 adult Barbary ewes. Effects on the protein and mineral content of offals were also measured. Animals were split in three groups: one was fed hay at maintenance level (M), another also received vetch-oat hay to cover 0.2 of maintenance energy requirements (L), and the third one was fed at 0.2 of maintenance requirements during 161 days, then refed at 1.3 times of energy requirements with a diet of hay and barley grain (LH) during 154 days. Underfed animals body weight (BW) at slaughter was 31kg. Animals of groups M and LH were slaughtered at similar BW (50kg). Underfeeding reduced empty BW by 38% and the weight of most metabolically active organs: skin (40%), blood (31%), rumen (34%) and liver (19%), but not others (small intestine). Total offals weight was reduced by 27%. Overfeeding of previously underfed animals (LH) induced a significant increase in liver weight in comparison to M group (18%), owing to a higher nutrient supply. The amount of protein in offals and their fat-free weight were decreased by underfeeding, whereas the amount of minerals was significantly modified only in components rich in bone. These results showed that splanchnic organ mass decreases with underfeeding which leads to energy requirements decrease and contributes towards resistance of Barbary ewes to harsh food conditions.

Journal Article↗

Hypophosphatemia during nutritional rehabilitation in anorexia nervosa: implications for refeeding and monitoring.

PURPOSE: To determine the incidence of hypophosphatemia in adolescents with anorexia nervosa (AN) hospitalized for nutritional rehabilitation and to examine factors predisposing to its development. METHODS: A retrospective chart review of 69 patients (66 female, 3 male) with AN consecutively admitted to an inpatient adolescent medical unit between July 1, 1998 and June 30, 2000. Mean age was 15.5 +/- 2.4 (range 8 to 22) years and mean % ideal body weight (IBW) was 72.7 +/- 7%. Serum phosphorus was measured daily for 1 week and then biweekly to weekly. Patients were started on 1200-1400 kcal/day and calories were increased by 200 kcal every 24-48 hours. RESULTS: Four (5.8%) patients developed moderate hypophosphatemia (<2.5 and > or = 1.0 mg/dl) and 15 (21.7%) had mild hypophosphatemia (<3.0 and > or = 2.5 mg/dl). Patients who developed moderate hypophosphatemia were significantly more malnourished than those who did not (p = 0.02). Phosphorus nadirs were directly proportional to % IBW (r = 0.3, p = 0.01). Over three-quarters of the patients (81%) reached their phosphorus nadir within the first week of hospitalization. The patient with the lowest phosphorus level experienced short runs of ventricular tachycardia. No other severe complications were seen. Overall, 19 (27.5%) patients required phosphorus supplementation. CONCLUSIONS: Phosphorus drops to its nadir during the first week of refeeding. We recommend daily monitoring of serum phosphorus with supplementation as needed during the first week of hospitalization, especially in those who are severely malnourished.

Adolescent↗

Effect of starvation and refeeding on amino acid uptake by mammary gland of the lactating rat. Role of ketone bodies.

Arteriovenous differences of amino acids across the mammary glands of lactating rats are diminished when the rats are starved for 24 h. When 24 h-starved rats were refed for 2 1/2 h, the arteriovenous differences of amino acids returned to values similar to those found in well-fed rats. In order to find a possible explanation for these rapid changes, we tested the effect of ketone bodies on amino acid uptake by the gland. At 5 min after injection of acetoacetate to fed rats, when the total concentration of ketone bodies in blood was similar to that found in starvation, the uptake of amino acids by the mammary gland was similar to that found after starvation, i.e. lower than in fed rats. However, 30 min after administration of acetoacetate, when the arterial concentration of ketone bodies had returned to values similar to those in fed rats, the arteriovenous differences of amino acids were similar to those found in fed rats. We conclude that the changes in blood ketone bodies may be responsible, at least in part, for the changes in amino acid uptake that occur in starvation and in the starvation--refeeding transition.

Acetoacetates↗

Long-term undernutrition followed by short-term refeeding effects on the corticotropin-releasing hormone containing neurones in the paraventricular nucleus: an immunohistochemical study in sheep.

The effect of nutritional level on the immunoreactivity of corticotropin-releasing hormone (CRH) in neurones of the hypothalamic paraventricular nucleus was described in sheep, a ruminant, whose feeding strategy differs from that of monogastric species. Two groups of ewes were underfed (40%), or fed at maintenance (100%) for 167 days, after which one-half of each group was killed or ad libitum refed (at least 150% of maintenance) for 4 days before killing. The presence of CRH in the paraventricular nucleus was examined by immunohistochemistry. The number of CRH immunoreactive neurones was increased in underfed ewes, but without modification of the plasma concentration of cortisol, indicating that the rise of CRH was not released in the portal blood nor linked to the pituitary-adrenal axis. Refeeding did not modify significantly the number of CRH immunoreactive neurones in the nucleus although these neurones were increased, only in refed ewes that were previously underfed. These data differ from those for rats and mice where CRH expression is decreased or not modified by underfeeding which could reflect different effects of undernutrition on CRH immunoreactive neurones in monogastric compared to ruminants species.

Animal Nutritional Physiological Phenomena↗

Effects of fasting and refeeding on insulin binding to liver plasma membranes and hepatocytes from normal rats.

The effect of acute and chronic starvation on insulin binding to liver cells and liver cell membranes was studied in normal rats. A short-term (1 day) fasting period did not induce significant changes in insulin binding to liver plasma membranes in spite of the hypoinsulinemia present in the rats, as compared with normo-insulinemic fed controls. Longer periods of fasting (2 and 4 days) elicited an increase in insulin binding to liver membranes that was due to an increase in the number of insulin receptors rather than to changes in affinity. All groups of membranes were similar with respect to the rates of association and dissociation of hormone, degree of negative cooperativity and extents of both hormone and receptor inactivation. The fasting-induced increase of insulin binding was not a consequence of the methodological procedure for membrane isolation since the same conclusions were obtained when intact hepatocytes were used. Refeeding of fasted animals resulted in a decrease of insulin binding together with an increase of insulinemia towards the fed control values. These results suggest that the number of insulin receptors is inversely related to the circulating levels of the hormone and support the hypothesis of insulin regulating its own receptor.

Animals↗

Changes in activity and molecular properties of fructose 1, 6-bisphosphatase during fasting and refeeding.

During prolonged starvation, fructose 1,6bisphosphatase (EC 3.1.3.11) activity in rabbit liver and kidney shows a transient decrease during the first 36 hr, before rising at 96 hr to levels severalfold higher than those found in the livers of fed animals. Proteolytic activity appears in the 105,000 x g supernatant fraction within several hours of starvation, and continues to increase during the entire 96-hr period. On refeeding, the activities return to nearly the control levels within 24 hr. The catalytic properties of fructose 1,6-bisphosphatase isolated from the livers of fasted rabbits are similar to those of the enzyme from fed animals, but its structure is modified, since it no longer contains the single tryptophan residue located near the NH(2)-terminus in the native enzyme. Thus this tryptophan residue is not required for the neutral pH optimum. The structural changes and the transient decrease in activity may be related to the observed increase in "free" proteolytic activity.

Animals↗

Effects of fasting and refeeding on energetic metabolism of cold acclimated rats.

In rats acclimated at 5 degrees C or 28 degrees C (thermal neutrality), overnight fasting induced decreases in body and brown adipose tissue (BAT) weights and led to a larger decrease in resting metabolism (RM) in the 5 degrees C rats than in the 28 degrees C group. Refeeding significantly enhanced RM (diet-induced thermogenesis) in a greater extent in 5 degrees C than in 28 degrees C rats. This effect was inhibited by propranolol (beta adrenergic receptor antagonist) in 28 degrees C but was only halved in 5 degrees C rats. The capacity for nonshivering thermogenesis as determined by norepinephrine infusion was reduced by fasting only in 28 degrees C group; it remained unchanged in cold acclimated rats despite the large lipid utilization induced by fasting.

Acclimatization↗