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Long-term effects of starvation-refeeding in the rat.

The effects of one vs. two episodes of starvation-refeeding were studied in young male rats as a function of elapsed time between the two episodes of starvation-refeeding. Starved-refed rats ate more and gained weight faster than ad libitum-fed rats. The difference in weight gains could be attributed to the greater amount of body fat in the starved-refed rats. The responses of four NADP-linked liver dehydrogenases:isocitrate dehydrogenase (ICD)/LS-isocitrate:NADP oxidoreductase (decarboxylating) (EC 1.1.1.42), glucose-6-phosphate dehydrogenase (G6PD)/D-glucose-6-phosphate:NADP oxidoreductase (EC 1.1.1.49); 6-phosphogluconate dehydrogenase (6PGD/6-phospho-D-gluconate:NADP oxidoreductase (decarboxylating) (EC 1.1.1.44); and malic enzyme (ME)/L-malate:NADP oxidoreductase (decarboxylating) (EC 1.1.1.40) were studied. Starvation-refeeding caused an overshoot of G6PD, 6PGD, and ME, but not of ICD. A second episode of starvation caused an even greater enzyme overshoot; this difference persisted for 3 weeks with G6PD and for 2 weeks with 6PGD and ME. No significant differences in blood cholesterol were detected.

Adipose Tissue↗

The effects of starvation, glucose infusion, and normal feeding, on muscle protein synthesis and catabolism in the newborn guinea pig.

We determined the effects of feeding, starvation, and glucose infusion after starvation in newborn guinea pigs. We determined the rate of 14C-leucine incorporation into skeletal muscle (KS) as a measure of muscle protein synthesis and the rate of excretion of 3-methylhistidine as a measure of muscle myofibrillar protein catabolism (Kc). Fed newborns, who were in positive nitrogen balance, had the highest Ks and lowest Kc, while starved newborns had the lowest Ks and highest Kc. Infusing glucose after starvation decreased net protein catabolism and Kc, but did not increase Ks. The magnitude of change of Kc in response to starvation and glucose infusion was much greater than Ks. Changes in catabolic rate may influence net muscle protein balance to a greater degree than changes in synthetic rate.

Animals↗

Modifications of brush border enzyme activities during starvation in the jejunum and ileum of adult rats.

Aminopeptidase, lactase and sucrase activities have been followed during 5 days in the jejunum and in the ileum of starved adult rats. Enzyme activities have been determined in the mucosal homogenates as well as in the purified brush border membranes and expressed as activities per intestinal length (segmental activities) or as activities per milligram of protein (specific activities). The segmental and specific activity of aminopeptidase was increased in the ileum during the first 2 days of starvation, suggesting that aminopeptidase may have during the first days of starvation a conservative role by preventing an important loss of tissue protein. In all conditions, lactase activity was strikingly enhanced by starvation whereas sucrase activity showed no changes or decreased activity. Lactase stimulation was initiated during the first 24 h of starvation reaching its maximum after 2 days. The various experimental conditions leading to a specific or to a nonspecific stimulation of intestinal lactase activity have been discussed.

Animals↗

Metabolic response to human growth hormone during prolonged starvation.

The metabolic response to human growth hormone (HGH) was studied in five obese subjects in the fed state and during prolonged (5-6 wk) starvation. In the fed state (three subjects), HGH induced an elevation in basal serum insulin concentration, a minimal increase in blood and urine ketone levels, and a marked reduction in urinary nitrogen and potassium excretion resulting in positive nitrogen and potassium balance. In prolonged fasting (four subjects), HGH administration resulted in a 2- to 3-fold increase in serum insulin which preceded a 50% elevation in blood glucose. Persistence of the lipolytic effects of HGH was indicated by a rise in free fatty acids and glycerol. The response differed markedly from the fed state in that blood beta-hydroxybutyrate and acetoacetate levels rose by 20-40%, resulting in total blood ketone acid concentrations of 10-12 mmoles/liter, ketonuria of 150-320 mmoles/day, and increased urinary potassium loss. The subjects complained of nausea, vomiting, weakness, and myalgias. Despite a 50% reduction in urea excretion during HGH administration, total nitrogen loss remained unchanged as urinary ammonia excretion rose by 50% and correlated directly with the degree of ketonuria. It is concluded that in prolonged starvation (a) HGH may have a direct insulinotropic effect on the beta cell independent of alterations in blood glucose concentration, (b) persistence of the lipolytic action of HGH results in severe exaggeration of starvation ketosis and interferes with its anticatabolic action by necessitating increased urinary ammonia loss, and (c) failure of HGH to reduce net protein catabolism in starvation suggests that this hormone does not have a prime regulatory role in conserving body protein stores during prolonged fasting.

Acetoacetates↗

Effect of starvation and total parenteral nutrition on electrolyte homeostasis in normal man.

Elemental balances, and skeletal muscle membrane potential (Em) and biopsy were utilized to evaluate electrolyte homeostasis and body composition in 11 healthy adult volunteers after 10 days of starvation. This controlled, acute malnutrition was followed by refeeding for 10 days with two different, commonly used, total parenteral nutrition (TPN) solutions. Six subjects were refed with crystalline amino acids and dextrose (dextrose group), while five subjects received amino acids, dextrose, and lipid (lipid group). During starvation, negative balances for potassium, phosphorous, magnesium, and nitrogen were observed in both groups. When compared to starvation, total parenteral nutrition produced statistically significant (p less than 0.05) equilibrium or positive electrolyte and nitrogen balances for both, the dextrose and lipid groups. During TPN, there was a significantly (p less than 0.001) positive chloride balance in the lipid group when compared to the dextrose group. At the conclusion of the 10-day period of TPN, there was a decrease (p less than 0.05) in skeletal muscle Em. This change, in concert with the electrolyte balance data obtained during parenteral repletion, lead us to postulate that restoration of lean tissue protein and cellular function does not occur at a rate which might be inferred from the positive nitrogen balance observed in this model. A persistent defect in cellular function which was evident after starvation, suggests that a brief period of TPN is insufficient to restore skeletal muscle integrity.

Adult↗

Effect of starvation on tissues from the young of four species, with emphasis on the number and diameter of skeletal muscular fibers.

Young rats, rabbits, guinea pigs, and hamsters were decreased in body weight by 39, 45, 34, and 35%, respectively, by a total deprivation of food for 3, 15, 4, and 4.5 days, respectively. The weight of the heart, liver, and kidneys from each of the four species (with the excepetion of the kidneys from the guinea pig) decreased significantly in the starved animals. After starvation in all four species, 0 to 15% of the original weight of the epididymal and perirenal fat pads remained. The effect of total starvation on the weight of skeletal muscles differed for the same muscle in different species and among the three muscles studied within a species. Starvation caused weight losses in the following muscles from the rat, rabbit, guinea pig, and hamster, respectively: soleus, 15, 8, 14, and 30% plantaris, 23, 54, 41 and 24%; biceps brachii, 27, 52, 42, and 29%. The significant loss of weight in the plantaris and biceps brachii muscles from rabbits and guinea pigs were caused by large decreases in the diameter of the fibers, with no change in the number of fibers. Soleus and plantaris muscles from hamsters decreased in weight by a reduction in fiber diameters but no change in the number of fibers; the weight of biceps brachii decreased by a reduction in fiber number only. A reduction in the number of fibers occurred in all muscles from starved rats; the diameter of the fibers was reduced in the plantaris and biceps brachii muscles. No structural damage to the fibers due to starvation was observed under the light microscope in any muscle from the four species.

Animals↗

The effects of starvation and surgical injury on the plasma levels of glucose, free fatty acids, and neutral lipids in newborn babies suffering from various congenital anomalies.

Blood glucose, plasma free fatty acids (FFA), cholesterol, phospholipids, and triglycerides were measured in blood obtained by heel prick from 32 neonatal surgical patients suffering from various cogenital malformations which prevented and adequate intake of milk. The result of almost complete starvation for up to 7 days was investigated and the effects of a surgical operation were studied in 12 of the babies. All the babies weighed more than 2 kg at birth. A surgical operation caused a rise in blood glucose concentration but a variable change in plasma concentration of FFA. Blood glucose returned to normal within 8 to 12 hr. The plasma concentrations of cholesterol and phospholipids did not change except in two babies in whom the concentration of both fell. Four to 24 hr after operation the plasma triglyceride level fell by an average of 25% but later rose. During starvation for 7 days the blood glucose concentration was maintained within normal limits. Plasma FFA concentration normally rose during the first 2 days of life and was very high between days 3 and 5. Plasma triglyceride, cholesterol, phospholipids, and total esterified fatty acids also increased after birth. The results suggest that during starvation in the neonate there is rapid mobilisation of fat from adipose tissue stores and a reduction in the peripheral utilisation of glucose. There was no evidence to suggest any impairment of fat mobilisation or metabolism even after starvation for 7 days. After surgical injury, these changes were accentuated because the rate of utilisation of fat was greater than that of mobilisation.

Blood Glucose↗

Prenatal starvation retards development of the ventilatory response to hypoxia in newborn guinea pigs.

Prenatal starvation causes pulmonary hypoplasia in newborn guinea pigs, and is associated with postnatal cyanosis, hypothermia, and respiratory failure. To determine the effects of such starvation on ventilation, neonates from litters either fed ad libitum throughout gestation (control) or given 50% rations in the last trimester of pregnancy (starved) were studied at 29 degrees C by plethysmography in 21, 11, and 5% O2. After 15 min (steady-state) in 11% and then 5% O2, 13 of 14 controls (mean = 95 g) sustained increases in weight-specific minute ventilation of 46 and 75% compared to values in air (p less than 0.01), due to increases in respiratory frequency. Seven of 11 starved neonates (mean = 76 g) also sustained increases in respiratory frequency and weight-specific minute ventilation in 11 and 5% O2 similar in magnitude to those of the normal controls, although at higher weight-specific tidal volumes. One abnormal control (85 g) and four starved neonates (mean = 70 g) hyperventilated in air, did not respond to 11% O2, and then hypoventilated in 5% O2 due to a reduced weight-specific tidal volume. Neonates with normal ventilatory patterns did not alter weight-specific minute ventilation in 100% O2 and did not show a biphasic response in acute (1-5 min) exposures to moderate hypoxia, as noted for newborn of other species. Thus, hypoxia identified those starved neonates in which pulmonary immaturity or other starvation-induced pathologies necessitated a maximal ventilatory effect in air. The sustainable hyperventilation among normal guinea pigs during hypoxia emphasizes the precocial development in this species at birth, which may be compromised by intrauterine starvation.

Animals↗

Sensitivity of thyrotropin (TSH) secretion to 3,5,3'-triiodothyronine and TSH-releasing hormone in rat during starvation.

The mechanisms by which plasma T3 and TSH decrease after a 3-day starvation period are not completely understood. In this study we tested the hypothesis of a possible modification in the sensitivity of thyrotroph cell to T3 and/or TRH. For that purpose, TRH tests were performed before and after a 3-day starvation in euthyroid, thyroidectomized, and T3-treated (75 or 175 ng/100 g BW) thyroidectomized male Wistar rats. TRH (10 to 500 ng/100 g BW) was injected iv through a chronically-implanted catheter. In another set of experiments, hypophyseal TSH content was also determined. Our results showed that after a 3-day-starvation plasma TSH decreased in all except hypothyroid rats; TSH responsiveness to TRH was unchanged in euthyroid rats but was increased in hypothyroid rats; and the T3-dependent increase in TSH responsiveness to TRH was significantly amplified. Moreover, there was a significant positive correlation between TSH responsiveness to TRH and hypophyseal TSH content. These results suggest that starvation induces an increased sensitivity of thyrotroph cell to T3.

Animals↗

Effect of starvation on the production and metabolism of thyroxine and triiodothyronine in euthyroid obese patients.

The metabolic clearance and production rates of thyroxine (T4) and triiodothyronine (T3) were measured in 9 obese euthyroid patients prior to and during prolonged starvation. The metabolic clearance rates (MCR) and serum concentrations of T4, and, therefore, the metabolic degradation or production rates of T4 were unchanged during starvation. Serum T3 concentrations decreased strikingly during starvation, from 145 +/- 7 ng/dl (mean +/- SE) to 66 +/- 9 ng/dl (P < 0.001), while the mean MCR of T3 was unchanged, with the result that T3 degradation or production rates were markedly decreased (36.4 +/- 4.5 μg/d vs. 11.2 +/- 0.7 μg/d; P < 0.001). These findings suggest that the decrease in serum T3 concentration observed during starvation results from a decrease in the peripheral conversion of T4 to T3.

Adult↗

Regulation of gastric mucosal pepsinogen and intrinsic factor contents, and their mRNA levels during starvation and refeeding in rats.

Gastric mucosal pepsinogen and intrinsic factor (IF) contents, and their mRNA levels during starvation and refeeding were studied. During starvation for 4 d, gastric mucosal pepsinogen and IF contents significantly decreased, whereas pepsinogen and IF mRNA levels increased by 30-50%. These results suggested that the mRNAs of pepsinogen and IF could be preserved for a long time so as to prepare for refeeding. After ceasing the starvation for 72 h, gastric mucosal pepsinogen and IF contents were significantly decreased at 1 h after refeeding, and their mRNA levels were increased by 20-30% at 30 min after refeeding. We examined whether the refeeding-induced changes in gastric mucosal pepsinogen and IF contents and their mRNA levels could be reproduced by the exogenous administration of secretagogues. They were not found to be affected by the administration of each secretagogue during starvation for 72 h at 30 min. However, by the simultaneous administration of 2 or 3 secretagogues (carbachol, cholecystokinin octapeptide (CCK-8) or secretin), the contents of pepsinogen and IF decreased to 70-80% and 50-80% of the control, respectively. However, their mRNA levels increased to 140-160% and 120-135% of the control, respectively. Therefore, refeeding-induced changes in pepsinogen and IF contents and their mRNA levels were partially reproduced by exogenously administered secretagogues. This showed that food intake influences huge changes in neural, hormonal and physical conditions on the stomach. It was indicated that the secretagogues stimulated not only pepsinogen and IF secretion, but also had a tendency to increase their mRNA.

Animals↗

Effects of starvation on microsomal cytochrome P-450 and laurate-omega-hydroxylation of rat kidney and liver.

Cytochrome P-450 (P-450) content and laurate-omega-oxidation activity in rat kidney and liver microsomes were investigated following starvation. Multiple forms of P-450 were analyzed by one dimensional separation using peroxidase stained SDS-continuous gradient polyacrylamide gel electrophoresis. Gels of the hepatic microsomes treated with phenobarbital showed three P-450 bands, and the renal microsomes showed one sharp band, which was induced remarkably by starvation and coincided with the middle molecular form of P-450 from the hepatic microsomes. Since laurate-omega-oxidation activity was induced specifically by starvation but not by drug treatment, in both the kidney and the liver microsomes, the middle molecular form of P-450 might catalyze laurate-omega-oxidation. It seemed, therefore, that a special P-450 subunit catalyzing laurate-omega-oxidation has a greater function in the renal rather than hepatic microsomes because the specific laurate-omega-oxidation activity per starvation induced P-450 content was relatively similar in both the kidney and the liver.

Animals↗

Starvation-induced impairment of metabolism in a freshwater catfish.

Starvation induced changes in citrate synthase (CS), glucose-6-phosphate dehydrogenase (G6-PDH), lactate dehydrogenase (LDH), DNA, RNA, RNA/DNA ratio and protein were studied in the freshwater catfish Clarias batrachus. Starvation gradually decreased the activity of CS, G6-PDH and LDH in brain, liver and skeletal muscle of the freshwater catfish. The maximum reduction in these enzyme activities upto 35-45% was observed after 35 days of fasting. This shows substantial decline in aerobic and biosynthetic capacity during starvation period. DNA, RNA, RNA/DNA ratio and protein contents were also reduced from 40-67% which reflects reduction in an overall capacity of the protein synthesis. Starvation-induced macromolecular changes indicate impairment of metabolism in fish.

Acclimatization↗

T4 degradation rate and plasma levels of TSH and thyroid hormones in ten young bulls during feeding conditions and 48 h of starvation.

The effect of starvation on thyroid hormones was studied during a starvation period of 48 h in 10 young bulls. Mean thyroxine degradation rate decreased from K/day 0.32 during feeding to 0.23 during fasting. Mean plasma concentration of T4 decreased to 75% of normal, and it was calculated that the mean thyroxine secretion rate during the starvation period was 24% of normal. Plasma concentration of free thyroxine decreased to 54% of normal, indicating that the concentration of binding protein was not decreased. T3 and reverse T3 decreased to about 60% of normal. This indicated a parallel decrease in the secretion of all 3 hormones. We did not find evidence of an inactivating pathway for T4 as has been shown in humans during starvation. TSH decreased to 85% of normal.

Animals↗

Starvation induced anoestrus: effect of chronic food restriction on body weight, its influence on oestrous cycle and gonadotrophin secretion in rats.

To test the effect of chronic starvation on gonadotrophin secretion and oestrous cycles, rats were fed 50% of their normal chow consumption for 16 days. This caused an increasing rate of anoestrus which became significant during the third expected cycle (6 of 10 rats, P less than 0.02) and increased to 8 of 10 rats (P less than 0.0001) between day 12 and 16. The accompanying weight loss was around 13 and 17%, respectively. Pituitary weights in intact rats killed on dioestrus became significantly different after 8 days of chow reduction (12.8 +/- 0.2 vs 11.3 +/- 0.4 mg, P less than 0.02) with further reductions in groups killed after 12 and 16 days. At this time dioestrous serum FSH levels were significantly increased in starved rats (112 +/- 16 vs 161 +/- 13 ng/ml, P less than 0.01), while serum LH levels decreased significantly after 12 days (25.0 +/- 3.4 vs 13.1 +/- 8.8 ng/ml, P less than 0.001). Starvation decreased the LH response to LRH administration compared to pro-oestrous controls (1934 +/- 672 vs 289 +/- 39 ng/ml, P less than 0.05), whereas the FSH response was not impaired (457 +/- 91 vs 336 +/- 54 ng/ml, P greater than 0.05). In contrast to this pituitary content of LH was similar in both groups, while FSH content was significantly higher in starved animals (13.6 +/- 1.7 vs 19.8 +/- 1.2 micrograms, P less than 0.01). Chronic starvation immediately after ovariectomy did not affect the post-castrational rise of gonadotrophins. However, LRH administration caused higher serum FSH levels in starved rats (1540 +/- 91 vs 1833 +/- 90 ng/ml, P less than 0.05), whereas LH values did not differ (908 +/- 192 vs 721 +/- 153 ng/ml, P greater than 0.05). Gonadotrophin content per pituitary in castrated rats after 16 days of starvation was unchanged.

Anestrus↗

Is thyrotropin-releasing hormone receptor involved in thyrotrope adaptation to starvation?

The aim of the present study was to delineate the involvement of TRH receptors in the thyrotrope adaptation to starvation (i.e. plasma TSH and thyroid hormone decrease, increased sensitivity to T3) by measuring [3H]TRH binding in euthyroid, hypothyroid and T3-substituted rats (175 ng/100 g body weight). Our results show that in euthyroid rats, starvation does not significantly modify either the affinity or the number of pituitary binding sites. In hypothyroid and T3-substituted rats, starvation does not alter the negative control exerted by T3 on the number of TRH binding sites. Our data indicate that the adaptation of thyrotrope to starvation does not primarily result from alterations of TRH binding sites.

Adaptation, Physiological↗

Short-term starvation increases calcidiol-24-hydroxylase activity and mRNA level in rat kidney.

The renal mitochondrial calcidiol-24-hydroxylase activity and the corresponding cytochrome P-450 mRNA level were measured in rats subjected to short-term starvation alone or in combination with calcitriol treatment. Short-term starvation of 24 and 48 h increased the mRNA level by five- and six-fold, respectively. The 24-hydroxylase activity increased by five- and threefold, respectively. Treatment with calcitriol markedly increased the enzyme activity about 20-fold and the mRNA level about six-fold. In rats subjected to calcitriol treatment combined with 24 h of starvation, a significant further increase in enzyme activity was observed. The mRNA levels increased but the difference was not significant statistically. The results indicate that the mechanism by which starvation stimulates the enzymes is different, at least in part, from that behind the stimulatory effect of calcitriol.

Animals↗

Effect of starvation and refeeding on the circadian rhythms of hematological and clinico-biochemical values, and water intake of rats.

We investigated the effect of starvation for 24 hr and subsequent refeeding for 12 hr on the circadian rhythms of 39 hematological and clinico-biochemical parameters, and water intake of F344 rats. The rats scarcely drank any water during the starvation period, but subsequently their intake of water were normal, even in the light period. During starvation, 12 parameters such as serum levels of alkaline phosphatase activity and PaCO2 decreased with time-related and time-related increases of 8 parameters such as the erythrocyte count and cholinesterase activity. During refeeding for 12 hr, almost all these biochemical parameters were normalized, but none of the hematological values except the leukocyte count returned to normal levels. Starvation and refeeding had little affect on the circadian rhythms of others.

Alkaline Phosphatase↗