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PubMed1984

Effects of fasting and refeeding on antral, duodenal, and serum gastrin levels and on colonic thymidine kinase activity in rats.

Antral, duodenal, and serum gastrin levels and colonic thymidine kinase activity were determined in 1- to 4-day-fasted rats and after refeeding of 4-day-fasted rats for 3-24 h. The effect of pentagastrin on colonic thymidine kinase activity was also determined. Total deprivation of food caused a drastic reduction in gastrin concentrations in serum and tissues. After 4 days of fasting, serum gastrin levels in most animals fell below the present detection limit of the assay (10-15 pg/ml), and antral and duodenal gastrin levels decreased to 15 and 50% of the respective initial fed control. After 9 and 24 h of refeeding, gastrin concentration in serum and antrum had increased to about 35% of the initial fed level. On the other hand, refeeding for 3-24 h produced no significant change in duodenal gastrin concentration. Fasting for 1-4 days resulted in a 60-70% reduction in colonic thymidine kinase activity, compared to the initial fed control. Refeeding caused a prompt stimulation in the enzyme activity, which after 6 h was found to be 72% above the 4-day-fasted group. Daily injection of pentagastrin, at doses between 125 and 500 micrograms/kg, during a 4-day fasting period resulted in a significant stimulation in colonic thymidine kinase activity, compared to the saline-treated control. The maximal stimulation of an enzyme activity 90% higher than in the saline control was attained with a pentagastrin dose of 125 micrograms/kg. Higher doses decreased the maximal stimulatory effect of pentagastrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1980

Adaptations of alpha2- and beta-cells of rat and mouse pancreatic islets to starvation, to refeeding after starvation, and to obesity.

The effects of starvation and refeeding and of obesity on pancreatic alpha2- and beta-cell responses to glucose or tolbutamide were studied with the isolated rat or mouse pancreas perfused with an amino acid mixture in the presence and absence of glucose. It was observed that the physiological adaptation to a regimen of fasting and realimentation and to obesity differed greatly in the two types of endocrine cells. Whereas beta-cells of rats showed a dramatic reduction of glucose- and tolbutamide-stimulated insulin release during starvation that was reversed by refeeding, alpha2-cells preserved their response to stimulators and inhibitors during this experimental manipulation. Amino acid stimulation of glucagon release occurred equally well with the pancreas from fed and starved rats and was suppressed efficiently by glucose and tolbutamide in both nutritional states. Surprisingly, the rate of onset of glucose suppression of alpha2-cells was significantly higher in the fasted than in the fed state. This glucose hypersensitivity was apparent 2 d after after food deprivation and had disappeared again on the 2nd d of refeeding. In the pancreas from animals starved for 3 d, glucose and tolbutamide suppression of alpha2-cells took place in the absence of demonstrable changes of insulin release. In the isolated perfused pancreas taken from the hyperphagic obese hyperglycemic mouse (C57 Black/6J; ob/ob), the observed rate of insulin secretion as a result of a combined stimulus of amino acids and glucose and of glucagon release stimulated by amino acids was about four times higher than achieved by the pancreas of lean controls. However, glucose was unable to suppress the alpha2-cells in the pancreas of obese animals, in spite of the hypersection of the beta-cells, again in contrast to the alpha2-cells of controls that were readily inhibited by glucose. These data imply that the acute suppression of alpha2-cells by glucose is largely independent of a concomitant surge of extracellular insulin levels and that the adaptation of the islet organ to starvation leads to decreased glucose sensitivity of beta-cells, which contrasts with an improved glucose responsiveness of alpha2-cells. However, hyperphagia, which is assumed to be the primary abnormality in the ob/ob mouse, leads to overproduction of insulin and glucagon by the pancreas while greatly reducing the alpha2-cell sensitivity to glucose. An attempt is made to incorporate these data on starvation, refeeding, and obesity, as well as previous results with experimental diabetes, in a comprehensive picture describing a regulative principle underlying the glucose responsivness of alpha2-cells.

Adaptation, Physiological↗

PubMed1998

Hypophosphatemia in malnourished children during refeeding.

Hypophosphatemia in malnourished children during nutritional recovery (refeeding hypophosphatemia) is recognized as a cause of morbidity and mortality in adolescents with anorexia nervosa but has been only rarely reported to occur in younger children with other diagnoses. Over a 6-year period, we encountered three cases of refeeding hypophosphatemia in malnourished children admitted to a pediatric rehabilitation hospital. Two children had neurologic dysphagia and one had been starved by an abusive parent. The one patient who was symptomatic had obtundation, hemolytic anemia, rhabdomyolysis, and hepatocellular injury that began during refeeding and resolved with treatment. The signs and symptoms, pathophysiology, and treatment of refeeding hypophosphatemia are reviewed.

Child↗

PubMed1990

Impact of refeeding on intestinal development and function in infant rabbits subjected to protein-energy malnutrition.

The impact of early postnatal protein-energy malnutrition and of 4, 7, and 14 d of nutritional rehabilitation on small intestinal growth, development, structure and function was examined in 28-, 32-, 35-, and 42-d-old infant rabbits. Malnutrition was induced by litter expansion 7 d postpartum and, in randomly selected malnourished animals, refeeding was begun at weaning, 28 d. Results are compared to ad libitum fed dietary controls. Malnutrition altered the small intestine of the developing rabbit, as evidenced by: 1) reduced jejunal and ileal mass as shown by decreased mucosal wt, protein, and DNA content; 2) depressed epithelial proliferation and enterocyte migration along the crypt-villus axis; 3) delayed epithelial maturation as measured by mucosal enzyme activities; and 4) enhanced glucose-stimulated Na+ transport. Refeeding stimulated rapid and complete recovery, as evidenced by: 1) restoration of jejunal and ileal mucosal mass within 4 d; 2) enhancement of epithelial renewal and enterocyte migration by 7 d; and 3) complete return of the normal pattern of mucosal enzymes by 14 d. With 7 d of refeeding, glucose-stimulated Na+ transport was down-regulated to the level of dietary controls. We conclude that early postnatal protein-energy malnutrition has a severe impact on small intestinal growth, development, structure, and function. Furthermore, a brief period refeeding induced a rapid and complete recovery of these parameters.

Animals↗

PubMed1983

The role of insulin and glucocorticoids in the regulation of hepatic glycogen metabolism: effect of fasting, refeeding, and adrenalectomy.

The roles of insulin, adrenal corticol hormones, and nutritional factors in the regulation of hepatic glycogen metabolism were investigated by means of fasting and refeeding normal and adrenalectomized (ADX) rats. More specifically, the hypothesis in question in this study is that certain hepatic phosphoprotein phosphatases are targets of insulin action in liver. In anesthetized rats, the hepatic glycogen concentration and the activities of hepatic glycogen synthase, glycogen synthase phosphatase, glycogen phosphorylase, and phosphorylase phosphatase were correlated with peripheral plasma glucose and immunoreactive insulin levels. Hepatic phosphatase activities were measured in (soluble) the high speed supernatant and smooth endoplasmic reticulum (SER). Fasting resulted in expected diminutions in circulating glucose and insulin levels and loss of hepatic glycogen. These changes were greater in ADX rats. The percentage of hepatic glycogen synthase in the active or I form increased with fasting in normal rats, but did not change in ADX rats. Hepatic synthase phosphatase activities were decreased in SER by fasting in both normal and ADX rats, but to a much greater extent in the latter; soluble synthase phosphatase was much less affected by fasting. The percentage of phosphorylase in the active or a form was significantly decreased in normal, but not ADX, rats. Phosphorylase phosphatase activities were not significantly changed by fasting in any of the subcellular fractions in normal liver, but were increased in the hepatic SER of ADX rats. Refeeding fasted rats for 2 and 6 h resulted in increased hepatic glycogen, activation of glycogen synthase, and increased circulating levels of both insulin and glucose. Refeeding also caused increases in SER-associated synthase phosphatase activity in ADX animals. SER phosphorylase phosphatase activities were significantly increased by refeeding in normal rats, but were decreased in ADX rats. Regression analysis of the data suggested statistically significant positive correlations between insulin levels and SER synthase phosphatase activity in ADX animals, on the one hand, and SER synthase phosphatase and the percentage of synthase in the I form, on the other. No statistically significant correlation between insulin levels and phosphorylase phosphatase activities could be demonstrated. These results are compatible with the hypothesis that glycogen synthase phosphatase activity in liver, especially that associated with SER, is subject to physiological regulation by circulating levels of insulin. In contrast, phosphorylase phosphatase activity seems to be much less influenced by changes in the circulating insulin level. The results are compatible with the proposition that SER-associated phosphoprotein phosphatases are physiologically relevant in the regulation of hepatic glycogen metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗

PubMed1984

Relationship between plasma somatomedin-C and liver somatogenic binding sites in neonatal rats during malnutrition and after short and long term refeeding.

To determine the mechanism(s) for the growth retardation associated with malnutrition early in life, the relationships among plasma somatomedin-C (SM-C), plasma GH, and hepatic bovine GH-binding sites were assessed in rat pups that were milk-deprived from birth until weaning (21 days). After this period of malnutrition, body weight, tail length, plasma SM-C, and liver GH-binding capacity of the malnourished animals were significantly (P less than 0.001) reduced below those of control, well fed rats [SM-C at 21 days, 0.06 +/- 0.01 vs. 0.30 +/- 0.04 U/ml (mean +/- SE); GH binding, 2.96 +/- 0.39 vs. 7.19 +/- 0.80 pmol/liver]. The number of GH-binding sites per mg DNA was also reduced (0.59 +/- 0.06 vs. 1.08 +/- 0.11 pmol/mg DNA; P less than 0.001). After 1 week of ad libitum refeeding (days 21-28), body weight and tail length of malnourished pups increased significantly but showed no signs of catching up with that of control pups. Plasma SM-C and liver GH-binding capacity in the malnourished rats also rose significantly (P less than 0.005) after refeeding, but remained as far below controls as at 21 days [SM-C on day 28, 0.19 +/- 0.02 vs. 0.53 +/- 0.02 U/ml (P less than 0.001); GH binding, 6.59 +/- 0.99 vs. 12.94 +/- 1.60 pmol/liver (P less than 0.005)]. After 7 weeks of refeeding (days 21-70), tail length but not body weight recovered, while plasma SM-C levels were normalized. The mean number of GH binding sites per mg DNA in the malnourished rats was not significantly different from that in controls and reached for the males and the females, respectively, 79% and 86% of control binding. When expressed per liver, GH binding followed a similar pattern; for the males, binding capacity returned to 73% of the control value (20.45 +/- 1.82 vs. 27.93 +/- 3.49 pmol/liver; P = NS), and for the females, it returned to 77% of the control value (36.42 +/- 1.76 vs. 47.42 +/- 4.13 pmol/liver; P less than 0.01). In the young rats up to day 28, liver GH-binding capacities correlated with plasma SM-C concentrations (r = 0.81; P less than 0.01), while in the adult rats no correlation was present. During malnutrition and refeeding, there were no changes in the affinity constants of the hepatic GH-binding sites or in plasma GH concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1992

The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins.

We studied the relationship of serum insulin-like growth factor-I (IGF-I), IGF-II, the IGF-binding proteins IGFBP-1, IGFBP-2, and IGFBP-3, and GH-binding protein (GHBP; which is postulated to be derived from the extracellular portion of the GH receptor) in normal volunteers and patients with anorexia nervosa before and after a refeeding program. Serum GHBP, IGF-I, and IGFBP-3 were all significantly decreased in low weight patients with anorexia nervosa and returned to nearly normal levels with refeeding. Fasting serum GH and serum IGFBP-1 and IGFBP-2 were significantly increased in low weight patients with anorexia nervosa and also returned to nearly normal levels with refeeding. Serum IGF-II was 27% lower in the low weight group than in normal subjects, but this difference was not statistically significant. Both serum IGF-I and IGF-II were positively correlated with serum IGFBP-3 and negatively correlated with serum IGFBP-1 and IGFBP-2. These data are consistent with the hypothesis that nutritional deprivation alters the GH-IGF axis by down-regulation of the GH receptor or its postreceptor mechanisms, and that this effect is reversible with refeeding.

Adult↗

PubMed2006

Effects of fasting and refeeding on expression of atrogin-1 and Akt/FOXO signaling pathway in skeletal muscle of chicks.

This experiment was conducted to study the effects of fasting and refeeding on expression of the atrogin-1 and Akt/FOXO signaling pathway in skeletal muscle of chicks. Chicks were fasted for 24 h and refed for 2 h. Atrogin-1 mRNA expression was increased by fasting, and their increment was reduced by refeeding. Phosphorylations of Akt and FOXO1 were not decreased by fasting, but, they were increased by refeeding. These results indicate that refeeding stimulates phosphorylation of Akt/FOXO, resulting in a decrease in atrogin-1 expression in skeletal muscle of chicks.

Animal Feed↗

PubMed1983

Suppression and stimulation of TSH and thyroid hormones in bulls during starvation and refeeding.

Sixteen bull calves were fasted during two periods, 31/2 and 7 months old. Blood samples were taken every 6 h during an experimental period of 9 days: 2 control days, 5 fasting days and 2 refeeding days. During the control days with ad libitum feeding, T3, T4 and TSH increased during the day. During the fasting period, T4 decreased with a half-life of 3.5 days and T3 with a half-life of 3 days. TSH decreased in a less regularly way to a mean of 60% of control mean. Six h after refeeding, TSH had increased to 300% of control mean. T3 and T4 had a maximum 12 h after refeeding. As the T4 decreased with a rate nearly similar to the T4 disappearance rate in starving bulls, the secretion of T4 from the thyroid gland must have been almost stopped during the starvation period. The morning values were below normal for all three hormones after 2 days of refeeding.

Animals↗

PubMed1998

Hypoleptinemia in patients with anorexia nervosa: loss of circadian rhythm and unresponsiveness to short-term refeeding.

Leptin is a protein encoded by the ob gene that is expressed in adipocytes and regulates eating behavior via neuroendocrine mechanisms. Plasma leptin levels have been shown to correlate with weight and body fat in normal, obese and anorexic subjects. In the last of these populations, the dynamic profile of plasma leptin levels during short-term refeeding has never been assessed. We thus investigated basal plasma leptin levels in 29 female patients with anorexia nervosa (AN) (age 21.9 +/- 1.4 years, body mass index (BMI) 15.2 +/- 0.3 kg/m2) and in 80 normal female controls (age 21.2 +/- 0.2 years, BMI 20.3 +/- 0.3 kg/m2, mean +/- S.E.M.). Basal plasma leptin levels in AN were decreased by 77% compared with controls (2.5 +/- 0.2 vs 11.1 +/- 0.7 ng/ml, P < 0.0001). In both AN subjects and controls, plasma leptin levels correlated significantly with BMI (r2 = 0.448, P < 0.0001 and r2 = 0.339, P < 0.0001 respectively). Five AN patients (four female, one male, age 22.0 +/- 4.7 years, BMI 14.2 +/- 0.4 kg/m2, body fat 4.3 +/- 0.9 kg or 11.0 +/- 1.9% of body weight, basal metabolic rate (BMR) 958 +/- 122 kcal/day) were studied during a 3-day refeeding period and compared with eight control subjects (two male, six female, age 25.7 +/- 1.2 years, BMI 21.3 +/- 0.8 kg/m2, body fat 15.1 +/- 0.9 kg or 24.6 +/- 1.7%, BMR 1455 +/- 78 kcal/day) submitted to 36-h fasting. The amount of calories administered was based on BMR + 20% (carbohydrate 60%, protein 17%, fat 23%). In contrast to the rise in leptin levels that occurred during refeeding after a prolonged fast period in normal subjects, plasma leptin levels remained low and unchanged throughout the 3 days of renutrition in AN patients. The circadian rhythm of leptin was also completely abolished. This contrasted with the preserved circadian variations of cortisol, whose mean levels were increased. In conclusion, we confirmed that plasma leptin levels are low in AN and correlate with body weight. We further demonstrated that plasma leptin levels do not respond to short-term refeeding in anorexic patients in whom circadian variations are not restored, which suggests that the acute regulation of leptin by positive changes in energy balance is not preserved under a critical threshold of body fat.

Adult↗

PubMed1996

Effects of fasting, refeeding, and intraluminal triglyceride on proglucagon expression in jejunum and ileum.

Intestinal proglucagon is thought to be synthesized primarily by the distal gut, although the role of proglucagon-derived glucagon-like peptide I (GLP-I) as a major physiological incretin would seem to be associated with production in proximal small bowel. To better characterize the sites of production of proglucagon and GLP-I in the small intestine and evaluate nutrient regulation of small bowel proglucagon and derived peptides, we evaluated the effects of fasting for 72 h and subsequent refeeding or jejunal infusion of long-chain triglyceride (LCT) for 24 h on local expression of proglucagon in proximal and distal small bowel. Proglucagon mRNA abundance and cellular localization were determined and correlated with wet weight of bowel. In jejunum, proglucagon mRNA abundance decreased by 40% with fasting (P < 0.005) and increased with refeeding to levels similar to those of ad libitum-fed animals. In ileum, fasting resulted in a 20% decrease in proglucagon mRNA (P < 0.005); in contrast to jejunum, refeeding did not result in a significant rise in ileal proglucagon mRNA abundance from fasting values. In jejunum, signal intensity of proglucagon mRNA per cell, determined by in situ hybridization, decreased with fasting (P < 0.05) and increased with refeeding (P < 0.005) in proportion to changes in mRNA abundance. Plasma enteroglucagon and GLP-I levels correlated with jejunal proglucagon mRNA. Intrajejunal infusion of LCT increased expression of proglucagon to a greater extent in jejunum than in ileum. In conclusion, enteral nutrient intake stimulates small bowel proglucagon expression; this effect is greater in jejunum than ileum, consistent with greater intraluminal nutrient exposure and the role of jejunum as a source of the major incretin GLP-I.

Animals↗

PubMed1998

Intestinal nutrient-gene interaction: the effect of feed deprivation and refeeding on cholecystokinin and proglucagon gene expression.

We tested the hypothesis that dietary components reaching the bovine small intestine influence the expression of genes that encode the gastrointestinal neuropeptides cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The amount of digesta reaching the intestine was manipulated during the experiment by withholding feed from five heifers fitted with ruminal, duodenal, and ileal cannulas for 48 h and then subsequent refeeding. Duodenal and ileal biopsies were collected using a fiber-optic endoscope. A Northern hybridization procedure was used to evaluate changes in gene expression. Blood concentrations of CCK and GLP-1 were determined with RIA. The data indicate that CCK blood concentration and mRNA abundance decreased during the period of feed deprivation, but they returned to predeprivation values within 16 to 24 h of refeeding. The GLP-1 blood concentration also decreased during feed deprivation and returned to predeprivation values within 4 to 8 h of refeeding, despite the fact that proglucagon mRNA abundance did not change significantly during feed deprivation and refeeding. These findings provide evidence that CCK and GLP-1 are released in response to nutrients that reach the small intestine and may be involved in the physiological process of digestion and possibly play a role in regulating feed intake in ruminants.

Animals↗

PubMed1991

Effects of refeeding subsequent to starvation on the plasma cell population in the villous lamina propria of the rat small intestine.

The effects of refeeding subsequent to starvation on the plasma cell population in the lamina propria of the small intestinal villi were studied in adult rats utilizing the immunohistochemical method to detect IgA, IgM and IgG. Under normal conditions of stimulation, intestinal plasma cells (IPC) occur only as a sparse population. However, the present study demonstrated that extensive hyperplasia of IPC could be induced by refeeding after starvation. Starvation for a period of 4 to 6 days alone produced only a small change in the IPC population. In contrast, refeeding subsequent to starvation (for 4 to 6 days) was accompanied by a large increase in the population of IPC: the proportions of these cells among the lamina propria cells often rose to more than 50% within 3 or 6 days. The large majority of the proliferating IPC were found to express IgA, whereas cells bearing IgM or IgG occurred in extremely small numbers in the lamina propria. The mechanism whereby extensive IPC hyperplasia can occur in response to refeeding after starvation is discussed in relation to the possible promotion of transmission of antigenic macromolecules across the mucosal barrier induced by this procedure. It is also suggested that the origin of the proliferating IPC may be correlated with the B cell precursors in the germinal centers of the Peyer's, patches, which are more resistant to starvation than other lymphoid cells.

Animals↗

PubMed1995

Histamine effect on ornithine decarboxylase of rat intestine in cases of ischemia-reperfusion compared with refeeding.

Our previous study suggested that histamine might enhance the increase of ornithine decarboxylase activity in injured intestinal mucosa. To test this hypothesis, we measured histamine content in mesenteric lymph and ornithine decarboxylase activity in intestinal mucosa after ischemia-reperfusion in the rat. We examined the effect of alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, on ornithine decarboxylase activity after ischemia-reperfusion and compared this with its effect on the rat after refeeding. Ischemia-reperfusion was performed by 15-min occlusion of the superior mesenteric artery. After ischemia-reperfusion, histamine content in mesenteric lymph increased, and this increase was completely suppressed by alpha-fluoromethylhistidine pretreatment. In contrast to ischemia-reperfusion, histamine content in mesenteric lymph did not change after refeeding. Ornithine decarboxylase activity increased markedly 3 and 6 hr after ischemia-reperfusion and refeeding, whereas alpha-fluoromethylhistidine attenuated the increase in ornithine decarboxylase activity only in the ischemia-reperfusion group. These results indicate that increase in histamine synthesis in the intestinal mucosa plays an important role in the increase of ornithine decarboxylase activity after ischemia-reperfusion but that histamine is not related to the increase in ornithine decarboxylase activity after refeeding.

Animals↗

PubMed1984

Effect of starvation-refeeding and an exogenous glucocorticoid on carbohydrate metabolism in chick liver.

Broiler chicks, 4 weeks of age, were subjected to a regimen of 48-hr starvation and 24-hr refeeding as a means of inducing hepatic glycogen supercompensation. A synthetic glucocorticoid (prednisolone) and transcription inhibitor (actinomycin D) treatment were superimposed on the starvation-refeeding regimen to examine the effect of an exogenous glucocorticoid and the necessity for de novo protein synthesis during glycogen supercompensation. Starvation decreased plasma glucose, immunoreactive insulin and liver glycogen. These parameters returned to, or overshot prefasting levels after a 48-hr refeeding period. Prednisolone magnified the overshoot response but some de novo protein synthesis was required. Glycogen synthase a activity was opposite that of liver glycogen content. A possible nonhormone stimulated glycogen synthetic mechanism in the starvation-refeeding response of the chick was noted.

Animals↗

PubMed1999

Translocation of protein kinase C isoforms in rat muscle in response to fasting and refeeding.

Weanling rats were offered food ad libitum, or fasted for 18 h, or fasted and refed for times ranging from 5 to 30 min. Five protein kinase C (PKC) isoforms (alpha, epsilon, zeta, theta and mu) were detected in the hindlimb muscles by Western immunoblotting. PKC forms epsilon and theta were abundant in plantaris, but not in soleus muscle, and no difference in localization was detected between fed rats and those fasted for 18 h. PKC forms alpha and mu were affected by fasting and refeeding. PKC-mu was found only in the cytosolic fraction of the plantaris muscle of the fasted animal, but in the fully-fed animals it was also associated with the membrane fraction. The pattern of localization observed in the fully-fed state was restored in the fasted rats by 20 min refeeding. In contrast, PKC-alpha was not detected in the cytosolic fraction of the plantaris in fasted animals but rapidly reappeared there on refeeding, being restored to 20% and 80% of the fed value within 5 and 30 min of refeeding respectively. The timing of these changes was correlated with the increase in serum insulin concentration, which was significantly elevated above the fasted value by 5 min and at subsequent times. These data suggest a possible role for PKC isoforms alpha and mu in the metabolic changes that occur in skeletal muscle on transition between the fasted and the fed state.

Animals↗

PubMed2000

Fibre-type specific modification of the activity and regulation of skeletal muscle pyruvate dehydrogenase kinase (PDK) by prolonged starvation and refeeding is associated with targeted regulation of PDK isoenzyme 4 expression.

Using immunoblot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoenzymes PDK2 and PDK4, we demonstrate selective changes in PDK isoenzyme expression in slow-twitch versus fast-twitch skeletal muscle types in response to prolonged (48 h) starvation and refeeding after starvation. Starvation increased PDK activity in both slow-twitch (soleus) and fast-twitch (anterior tibialis) skeletal muscle and was associated with loss of sensitivity of PDK to inhibition by pyruvate, with a greater effect in anterior tibialis. Starvation significantly increased PDK4 protein expression in both soleus and anterior tibialis, with a greater response in anterior tibialis. Starvation did not effect PDK2 protein expression in soleus, but modestly increased PDK2 expression in anterior tibialis. Refeeding for 4 h partially reversed the effect of 48-h starvation on PDK activity and PDK4 expression in both soleus and anterior tibialis, but the response was more marked in soleus than in anterior tibialis. Pyruvate sensitivity of PDK activity was also partially restored by refeeding, again with the greater response in soleus. It is concluded that targeted regulation of PDK4 isoenzyme expression in skeletal muscle in response to starvation and refeeding underlies the modulation of the regulatory characteristics of PDK in vivo. We propose that switching from a pyruvate-sensitive to a pyruvate-insensitive PDK isoenzyme in starvation (a) maintains a sufficiently high pyruvate concentration to ensure that the glucose-->alanine-->glucose cycle is not impaired, and (b) may 'spare' pyruvate for anaplerotic entry into the tricarboxylic acid cycle to support the entry of acetyl-CoA derived from fatty acid (FA) oxidation into the tricarboxylic acid cycle. We further speculate that FA oxidation by skeletal muscle is both forced and facilitated by upregulation of PDK4, which is perceived as an essential component of the operation of the glucose-FA cycle in starvation.

Animals↗

PubMed2001

Effect of fasting and refeeding on duodenal alkaline phosphatase activity in monosodium glutamate obese rats.

In the present work the effects of fasting and refeeding on fat pad weight and alkaline phosphatase activity in the brush border of individual duodenal enterocytes have been evaluated in male Wistar rats with obesity induced by monosodium glutamate (MSG) treatment during the early postnatal period. Neonatal rats were treated subcutaneously with MSG (2 mg/g b.w.) or saline (controls) for 4 days after birth. At 4 months of age, two types of experiments were performed. In the first experiment rats, were submitted to 3 or 6 days lasting food deprivation. In the second experiment the rats were refed for 3 or 6 days ad libitum or restrictedly (60% of pre-fasting intake) after a 6 day-fasting period. Fasting and refeeding influenced the body fat and function of the duodenum in MSG-treated rats differently as compared to the controls. However, alkaline phosphatase activity and the weight of epididymal and retroperitoneal fat depots were significantly increased in MSG obese rats (P<0.001) during all the periods examined. While 3 days of food deprivation resulted in both groups in a similar loss of adipose tissue weight and alkaline phosphatase activity, the decrements of these parameters after 6 days of fasting were lower in obese rats suggesting that their capacity to spare body fat stores was enhanced. After 3 days of ad libitum refeeding, a more marked adaptational increase of food consumption and also a significantly increased alkaline phosphatase activity above the pre-fasting level (P<0.01) was observed in the MSG-treated rats. Consequently, a more rapid body fat restoration was demonstrated in these animals. Refeeding of rats at 60% of the pre-fasting intake level resulted in a significant increase of alkaline phosphatase activity in both the MSG and control group; moreover, as food restriction continued, MSG-treated rats tended to further increase the enzyme activity. Our results revealed that MSG treatment of neonatal rats may significantly change the intestinal functions. Permanently increased alkaline phosphatase activity observed in MSG obese rats during all investigated periods suggests that this functional alteration is probably not a consequence of actual nutritional variation but could be a component of regulatory mechanisms maintaining their obesity at critical values.

Adipose Tissue↗