Metabolic response to starvation in late pregnant rats. I. Maternal response

The aim of the present study was to examine effect of prolonged fasting on muscle glycogen and triglyceride concentration as well as on non-protein nitrogen excretion with urine in late pregnant rats. They were divided into four groups: I--fed, pregnant for 21 days, II--fasted for one day (from 20 to 21 day of pregnancy), III--fasted for two days (from 19 to 21 day) and IV--fasted for three days (from 18 to 21 day). The concentration of glycogen and triglycerides was determined in the following tissues: the white and red layers of the vastus lateralis, the soleus, the diaphragm, the heart and the liver. The urine was collected in each group 24 h (from 20 to 21 day). It has been found that concentration of glycogen in the leg muscles is reduced by about 50% and in the diaphragm by 75% already after 24 h fasting and then remains stable. The concentration of glycogen in the heart increases after one day of fasting and then returns to the control value. The effect of fasting on the concentration of triglycerides in the tissues depends on a tissue studied. It decreases gradually in the white vastus, and in the soleus only on the third day. It is elevated during the first two days of fasting in the red vastus, diaphragm and liver and returns to the control level on the third day. The fasting doubled the concentration of triglycerides in the heart. The urinary urea, creatinine, and uric acid excretion decreases and ammonia excretion increases during fasting. The results obtained indicate that the late gestation does not alter response of muscle glycogen metabolism to fasting as compared to the male rats. It does effect metabolism of triglycerides.     

Gestational profiles of rat placental lactogen-II (rPL-II) and growth hormone (GH) in maternal and fetal serum, amniotic fluid, and placental tissue.

Rat placental lactogen-II (rPL-II) and growth hormone (rGH) in maternal and fetal serum, amniotic fluid, and placental tissue were measured by a homologous radioimmunoassay during the last half of pregnancy. rPL-II appeared first in maternal circulation and the placental tissue on day 11 of pregnancy. The maternal serum rPL-II concentration increased progressively and reached the peak value (684 +/- 76 ng/ml) on day 19, and declined thereafter up to term. rPL-II content in the tissue had a similar pattern to the maternal serum profile of rPL-II, while its concentration in the tissue increased dramatically on day 12 and remained high until day 19. Fetal serum rPL-II was detected on days 17 and 18, though its concentration was much lower (ranged between 3-10 ng/ml) than that of maternal serum. rPL-II in amniotic fluid was also detectable only on days 12-14 of pregnancy, and the peak value on day 13 was 22% of the maternal serum rPL-II concentration. The rGH concentration increased gradually as pregnancy advanced with a decline on the day before parturition. Although rGH in fetal serum increased on day 20 with a decline on the following day, it was slightly detectable in amniotic fluid on the last two days of pregnancy. The molecular profile of rPL-II in amniotic fluid and maternal serum of day 13 pregnant rats were examined by Western blotting. Anti-rPL-II serum detected two proteins with molecular weights (mol wt) of 19.5K and 20.5K in amniotic fluid and one protein with a mol wt of 20.5K in maternal serum under nonreducing conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of maternal exercise on fetal liver glycogen late in gestation in the rat

To determine the effect of maternal exercise on fetal liver glycogen content, fed and fasted rats that were pregnant for 20.5 or 21.5 days were run on a rodent treadmill for 60 min at 12 m/min with a 0% grade or 16 m/min up a 10% grade. The rats were anesthetized by intravenous injection of pentobarbital sodium, and fetal and maternal liver and plasma samples were collected and frozen. Fetal liver glycogenolysis did not occur as a result of maternal exercise. Fetal blood levels of lactate increased 22-60%, but glucose, plasma glucagon, and insulin were unchanged during maternal exercise. Maternal liver glycogen decreased as a result of exercise in all groups of rats except the fasted 20.5-day-pregnant group. Plasma free fatty acids increased in all groups and blood lactate increased in fed (20.5 days) and fasted (21.5 days) pregnant rats. Maternal glucose, glucagon, and insulin values remained constant during exercise. The fetus appears to be well-protected from metabolic stress during moderate-intensity maternal exercise.     

Regulation of rabbit fetal glycogen: effect of in utero fetal decapitation on the metabolism of glycogen in fetal heart, lung, and liver

To understand the control mechanisms involved in the regulation of fetal glycogen, we have studied the effect of in utero fetal decapitations on glycogen metabolism in rabbit fetal heart, lung, and liver. In utero fetal decapitations were performed between days 18 and 21 of gestation. Two to four fetuses on one side of the horn were decapitated. Fetuses were delivered between days 23 and 26 or between days 28 and 30 of gestation. Fetal heart, lungs, and liver were analyzed for DNA, protein, glycogen, glycogen synthase (I and D forms), glycogen phosphorylase (a and b forms), phosphofructokinase, pyruvate kinase, and lactic dehydrogenase. In fetal heart and lung, no difference was observed in any of the above measurements in the intact and decapitated fetuses. In contrast, fetal liver does not appear to develop the glycogen system as indicated by the very low levels of glycogen (0.02 mg/mg DNA) in decapitated fetuses as compared with intact fetuses (0.4 mg/mg DNA). Similarly the levels of glycogen synthase and phosphorylase were two to three times lower in livers from decapitated fetuses as compared with the livers from intact fetuses. The three enzymes phosphofructokinase, pyruvate kinase, and lactic dehydrogenase were not affected by fetal decapitation in all three tissues. These results indicate that the fetal hypothalamic-pituitary-adrenal (thyroid) axis is not required at least after day 18 of gestation for the normal accumulation and subsequent utilization of glycogen in fetal heart and lungs, while it is an absolute requirement for the development of the fetal liver glycogen system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fetal lung development in streptozotocin-induced experimental diabetes: cytidylyl transferase activity, disaturated phosphatidyl choline and glycogen levels

The influence of streptozotocin-induced maternal diabetes on choline phosphate cytidylyltransferase activity (EC.2.7.7.15) glycogen content and disaturated phosphatidyl choline in fetal lung was studied between 19 and 21 days of gestation. In this experimental model, induction of maternal diabetes two days after mating, resulted in fetal hyperglycemia and hyperinsulinemia; the fetuses were neither macrosomic nor showed any evidence of fetal growth retardation. The glycogen content of lungs on days 19 and 20, but not on day 21 of gestation was significantly higher in fetuses of diabetic rats than in controls. The pulmonary cytosol cytidylyltransferase activity was similar in the two groups of fetuses on days 19 and 20. On day 21 of gestation the enzyme activity was significantly lower in fetuses of diabetic rats than in those of controls. On day 21 of gestation and in newborns of diabetic mothers, although there was no difference in the total pulmonary phospholipids, the levels of disaturated phosphatidyl cholines were significantly lower than in controls.     

Iron and copper concentrations in the maternal and fetal serum, placenta and amniotic fluid during the reproductive stadium as well as in the milk of rabbits

Serum concentrations of iron and copper from rabbits (New Zealand White hybrids; N = 12) were determined during the reproductive stadium (gestation and four weeks of lactation). Samples of serum from fetuses, placental tissue and amniotic fluid were also examined. Iron: a decrease of iron in the maternal serum during the second half of gestation was observed, whilst a significant rise occurred in the first week of lactation. The content of iron in the fetal serum dropped from day 21 to day 28 of gestation. The iron concentration in the placental tissue decreased during this time. A rise of the iron level in the amniotic fluid was determined from day 21 to day 28 of gestation. The iron content in the milk was about 33 mumol/l (first and second day of lactation). Copper: in the first half of pregnancy the copper level diminished slightly compared with the content of non-pregnant, non-lactating rabbits, while a rise was observed in the fourth week of this period. The copper concentration decreased in the first week of lactation and then reached the peak level in the second week of this phase. The copper level in the fetal serum declined from day 21 to day 28 of gestation, while the copper content in the amniotic fluid increased significantly on day 28, in comparison with day 21 of gestation. In contrast, a decline of the copper concentration in the placental tissue was noticed from day 21 to day 28 of this period. The copper content in the milk was nearly 25 mumol/l (first and second day of lactation).     

The influence of experimentally produced oligohydramnios on lung growth and pulmonary surfactant content in fetal rabbits.

To study the effect of oligohydramnios on lung growth and biochemical lung development in fetal rabbits, amniotic fluid was drained through a tube inserted into the maternal peritoneal cavity on the 23 day of gestation. Littermate fetuses without an amniotic shunt were used as controls. The fetuses were delivered abdominally on the 28 day of gestation. In a total of 8 pregnant does, 17 fetuses underwent amniotic shunting and 22 fetuses were used as controls. The amniotic shunt produced a significant reduction in the amniotic fluid volume. There were no differences in the wet weights of the fetal body, liver or brain between the two groups. However, the amniotic shunt significantly decreased the wet weight of the fetal lung, fetal lung wet weight/body weight ratio, and protein concentration per lung as compared to the control fetuses. In the fetal liver and brain tissues, no changes were found in the concentrations of total phospholipids, phosphatidylcholine (PC) or disaturated phosphatidylcholine (DSPC, the main component of lung surfactant) per g of wet tissue and per mg of protein. However, the lungs of the fetuses with amniotic shunts contained significantly more PC and DSPC, and the L/S ratio was higher than in the control fetuses. These results suggest that the oligohydramnios produced by an amniotic shunt causes pulmonary hypoplasia, but raises the pulmonary surfactant content of fetal rabbit lung.     

Metabolism and function of platelet-activating factor in fetal rabbit lung development

Previously, platelet-activating factor (PAF, PAF-acether, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) had been identified in association with a lamellar-body-enriched fraction of human amniotic fluid obtained from women in labor. In consideration of the fact that fetal lung is the source of lamellar bodies, we have investigated the capacity of the developing lung to synthesize PAF. The specific activity of the PAF biosynthetic enzyme, 1-alkyl-2-lyso-sn-glycero-3-phosphocholine: acetyl-CoA acetyltransferase, increased from 116 pmol/min per mg protein in day 21 fetal rabbit lung to 332 pmol/min per mg protein by day 31. Although this enzymatic activity in fetal kidney also increased, it never reached the level found in lung. In contrast, the actyltransferase activity decreased by 80% in fetal liver between days 21 and 31. The acetyltransferase activity in lung was primarily localized in the microsomal fraction (105 000 X g pellet); however a significant proportion of the activity was found in the 18 000 X g pellet. The specific activity of acetyltransferase in adult alveolar type II rat pneumonocytes was significantly higher than that of adult rat lung or rat alveolar macrophages, suggesting that type II cells make a significant contribution to the actyltransferase activity of lung tissue. PAF acetylhydrolase remained relatively constant throughout the gestation in all tissues. The concentration of PAF in the fetal lung increased by 3-fold from 12 to 35 fmol/mg protein, between day 21 and day 31 of development. The concentrations of the PAF precursors, 2-lyso-PAF (1-alkyl-2-lyso-sn-glycero-3-phosphocholine) and the 2-acyl derivative, were several orders of magnitude higher than the PAF concentration. The pulmonary glycogen content decreased from 163 at day 21 to 35 micrograms/mg protein at day 31 of gestation. We suggest that the increase in PAF concentration may participate in the regulation of glycogen breakdown in fetal lung as it does in perfused rat liver (Shukla, S.D., Buxton, D.B., Olson, M.S. and Hanahan, D.J. (1983) J. Biol. Chem. 258, 10212-10214). The formation of PAF in the developing lung and its secretion, in association with lamellar bodies, into amniotic fluid is discussed in relation to parturition.     

Maternal diabetes and its effect on biochemical and functional development of rabbit fetal lung

The effect of maternal diabetes on functional and biochemical maturation of the fetal lung was studied in a rabbit model. Pregnancy was initiated only after diabetes had been established. Both the pregnant doe and its fetuses were hyperglycemic. For comparison, the fetal heart and liver were also studied. In the diabetic group, the DNA content was lower in the fetal heart and lung while the protein content was higher in all three tissues. The glycogen levels were higher only in the fetal lung. Glycogen synthase was higher in the fetal lung and heart while phosphorylase activity was higher in all three tissues from the diabetic group. The activities of key enzymes involved in glycolysis were not affected. No difference was observed in the concentration of total phospholipids or in the ability of the airway fluid to reduce surface tension. In contrast, fetal lungs from diabetic does did not expand as well as the controls and retained less air on deflation. These findings suggest that the utilization of glycogen in fetal lungs from the diabetic does was not complete and that the increased incidence of respiratory distress in infants of diabetic mothers may not be due to a lack of surfactant.     

Metabolic and hormonal response to short term fasting after endurance training in the rat

The metabolic and hormonal response to short term fasting was studied after endurance exercise training. Rats were kept running on a motor driven rodent treadmill 5 days/wk for periods up to 1 h/day for 6 wk. Trained and untrained rats were then fasted for 24 h and 48 h. Liver and muscle glycogen, blood glucose, lactate, beta OH butyrate, glycerol, plasma insulin, testosterone and corticosterone were measured in fed and fasted trained and untrained rats. 48 h fasted trained rats show a lower level of blood lactate (1.08 +/- 0.05 vs 1.33 +/- 0.08 mmol/l-1 of blood glycerol (1 +/- 0.11 vs 0.84 +/- 0.08 mmol/l-1), and of muscle glycogen. There is a significant increase in plasma corticosterone in 48 h fasted trained rats from fed values. Plasma testosterone decreases during fasting, the values are higher in trained rats. Plasma insulin decreases during fasting without any difference between the two groups. These results show higher lipolysis, and decreased glycogenolysis in trained animals during 48 h fasting. The difference between the groups in steroid hormone response could reduce neoglucogenesis and muscle proteolysis in trained animals.     

Ontogeny of pyruvate dehydrogenase complex and key enzymes involved in glycolysis and tricarboxylic acid cycle in rabbit fetal lung, heart, and liver

The metabolic pathways by which the glycogen is utilized by fetal tissues is not well established. In the present study the ontogeny of seven key enzymes involved in glycolysis and the tricarboxylic acid cycle has been established for rabbit fetal lung, heart, and liver. In the fetal lung the activities of phosphofructokinase, pyruvate kinase, lactic dehydrogenase, citrate synthase, and malate dehydrogenase increase from day 21 to 25. Thereafter the levels either drop to day 19 levels or do not change. The isocitrate dehydrogenase activity continues to increase from day 19 of gestation to maximum level on day 31 of gestation. In fetal heart the pattern of activity is similar, but in fetal liver most of the enzymes reach maximum levels earlier and, with the exception of pyruvate kinase, do not show a significant fall in activity near term. The pattern of development of pyruvate dehydrogenase complex is different; maximum activity is observed on day 27 in fetal lung and heart and on day 21 in fetal liver. These results indicate that all three fetal tissues can oxidize glucose. Also, the accumulation of glycogen, particularly in fetal lung, appears to ensure that at specific times during gestation adequate quantities of energy (ATP) and substrates, required for surfactant phospholipid synthesis, are available independent of maternal supply of glucose or during brief episodes of hypoxia.     

Arginine nutrition and fetal brown adipose tissue development in diet-induced obese sheep

The global incidence of human obesity has more than doubled over the past three decades. An ovine model of obesity was developed to determine effects of maternal obesity and arginine supplementation on maternal, placental, and fetal parameters of growth, health, and well being. One-hundred-twenty days prior to embryo transfer, ewes were fed either ad libitum (n?=?10) to induce obesity or 100% National Research Council-recommended nutrient requirements (n?=?10) as controls. Embryos from superovulated ewes with normal body condition were transferred to the uterus of control-fed and obese ewes on day 5.5 post-estrus to generate genetically similar singleton pregnancies. Beginning on day 100 of gestation, obese ewes received intravenous administration of saline or L-arginine-HCl three times daily (81?mg arginine/kg?body?weight/day) to day 125, whereas control-fed ewes received saline. Fetal growth was assessed at necropsy on day 125. Maternal obesity increased (1) percentages of maternal and fetal carcass lipids and (2) concentrations of leptin, insulin, glucose, glutamate, leucine, lysine and threonine in maternal plasma while reducing (1) concentrations of progesterone, glycine and serine in maternal plasma and (2) amniotic and allantoic fluid volumes. Administration of L-arginine to obese ewes increased arginine and ornithine concentrations in maternal and fetal plasma, amniotic fluid volume, protein content in maternal carcass, and fetal brown adipose tissue (+60%), while reducing maternal lipid content and circulating leptin levels. Fetal or placental weight did not differ among treatments. Results indicate that arginine treatment beneficially reduces maternal adiposity and enhances fetal brown adipose tissue development in obese ewes.     

Effects of exercise on maternal glycogen storage patterns and fetal outcome in mature rats.

The purpose of the present study was to examine the effects of exercise on maternal glycogen storage patterns and fetal outcome in mature (approximately 12 months of age) Sprague-Dawley rats. The exercise consisted of treadmill running at 30 m.min-1, on a 10 degree incline, for 60 min, 5 days per week, for 4 weeks prior to pregnancy, which continued until day 19 of gestation. In mature animals, chronic exercise increased (p < 0.05) liver glycogen concentration in both pregnant and nonpregnant rats. In pregnant exercised animals, the glycogen concentration of the maternal liver increased almost twofold (p < 0.05) compared with the sedentary pregnant group. There was no difference in the amount of glycogen stored in the gastrocnemius or soleus muscles in response to training, pregnancy, or chronic maternal exercise in the mature rat. In the pregnant groups, there were fewer (p < 0.05) viable fetuses and more (p < 0.05) resorption sites than in young rats. In addition, exercise during pregnancy in the mature animal decreased (p < 0.05) fetal body weight. These results demonstrate that a conflict may exist between maternal exercise and fetal demands for energy in the mature rat. This conflict seems to favour the maternal system, as evidenced by the enhanced maternal liver glycogen storage and the negative effect on fetal growth.     

Regulation of lipid flux between liver and adipose tissue during transient hepatic steatosis in carnitine-depleted rats

Rats with carnitine deficiency due to trimethylhydrazinium propionate (mildronate) administered at 80 mg/100 g body weight per day for 10 days developed liver steatosis only upon fasting. This study aimed to determine whether the transient steatosis resulted from triglyceride accumulation due to the amount of fatty acids preserved through impaired fatty acid oxidation and/or from up-regulation of lipid exchange between liver and adipose tissue. In liver, mildronate decreased the carnitine content by approximately 13-fold and, in fasted rats, lowered the palmitate oxidation rate by 50% in the perfused organ, increased 9-fold the triglyceride content, and doubled the hepatic very low density lipoprotein secretion rate. Concomitantly, triglyceridemia was 13-fold greater than in controls. Hepatic carnitine palmitoyltransferase I activity and palmitate oxidation capacities measured in vitro were increased after treatment. Gene expression of hepatic proteins involved in fatty acid oxidation, triglyceride formation, and lipid uptake were all increased and were associated with increased hepatic free fatty acid content in treated rats. In periepididymal adipose tissue, mildronate markedly increased lipoprotein lipase and hormone-sensitive lipase activities in fed and fasted rats, respectively. On refeeding, carnitine-depleted rats exhibited a rapid decrease in blood triglycerides and free fatty acids, then after approximately 2 h, a marked drop of liver triglycerides and a progressive decrease in liver free fatty acids. Data show that up-regulation of liver activities, peripheral lipolysis, and lipoprotein lipase activity were likely essential factors for excess fat deposit and release alternately occurring in liver and adipose tissue of carnitine-depleted rats during the fed/fasted transition.     

Characteristics of ceruloplasmin synthesis in embryogenesis and in the early postnatal period of laboratory white rats

The dynamics of ceruloplasmin content was studied by immunochemical methods in the postimplantation rat embryos and postnatal animals. Ten to twenty two day old embryos contained ceruloplasmin (CP) in yolk sac, serum, and amniotic fluid. The highest CP levels were found in yolk sac. CP concentration profiles were almost identical in the serum and amniotic fluid being the highest on the 12th day (0.26 mg%) and the lowest (0.04) on the 16th day of gestation. CP concentration in the serum increased rapidly up to 3.5 mg% from the 17th day of gestation till the term (22nd day) while remaining at a constant and rather low level in the amniotic fluid. Within 16-18 days after birth, CP concentration in the serum remained at the level of 11 +/- 0.3 mg%. Later on it gradually increased and attained plateau (46-48 mg%) by the time of sex maturity. The maternal serum CP does not penetrate, in the embryo, as can be inferred from the experiments with 125I-CP injected into pregnant rats. Differences in the CP degradation rate and modes were found between the embryos and postnatal rats. It is suggested that CP is initially synthesized by the yolk sac endoderm during organogenesis (10-16 days of gestation) and predominantly by the liver during the foetal period (17-22 days).     

Opposite metabolic response to fenofibrate treatment in pregnant and virgin rats.

The level of maternal circulating triglycerides during late pregnancy has been correlated to newborns' weight in humans. To investigate the response to fenofibrate, a hypotriglyceridemic agent, in pregnant rats, 0, 100, or 200 mg of fenofibrate/kg body weight as oral doses were given twice a day from day 16 of gestation and studied at day 20. Virgin rats were studied in parallel. Liver weight was higher in pregnant than in virgin rats, and either dose of fenofibrate increased this variable in both groups. The highest dose of fenofibrate decreased fetal weight. Although plasma triglycerides decreased during the first 2 days of fenofibrate treatment in pregnant rats, the effect disappeared on day 3, and plasma triglycerides were even enhanced at day 4. In virgin rats, fenofibrate decreased plasma triglycerides throughout the experiment. Plasma cholesterol levels in pregnant rats decreased during the first 3 days of treatment, and the effect disappeared on day 4, whereas in virgin rats, values remained decreased. Changes in plasma triglycerides paralleled those of VLDL triglycerides. In pregnant rats, VLDL cholesterol levels increased while LDL cholesterol decreased with the treatment, whereas in virgin rats, cholesterol levels decreased in all lipoprotein fractions. Only in virgin rats did liver triglyceride concentration increase with fenofibrate treatment. Lumbar adipose tissue LPL was lower in pregnant than in virgin rats, and fenofibrate treatment decreased this variable in both groups. Maternal fenofibrate treatment increased fetal plasma and liver triglyceride and cholesterol concentrations.It is proposed that the opposite effects of fenofibrate treatment in virgin and pregnant rats are a consequence of both the enhanced liver capability for VLDL triglyceride production and a rebound response to the drug in the latter.     

Effects of maternal exercise on liver and skeletal muscle glycogen storage in pregnant rats.

To examine the effects of maternal exercise on liver and skeletal muscle glycogen storage, female Sprague-Dawley rats were randomly divided into control, nonpregnant runner, pregnant nonrunning control, pregnant runner, and prepregnant exercised control groups. The exercise consisted of treadmill running at 30 m/min on a 10 degree incline for 60 min, 5 days/wk. Pregnancy alone, on day 20 of gestation, decreased maternal liver glycogen content and increased red and white gastrocnemius muscle glycogen storage above control values (P less than 0.05). In contrast, exercise in nonpregnant animals augmented liver glycogen storage and also increased red and white gastrocnemius glycogen content (P less than 0.05). By combining exercise and pregnancy, the decrease in liver glycogen storage in the pregnant nonexercised condition was prevented in the pregnant runner group and more glycogen was stored in both the red and white portions of the gastrocnemius than all other groups (P less than 0.05). Fetal body weight was greatest (P less than 0.05) in the pregnant runner group and lowest (P less than 0.05) in the prepregnant exercise control group. These results demonstrate that chronic maternal exercise may change maternal glycogen storage patterns in the liver and skeletal muscle with some alteration in fetal outcome.     

Rat alpha-fetoprotein: isolation, radioimmunoassay and fetal-maternal distribution during pregnancy.

A method is described for the isolation of mg quantities of two forms of rat alpha-fetoprotein (AFP) from amniotic fluid by preparative disc-gel column electrophoresis using a continuous elution system. AFP isolated by this method is suitable for use as an antigen, can be labelled for use in a radioimmunoassay and serves as a reference standard. The characteristics of a new antiserum to AFP are also described. The protocol for a radioimmunoassay is outlined which permits the measurement of AFP in several fetal-maternal physiological compartments throughout gestation. Levels of AFP in fetal liver and fetal plasma suggest that secretion of AFP from liver occurs soon after synthesis with minimal hepatic storage. The pattern for AFP in maternal serum parallels that observed in amniotic fluid and fluctuations in maternal serum levels of AFP appear to be buffered by AFP accumulation in amniotic fluid. Fetal clearance of AFP under normal conditions may be relatively constant from Days 11-20 of gestation since an amniotic fluid: maternal serum AFP ratio of 30:1 is maintained during this period.     

Metabolic responses to exercise after fasting

Fasting before exercise increases fat utilization and lowers the rate of muscle glycogen depletion. Since a 24-h fast also depletes liver glycogen, we were interested in blood glucose homeostasis during exercise after fasting. An experiment was conducted with human subjects to determine the effect of fasting on blood metabolite concentrations during exercise. Nine male subjects ran (70% maximum O2 consumption) two counterbalanced trials, once fed and once after a 23-h fast. Plasma glucose was elevated by exercise in the fasted trial but there was no difference between fed and fasted during exercise. Lactate was significantly higher (P less than 0.05) in fasted than fed throughout the exercise bout. Fat mobilization and utilization appeared to be greater in the fasted trial as evidenced by higher plasma concentrations of free fatty acids, glycerol, and beta-hydroxybutyrate as well as lower respiratory exchange ratio in the fasted trial during the first 30 min of exercise. These results demonstrate that in humans blood glucose concentration is maintained at normal levels during exercise after fasting despite the depletion of liver glycogen. Homeostasis is probably maintained as a result of increased gluconeogenesis and decreased utilization of glucose in the muscle as a result of lowered pyruvate dehydrogenase activity.     

Are Kupffer cells involved in the metabolic adaptation of the liver to dietary carbohydrates given after fasting?

In rats, a high carbohydrate fat-free (HCFF) diet, given after fasting, induces both hepatic lipogenic and glycogenic enzymes. In the present study, we evaluated the involvement of Kupffer cells in the metabolic events occurring in the liver during the fasting-refeeding transition. Male Wistar rats were fasted for 48 h and received an intravenous injection of either NaCl 0.9% (Gd-) or 10 mg/kg GdCl(3) (Gd+), an inhibitor of Kupffer cells, then fed for 12 h with a HCFF diet. The comparison of colloidal carbon uptake was similar in rats fasted and in rats fasted and then refed a HCFF diet, thus indicating that refeeding does not affect per se Kupffer cell phagocytic activity. The inhibition of Kupffer cells by GdCl(3) did not affect fatty acid synthase (FAS) induction, as shown by the analysis of both FAS mRNA and activity; refeeding a HCFF diet increased the hepatic triglyceride and glycogen content to the same extent in Gd+ and Gd- rats. Our results do not support the involvement of Kupffer cells in the metabolic events occurring in the liver tissue by feeding a HCFF diet after fasting. However, the discussion supports the involvement of Kupffer cells in the modulation of the hepatic lipid metabolism by other nutrients than carbohydrates.