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Leucine and alpha-ketoisocaproate metabolism and interconversions in fed and fasted sheep.

Fed and three-day-fasted sheep were infused with [1-14C] alpha-ketoisocaproate (KIC), L-[1-14C] leucine, and [14C] bicarbonate for determination of their whole-body turnovers, interconversions, and oxidation. Protein synthesis (PS), protein degradation (PD), net tissue metabolism, unidirectional utilization, and production rates also were estimated for the portal-drained viscera, liver, and hindquarters. KIC and leucine arterial concentrations (6.5 and 95 mumol X L-1) both increased with fasting. KIC turnover (9 mumol X min-1) also increased but leucine turnover (108 mumol X min-1) decreased. About 40% of KIC and 15% of leucine were oxidized, but they contributed less than 1% of whole-body CO2 production. The portal-drained viscera released KIC and leucine into the blood only in fed sheep. Hepatic net utilization of KIC and leucine (approximately 2 and 12 mumol X min-1) changed only little with fasting; thus, total splanchnic tissues utilized both in fasted sheep. Net metabolism by the hindquarters (representative of skeletal muscle) was always opposite to splanchnic metabolism. Thus, muscle must produce both KIC and leucine during fasting. In fed sheep whole-body PS, expressed as mumol X min-1 of leucine, was 92 +/- 6 and PD was 71 +/- 5. After fasting, PS decreased by 27%. Calculated liver protein metabolism was unaffected by the fast; PS (fixed and plasma) remained at about 25 and PD at about 15 mumol X min-1. However, protein metabolism by the hindquarters was sensitive to fasting; PS decreased from 30 +/- 4 in fed sheep to 20 +/- 3 mumol X min-1 after fasting and PD increased from 27 +/- 2 to 35 +/- 6 mumol X min-1. Thus, hepatic PS was maintained at the expense of muscle. If the total muscle mass of the body is considered, muscle PS contributed more than one half of whole-body PS.

Animals↗

Insulin inhibits protein degradation in skeletal muscles of eviscerated fasted rats.

The inhibitory effect of insulin on skeletal muscle protein breakdown was tested in fed or fasted rats whose muscles had been isolated by evisceration. Degradation was estimated from the accumulation of tyrosine in the plasma after protein synthesis was blocked with cycloheximide. According to earlier results from this method, fasting for 20 hours increases proteolysis. In the present work, in fasted preparations whose plasma insulin concentrations were maintained at higher levels by intravenous infusions of insulin and glucose, proteolysis was inhibited by insulin. In fed eviscerated rats, insulin was ineffective. To examine more closely the response of fasted skeletal muscles to insulin, plasma insulin concentrations in preparations of 20-hour fasted rats were varied over a wide range by treatment with an initial bolus of insulin, and then proteolysis was measured as change in tyrosine concentration during a 90-minute period. In fasted rats, insulin inhibited proteolysis in a dose-dependent fashion, with a half-maximum concentration of 35 microU/mL. However, at insulin levels equal to concentrations found in normal fed rats, compensation for the fast-induced proteolytic effect was still incomplete. The results suggest that in these more intact preparations, insulin does have a physiologically significant inhibitory effect on fast-induced muscle protein degradation, but that changes in fasting and feeding cannot be entirely explained by the action of insulin.

Animals↗

Fasting hyperglycemia in non-insulin-dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake.

The factors responsible for fasting hyperglycemia were investigated in 77 normal weight non-insulin-dependent diabetic (NIDD) and 72 age-, sex-, and weight-matched control individuals. In diabetic subjects with mild fasting hyperglycemia (less than 140 mg/dL) hepatic glucose production (1.85 +/- 0.03 mg/kg.min) was similar to controls (1.84 +/- 0.02); the major factor responsible for the elevated basal glucose level in the diabetic group was a decreased efficiency in the tissue uptake of glucose, as reflected by a 30% decline in the rate of glucose clearance (1.56 +/- 0.03 v 2.00 +/- 0.03 mL/kg.min, P less than .001). In contrast, in diabetic subjects with fasting plasma glucose concentrations above 140 mg/dL, basal hepatic glucose production was significantly elevated (2.42 +/- 0.08 mg/kg.min, P less than .001) and correlated closely with the increase in fasting plasma glucose concentration (r = .796, P less than .001). The basal rate of whole body glucose clearance reached a plateau value at fasting glucose levels of 160 to 180 mg/dL and did not contribute to the further rise in fasting plasma glucose concentrations above 160 to 180 mg/dL. Decreased efficiency of tissue glucose uptake is responsible the development of fasting hyperglycemia in patients with mild NIDDM (fasting plasma glucose less than 140 mg/dL). As the diabetic state worsens, an increase in basal hepatic glucose production is the major factor responsible for the progressive rise in fasting glucose levels.

Blood Glucose↗

Growth hormone receptors in rat liver membranes: effects of fasting and refeeding, and correlation with plasma somatomedin activity.

The effects of fasting and refeeding on hepatic growth hormone receptors, on insulin receptors and on plasma somatomedin activity were studied. Female rats were either subjected to fasting for 4 days, refed for 3 days after a 4-day fasting, or allowed free access to food (controls). The specific binding of 125I-labelled bovine growth hormone was low in liver microsomal membranes (45% that of controls) and in plasma membranes (52% that of controls) of fasted rats. The number of somatotropic sites rather than the affinity of the binding was decreased. Lactogenic sites as judged by the binding of 125I-labelled human growth hormone were not significantly reduced in liver membranes of fasted rats. 125I-labelled insulin specific binding was enhanced in microsomal (184% that of controls) and plasma membranes (136% that of controls) of fasted rats; these modifications were associated with a decreased insulinemia. But immunoreactive rat growth hormone levels were not different in plasma of fasted, refed and control animals. Decreased plasma bioassayable somatomedin was associated with the low number of somatotropic binding sites in liver membranes of fasted rats. Somatomedin activity of refed animals was comparable to controls. A significant correlation between the plasma bioassayable somatomedin and the hepatic level of somatotropic binding sites was found. It is proposed that, in fasting, the loss of somatotropic binding sites in the liver is one of the possible causes of the decreased plasma somatomedin bioactivity.

Animals↗

Effects of estradiol-17 beta on the net hepatic extraction of triglyceride in vivo in fed and fasted sheep.

The effects of estrogen and fasting on hepatic metabolism were studied by an arteriovenous difference technique in six multicatheterized ewes. In each experiment samples were collected during fed and 3- and 5-day fasted states before, and 10 to 17 days after the animals had been implanted with 550 mg of estradiol-17 beta. The implants elevated plasma estradiol five- to seven-fold. Plasma concentrations of insulin and triglyceride (TG) were increased (P less than 0.01) by 131% and 62% respectively by estradiol in fed sheep. Concurrent circulating concentrations of glucose, glycerol, free fatty acids, and beta-hydroxybutyrate were unaffected. During fasting estradiol elevated circulating concentrations of beta-hydroxybutyrate slightly, while levels of other metabolites and insulin were not different from fasted controls. In fed animals estradiol had no effect on the net hepatic uptake (NHU) of TG or glycerol but during fasting estradiol reduced the NHU of TG and glycerol by 47% and 31% (P less than 0.01) respectively. In addition, estradiol reduced the net hepatic production of beta-hydroxybutyrate in fed, but not in fasted animals. Net hepatic exchanges of glucose, or FFA were not affected by estradiol in either the fed or fasted state. Fasting increased the NHU of TG (P less than 0.05) and glycerol (P less than 0.01). The results of this study suggest that estradiol, at physiological concentrations, has lipotropic and anti-ketogenic effects on the ruminant liver. However, the anti-ketogenic effect is not apparent in fasted animals. Secondly, it appears that the hepatic lipidosis which often occurs in ruminants during negative energy balance is due largely to an increase in the NHU of circulating TG.

Animals↗

Mobilization of PCBs from blubber to blood in northern elephant seals (Mirounga angustirostris) during the post-weaning fast.

Northern elephant seals (Mirounga angustirostris) are characterized by extended fasting during which they rely entirely on their own body reserves. During fasts, lipids are mobilized from blubber to match the energy requirements of the animal. This transfer frees toxic fat-soluble pollutants into the blood circulation, which may exert adverse health effects, especially in young and developing animals. We investigated the dynamics of mobilization of polychlorinated biphenyls (PCBs) from the blubber of northern elephant seal pups during the post-weaning fast. Longitudinal samples of blubber and serum were collected from free-ranging animals throughout the fast at Año Nuevo, California. Blubber biopsies were separated into inner and outer layers. The PCB profiles of blubber and serum consisted mainly of penta- (PCB-101, -110, -118), hexa- (PCB-138, -153) and hepta- (PCB-180, -183, -187) chlorobiphenyls, which accounted for almost 90% of the total PCB burden. Total PCB concentrations in inner blubber increased significantly between early and late fasting (563.6+/-162.0 microg/kg lipids at early versus 911.6+/-513.1 microg/kg lipids at late fasting) whereas they remained fairly constant in outer blubber (572.6+/-134.8 microg/kg lipids at early versus 659.2+/-158.8 microg/kg lipids at late fasting). A corresponding rise of PCB concentrations was observed in serum during the second half of the fast (3.8+/-1.1 microg/l serum at early versus 7.2+/-0.9 microg/l at late fasting). The longitudinal changes in circulating total PCBs could not be explained by the changes in serum lipid fractions (cholesterol, phospholipids, triacylglycerols and free fatty acids). The increases in total PCB concentrations in inner blubber and serum were more pronounced in leaner animals, which suggests that they might be more at risk to potential toxic effects.

Adipose Tissue↗

Association between fasting glucose and C-reactive protein in a Japanese population: the Minoh study.

To investigate the association between fasting glucose and C-reactive protein (CRP), we examined 1715 Japanese individuals (723 men and 992 women) aged 40-69 years who did not have medication for hypertension, diabetes, or dyslipidemia, a history of cardiovascular disease or CRP levels>10mg/l. There was a statistically significant unadjusted correlation between CRP and each component of the metabolic syndrome, including fasting glucose, fasting insulin, body mass index, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol (negative), and triglycerides in both men and women. With adjustment for age, cigarette smoking, alcohol intake, and other components of the metabolic syndrome, the CRP increments (as back-transformed) compared with the lowest tertile of normal fasting glucose were 0.99, 1.05, 1.21, and 1.34mg/l (P for trend=0.008) with the second lowest and highest tertiles of normal fasting glucose, impaired fasting glucose, and type-2 diabetes, respectively in men. The respective adjusted CRP increments were 1.12, 1.23, 1.33, and 1.93mg/l (P for trend<0.001) in women. In the stratified analyses of CRP levels by sex, obesity status, and fasting glucose category or the number of components of the metabolic syndrome, an increase in CRP levels was greater in women than men with obesity and higher fasting glucose category (gender interaction: P<0.001) or an increased number of components of the metabolic syndrome (gender interaction: P=0.003). These results indicate that CRP levels increase continuously across the spectrum of fasting glucose in both sexes. This association is more pronounced in women.

Adult↗

The effect of intracerebroventricular infusions of leptin on the immunoreactivity of neuropeptide Y and gonadotrophin releasing hormone neurons in the hypothalamus of prepubertal sheep in conditions of short fasting.

In the study we evaluated the effects of infusion of exogenous leptin to the third ventricle of the brain on the expression of immunoreactive (ir) neuropeptide Y (NPY) neurons in the hypothalamus and ir gonadotrophin releasing hormone (GnRH) nerve terminals in the median eminence of prepubertal lambs in the conditions of short fasting. Merino female sheep (n=16) were randomly divided into four groups, two fed with standard feeds and two fasted for 72 h. One standard and one fasted groups were infused with Ringer saline (controls), remaining standard and fasted groups with leptin (25 microg/120 microl/h), for 4 h during three consecutive days, and then slaughtered. Ir NPY and ir GnRH were localized by immunohistochemistry using specific polyclonal antibodies. Detection of both hormones was followed by the image analysis and expressed as the percent area stained and integral density of immunostaining. In the hypothalami from all groups the ir NPY perikarya and varicose nerve fibers were localized in three distinct sub-areas, in the arcuate (ARC), paraventricular and periventricular nuclei. In fasted sheep the percent area and integral density for immunoreactivity of NPY increased significantly (P<0.001) in three sub-areas compared to the standard-fed animals. Leptin infusion lowered the both parameters (P<0.001) but solely in the ARC NPY population of fasted sheep. The percent area and integral density of immunostaining for ir GnRH in fasted sheep revealed the augmentation (P<0.001) compared to standard-fed sheep. Leptin infusions diminished (P<0.001) both parameters in fasted, without effects in standard-fed lambs. In conclusion, the enhanced by fasting immunoreactivity of the ARC NPY perikarya and varicose nerve fibers and restrained immunoreaction of GnRH terminals in the median eminence were reversed by exogenous leptin. It is suggested that leptin can affect GnRH release via ARC NPY neurons in conditions of deficit of nutrients in prepubertal, female lambs.

Age Factors↗

Does peroxisome proliferator-activated receptor gamma genotype (Pro12ala) modify the association of physical activity and dietary fat with fasting insulin level?

Peroxisome proliferator-activated receptor gamma (PPARgamma) has a role in controlling adipogenesis and insulin sensitivity. Previous studies have suggested that a common polymorphism (Pro12Ala) in the PPARgamma-2 isoform of this gene may be associated with markers of insulin resistance. We have previously shown that in combination, the relationships with fasting insulin of dietary polyunsaturated to saturated fatty acid ratio (P:S ratio) and physical activity are additive. We have also demonstrated that the association between P:S ratio and fasting insulin level is modified by the Pro12Ala genotype. The purpose of the present study was to investigate whether the Pro12Ala genotype modified the combined relationships of P:S ratio and physical activity level (PAL) on fasting insulin concentration. A population-based cohort of 506 Caucasian men and women aged 31 to 71 years was genotyped for the Pro12Ala polymorphism. P:S ratio was assessed by food-frequency questionnaire (FFQ) and PAL was estimated from 4 days of free-living heart rate monitoring following individual calibration of heart rate against energy expenditure during an exercise stress test. The combined associations of PAL and P:S ratio on fasting insulin level were examined stratified by Pro12Ala genotypes in a dominant model for the Ala allele. Among Pro allele homozygotes, there was no interaction between PAL and P:S ratio on fasting insulin (P =.929). However, in carriers of the Ala allele the association of P:S ratio with fasting insulin was modified by activity level (interaction P = 0.038). In those who were inactive and carried the Ala allele, the age-, sex-, and body mass-adjusted relationship between P:S ratio and log insulin was not significant (beta = -0.03, P =.93). In contrast, in physically active Ala carriers, the association of P:S ratio with log fasting insulin was highly significant (beta = -0.93, P =.004). In conclusion, this study examined the modification by PPARgamma genotype of the association between energy expenditure, P:S ratio, and fasting insulin level, a measure of insulin resistance. These data show that in Pro allele homozygotes the combined associations of P:S ratio and PAL are additive. In contrast, in Ala allele carriers, PAL modifies the association between P:S ratio and fasting insulin level in a multiplicative manner.

Adult↗

Effect of two fasting periods of different duration on ghrelin response to a mixed meal.

BACKGROUND AND AIM: The inhibitory effect of food on ghrelin secretion is reduced in several eating disorders such as restricting type anorexia nervosa, bulimia and obesity. These conditions are frequently characterised by irregular distribution of meals during the day. It is unknown whether two short fasting periods different duration affect ghrelin response to a mixed meal. Aim of the present study was to examine, in healthy volunteers, the effects of two fasting periods of different duration on pre- and post-prandial ghrelin concentrations after a standard mixed meal. METHODS AND RESULTS: Nine healthy men (mean age+/-S.E.M., 25.1+/-0.2 years; mean body mass index+/-S.E.M., 22.6+/-0.3kg/m2) were studied in 2 days after 12h of fasting (12F) and 17h of fasting (17F) with a within-subject repeated measure design. On both days they ate a standardized mixed meal. Before each meal hunger rating was evaluated with a visual analogue score. Blood samples for ghrelin, insulin, and glucose were collected at 0, 45, 60, 90, 120, 150 and 180min after meal. Comparing fasting values of 17F with 12F there was a significant increase in plasma ghrelin (160+/-20 vs. 146+/-18fmol/mL, P=0.015) and hunger rating (evaluated with a visual analogue scores) (7.0+/-0.3 vs. 5.1+/-0.4, P<0.003). A positive correlation between fasting ghrelin and hunger rating (r=0.52, P<0.01) was found. Circulating ghrelin decreased after both meals without any significant difference in relation with the previous length of fasting. Also postmeal ghrelin AUC as well as fasting and postmeal concentrations of insulin and glucose were similar after 12F and 17F. CONCLUSIONS: In healthy subjects a longer fasting period increases ghrelin concentration but did not affect post-prandial ghrelin response to a mixed meal.

Adult↗

Impact of Ramadan fasting on renal allograft function.

Fasting during the holy month of Ramadan is a religious duty for all healthy adult Muslims. They are only allowed to eat and drink between sunset and dawn. This study was designed to find the effect of Ramadan fasting on allograft function. We prospectively studied 19 kidney transplant recipients who voluntarily chose to fast during Ramadan versus 20 matched recipients, who had not fasted for 3 consecutive years. Data were recorded before, during, and after the fasting month. The mean posttransplant periods in the fasting and control groups were 52.6 +/- 30.3 and 56.6 +/- 30.0 months, respectively. A statistical analysis showed no significant changes in serum creatinine concentrations before and after Ramadan 1.07 +/- 0.24 versus 1.08 +/- 0.22 mg/dL (P > .05) and 1.00 +/- 0.24 versus 1.03 +/- 0.28 mg/dL (P > .05) in fasting and control groups, respectively. The results did not show any adverse effects of fasting in recipients with stable renal function. In conclusion, our study suggests that fasting during the month of Ramadan is safe and has no significant harmful effects on kidney transplant recipients with normal renal function.

Fasting↗

Potentiation of 1,1-dichloroethylene hepatotoxicity: comparative effects of hyperthyroidism and fasting.

The responses of fed, fasted, and hyperthyroid (T4) Sprague-Dawley male rats to 50 mg 1,1-dichloroethylene (1,1-DCE)/kg were compared. Hyperthyroid rats received three sc injections of thyroxine (100 micrograms/100 g) at 48-hr intervals; all other rats were sham-injected. 1,1-DCE was given po in mineral oil 24 hr after the last T4 dose; controls received only mineral oil. Animals were killed at 2, 4, and 8 hr. Liver GSH contents were lowered about 55% by both fasting and T4 while GSH transferase activities were lowered about 20% by fasting and 35% by T4. Only T4 pretreatment lowered alcohol dehydrogenase activities. Liver injury (i.e., serum glutamate pyruvate transaminase, histology) after 1,1-DCE was minimal in fed rats, moderate in fasted rats, and intermediate in T4 rats. Fasted rats showed a more pronounced depletion of liver GSH after 1,1-DCE than T4 rats and only in fasted rats did the toxicant decrease activities of the detoxification enzymes. Hypoglycemia after 1,1-DCE occurred in fed rats, but more rapidly in T4 rats. In contrast, fasted rats unexpectedly became hyperglycemic after the toxicant. Patterns of body temperature change after the toxicant, which might be due to its metabolites, were dissimilar. Hypothermia was not observed in fed rats, was only transiently evident in T4 rats, but occurred rapidly within 1 hr in fasted rats and steadily became more severe. The dissimilar patterns of liver enzyme and body temperature and serum glucose change after the toxicant in the three groups are indicative of different pathways of injury potentiation by fasting and hyperthyroidism.

Alcohol Dehydrogenase↗

The role of adrenal hormones in the response of glutamine synthetase to fasting in adult and old rats.

BACKGROUND & AIMS: During fasting, skeletal muscle exports increased amounts of glutamine (Gln) while increasing the production of this amino acid by glutamine synthetase (GS) in order to maintain the intramuscular Gln pool. Glucocorticoid hormones are believed to be the principal mediators of GS induction during stress conditions. The aim of this study was to evaluate (1) the effect of fasting on GS activity and expression in skeletal muscle during aging and consequently, (2) the role of glucocorticoids in fasting-induced GS activity. METHODS: Male Wistar rats (6-, 22-month old) were fasted for 5 days and both the activity and expression of GS were measured in tibialis anterior muscle. To better demonstrate the role of glucocorticoids in the response of GS to fasting, we suppressed their action by RU38486 administration (a potent glucocorticoid antagonist) and their production by adrenalectomy in fed and fasted rats. RESULTS: An increase in fasting-induced GS activity was observed in skeletal muscles from both adult and aged rats. Adrenalectomy, but surprisingly not RU38486, suppressed the fasting-induced increase in GS activity and expression. CONCLUSION: The data clearly show that the GS responsiveness to fasting was not modified by aging in skeletal muscle.

Adrenal Glands↗

Antioxidant property of metallothionein in fasted mice.

Metallothionein (MT) is a low-molecular-weight and sulfur-rich protein that is induced by not only heavy metals but also physiological stresses such as fasting and restraint stresses. Although MT plays a role as a radical scavenger and a regulator of metabolism of metals, the biological function of MT induced by fasting stress has not been elucidated. In this study, we investigated the antioxidative role of MT in fasted mice. In fasted mice, the lipid peroxidation level of the liver was elevated by 24-h fasting stress, and pre-induction of hepatic MT by Zn diminished hepatic lipid peroxidation. Although 24-h fasting stress induced MT synthesis in the liver, other antioxidants such as catalase, manganese-superoxide dismutase (Mn-SOD), and glutathione peroxidase (GSHPx) were not activated in the liver. Moreover, the hepatic MT level was still elevated by fasting stress after seven cycles of repetition of alternate fasting and feeding every 24 h, but the activities of catalase, Mn-SOD and GSHPx were unchanged. These results indicate that MT induced by fasting stress plays partly as an antioxidant.

Animals↗

Troglitazone treatment of aging Brown Norway rats improves food intake and weight gain after fasting without increasing hypothalamic NPY gene expression.

Compared to younger animals, aged male Brown Norway (BN) rats demonstrate increased body fat and serum insulin, and lower prepro-neuropeptide Y (ppNPY) mRNA content in the arcuate nucleus (ARC), and blunted food intake (FI) and body weight (BW) gain in response to a 72 h fast. Since centrally administered insulin decreases FI and weight of young rats and inhibits fasting-induced increases of NPY gene expression, we hypothesized that hyperinsulinemia in old rats contributes to an age-related central dysregulation of energy balance. Young, middle-aged and old BN rats were fed chow with troglitazone (Trog; 200 mg/kg BW/d) or without drug for 75 d (Experiment 1) or 66 d (Experiment 2). Rats were then fasted for 72 h, refed for 2 weeks and sacrificed after an overnight fast (Experiment 1) or fasted for 72 h and sacrificed (Experiment 2). Serum insulin and leptin were measured from trunk blood and brains were analyzed for ppNPY mRNA by in situ hybridization. In Experiment 1, troglitazone treatment resulted in increased post-fast weight gain, rate of gain and FI in old rats. Troglitazone decreased serum insulin by 50% in old rats, while leptin levels decreased 20-30% in all age groups in Experiment 1. No differences in serum insulin or leptin were detectable with troglitazone treatment in Experiment 2, due to the extreme suppression caused by the 72 h fast. Troglitazone treatment did not increase ARC NPY gene expression either after a 72 h fast and re-feeding for 2 weeks (Experiment 1) or immediately after a 72 h fast (Experiment 2). These findings suggest that increased insulin levels may contribute to age-related impairments of FI and BW regulation. However, improvements in these defects in energy regulation induced by troglitazone do not appear to result from changes in NPY gene expression, and may be due to alterations in other hypothalamic neuropeptides that regulate energy balance.

Aging↗

Expression of IGF-binding protein-1 phosphoisoforms in fasted rat skin and its role in regulation of collagen biosynthesis.

Insulin-like growth factor-I (IGF-I) is an important stimulator of collagen and glycosaminoglycan (GAG) biosynthesis in tissues. IGF-I activity is modulated by a family of IGF-binding proteins (IGFBPs) with different IGF-I binding affinities. At least IGFBP-1 and IGFBP-2 are known as inhibitors of IGF functions. Some IGFBPs (IGFBP-1, IGFBP-3 and IGFBP-5) may undergo phosphorylation that dramatically increase their affinity for IGF. During fasting of animals there is a significant decrease of the collagen and GAG content of the skin, accompanied by a reduction of plasma IGF-I levels. However, in previous studies we showed that in the skin of fasted rats IGF-I as well as IGFBP-1 and IGFBP-2 expressions were not different, compared to control rat skin, although collagen content was significantly decreased. In the present study we show that fasted rat skin contains similar amounts of IGF-I, IGFBP-3 and IGFBP-1, although extract from fasted rat skin induced inhibition of collagen biosynthesis in cultured fibroblasts, compared to control rat skin extract. Western immunoblot analysis of control and fasted rat skin extracts, using anti-phosphoserine antibodies for immunoprecipitated IGFBP-1 and IGFBP-3, revealed that both proteins are present in phosphorylated form. Although no differences were found in the expression of phosphorylated IGFBP-3 between control and fasted rat skins, that of phosphorylated IGFBP-1 in fasted rat skin extract was higher than in control one. We suggest that there is an increased level of IGFBP-1 phosphoisoform in fasted rat skin, associated with increased affinity for IGF-I. The increase of phosphorylated IGFBP-1 in fasted rat skin tissue may augment IGF-I binding affinity for IGF and decrease its bioavailability for receptor interaction. This mechanism may prevent IGF-I dependent stimulation of fibroblasts to produce extracellular matrix components. The specific expression of IGFBPs and their phosphoisoforms in tissues may play an important role in regulation of IGF-I action during physiologic and pathologic responses.

Animals↗

Overwinter fasting and re-feeding in rainbow trout: plasma growth hormone and cortisol levels in relation to energy mobilisation.

This study investigated the roles of cortisol and growth hormone (GH) during a period of fasting in overwintering salmonid fish. Indices of carbohydrate (plasma glucose, liver glycogen), lipid (plasma free fatty acids (FFAs)) and protein metabolism (plasma protein, total plasma amino acids) were determined, together with plasma GH, cortisol and somatolactin (SL) levels at intervals in three groups of rainbow trout (continuously fed; fasted for 9 weeks then fed; fasted for 17 weeks). In fasted fish, a decline in body weight and condition factor was accompanied by reduced plasma glucose and hepatic glycogen and increased plasma FFA. No consistent elevation of plasma GH occurred until after 8 weeks of fasting when plasma GH levels increased ninefold. No changes were observed in plasma total protein and AA until between weeks 13 and 17 when both were reduced significantly. When previously fasted fish resumed feeding, plasma glucose and FFA, and hepatic glycogen levels rapidly returned to control values and weight gain resumed. No significant changes in plasma cortisol levels, related to feeding regime, were evident at any point during the study and there was no evidence that SL played an active role in the response to fasting. The results suggest that overwinter fasting may not represent a significant nutritional stressor to rainbow trout and that energy mobilisation during fasting may be achieved without the involvement of GH, cortisol or SL.

Amino Acids↗

Influence of Ramadan-type fasting on enzymes of carbohydrate metabolism and brush border membrane in small intestine and liver of rat used as a model.

During Ramadan, Muslims the world over abstain from food and water from dawn to sunset for a month. We hypothesised that this unique model of prolonged intermittent fasting would result in specific intestinal and liver metabolic adaptations and hence alter metabolic activities. The effect of Ramadan-type fasting was studied on enzymes of carbohydrate metabolism and the brush border membrane of intestine and liver from rat used as a model. Rats were fasted (12 h) and then refed (12 h) daily for 30 d, as practised by Muslims during Ramadan. Ramadan-type fasting caused a significant decline in serum glucose, cholesterol and lactate dehydrogenase activity, whereas inorganic phosphate increased but blood urea N was not changed. Fasting resulted in increased activities of intestinal lactate (+34%), isocitrate (+63%), succinate (+83%) and malate (+106%) dehydrogenases, fructose 1,6-bisphosphatase (+17%) and glucose-6-phosphatase (+22%). Liver lactate dehydrogenase, malate dehydrogenase, glucose-6-phosphatase and fructose 1,6-bisphosphatase activities were also enhanced. However, the activities of glucose-6-phosphate dehydrogenase and malic enzyme fell significantly in the intestine but increased in liver. Although the activities of alkaline phosphatase, gamma-glutamyl transpeptidase and sucrase decreased in mucosal homogenates and brush border membrane, those of liver alkaline phosphatase, gamma-glutamyl transpeptidase and leucine aminopeptidase significantly increased. These changes were due to a respective decrease and increase of the maximal velocities of the enzyme reactions. Ramadan-type fasting caused similar effects whether the rats fasted with a daytime or night-time feeding schedule. The present results show a tremendous adaptation capacity of both liver and intestinal metabolic activities with Ramadan-type fasting in rats used as a model for Ramadan fasting in people.

Adaptation, Physiological↗