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Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet.

OBJECTIVE: Animal studies show that the leptin decline after acute severe caloric restriction is a peripheral signal to increase food intake. However, most human studies have failed to observe such a relationship. We studied the acute effects of severe caloric restriction on the association between serum leptin concentrations and subjective appetite. SUBJECTS: A total of 44 healthy adult men (aged: 43 +/- 5 years; BMI: 27.3 +/- 3.2 kg/m(2)). MEASUREMENTS: Fasting serum leptin concentrations and self-perceived appetite levels were measured during a 4-day diet containing 36% of the estimated energy requirements. Appetite levels were assessed with a 10-point Likert scale, reflecting hunger, fullness, desire to eat, prospective consumption and total appetite. RESULTS: After the 4-day energy deficit, fasting leptin concentrations decreased by 39.4% (95% CI: -43.6; -34.9%). This decline was associated with an increase in fasting hunger (r = -0.42; P < 0.01), desire to eat (r = -0.39; P < 0.05) and total appetite (r = -0.38; P < 0.05). Furthermore, the association between fasting leptin concentrations and fasting appetite levels became stronger during the energy restriction period (for total appetite: day 0 r = -0.15, P = 0.32; day 2 r = -0.31, P =< 0.05; day 4 r = -0.41, P < 0.01). CONCLUSIONS: The acute proportional reduction in fasting leptin after 4-day energy restriction is associated with an increase in self-perceived appetite. Additionally, the inverse association between proportional fasting leptin concentrations and self-perceived appetite response becomes stronger as energy restriction is prolonged. These findings suggest that leptin has an instrumental role in restoring energy balance in humans through the expression of appetite.

Adult↗

Maternal Ramadan fasting and neonatal health.

This retrospective cohort study sought to determine the effects of maternal Ramadan fasting during pregnancy on neonatal birth weight as an important aspect of fetal health. It was carried out among healthy women who were admitted for their neonate delivery at two medical centers in Tehran from January to September 2000. Neonates of 284 mothers with a history of Ramadan fasting during pregnancy were compared with neonates of 255 mothers who did not have a history of fasting during their pregnancies. On univariate analysis, neonatal birth weight of the fasted group was 100 g more than those of the nonfasted group (p=0.009). However, body mass index (BMI) of the fasted mothers was greater than that of the nonfasted mothers. When controlling for maternal BMI on neonatal birth weight, multiple linear regression models showed that neonates of fasted women were 71 g heavier than those of the nonfasted group, which was not statistically significant (p=0.1). We conclude that maternal fasting during Ramadan did not have a significant effect on the neonatal birth weight. Other health effects that we did not observe could have occurred.

Adult↗

Effect of diabetes and fasting on GLUT-4 (muscle/fat) glucose-transporter expression in insulin-sensitive tissues. Heterogeneous response in heart, red and white muscle.

1. GLUT-4 glucose-transporter protein and mRNA levels were assessed in heart, red muscle and white muscle, as well as in brown and white adipose tissue from 7-day streptozotocin-induced diabetic and 48 h-fasted rats. 2. In agreement with previous data, white adipose tissue showed a substantial decrease in GLUT-4 mRNA and protein levels in response to both diabetes and fasting. Similarly, GLUT-4 mRNA and protein markedly decreased in brown adipose tissue in both insulinopenic conditions. 3. Under control conditions, the level of expression of GLUT-4 protein content differed substantially in heart, red and white skeletal muscle. Thus GLUT-4 protein was maximal in heart, and red muscle had a greater GLUT-4 content compared with white muscle. In spite of the large differences in GLUT-4 protein content, GLUT-4 mRNA levels were equivalent in heart and red skeletal muscle. 4. In heart, GLUT-4 mRNA decreased to a greater extent than GLUT-4 protein in response to diabetes and fasting. In contrast, red muscle showed a greater decrease in GLUT-4 protein than in mRNA in response to diabetes or fasting, and in fact no decrease in GLUT-4 mRNA content was detectable in fasting. On the other hand, preparations of white skeletal muscle showed a substantial increase in GLUT-4 mRNA under both insulinopenic conditions, and that was concomitant to either a modest decrease in GLUT-4 protein in diabetes or to no change in fasting. 5. These results indicate that (a) the effects of diabetes and fasting are almost identical and lead to changes in GLUT-4 expression that are tissue-specific, (b) white adipose tissue, brown adipose tissue and heart respond similarly to insulin deficiency by decreasing GLUT-4 mRNA to a larger extent than GLUT-4 protein, and (c) red and white skeletal muscle respond to insulinopenic conditions in a heterogeneous manner which is characterized by enhanced GLUT-4 mRNA/protein ratios.

Adipose Tissue↗

Gene expression of calpains and their specific endogenous inhibitor, calpastatin, in skeletal muscle of fed and fasted rabbits.

To investigate the role of calpains in myofibrillar protein degradation in skeletal muscle and the regulation of their activity in vivo, we studied the effects of fasting on gene expression of calpains and calpastatin in the skeletal muscle of rabbits. In response to fasting, myofibrillar protein degradation increased 2-fold and mRNA levels of calpain I, calpain II and calpastatin were also increased. However, calpain and calpastatin activities remained unchanged. To investigate this discrepancy, we analysed polysomal calpain mRNA. Results indicated that fasting caused a 2-fold increase in the loading of calpain I and II mRNAs on ribosomes. Thus transcription of genes encoding calpain may be increased during fasting to ensure adequate synthesis of the proteinases needed to mobilize muscle protein reserves. The effect of fasting on calpain and calpastatin mRNA expression is shared by cathepsin D and proteasome C2 but not by beta-actin, implying that fasting invokes control of several proteolytic systems in skeletal muscle and underscores the possibility that each proteolytic system plays a role in the adaptation of skeletal muscle to the fasted state.

Animals↗

Adrenomedullectomy prevents the suppression of pulsatile luteinising hormone release during fasting in female rats.

Fasting inhibits the pulsatile secretion of luteinising hormone (LH) in female rats, an effect which is potentiated by the presence of oestradiol (E2). We have previously described various pharmacological or surgical treatments that can rapidly restore the pulses in a fasting animal. Nevertheless, the central and peripheral mechanisms that mediate this suppression of the pulses remain unclear. We have recently shown that adrenomedullectomy prevents the suppression of LH pulses by insulin-induced hypoglycaemia, a state which activates the sympathoadrenal axis. The present study was undertaken to establish whether this axis might contribute to the loss of the pulses that occurs in ovariectomised E2-treated rats that have been fasted for 48 h. Following sham adrenomedullectomy LH pulses were observed in animals fed ad libitum; after 48 h of fasting the animals that had received this sham procedure showed a significant suppression of LH levels and LH pulse frequency. In contrast, adrenomedullectomy prevented the inhibition of the pulses by 48 h of fasting; it had no effect on the pulses in the absence of fasting. These results suggest that adrenomedullary activity plays a significant role in the fasting-induced suppression of LH pulses in rats.

Adrenal Medulla↗

[13C]-urea breath test without prior fasting and without test meal is accurate for the detection of Helicobacter pylori infection in Chinese.

BACKGROUND AND AIM: Conventional [13C]-urea breath test ([13C]-UBT) requires prior fasting and a test meal, which theoretically improves the accuracy of the test. However, recent studies have suggested that prior fasting and test meal may not be essential. We aimed to determine the accuracy of a new [13C]-UBT protocol without fasting in Chinese. METHODS: Dyspeptic patients referred for upper endoscopy were recruited. The gold standard for Helicobacter pylori infection was the combination of Campylobacter-like organism (CLO) test and histology. Group I (n = 213) patients underwent [13C]-UBT with prior fasting and with citrate acid test meal. Group II (n = 123) patients underwent [13C]-UBT without prior fasting but with test meal. Group III (n = 90) patients underwent [13C]-UBT without prior fasting and without test meal. RESULTS: The highest accuracy for groups I, II and III was 96.7, 95.1 and 95.5% using a cut-off value of 5.0, 5.5 and 3.5, respectively. The sensitivities and specificities were 97.4 and 95.8% in group I, 93.3 and 96.8% in group II, and 96.5 and 93.9% in group III, respectively. CONCLUSION: The [13C]-UBT protocols without prior fasting and either with or without test meal produce highly accurate and reliable results in the Chinese population.

Adult↗

Concordance between fasting and 2-h post-glucose challenge criteria for the diagnosis of diabetes mellitus and glucose intolerance in high risk individuals.

AIMS: To compare the new fasting with the 2-h post glucose challenge diagnostic criteria for diabetes mellitus in a high-risk Central European population. METHODS: The results of the 75-g oral glucose tolerance tests (OGTT) performed between 1st January 1990 and 31st December 1998 in patients at high risk of glucose metabolism disturbance were analysed. RESULTS: From 1554 patients with OGTT results available for the study, 1360 (759 women and 601 men, aged 65.5+/-6.9 years, body mass index 28.2 +/- 4.5 kg/m2) were included into the study. With the use of the post-challenge criteria, 41.3% of the analysed population had diabetes or impaired diabetes tolerance (IGT), whereas with the new fasting system only 16.6% would have been diagnosed with any type of glucose intolerance. Diabetes was significantly more often diagnosed with the post-challenge criteria than with the fasting ones: 16.2 vs. 5.3% (P < 0.0001). The subjects with diabetes diagnosed upon fasting glucose value were significantly younger than the subjects with diabetes diagnosed according to the 2-h glucose challenge: 65.7 +/- 6.2 vs. 68.8 +/- 7.0 years, respectively (P < 0.01). The sensitivity of the new criteria for the diagnosis of diabetes was 18.2%, and specificity 97.2%. A total of 77.8% of IGT cases would have been diagnosed as having normal glucose metabolism according to the fasting glucose. The sensitivity of the new criteria for the diagnosis of impaired glucose tolerance (IGT or impaired fasting glucose) was 14.6%, and specificity 89.8%. The overall kappa statistic (k) was low; 0.211 (95% confidence interval 0.149-0.27). CONCLUSIONS: The new lower fasting criteria might be too insensitive to identify a large proportion of individuals with diabetes or impaired glucose intolerance, particularly in a high-risk population.

Age Factors↗

C-reactive protein is more strongly related to post-glucose load glucose than to fasting glucose in non-diabetic subjects; the Insulin Resistance Atherosclerosis Study.

AIMS: It has been suggested that cardiovascular disease may be more strongly related to post-challenge glycaemia than to fasting glucose concentrations. We hypothesized that subclinical inflammation, as indicated by elevated serum levels of C-reactive protein (CRP), may partially explain the association of cardiovascular disease with post-challenge glycaemia. METHODS: We studied the relationship of CRP (measured with a highly sensitive immunoassay) with fasting glucose and 2-h glucose concentrations during an oral glucose tolerance test in non-diabetic subjects from the Insulin Resistance Atherosclerosis Study. RESULTS: Spearman correlation analyses and multiple linear regression analyses showed a significant association of both fasting glucose and 2-h glucose concentrations with CRP levels, after adjusting for demographic covariates (age, sex, ethnicity, clinical centre; Spearman correlation coefficients: r = 0.18 for fasting glucose, r = 0.27 for 2-h glucose, both P < 0.0001). However, after additional adjustment for body mass index and waist-hip ratio only 2-h glucose (and not fasting glucose) was significantly related to CRP (r = 0.03 for fasting glucose, P = NS; r = 0.14 for 2-h glucose, P < 0.0001). Adding insulin sensitivity to the multivariate models further weakened the relationship of CRP to 2-h glucose (r = 0.07, P < 0.05). CRP mean values increased by 2-h glucose category (normal vs. impaired glucose tolerance vs. isolated post-challenge hyperglycaemia). CONCLUSIONS: Chronic, subclinical inflammation, as indicated by elevated circulating CRP levels, is more strongly associated with post-challenge glycaemia than with fasting glucose levels in non-diabetic subjects. This association is partially independent of body fat and insulin resistance.

Adipose Tissue↗

Fasting headache, weight loss, and dehydration.

Recently, we showed that fasting is a strong headache precipitator unrelated to coffee, tea, or smoking withdrawal or to oversleeping. In the current study, we evaluated the role of dehydration as a possible precipitator of fasting headache. The effects of a 25-hour fast of the Jewish Yom Kippur (Day of Atonement) were studied in women who participated in our previous Yom Kippur study. We asked the subjects to weigh themselves at the beginning and at the end of the Yom Kippur fast, assuming that the weight loss would largely reflect dehydration. In all but 1 of the 56 participants, the fast resulted in weight loss but only 28 (50%) reported headache. The average weight loss was 1.4 +/- 0.8 kg in those who developed headache and 1.2 +/- 0.5 kg in those who did not. This small difference was not statistically significant. We conclude that dehydration, as reflected by acute weight loss, is an unlikely cause of headache during a single day of fasting. The mechanism of fasting headache remains unclear.

Adult↗

Effect of fasting on the uptake of bilirubin and sulfobromophthalein by the isolated perfused rat liver.

BACKGROUND & AIMS: Occurrence of hyperbilirubinemia after fasting has been recognized for many years. The pathogenesis of this syndrome is unclear. Although recent studies suggest that increased intestinal deconjugation and reabsorption of bilirubin may play a major role in establishment of hyperbilirubinemia during fasting, other studies have suggested that fasting down-regulates intrinsic hepatocyte transport of bilirubin. The present study was designed to examine this possibility in the isolated perfused rat liver. METHODS: Transport of 3H-bilirubin and 35S-sulfobromophthalein (BSP) was examined in isolated perfused livers from 48-hour fasted or control rats using a multiple indicator dilution technique. Data were analyzed to quantify single-pass extraction (model-independent analysis) and were also fit by computer to the model of Goresky to quantify unidirectional fluxes. RESULTS: Fasting for 48 hours resulted in an approximately 40% reduction in liver weight but had no effect on model-dependent or model-independent parameters of transport. Despite the fact that the liver was smaller, single-pass extraction of bilirubin and BSP by livers from fasted animals did not differ from control, indicating a greater efficiency at uptake of bilirubin and BSP. CONCLUSIONS: Enhanced enterohepatic circulation of bilirubin, not altered hepatic transport, is a major factor in the pathogenesis of fasting-induced hyperbilirubinemia.

Animals↗

Effect of fasting on the incorporation of [3H]-L-phenylalanine into proinsulin-insulin and total protein in isolated rat pancreatic islets.

Pancreatic islets of fed, 24 hr and 72 hr fasted rats were incubated with [3H]-L-phenylalanine at verious concentrations of glucose. Total islet protein was isolated by TCA-precipitation, proinsulin-insulin by polyacrylamide gel electrophoresis. The incorporation of label was expressed per mug dry islet weight. Fasting for 24 hr reduced the incorporation of label into (pro)insulin at glucose 3 mg/ml, but not at glucose 1 mg/ml. After 72 hr of fasting the incorporation into (pro)insulin was decreased both at glucose 1 and 3 mg/ml and the slope of the dose-response curve for glucose stimulation was reduced by 31%. In contrast, fasting caused the incorporation into total islet protein to increase. A similar tendency was observed in an unidentified protein fraction, which failed to migrate from the spacer gel on disc electrophoresis. Fasting did not affect the islet DNA content per mug dry weight. These results suggest that fasting reduces the rate of insulin biosynthesis by decreasing the glucose sensitivity of this process. Fasting may stimulate, however, the biosynthesis of an unidentified islet protein component.

Animals↗

Age-dependent relationship of fasting C-peptide concentration and insulin secretion in non-obese subjects with normal glucose tolerance.

The age-dependent relationship of fasting immunomeasurable C-peptide to fasting immunomeasurable insulin (IRI) and IRI response to glucose was studied in 113 non-obese healthy subjects with normal glucose tolerance (oGTT according to the new WHO recommendations), ranging in age from 6 to 44 years. Fasting C-peptide concentration increased significantly in adolescents and adults when compared with children. The higher fasting C-peptide concentration in the adult group might be explained by the concomitant higher fasting blood glucose concentration whereas such relationship was lacking in adolescents. In contrast to this we failed to demonstrate such relationship with regard to fasting IRI levels. There was, however, a relationship between advancing age and early (IRI area 0-30 min), late (IRI area 30-120 min) and total (IRI area 0-120 min) insulin response to glucose. There was a significant correlation between fasting C-peptide concentration and estimates of IRI response in children and adolescents, whereas such relationship was lacking in adults. Based on these results, the present study demonstrates an age-related increase of the pancreatic beta-cell function which might be partly explained by the concomitant higher blood glucose concentration.

Adolescent↗

Glucose phosphorylating activities in the islets of Langerhans of the rat. Effect of fasting.

In the present study, the characterization of glucose phosphorylating activities in islet extracts and the effect of fasting on these activities have been studied. 4 mM glucose 6-phosphate strongly inhibits hexokinase activity, while glucokinase increased its activity. N-acetyl-glucosamine inhibits hexokinase activity (40% inhibition), while glucokinase increased its activity (19% increment). Both phosphorylating activities reaches a maximum when the Mg/ATP ratio is 1; increments in Mg/ATP ratio inhibits glucokinase activity while hexokinase activity is less dependent of Mg/ATP ratio. Fasting induces a progressive decrease of both phosphorylating activities in islet extracts. After 48 h fasting both activities are decreased 50%. After 96 h fasting, glucokinase activity disappeared completely, while hexokinase was 80% reduced. Our data suggest that hexokinase is less affected by fasting than glucokinase. In addition, other authors have reported that other glycolytic enzymes are little altered by fasting. Hence the fasting-induced-adaptation of glucokinase could account for the reduced rate of glycolysis and subsequently reduced insulin secretory response towards glucose.

Adenosine Triphosphate↗

Enzyme activities of hepatic glucose utilization in the fed and fasting genetically obese mouse at 4-5 months of age.

Activities of key enzymes in hepatic glucose utilization were compared between obese (C57BL/6J ob/ob) mice, their lean controls and outbred Swiss albino mice in the fed condition and during fasting. As liver hyperplasia and hepatocyte hypertrophy were present in the ob/ob mice at 4-5 months of age and changes in hepatic cellularity did occur with fasting, enzyme activity was expressed on the basis of protein, DNA, and wet weight. In the fed state, activities of glucokinase + hexokinase (glucose phosphorylating capability), phosphofructokinase and pyruvate kinase were significantly greater in livers of ob/ob mice when compared to those of the lean control. Glucokinase + hexokinase activities in livers of ob/ob mice remained significantly higher throughout the 48 h fast yet the activities of hepatic phosphofructokinase and pyruvate kinase, when expressed per g wet wt or mg protein, decreased so that a statistical difference from the fasted lean control was no longer detected. When expressed per 100 g body weight, hepatic glucokinase + hexokinase as well as phosphofructokinase and pyruvate kinase activities in obese mice were higher both in the fed and fasted states when compared to lean controls in the comparable nutritional condition. This increased capacity of key enzyme activities in hepatic glucose utilization can be attributed to liver hyperplasia found in ob/ob mice in both the fed and fasted condition. While higher hepatic glucose phosphorylating capability was maintained during fasting, the elevated specific activities of hepatic phosphofructokinase and pyruvate kinase in the obese mouse in the fed state decreased with starvation to values found in the lean control.

Animals↗

Oxidation of exogenous carbohydrate during prolonged exercise in fed and fasted conditions.

The oxidation of glucose and fructose ingested during moderate exercise performed on a cycle ergometer (120 min, 52% VO2max) was compared in ten young males fasted (n = 5) or fed (n = 5) before exercise. The subjects ingested randomly 1.33 g/kg body weight (approximately 96 +/- 9 g) of either enriched 13C-glucose (G), 13C-fructose (F), or water only (W); the solutions were evenly distributed over the exercise period. The fasted subjects began the three exercises with a lower blood glucose (P less than or equal to 0.05 for F only) and insulin (P less than or equal to 0.05) levels and a higher free fatty acid (FFA) concentration (P less than or equal to 0.05) than the fed ones. Throughout the exercise period, blood glucose level was maintained in fasted as well as in fed group for G and F ingestions, while it decreased (P less than or equal to 0.05 at the 100th min in fasted subjects) with water ingestion. Insulin level was similar in both fed and fasted conditions with F and W ingestions and lower than G trials for the fed subjects. For the three ingestions, FFA was lower (P less than or equal to 0.05) in the fasted than in the fed group over the exercise period. Over the 2-h period of exercise, a greater (P less than or equal to 0.05) amount of exogenous F was oxidized in the fasted (49 +/- 6 g) than in the fed (36 +/- 5 g) group, which represent 31% and 20% of the total carbohydrate energy supply, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary Carbohydrates↗

Effects of long-term fasting on insulin responses to fatty acids in man.

OBJECTIVE: To investigate whether the prolonged physiological elevation of nonesterified fatty acids (NEFA) seen in man during fasting associates with an altered acute insulin response to NEFA. SUBJECTS AND METHODS: Fourteen non-diabetic subjects, age 18-25 years, BMI 23.2 +/- 0.8 kg/m2 underwent hyperglycemic clamps (blood glucose 11 mM) for 120 min, during which either saline or Intralipid was administered in the last 60 min. Subjects were tested after an overnight as well as after a 58 h fast. RESULTS: After the overnight fast, insulin levels increased during Intralipid infusion, at min 120 reaching an increment of 33.0 +/- 8.5 microU/ml vs. 9.5 +/- 4.4 microU/ml during saline; p<0.05 for difference. Conversely, after the 58 h fast. Intralipid failed to promote a successive increase of insulin levels (increment during Intralipid at min 120: 0.5 +/- 5.8 microU/ml vs. -4.3 +/- 2.5 microU/ml during saline, NS). Insulin sensitivity as assessed by the amount of infused glucose and its ratio to insulin was enhanced by Intralipid after an overnight fast, but was decreased after a 58 h fast. CONCLUSION: Long-term elevated NEFA during fasting associates with diminished beta cell responsiveness to an acute elevation of fatty acids in conjunction with negative effects on insulin sensitivity.

Adolescent↗

The effect of intermittent maternal fasting on human fetal breathing movements.

In order to determine the effect of maternal fasting on human fetal breathing movements (FBM), 63 healthy pregnant women with singleton uncomplicated pregnancies of 30 weeks' gestation or more, and who were fasting during Ramadan, were recruited. Maternal blood glucose level and fetal movements were recorded during and after fasting. Statistical comparison of samples before and after a meal was made using Wilcoxon's signed-ranks test. Maternal glucose level during fasting (5.1 +/- 0.5 mmol/l) was significantly (P = 0.01) lower than after breakfast (5.3 +/- 1.0 mmol/l). There was a significant association between maternal glucose levels and numbers of days faster (P = 0.01). The time needed to detect breathing movements was significantly longer (P = 0.005) during fasting than postprandial. The continuous variety of fetal breathing movement was significantly (P = 0.02) less during fasting compared to postprandial. It is concluded that intermittent maternal fasting is associated with a significant alteration in the frequency and pattern of human FBM.

Adult↗

Fasting-refeeding stimulates the development of mammary tumors induced by 7,12-dimethylbenz[a]anthracene.

The effect of fasting-refeeding during the promotion phase of dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis has been investigated. Female Sprague-Dawley rats were given 130 mg/kg of DMBA and divided into four groups: Group 1 was fed ad libitum; Group 2 was fed ad libitum and, in addition, received daily subcutaneous injections of beta-estradiol and haloperidol for eight days, beginning two weeks after DMBA administration; Group 3 was exposed to three days of fasting one week after carcinogen injection, then fed ad libitum until the end of the experiment; Group 4 was treated as Group 2, except the animals were fasted for three days beginning one week after DMBA administration. Treatment with beta-estradiol and haloperidol enhanced the development of DMBA-induced mammary tumors. Rats fasted after DMBA administration showed increased genesis and growth and reduced latency of mammary tumors. Fasting before beta-estradiol and haloperidol injection resulted in a more pronounced effect on tumor yield and latency than hormones or fasting alone. The data indicate that, in rats fasted during the promotion phase, tumor growth is enhanced and the permissive effects of hormones on mammary carcinogenesis are potentiated.

9,10-Dimethyl-1,2-benzanthracene↗