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PubMed2003

Effect of fasting on vascular contractility in lean and obese Zucker rats.

We compared the effects of fasting (36 h) on blood pressure and aortic contractile responsiveness in lean and obese Zucker rats. Fasting of lean animals resulted in a significant loss in body weight (-9.1 +/- 0.1%) and reduction in systolic blood pressure (-11.4 +/- 1.9 mmHg). Fasting plasma triacylglycerols (-76%) and beta-hydroxybutryic acid (beta-HBA) (+ 218%) were significantly decreased and increased, respectively. The fasting plasma concentrations of insulin (-72%) were significantly decreased, whereas glucose and epinephrine (Epi) were not changed in lean rats. The fasting of obese rats also resulted in weight loss (-5.6 +/- 1.3%) but did not cause a significant reduction of blood pressure. The plasma total cholesterol (+18%) was increased, triacylglycerols (-42%) were decreased and beta-HBA levels were unchanged in fasted obese rats. Similar to lean animals, the insulin levels of fasted obese rats were significantly decreased (-85%), whereas glucose and Epi concentrations were not significantly changed. Fasting of lean animals had no effect on the maximal contractile response of aortae to high K(+) and phorbol 12, 13 dibutyrate (PDBu) but significantly reduced the response to norepinephrine (NE) (% reference: fed, 61.1 +/- 11.0; fasted, 45.6 +/- 4.5). In addition, the concentration for half-maximal response (ED(50)) to NE was increased in fasted lean rats (fed, 1.8+/-0.2 x 10(-8)M; fasted, 3.0+/-0.3 x 10(-8)M). By comparison, fasting of obese rats had no significant effect on the contractile response to K(+), NE, or PDBu. The results show that short-term food withdrawal induces significant changes in vascular contractile properties of lean but not obese rats. Because fasting-induced changes were variable depending on the agonist, the results further suggest that the mechanism did not involve a general loss or enhancement in functional status.

3-Hydroxybutyric Acid↗
PubMed2002

Fasting-induced suppression of pulsatile luteinizing hormone secretion is related to body energy status in ovariectomized goats.

The effect of energy status on the response of luteinizing hormone (LH) pulse frequency to acute short-term energy deficiency created by fasting in estradiol-treated ovariectomized Shiba goats was studied in two experiments. In experiment 1, eight goats whose mean body weight (BW) was 25.6 +/- 5.8 (mean +/- S.D.)kg were fed 500 g hay cubes daily for 1 week. Then they were fasted for 3 days. Blood samples were collected for 4 h at 6 min intervals on the last day of feeding, first, second and third day of fasting for LH analysis. The goats were divided into light (<24 kg, n = 4) and heavy (> or =24 kg, n = 4) groups for data analysis. There was no difference in LH pulse frequency between the last day of feeding and each day of fasting in the heavy group. LH pulse frequency was significantly (P < 0.05) suppressed on the second day (3.3 +/- 1.3 pulses/4 h) and on the third day (2.3 +/- 1.9 pulses/4 h) relative to the day prior to fasting (4.8 +/- 1.5 pulses/4 h) in the light group. In experiment 2, BW plus a body mass index (BMI (body weight (kg)/withers height (m)/body length (m))/10 [corrected]) were measured to define energy status. Nine goats (BW, 25.6 +/- 5.8 kg) were fed 500 g hay cubes daily for a week and then fasted for 3 days. Then they were divided into two groups offered either a maintenance (n = 4) or a restricted (n = 5) level of feeding for 4 weeks. The restricted level of feeding was 30% of maintenance requirement based on the BW recorded weekly. The feeding level was then adjusted to maintain BW for a further week followed by 3 day fasting for restricted animals. Blood samples were collected for 6 h at 10 min intervals on the day prior to fasting and on third day of fasting before and after the dietary manipulation. BW (26.6 +/- 2.2 to 26.8 +/- 3.8 kg) and gBMI (8.4 +/- 0.4 to 7.8 +/- 0.3) remained constant over the period prior to fasting for the maintenance animals but were significantly lower (P < 0.05) after 4 weeks for the restricted goats (BW, 26.3 +/- 2.1 to 21.5 +/- 2.4 kg; gBMI, 8.4 +/- 0.9 to 6.9 +/- 0.7). There was no significant difference in the LH pulse frequency between feeding and fasting day in both sampling periods in the maintenance group. In the restricted group, LH pulse frequency was not suppressed by fasting in the first sampling period (6.8 +/- 2.9 to 5.2 +/- 2.5 pulses/6 h), whereas it tended to be suppressed (4.8 +/- 3.1 to 1.6 +/- 2.3 pulses/6 h; P < 0.06) and was significantly (P < 0.05) correlated to body weight (r = 0.70) and gBMI (r = 0.81) after the dietary manipulation. These results suggest that the suppressive effect of short-term energy restriction (fasting) on pulsatile LH secretion is related to body energy status.

Animals↗
PubMed1984

The effect of a 48 h fast on the thermoregulatory responses to graded cooling in man.

The thermoregulatory responses to graded cooling were measured in 11 healthy male subjects after a 12 h fast and after a 48 h fast. The cooling stimulus was produced by changing the temperature of the skin of the trunk and legs with a water-perfused suit. Five levels of skin temperature from 35.5 to 24 degrees C were applied on each occasion. After a 12 h fast, core temperature was maintained during cooling. This maintenance of core temperature was associated with an increase in metabolic rate and a reduction in blood flow to the hand and to the forearm. After 48 h of fasting, the subjects could not maintain core temperature during cooling, and a decrease of 0.36 +/- 0.05 degrees C occurred as the suit temperature was reduced from 35.9 to 24 degrees C. Metabolic rate was slightly higher after the 48 h fast than after the 12 h fast, but similar increases in metabolic rate were observed during cooling. Vasoconstriction in the hand was initially less after a 48 h fast than after a 12 h fast, but at the lowest suit temperature, hand blood flow was similar, and low, on both occasions. After 48 h of fasting, forearm blood flow was elevated at all suit temperatures, being approximately twice the level recorded after the 12 h fast. Venous plasma noradrenaline levels did not change during cooling after the 12 h fast, whilst after 48 h of fasting a significant increase in noradrenaline level was observed at the lowest suit temperature. The results of this study provide further evidence that fasting induces an impairment of autonomic reflex mechanisms, but it is not clear whether this is due to a suppression of sympathetic nervous activity.

Adult↗
PubMed2004

Association between fasting glucose and C-reactive protein in middle-aged subjects.

AIMS: C-reactive protein (CRP), a marker of subclinical inflammation, predicts the occurrence of coronary heart disease in healthy subjects. Hyperglycaemia is known to stimulate the release of inflammatory cytokines from various cell types and can lead to the induction and secretion of acute-phase reactants by adipocytes. The aim of the present study was to determine the relation between glycaemic status and CRP in healthy subjects. METHODS: We studied the relation of high-sensitivity CRP to fasting glucose and other components of the metabolic syndrome in a population-based cross-sectional study (n = 1000; age 50 +/- 9 years). RESULTS: Plasma CRP levels increased continuously from the lowest quartile of normal fasting glucose level to impaired fasting glucose and to diabetes (ln CRP 0.47 +/- 0.09, 0.95 +/- 0.12, and 1.11 +/- 0.13, respectively; Ptrend < 0.0001). Increasing CRP with higher fasting glucose levels was apparent even among subjects with fasting glucose in the normal range (Ptrend = 0.039), and subjects with fasting glucose level in the upper quartile of normal fasting glucose had higher CRP levels compared with subjects in the lower quartile (P = 0.035). There was a positive crude correlation between CRP and smoking, post-menopausal hormone use, body mass index, fasting glucose, triglycerides, hypertension, and uric acid (r = 0.11-0.36, P = 0.002-0.0001). A negative correlation was found between CRP and HDL-cholesterol (r = 0.12, P < 0.0001) and physical activity (r = 0.11, P = 0.002). After adjustment for potential confounders in a stepwise multivariate linear regression model, fasting glucose remained significantly and independently related to CRP levels (correlation coefficient 0.06; 95% confidence interval 0.014-0.11, P = 0.011). CONCLUSIONS: Fasting glucose is significantly and positively associated with plasma CRP in middle-aged subjects. CRP levels increase continuously across the spectrum of fasting glucose, beginning in the lowest quartile of normal fasting glucose. This finding suggests that a proinflammatory effect may contribute to the adverse cardiovascular outcome associated with diabetes, impaired fasting glucose, and increasing glucose levels within the normal range.

Blood Glucose↗
PubMed2005

Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism.

BACKGROUND: Prolonged dietary restriction increases the life span in rodents. Some evidence suggests that alternate-day fasting may also prolong the life span. OBJECTIVE: Our goal was to determine whether alternate-day fasting is a feasible method of dietary restriction in nonobese humans and whether it improves known biomarkers of longevity. DESIGN: Nonobese subjects (8 men and 8 women) fasted every other day for 22 d. Body weight, body composition, resting metabolic rate (RMR), respiratory quotient (RQ), temperature, fasting serum glucose, insulin, free fatty acids, and ghrelin were assessed at baseline and after 21 d (12-h fast) and 22 d (36-h fast) of alternate-day fasting. Visual analogue scales were used to assess hunger weekly. RESULTS: Subjects lost 2.5 +/- 0.5% of their initial body weight (P < 0.001) and 4 +/- 1% of their initial fat mass (P < 0.001). Hunger increased on the first day of fasting and remained elevated (P < 0.001). RMR and RQ did not change significantly from baseline to day 21, but RQ decreased on day 22 (P < 0.001), which resulted in an average daily increase in fat oxidation of > or =15 g. Glucose and ghrelin did not change significantly from baseline with alternate-day fasting, whereas fasting insulin decreased 57 +/- 4% (P < 0.001). CONCLUSIONS: Alternate-day fasting was feasible in nonobese subjects, and fat oxidation increased. However, hunger on fasting days did not decrease, perhaps indicating the unlikelihood of continuing this diet for extended periods of time. Adding one small meal on a fasting day may make this approach to dietary restriction more acceptable.

Adult↗
PubMed1994

Short-term fasting in normal women: absence of effects on gonadotrophin secretion and the menstrual cycle.

OBJECTIVE: In men and male monkeys, a short-term fast has been reported to have a major effect on the reproductive axis. In this study we investigated the effects of a short-term fast (72 hours) on female reproductive hormone secretion and menstrual function. DESIGN: The study consisted of an admission day (control), three successive fasting days (fast 1, 2 and 3) and a refeeding day (post fast). PATIENTS: Eight normal cycling women, ages 21-35, within 10% of ideal body weight, were fasted for 72 hours during the follicular phase of their menstrual cycle. MEASUREMENTS: On the admission day, the last day of the fast and the day of refeeding, blood samples were collected at 10-minute intervals from 0800 to 2000 h for determination of the LH pulse pattern. Daily determinations of immuno LH, FSH, oestradiol (E) and progesterone (P) were performed throughout the menstrual cycle in which the fast occurred. RESULTS: Throughout the fasting days, the consistently low serum levels of glucose and insulin confirmed that all the subjects were fasting. However, in spite of profound metabolic changes and a significant loss of weight, the short-term fast did not have discernible effects upon the reproductive hormones studied. Basal mean LH concentrations did not show any significant variation throughout the study period. The mean +/- SEM number of LH pulses was 13.4 +/- 1.5/12 h on the control day, 12.4 +/- 1.2/12 h (NS) on the third day of fasting and 11.0 +/- 1.5/12 h (NS) the day of refeeding. Each woman maintained a physiological pattern of LH, FSH, E and P throughout the menstrual cycle including the LH surge; ultrasound evidence of normal growth of a dominant follicle; and cycle length consistent with previous cycles. CONCLUSIONS: Our results indicate that in spite of profound metabolic changes, a 72-hour fast during the follicular phase does not affect the menstrual cycle of normal cycling women. It appears that the female reproductive axis during this phase of the cycle is more resistant to an acute caloric deprivation than that of men or male monkeys.

Adult↗
PubMed1976

Sodium balance and renal tubular sensitivity to aldosterone during total fast and carbohydrate refeeding in the obese.

In man the first days of fasting are characterized by enhanced natriuresis despite an increase in aldosterone secretion. Therefore the possibility of a decreased renal tubular sensitivity to this hormone was considered. The response to aldosterone infused before a fast and again on day 4 of fasting was evaluated in 12 starving obese women in terms of urinary sodium, chloride and potassium excretion. The data were compared to those obtained from 20 untreated starving obese women. In addition, salivary flow and sodium output were measured before and after aldosterone infusion in 4 out of the 12 patients treated. The involvement of aldosterone in the mechanism of fasting natriuresis and glucose-induced sodium retention was evaluated by means of spironolactone treatment (Aldactone A; 300 mg/day p.o.) on days 6 to 8 of the fast, with an oral glucose load (100 g) on day 7. Aldosterone infused on day 4 of the fast caused on average only 40% of the antinatriuretic effect it achieved before the fast. On the other hand even before aldosterone infusion, salivary sodium output was markedly reduced during the fast to levels comparable to those observed after aldosterone treatment in the pre-fast period. Furthermore, spironolactone administration on day 6 of the fast was associated with a prompt and marked increase in natriuresis. These 3 sets of facts indicate a definite biological activity of aldosterone during the initial phase of fasting with factor(s) interfering at the renal level with the normal expression of the hormonal action on sodium balance. There was still a distinct antinatiuretic effect of glucose in the presence of spironolactone, but less pronounced than when glucose was administered alone. The well-documented hyperaldosteronism of a total fast may represent a compensatory mechanism to decrease sodium loss at the end of a week-long fast. In addition a marked sodium-retaining effect of glucose can be demonstrated after aldosterone action is blocked by spironolactone. This provides another indication that glucose stimulates sodium retention through mechanism(s) which do not involve aldosterone.

Aldosterone↗
PubMed1983

Suppression of norepinephrine-induced thermogenesis in brown adipose tissue by fasting.

Fasting-induced changes in thermogenic responses to norepinephrine (NE, 4.0 micrograms X kg-1 X min-1 iv) were studied in anesthetized rats previously cold acclimated. The rats were divided into five groups at the end of 30-40 days of cold acclimation (5 degrees C). The five groups were kept for 5 days at 25 degrees C and fed (intact fed), fasted (intact fasted), fasted with daily treatment with thyroxine (T4, 2 micrograms/kg sc), thyroidectomized and fed, or thyroidectomized and fasted. In the intact fasted group, in which the weight of brown adipose tissue decreased, NE-induced increases in oxygen consumption, colonic temperature (T col), and temperature of the interscapular brown adipose tissue (TBAT) were markedly suppressed. The two thyroidectomized groups also showed a reduction in thermogenic response. In these three groups, TBAT was lower than Tcol throughout NE infusion. In the T4-treated fasted group, fasting-induced suppression of thermogenic response to NE was largely prevented. In the intact fed and the T4-treated fasted groups, TBAT attained higher values than Tcol during NE infusion. Plasma levels of thyroid hormones were significantly lower in the intact fasted group than in the intact fed or the T4-treated fasted group. These results suggest that fasting-induced suppression of the thermogenic response to NE is largely due to the reduced thermogenic response of brown adipose tissue to NE. The lowering of the levels of the thyroid hormones induced by fasting may be one of a number of causes of the reduction in the thermogenic response of brown adipose tissue.

Acclimatization↗
PubMed1994

Regulation of hormone-sensitive lipase during fasting.

Hormone-sensitive lipase (HSL) is the rate-limiting enzyme in lipolysis. The activity of HSL is thought to be primarily regulated by phosphorylation-dephosphorylation reactions. Although FFA levels are elevated during fasting, it has been difficult to demonstrate an increase in HSL activity with fasting. The current studies were undertaken to explore directly the regulation of HSL expression in adipose tissue in the rat during fasting. Rats were fasted for periods up to 5 days and HSL activity, HSL immunoreactive protein, and HSL mRNA levels were measured both in intact epididymal adipose tissue and in isolated adipose cells. Fasting caused a progressive decline in total body weight and the weight of epididymal fat pads, whereas adipose cell size decreased approximately 50% after 2 days of fasting. Serum FFA levels approximately doubled within 1 day of fasting and remained elevated thereafter. Basal lipolysis, measured as glycerol release, did not increase until 2 days of fasting. HSL activity remained relatively unchanged until 3 days of fasting when it was increased twofold after 3-5 days of fasting. Likewise, HSL immunoreactive protein and HSL mRNA levels increased twofold after 3-5 days of fasting. Thus HSL activity appears to be regulated by pretranslational mechanisms during prolonged fasting. However, increases in FFA flux during short-term fasting appear to involve either post-translational control of HSL or the regulation of other enzymes.

Animals↗
PubMed2001

Fasting downregulates renal water channel AQP2 and causes polyuria.

Starvation causes impairment in the urinary concentrating ability. The mechanism of this defect, however, remains unknown. We tested the possibility that food deprivation might affect the expression and activity of aquaporins (AQP1, 2), thereby impairing renal water reabsorption in the kidney. Rats fasted for 24 h exhibited severe polyuria (urine volume increased from 11 before fasting to 29 ml/24 h after fasting, P < 0.0001) along with failure to concentrate their urine (urine osmolality decreased from 1,485 before fasting to 495 mosmol/kgH(2)O after fasting, P < 0.0001). Refeeding for 24 h returned the urinary concentrating ability back to normal. Northern hybridization and immunoblot analysis demonstrated that fasting was associated with a decrease in AQP2 protein (-80%, P </= 0.002) and mRNA levels (-69%, P </= 0.003) in the outer medulla. In the cortex, fasting decreased AQP2 protein abundance by 60% (P </= 0.004) but did not alter its mRNA expression. During the recovery phase, AQP2 expression returned to normal level in both tissues. In the inner medulla, the expression of AQP2 was not altered in fasting, but was increased significantly at both protein ( +/- 92%) and mRNA ( +/- 43%) levels during the recovery from fasting. The proximal nephron water channel (AQP1) was not affected in response to fasting or recovery from fasting. We conclude that 1) fasting impairs the urinary concentrating ability in rats, and 2) the renal water-handling defect in fasting results specifically from the downregulation of AQP2 in the cortical and outer medullary collecting duct.

Animals↗
PubMed1997

Excess prevalence of fasting and postmethionine-loading hyperhomocysteinemia in stable renal transplant recipients.

Hyperhomocysteinemia, either fasting or after methionine loading, may contribute to the increased incidence of cardiovascular disease events experienced by renal transplant recipients. Limited data are available on fasting homocysteine (Hcy) levels, and none on postmethionine-loading Hcy levels, in these patients. We assessed the prevalence and potential determinants of fasting and postmethionine-loading hyperhomocysteinemia in 29 stable renal transplant recipients and 58 age- and sex-matched, population-based controls free of renal disease with serum creatinine levels of 1.5 mg/dL or less. Total (t) plasma Hcy was determined fasting and 2 hours after methionine loading, along with fasting determinations of the B-vitamin cofactors/substrates for Hcy metabolism, ie, pyridoxal 5'-phosphate, B-12, and folate and serum creatinine. Geometric mean fasting (18.1 versus 9.8 microM, P < .001) and postmethionine-loading increase (22.0 versus 15.2, P = .001) in tHcy levels were significantly greater in the renal transplant recipients, as were the prevalence odds (with 95% confidence intervals) for fasting [14.8 (3.4-64.7)], postmethionine loading [6.9 (1.5-32.8)], combined fasting and postmethionine-loading [18.0 (2.3-142.1)] hyperhomocysteinemia, and inadequate circulating folate [4.2 (1.1-16.5)] or pyridoxal 5'-phosphate [3.2 (0.9-11.0) status. Correlation analyses suggested important potential relationships between creatinine and both fasting (+0.64, P < .001) and postmethionine-load increase (+0.38, P = .045) in tHcy, folate and fasting (-0.41, P = .025) tHcy, and pyridoxal 5'-phosphate and postmethionine-loading increase (-0.33, P = .091) in tHcy. We conclude that there is an excess prevalence of fasting and postmethionine-loading hyperhomocysteinemia in stable renal transplant recipients. Renal function is related to both fasting and postmethionine loading-hyperhomocysteinemia, inadequate folate status is associated with fasting hyperhomocysteinemia, and inadequate vitamin B-6 status may be related to postmethionine-loading hyperhomocysteinemia in this patient population.

Adult↗
PubMed2003

Role of glucocorticoids in mediating effects of fasting and diabetes on hypothalamic gene expression.

BACKGROUND: Fasting and diabetes are characterized by elevated glucocorticoids and reduced insulin, leptin, elevated hypothalamic AGRP and NPY mRNA, and reduced hypothalamic POMC mRNA. Although leptin replacement can reverse changes in hypothalamic gene expression associated with fasting and diabetes, leptin also normalizes corticosterone; therefore the extent to which the elevated corticosterone contributes to the regulation of hypothalamic gene expression in fasting and diabetes remains unclear. To address if elevated corticosterone is necessary for hypothalamic responses to fasting and diabetes, we assessed the effects of adrenalectomy on hypothalamic gene expression in 48-hour-fasted or diabetic mice. To assess if elevated corticosterone is sufficient for the hypothalamic responses to fasting and diabetes, we assessed the effect of corticosterone pellets implanted for 48 hours on hypothalamic gene expression. RESULTS: Fasting and streptozotocin-induced diabetes elevated plasma glucocorticoid levels and reduced serum insulin and leptin levels. Adrenalectomy prevented the rise in plasma glucocorticoids associated with fasting and diabetes, but not the associated reductions in insulin or leptin. Adrenalectomy blocked the effects of fasting and diabetes on hypothalamic AGRP, NPY, and POMC expression. Conversely, corticosterone implants induced both AGRP and POMC mRNA (with a non-significant trend toward induction of NPY mRNA), accompanied by elevated insulin and leptin (with no change in food intake or body weight). CONCLUSION: These data suggest that elevated plasma corticosterone mediate some effects of fasting and diabetes on hypothalamic gene expression. Specifically, elevated plasma corticosterone is necessary for the induction of NPY mRNA with fasting and diabetes; since corticosterone implants only produced a non-significant trend in NPY mRNA, it remains uncertain if a rise in corticosterone may be sufficient to induce NPY mRNA. A rise in corticosterone is necessary to reduce hypothalamic POMC mRNA with fasting and diabetes, but not sufficient for the reduction of hypothalamic POMC mRNA. Finally, elevated plasma corticosterone is both necessary and sufficient for the induction of hypothalamic AGRP mRNA with fasting and diabetes.

Adrenal Medulla↗
PubMed2002

Impairment of liver GH receptor signaling by fasting.

Fasting causes a state of GH resistance responsible for low circulating IGF-I levels. To investigate whether this resistance may result from alterations in the GH signaling pathway, we determined the effects of fasting on the GH transduction pathway in rat liver. Forty-eight-hour fasted or fed male rats were injected with recombinant rat GH via the portal vein. Liver was removed 0 and 15 min after injection. Although GH stimulated Janus kinase 2 (JAK2) phosphorylation in all animals, this was severely blunted in fasted animals. Similarly, the phosphorylation of the GH receptor, although observed in both fasted and fed rats after GH injection, was markedly reduced in fasted rats. A rapid signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation was also induced in the liver of fed animals in response to GH. In contrast, in fasted rats only a slight phosphorylated STAT5 signal was observed. The inhibitory effect of fasting on these GH signaling molecules occurred without changes in their protein content. Furthermore, the impairment of the JAK-STAT pathway in fasted animals was associated with increased liver suppressor of cytokine signaling 3 mRNA levels. Although glucocorticoids, which are increased by fasting, may cause GH resistance, adrenalectomy failed to prevent alterations in the JAK-STAT pathway caused by fasting. In conclusion, the GH resistance induced by fasting is associated with impairment of the JAK-STAT signaling pathway. This might contribute to the decrease in liver IGF-I production observed in fasting.

Adrenalectomy↗
PubMed1997

Pulsatile intravenous gonadotropin-releasing hormone administration averts fasting-induced hypogonadotropism and hypoandrogenemia in healthy, normal weight men.

Fasting or severe caloric restriction in the human or experimental animal suppresses serum LH and sex steroid concentrations. In healthy men undergoing prolonged (5-day) nutrient deprivation, the daily LH secretion rate, the mass of LH secreted per burst, and the serum testosterone concentration fall markedly, with no decrease in responsiveness to a single bolus of GnRH. Here we test the hypothesis that the hypogonadotropic hypoandrogenemia accompanying fasting reflects decreased endogenous GnRH release. To this end, six healthy young men were studied on a fed day and during two 83-h fasting sessions with concurrent saline or pulsatile GnRH administration (100 ng/kg, i.v., every 90 min for 24 h) followed by a single bolus of 10 microg GnRH, i.v., to evaluate pituitary responsiveness. We employed a highly sensitive LH immunoradiometric assay, which correlates well with an in vitro Leydig cell bioassay, and deconvolution analysis to calculate in vivo LH secretory burst frequency, amplitude, duration, mass, and LH half-life. Fasting resulted in 30-50% declines in serum total and free testosterone and LH concentrations, and a 3-fold decrease in the calculated 24-h LH secretion rate (fed, 42 +/- 12; fasting, 14 +/- 1.9 U/L distribution volume x day; mean +/- SEM; P < 0.05, by ANOVA). Reduced LH secretion was accounted for by dual mechanisms, viz. a fall in both the apparent number of computer-resolved LH secretory bursts per 24 h (fed, 16 +/- 1.1; fasting, 10 +/- 1.2; P < 0.01) and the mass of LH secreted per burst (fed, 2.5 +/- 0.5; fasting, 1.5 +/- 0.1 U/L; P < 0.05). Fasting also decreased the mean value of the 24-h (nyctohemeral) rhythm in serum LH concentrations and reduced the approximate entropy (disorderliness) of LH release. Exogenous pulsatile GnRH injections prevented both the reduction in the calculated daily LH secretion rate (fed, 42 +/- 12; fasting plus GnRH, 64 +/- 16 IU/L; P = NS) and the decline in serum testosterone concentrations (fed, 556 +/- 71 ng/dL; fasting, 391 +/- 41; fasting plus GnRH, 859 +/- 65). Pulsatile GnRH treatment also restored the nyctohemeral mesor of serum LH concentrations and the approximate entropy value to baseline. Administration of a submaximal dose of exogenous GnRH (10 microg, i.v.) at the end of the fasting interval revealed statistically identical LH release in the three study groups, suggesting that pituitary responsiveness to GnRH was unchanged in this paradigm. In summary, a pulsatile iv GnRH infusion in young men averts completely the fasting-induced decline in LH secretory burst mass/amplitude and frequency, reinstates serum total and free testosterone concentrations, and restores the mesor of LH's nyctohemeral rhythmicity and the approximate entropy of LH release. Rescue of hypogonadism by pulsatile GnRH stimuli supports the thesis that nutrient withdrawal decreases the output of the human hypothalamic GnRH burst generator.

Adult↗
PubMed1998

A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) are profoundly insulin resistant, and the resultant hyperinsulinemia exacerbates the reproductive abnormalities of the syndrome. Agents that ameliorate insulin resistance and reduce circulating insulin levels could provide a new therapeutic modality for PCOS. Identifying the subset of PCOS women who are most insulin resistant may therefore be useful for selecting women who will respond to this therapy. We examined the correlation of basal and oral glucose-stimulated glucose and insulin levels and fasting and stimulated glucose/insulin (G:I) ratios with parameters of insulin sensitivity obtained by frequently sampled i.v. glucose tolerance test (FSIGT) to assess whether there is a simple screening test for insulin resistance in PCOS. Forty PCOS women (aged 18-40 yr; body mass index, >26 kg/m2) and 15 control women matched for age, weight, and ethnicity underwent both a 75-g oral glucose tolerance test (OGTT) and a FSIGT. The insulin sensitivity index (S(I)) was calculated by application of the minimal model of glucose kinetics to the dynamics of plasma glucose and insulin levels during the FSIGT. The best correlation in PCOS between S(I) and a fasting level was found with fasting G:I ratios (r = 0.73; P < 0.0001). A less substantial, but significant, correlation was found with fasting insulin levels (r = 0.50; P < 0.001), and no significant correlation was found with fasting glucose levels (r = 0.24; P = NS). The fasting G:I was more strongly correlated with S(I) than with integrated glucose and insulin responses during the OGTT. The only stronger correlation was with the OGTT 2 h G:I ratio (r = 0.74; P < 0.001). Stepwise regression analysis with S(I) as the dependent variable and fasting glucose and insulin levels, area under the curve for glucose and insulin, and a fasting G:I ratio showed that only the fasting G:I ratio was significantly predictive of S(I) in the model (F to remove value = 38.1; P < 0.001). When viewed as a screening test for insulin resistance in PCOS, setting a value of the fasting G:I ratio of less than 4.5 as abnormal (using an S(I) value below the 10th percentile of our control population as evidence for insulin resistance), the sensitivity of a fasting G:I ratio was 95%, the specificity was 84%, the positive predictive value was 87%, and the negative predictive value was 94%. Receiver operator curve analysis showed that this fasting G:I ratio was the single best screening measure for detecting insulin resistance. We conclude that a fasting G:I ratio may be useful as a screening test for insulin resistance in obese non-Hispanic white PCOS women. This may be a clinically useful parameter for selecting PCOS women most likely to respond to therapeutic interventions that improve insulin sensitivity.

Adolescent↗
PubMed1990

Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver.

Previous studies have indicated that the concentration of circulating insulin-like growth factor-I (IGF-I) declines in young growing rats that have been fasted or maintained on a protein-deficient diet. To investigate the molecular mechanism(s) by which IGF-I levels are regulated by nutrition, we measured the levels of IGF-I mRNA in 6-week-old male control rats fed ad libitum, rats fasted for 24, 48, or 72 h, and rats fasted for 48 or 72 h and then refed for 24 h. The abundance of several IGF-I mRNA species (8.0, 4.0, 1.7, and 1.0 kilobases) decreased in the fasting animals and rebounded after 24 h of refeeding, although not to the initial control levels. The 1 kilobase IGF-I mRNA species exhibited a 43% decrease after 24 h of fasting, a 76% decrease after 48 h of fasting, and an 82% decrease after 72 h of fasting. Hepatic GH receptor mRNA also decreased in fasting rats. This indicates that the GH receptor down-regulation that occurs in fasting is accompanied by and probably at least partly caused by a decline in GH receptor mRNA. The magnitude and kinetics of the decline in GH receptor mRNA were similar to the magnitude and kinetics of the decline in IGF-I mRNA, suggesting that the two mRNAs may be regulated by a similar mechanism. There was no significant change in the levels of liver beta-actin or serum albumin mRNA under the same conditions, indicating that the regulation of IGF-I and GH receptor mRNA was specific. In addition, the levels of brain IGF-II, beta-actin, and alpha-tubulin mRNAs were not significantly changed by fasting. To further elucidate the molecular mechanism for regulation of hepatic IGF-I mRNA, nuclear transcription elongation assays were performed using nuclei isolated from the liver of control rats, rats fasted for 72 h, and fasted-refed rats. There was considerable animal-to-animal variability in IGF-I gene transcription within each group. The mean level of IGF-I gene transcription was lower in the fasting animals than in the fed controls. However, this decrease was not statistically significant, and the magnitude of the decrease did not account for the 79% decrease in total IGF-I mRNA. These results suggest that IGF-I mRNA is regulated at least partly at the posttranscriptional level.

Actins↗
PubMed1998

Growth hormone responses to growth hormone-releasing hormone and hexarelin in fed and fasted dogs: effect of somatostatin infusion or pretreatment with pirenzepine.

Using unanesthetized young male and female beagle dogs, before and after a 2-day fast, we studied the effect of an i.v. infusion of 0.9% saline (5 ml/h), somatostatin (SS, 4 or 8 micrograms/kg/h), or pretreatment with pirenzepine (PZ, 0.6 mg/kg i.v.), a muscarinic cholinergic antagonist which allegedly releases SS, on the GH release evoked by acute administration of GHRH (2 micrograms/kg i.v.), hexarelin (HEXA), a member of the GH-releasing peptide family (250 micrograms/kg i.v.) or GHRH plus HEXA. In fasted dogs, GHRH delivered during saline infusion induced a clear-cut rise in plasma GH levels, significantly higher than that which it induced in fed dogs. In contrast, HEXA, although very effective in causing the release of GH, only slightly increased GH secretion in fasted dogs over that which it induced in fed dogs. Co-administration of GHRH plus HEXA into fed dogs induced a synergic GH response that further increased with fasting. The action of GHRH in fed dogs was abolished by the lower dose of SS, whereas SS at either dose was ineffective in suppressing the GH-releasing effect during fasting. Infusion of the lower dose of SS failed to counter the action of HEXA, either before or during fasting, whilst the higher SS dose partially reduced it in both conditions. In contrast to SS, PZ reduced the GH-releasing effect of GHRH and HEXA, both in the fed state and, though to a lesser extent, during fasting. Pirenzepine only slightly reduced the robust GH rise elicited by GHRH plus HEXA in fed dogs. The suppressive effect of PZ on the GH response to combined administration of the peptides was lowest in fasted dogs. These data show that: (1) fasting augmented the GH response to GHRH and (to a lesser degree) to HEXA; (2) SS inhibited the GH response to GHRH in the fed state, but not in the fasted state; (3) only the higher dose of SS partially reduced the GH stimulation by HEXA in either the fed or the fasted state; (4) PZ lowered the GH response to GHRH and to HEXA in both the fed and (to a lesser degree) the fasted state; (5) PZ did not modify the GH release due to the combined administration of GHRH and HEXA. It is suggested that: (1) during fasting the greatly enhanced GH response to GHRH alone or GHRH plus HEXA probably reflects an augmented GHRH secretion; (2) somatotrope refractoriness to SS may contribute to the enhanced GH secretion in states of calorie deprivation; (3) in contrast to a general belief, muscarinic cholinergic antagonists, e.g. PZ, do not act exclusively via release of SS, but probably also through inhibition of GHRH function.

Analysis of Variance↗
PubMed2004

A survey of fasting during pregnancy.

INTRODUCTION: Fasting during the month of Ramadan is compulsory in the Muslim faith. Although pregnant women may be exempted, many still choose to fast while others are more careful in practising it. This survey examines the practice of fasting among pregnant Muslim women in Singapore based on the prevalence in relation to factors such as parity, social and economic circumstances. It also analyses the factors that influence the decision to fast and the successful completion of the fast, and examines their knowledge, belief and attitudes on fasting during the holy month of Ramadan. METHODS: This is a retrospective study of all Muslim women who were pregnant and received antenatal care in our hospital during the month of Ramadan from 17 November 2001 to 16 December 2001. A four-page questionnaire was mailed to all eligible subjects in March 2002. RESULTS: Of 202 eligible subjects, 125 responded via mail and 57 via the phone, yielding a response rate of 90 percent. Most women chose to fast during pregnancy, and they do so with adequate support from their spouses and family members. Most of them do not experience any adversities during fasting and even if they do, most were able to overcome them. Most women adopt a positive attitude towards fasting. However, there is a lack of basic religious knowledge among many pregnant women pertaining to the Muslim law of fasting during pregnancy. CONCLUSION: Doctors and health workers need to understand the religious obligations of a Muslim towards fasting during Ramadan. Only through this can a doctor adequately counsel Muslim patients and allow informed decision with regards to fasting. With respect to pregnant women, provisions are allowed for them not to observe fasting.

Adult↗