Lipid metabolism during fasting

These studies were conducted to understand the relationship between measures of systemic free fatty acid (FFA) reesterification and regional FFA, glycerol, and triglyceride metabolism during fasting. Indirect calorimetry was used to measure fatty acid oxidation in six men after a 60-h fast. Systemic and regional (splanchnic, renal, and leg) FFA ([(3)H]palmitate) and glycerol ([(3)H]glycerol) kinetics, as well as splanchnic triglyceride release, were measured. The rate of systemic FFA reesterification was 366 +/- 93 micromol/min, which was greater (P < 0.05) than splanchnic triglyceride fatty acid output (64 +/- 6 micromol/min), a measure of VLDL triglyceride fatty acid export. The majority of glycerol uptake occurred in the splanchnic and renal beds, although some leg glycerol uptake was detected. Systemic FFA release was approximately double that usually present in overnight postabsorptive men, yet the regional FFA release rates were of the same proportions previously observed in overnight postabsorptive men. In conclusion, FFA reesterification at rest during fasting far exceeds splanchnic triglyceride fatty acid output. This indicates that nonhepatic sites of FFA reesterification are important, and that peripheral reesterification of FFA exceeds the rate of simultaneous intracellular triglyceride fatty acid oxidation.     

Leucine metabolism during fasting and exercise

Whole body leucine kinetics were examined in seven healthy young men while in a 14-h postabsorptive state (PAS) and after a 3.5-day fast (FS). Subjects received a primed constant intravenous infusion of L-[1-13C]leucine while resting for 3 h and then while exercising on a cycle ergometer at 45% maximal O2 uptake to exhaustion. Blood samples drawn during isotopic steady state were analyzed for 13C enrichment of leucine and alpha-ketoisocaproic acid, and expired gas samples were analyzed for 13CO2. Resting leucine flux was higher in the FS, and there was a slight increase in leucine oxidation. During exercise, leucine flux did not differ between PAS and FS but leucine oxidation rose markedly. In the FS, leucine oxidation was 25 +/- 7 (SD) mumol.kg-1.h-1 at rest and rose to 75 +/- 21 mumol.kg-1.h-1 during exercise; in the PAS, oxidation was 20 +/- 5 mumol.kg-1.h-1 at rest and 52 +/- 17 mumol.kg-1.h-1 during exercise. These data indicate that the high rate of leucine oxidation previously found during exercise was increased further by a 3.5-day fast.     

Opioidergic control of gonadotrophin secretion in the prepubertal gilt during restricted feeding and realimentation

Prepubertal gilts, having undergone a 7-day period of feed restriction to a maintenance ration, were allocated to one of 4 treatments; restricted feeding at 09:00 and 17:00 h for an 8th day both with (Group RN) and without (Group R) administration of the opioid antagonist naloxone hydrochloride (1 mg.kg-1 at 09:30 h followed by 0.5 mg.kg-1 at hourly intervals for 7 h), or feed to appetite with (Group ALN) and without (Group AL) naloxone administration. Gilts were bled at 10-min intervals on Day 8 from morning to evening feed and plasma LH, FSH and prolactin concentrations were measured by radioimmunoassay. Compared with Group R gilts, Group AL gilts exhibited significantly (P less than or equal to 0.05) higher mean and maximum LH concentrations and pulsatility, lower prolactin concentrations (P less than 0.05) but no significant difference in FSH secretion. Naloxone significantly depressed the increase in LH after re-feeding (Group ALN) (P less than 0.05). Once again there were no significant effects on FSH secretion. Naloxone also significantly depressed prolactin secretion in feed-restricted gilts (P less than 0.05). These results confirm that re-feeding of feed-restricted prepubertal gilts stimulates an immediate increase in LH secretion and that this elevation is not mediated via a suppression of inhibitory endogenous opioidergic tone. Rather, naloxone treatment appeared to expose a latent inhibition of LH secretion. The control of LH secretion is distinct from that of FSH in this model.     

The melanocortin system during fasting

This paper sets out to review the implication of the melanocortin system in regulating feeding behavior and energy balance during short- and long-term food deprivation. It is discussed in relation to: (1) body fat exhaustion and the known enhanced drive for refeeding in late fasting and (2) peripheral hormonal status with emphasis on the effect of leptin administration on melanocortin gene expression according to fat store mobilization.     

Impaired regulation of corticosterone levels during fasting in aging rats.

The concentration of corticosterone in aortal blood of 3-day fasted rats decreases approximately 75% between 2- and 24-months of age. The reduced level of hormone in aging rats is not attributable to an enhanced rate of corticosterone utilization from the blood or to a diminished steroidogenic capacity of the adrenal cortex, but apparently reflects a deficiency in extraadrenal regulatory mechanisms.     

Nutritionally induced anovulation in beef Heifers: ovarian and endocrine function during realimentation and resumption of ovulation

Nutritionally induced anovulatory and cyclic Angus x Hereford heifers were used to evaluate follicular growth and concentrations of hormones and metabolites during anovulation and resumption of ovulation. Anovulatory heifers were fed to gain 0.6 (LGAIN) or 1.5 (HGAIN) kg/day until resumption of ovulation, and heifers with normal estrous cycles were fed a maintenance diet (M). Follicles >/= 4 mm in diameter were measured by daily ultrasonography in HGAIN and LGAIN heifers during one follicular wave before realimentation (Wan) and in two waves (W-2, W-1) immediately before the wave resulting in first ovulation or luteinization (W0). Ovaries of M heifers were evaluated to determine the day of ovulation of the second-wave dominant follicle (DF). Resumption of ovulation after realimentation occurred 23 days earlier in HGAIN than in LGAIN. Maximum diameter, growth rate, and persistence of dominant follicles increased, while persistence of first subordinate follicles decreased between anovulation and resumption of ovulation in anovulatory heifers. Concentrations of LH in serum were similar for HGAIN and LGAIN and gradually increased during realimentation. The increase in estradiol before the first ovulation was less in realimented heifers compared with cyclic heifers. Concentrations of insulin-like growth factor-I (IGF-I) in HGAIN and LGAIN gradually increased during realimentation but were lower than concentrations of IGF-I in cyclic heifers at ovulation. Increased diameter, growth rate, and persistence of the DF were associated with increased concentrations of LH, estradiol, and IGF-I during the transition from nutritionally induced anovulation to resumption of ovulatory cycles.     

Plasma beta-endorphin during fasting in man

To identify the effects of acute starvation on endogenous opioids in man, plasma beta-endorphin (beta-EP) was measured in 17 patients before, during and after fasting. Patients were assigned a posteriori into two groups: group A, comprised of 11 patients able to tolerate 5-7 days of fasting, and group B, comprised of 6 patients able to tolerate 10 days of fasting. Changes in plasma beta-EP, serum cortisol, circulating nutritional markers, and their relative levels were assessed on the 5th and 10th days of fasting, and on the 5th and 10th days of the refeeding period. Beta-EP had increased by the 5th day (group A: 4.74 +/- 0.42 to 6.91 +/- 0.65 pmol/l, p less than 0.01; group B: 3.60 +/- 0.48 to 5.14 +/- 0.22 pmol/l, p less than 0.05, and remained at 5.05 +/- 0.65 pmol/l on the 10th day (group B: 0.05 less than p less than 0.1) during fasting. Group B had lower levels of plasma beta-EP on the 5th day of fasting than group A (p less than 0.05). However, serum cortisol levels changed similarly in both groups. Plasma beta-EP showed no significant correlation with either the percentage of body weight lost or the body mass index (kg/m2) over this study period. These findings indicate that plasma beta-EP is elevated in the early phase of fasting, while not directly being associated with body weight changes. Plasma beta-EP is lower and less activated in subjects who are able to tolerate fasting for longer periods.     

Angiotensin-converting enzyme activity decreases during fasting

Serum angiotensin-converting enzyme (ACE) activity varies directly with thyroid hormone levels in states of altered thyroid function. Because T3 levels decrease during fasting, ACE activity was examined to ascertain if it was reduced in this low T3 condition. Eighteen obese euthyroid subjects were hospitalized and placed on a weight-maintaining diet for 4 days. Nine subjects (Group 1) underwent a fast (50 kcal/day) for 8 days. Nine (Group 2) subjects received T3 (5 micrograms q 3 h) during an identical fast. Weight loss was identical in both groups (-4.4 kg). Serum T3 fell in Group 1 from 104 +/- 8 to 50 +/- 4 ng/d/(p less than .05) but was unchanged in Group 2 (114 +/- 11 ng/dl fed vs. 120 +/- 14 ng/dl fasted). Blood pressures fell significantly in Group 1 (mean systolic: 112----104 mmHg; diastolic: 71----65 mmHg, p less than 0.05), but not in Group 2 subjects. ACE activity fell progressively in Group 1 subjects during fasting (14.4 +/- 1.6 U/ml fed vs. 12.8 +/- 1.4 U/ml fasted p less than 0.05). ACE activity was not decreased significantly early in the fast in patients given T3, but by late fast (days 6-8) was reduced to the same degree as in Group 1 subjects. Glucose and insulin levels fell similarly in both groups. Conclusions: (1) ACE activity is reduced during starvation. This effect is not mediated by T3. (2) Blood pressure reduction during fasting may result from the low T3 levels, but not from decreased ACE activity. Interpretation of serum ACE activity must be viewed in the context of a patient's diet.     

Sources of blood glycerol during fasting

To determine the source(s) of blood and very low density lipoprotein (VLDL)-triglyceride glycerol during fasting, four men ingested (2)H(2)O from 14 to 20 h into a 60-h fast to achieve ~0.5% body water enrichment. At 60 h of fasting, glycerol flux was measured using [2-(14)C]glycerol. Blood was taken for measurement of (2)H enrichment at carbon 6 of glucose and at carbon 3 of free glycerol and VLDL-triglyceride glycerol. (2)H enrichment of the 2 hydrogens bound to carbon 3 of VLDL-triglyceride glycerol was 105 +/- 2% of the (2)H enrichment of the 2 hydrogens bound to carbon 6 of glucose, indicating isotopic equilibrium between hepatic glyceraldehyde 3-P and glycerol 3-P. The (2)H enrichment of the 2 hydrogens bound to carbon 3 of free glycerol was 17 +/- 3% of VLDL-triglyceride glycerol, indicating that a significant percentage of free glycerol in blood originated from the hydrolysis of circulating VLDL-triglyceride or a pool of glycerol with similar (2)H enrichment. Glycerol flux was 6.3 +/- 1.1 micromol. kg(-1). min(-1). Glycerol appearing from nonadipose tissue sources was then approximately 1.1 micromol. kg(-1). min(-1). Seven other subjects were fasted for 12, 42, and 60 h. A small percentage of glycerol in the circulation after 12 h of fasting was enriched with (2)H. The enrichment of the 2 hydrogens bound to carbon 3 of free glycerol in the longer periods of fasting was approximately 16% of the enrichment of the 2 hydrogens bound to carbon 6 of glucose. Therefore, as much as 15-20% of systemic glycerol turnover during fasting is not from lipolysis of adipose tissue triglyceride.     

Analysis of the renin-angiotensin system during fasting in adult male rabbits.

Caloric deprivation for 3 days in adult male rabbits induced significant increases in daily urinary Na+ excretion, urinary volume and fluid intake as previously reported. These changes were accompanied by: (a) a significant reduction in plasma renin concentration; (b) an unchanged plasma renin activity; (c) a marked increase in the plasma angiotensinogen concentration; (d) a significant reduction in plasma angiotensin I; and (e) a significant increase in plasma angiotensin II. In a separate group of adult male rabbits, 3 days of caloric deprivation significantly increased the amount of converting enzyme in pulmonary parenchymal tissue. These findings correlate with the previously reported enhancement of mineralocortical hormone secretion and limiting effect of the latter on the natriuresis of caloric withdrawal. Since the increased mineralocortical hormone secretion does not prevent the natriuresis, the possibility that these striking changes in the components of the renin-angiotensin system during caloric deprivation may exert intrarenal effects is discussed.