Comasia Raguso

Fat metabolism during high-intensity exercise in endurance-trained and untrained men

To determine whether trained individuals rely more on fat than untrained persons during high-intensity exercise, six endurance-trained men and six untrained men were studied during 30 minutes of exercise at 75% to 80% maximal oxygen consumption (VO2max). The rates of appearance (Ra) and disappearance (Rd) of glycerol and free fatty acids (FFAs) were determined using [1,1,2,3,3-2H]glycerol and [1-13C]palmitate, respectively, whereas the overall rate of fatty acid oxidation was determined using indirect calorimetry. During exercise, the whole-body rate of lipolysis (ie, glycerol Ra) was higher in the trained group (7.1 +/- 1.2 v 4.5 +/- 0.7 micromol x min(-1) x kg(-1), P < .05), as was the Ra (approximately Rd) of FFA (9.0 +/- 0.9 v 5.0 +/- 1.0 micromol x min(-1) x kg(-1), P < .001). FFA utilization was higher in trained subjects even when expressed as a percentage of total energy expenditure (10% +/- 1% v 7% +/- 1%, P < .05). However, this difference in plasma FFA flux could not account for all of the difference in fatty acid oxidation between trained and untrained subjects (20.8 +/- 3.3 v 7.9 +/- 1.6 micromol x min(-1) x kg(-1), or 23% +/- 3% v 13% +/- 2% of total energy expenditure, both P < .05). Thus, the oxidation of fatty acids derived from some other source also must have been greater in the trained men. We conclude that trained athletes use more fat than untrained individuals even during intense exercise performed at the same percentage of VO2max. The additional fatty acids appear to be derived from both adipose tissue and, presumably, intramuscular triglyceride stores.

Effect of theophylline on substrate metabolism during exercise

We tested the hypothesis that adenosine is involved in regulating substrate metabolism during exercise. Seven trained cyclists were studied during 30 minutes of exercise at approximately 75% maximal oxygen uptake (VO2max). Lipid metabolism was evaluated by infusing [2H5]glycerol and [1-13C]palmitate, and glucose kinetics were evaluated by infusing [6,6-2H]glucose. Fat and carbohydrate oxidation were also measured by indirect calorimetry. The same subjects performed two identical exercise tests, but in one trial theophylline, a potent adenosine receptor antagonist, was infused for 1 hour before and throughout exercise. Theophylline did not increase whole-body lipolysis (glycerol rate of appearance [Ra]) or free fatty acid (FFA) release during exercise, but fat oxidation was lower than control values (9.5 +/- 3.0 v 18.0 +/- 4.2 micromol x min(-1) x kg(-1), P < .01). Glucose Ra was not affected by theophylline infusion, but glucose uptake was lower (31.6 +/- 4.1 v 40.4 +/- 5.0 micromol x min(-1) x kg(-1), P < .05) and glucose concentration was higher (6.4 +/- 0.6 v 5.8 +/- 0.4 mmol/L, P < .05) than in the control trial. Total carbohydrate oxidation (302.3 +/- 26.2 v 265.5 +/- 11.7 micromol x min(-1) x kg(-1), P < .06), estimated muscle glycogenolysis (270.7 +/- 23.1 v 225.1 +/- 9.7 micromol x min(-1) x kg(-1), P < .05), and plasma lactate concentration (7.9 +/- 1.6 v 5.9 +/- 1.1 mmol/L, P < .001) were also higher during the theophylline trial. These data suggest that adenosine may play a role in stimulating glucose uptake and restraining glycogenolysis but not in limiting lipolysis during exercise.

Lipid and Carbohydrate Metabolism in IDDM During Moderate and Intense Exercise

Insulin-dependent diabetes mellitus (IDDM) is characterized by a metabolic and hormonal disarray that may be more evident during exercise. However, the metabolic response to exercise of different intensities has not been evaluated in IDDM. We therefore used stable isotope techniques and indirect calorimetry to quantify substrate kinetics and oxidation during 30 min of exercise at 45 and 75% of maximal oxygen uptake (Vo2max) in seven men with IDDM (D group) infused with insulin at a constant basal rate. Normal control subjects (C group) matched for age, weight, and Vo2max were also studied. During moderate exercise, glucose uptake (Rd) was lower in the D than in the C group (15.3 ± 1.0 vs. 20.8 ± 1.6 μmol · min−1 · kg−1; P < 0.05). Carbohydrate oxidation also tended to be lower in the D group (71.0 ± 7.2 vs. 87.5 ± 10.6 μmol · min−1 · kg−1; P = 0.08). The D group relied on fat oxidation to a greater extent than did the C group (16.9 ± 1.1 vs. 10.4 ± 1.6 μmol · min−1 · kg−1; P < 0.05). The enhanced fat oxidation was not due to increased lipolysis because no differences occurred in glycerol release (Ra) or in plasma free fatty acid Ra or concentration, and the source of the extra lipid appeared to be intramuscular fat stores. These differences in substrate metabolism were not evident during exercise at 75% of Vo2max. The lower glucose uptake and oxidation in the diabetic subjects during moderate, but not intense, exercise suggest that glucose metabolism is regulated differently depending on exercise intensity. During moderate exercise, glucose uptake into muscle seems to be limiting, and the higher intramuscular triglyceride oxidation observed in IDDM might be a compensatory adaptation needed to maintain energy supply.

Metabolic Effects and Disposition of Sebacate, an Alternate Dicarboxylic Fuel Substrate

Disodium sebacate is a 10-carbon-atom dicarboxylic acid, proposed as substrate for parenteral nutrition. We investigated its pharmacokinetic profile and thermogenic effect during a short-time infusion (5 h at 10 g/h) in 7 male volunteers. Sebacate in serum and urine was measured by high-performance liquid chromatography. A single-compartment model with two linear elimination routes was fitted. Metabolic measurements (VO2, VCO2, respiratory quotient, metabolic rate) were continuously performed for 8 h (5 h during and 3 h after the infusion) by a canopy indirect calorimeter. The apparent volume of distribution of sebacate was 8.39 +/- 0.69 liters, and the plasma fractional removal rate constant was 0.0086 +/- 0.00077 min-1. The average half-life and plasma clearance were 80.6 min and 72 ml/min, respectively. The increase in metabolic rate, the decrease in respiratory quotient and the changes in ketone body, glucagon and insulin levels during the infusion were not significant. 24-hour catecholamine excretion was within normal limits. Calories administered by sebacate seem to be available for utilization without relevant metabolic side effects.

Kinetics and Thermogenesis of Medium-Chain Monocarboxylic and Dicarboxylic Acids in Man: Sebacate and Medium-Chain Triglycerides

The effects on oxygen consumption and carbon dioxide production of a constant intravenous infusion of 0.15 g of disodium sebacate (Sb), the sodic salt of a medium-chain dicarboxylic acid with 10 carbon atoms, per kilogram of body weight per hour over 5 hours and a 50% mixture of medium- and long-chain triglycerides (MCT/LCT) were compared in 10 healthy men. Oxygen consumption and carbon dioxide production were measured by indirect calorimetry. Mean oxygen consumption was about 19% higher than the basal oxygen consumption at the end of MCT/LCT infusion but was only 5% higher than the basal oxygen consumption when Sb was infused. There was an eightfold increase in plasma beta-hydroxybutyrate and acetoacetate concentrations and a threefold increase in serum insulin levels during MCT/LCT infusion, but no significant change in ketone bodies and insulin from basal values was observed during and after Sb infusion. Pharmacokinetic parameters were also computed, showing an average apparent volume of distribution of 167 mL/kg of body weight for MCTs and 112 mL/kg of body weight for Sb. The t1/2 of MCTs was 50 minutes and that of Sb was 78 minutes. Urinary excretion of Sb and its beta-oxidative by-product, suberic acid, globally accounted for 48% of the given amount of Sb. In spite of its urinary loss and slower tissue uptake compared with MCTs, Sb avoided ketone body formation or elevation in insulin levels and did not induce a significant increase in oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetics of Medium-Chain Triglycerides and Free Fatty Acids in Healthy Volunteers and Surgically Stressed Patients

To determine the hydrolysis rate of medium-chain triglycerides (MCTs) to medium-chain free fatty acids (MCFAs) and the disposition rate of MCFAs, five healthy volunteers (H) and eight surgically stressed patients (S) received 0.5 mL of Lipofundin 20% per kilogram body weight as an intravenous bolus. Serum MCTs (C8 and C10) and MCFAs were measured by high-performance liquid chromatography during the 120 minutes postinjection. A linear two-compartment model was found to be descriptive and robust: the apparent volumes of distribution were found to be similar in healthy and surgical subjects for both MCTs and MCFAs. The first-order transformation rate constant (hydrolysis) from MCTs to MCFAs was not significantly different between the H and S groups (overall 0.112 +/- 0.022/min, C8; 0.078 +/- 0.020/min, C10). The rate constant for tissue MCFA uptake from plasma was significantly different between S and H subjects both for C10 alone (H: 0.0337 +/- 0.0078; S: 0.1194 +/- 0.0240; p = .020) and for C8 and C10 together (H: 0.0382 +/- 0.0054; S: 0.1012 +/- 0.0168; p = .008), whereas it failed to attain significance when C8 alone was considered (H: 0.047 +/- 0.0077; S: 0.0829 +/- 0.0230; p = .210). These results show that use of MCTs is increased in surgical patients because of enhanced tissue uptake of the corresponding free fatty acids, whereas there does not seem to be an increase of MCT hydrolysis in response to acute disease. This would indicate that the stressed patient is in fact able to effectively use this alternative lipid substrate in the face of increased metabolic demand.

Tracer study of metabolism and tissue distribution of sebacic acid in rats.

The present study investigates the metabolic disposition of sebacic acid in rats. Three groups of experimental animals received different doses of disodium sebacate with 25 microCi of 14C-labeled molecule by intravenous injection. In the first group radioactivity plasma elimination curves were examined for two administered doses (80 and 160 mg). In the second group, expired 14CO2, urine tracer and feces tracer were counted after intravenous administration of 160 mg of sebacate. The animals of the third group were sacrificed at different times after intravenous administration of 160 mg of sebacate, and tracer elimination curves were obtained for several organs. The plasma half-life of sebacate is 38.71 min; about 35% of the administered tracer was excreted in the urine as unchanged sebacate; about 25% was eliminated as 14CO2 in expired air. Disposition of sebacate was complete within 4 h of administration. The sebacate half-life is longest in adipose tissue (135 min) and in liver (74 min), sites of likely transformation. In all other organs examined, the sebacate half-life is similar to that in plasma.

A rapid GLC method for the direct analysis of plasma medium chain fatty acids

A new, rapid, gas-liquid-chromatographic (GLC) method for the direct determination of plasma medium-chain fatty acids (MCFA) (from C8 to C12) which does not require derivatization procedures is described. Analysis of underivatized MCFA by GLC showed a detection limit ranging from 0.50 to 0.217 microgram depending on chain length: the longer the chain, the higher the detection limit. Compared with the HPLC and GLC methods currently described in the literature, this GLC procedure appears to be easy, adequately sensitive, accurate and well reproducible for those MCFA, like n-octanoic and n-decanoic acids, present in plasma after p.o. or i.v. MCT administration and it requires a short time (about 30 min) for complete processing.