Effects of high fat provision on muscle PDH activation and malonyl-CoA content in moderate exercise.

This study examined the effects of elevated free fatty acid (FFA) provision on the regulation of pyruvate dehydrogenase (PDH) activity and malonyl-CoA (M-CoA) content in human skeletal muscle during moderate-intensity exercise. Seven men rested for 30 min and cycled for 10 min at 40% and 10 min at 65% of maximal O(2) uptake while being infused with either Intralipid and heparin (Int) or saline (control). Muscle biopsies were taken at 0, 1 (rest-to-exercise transition), 10, and 20 min. Exercise plasma FFA were elevated (0.99 +/- 0.11 vs. 0.33 +/- 0.03 mM), and the respiratory exchange ratio was reduced during Int (0.87 +/- 0.02) vs. control (0.91 +/- 0.01). PDH activation was lower during Int at 1 min (1.33 +/- 0.19 vs. 2.07 +/- 0.14 mmol. min(-1). kg(-1) wet muscle) and throughout exercise. Muscle pyruvate was reduced during Int at rest [0.17 +/- 0.03 vs. 0.25 +/- 0.03 mmol/kg dry muscle (dm)] but increased above control during exercise. NADH was higher during Int vs. control at rest and 1 min of exercise (0.122 +/- 0.016 vs. 0.102 +/- 0.005 and 0.182 +/- 0.016 vs. 0.150 +/- 0.016 mmol/kg dm), but not at 10 and 20 min. M-CoA was lower during Int vs. control at rest and 20 min of exercise (1.12 +/- 0.22 vs. 1.43 +/- 0.17 and 1.33 +/- 0.16 vs. 1.84 +/- 0.17 micromol/kg dm). The reduced PDH activation with elevated FFA during the rest-to-exercise transition was related to higher mitochondrial NADH at rest and 1 min of exercise and lower muscle pyruvate at rest. The decreased M-CoA may have increased fat oxidation during exercise with elevated FFA by reducing carnitine palmitoyltransferase I inhibition and increasing mitochondrial FFA transport.

Skeletal muscle malonyl-CoA content at the onset of exercise at varying power outputs in humans.

To investigate the regulation of intramuscular fuel selection, we measured the malonyl-CoA (M-CoA) content in human skeletal muscle at three exercise power outputs [35, 65, and 90% maximal rate of O2 consumption (VO2 max)]. Four males and four females cycled for 10 min at one power output on three separate occasions with muscle biopsies sampled at rest and at 1 and 10 min. The respiratory exchange ratio was 0.84 +/- 0.03, 0.92 +/- 0.02, and >1.0 at 35, 65 and 90% VO2 max, respectively. Muscle lactate content increased and phosphocreatine content decreased as a function of power output. Pyruvate dehydrogenase a activity increased from 0.40-0.64 mmol . kg wet muscle-1 . min-1 at rest to 1.57 +/- 0.28, 2.80 +/- 0.41, and 3. 28 +/- 0.27 mmol . kg wet muscle-1 . min-1 after 1 min of cycling at the three power outputs, respectively. Mean resting M-CoA contents were similar at all power outputs (1.85-1.98 micromol/kg dry muscle). During exercise at 35% VO2 max, M-CoA decreased from rest at 1 min (1.85 +/- 0.29 to 1.20 +/- 0.12 micromol/kg dry muscle) but returned to rest level by 10 min (1.86 +/- 0.25 micromol/kg dry muscle). M-CoA content did not decrease during cycling at 65% VO2 max. At 90% VO2 max, M-CoA did not increase despite significant acetyl-CoA accumulation (the substrate for M-CoA synthesis). The data suggest that a decrease in M-CoA content is not required for the increase in free fatty acid uptake and oxidation that occurs during exercise at 35 and 65% VO2 max. Furthermore, M-CoA content does not increase during exercise at 90% VO2 max and does not contribute to the lower rate of fat oxidation at this power output.

Effects of increased fat availability on fat-carbohydrate interaction during prolonged exercise in men.

The study examined the existence and regulation of fat-carbohydrate interaction during low- and moderate-intensity exercise. Eight males cycled for 10 min at 40% and 60 min at 65% maximal O2 uptake (VO2max) while infused with either Intralipid and heparin (Int) or saline (Con). Before exercise, plasma arterial free fatty acid (FFA) was 0.69 +/- 0.04 mM (Int) vs. 0.25 +/- 0.04 mM (Con). Muscle biopsies were taken at rest and at 10, 20, and 70 min of exercise. Arterial and femoral venous blood samples and expired gases were collected simultaneously throughout exercise, and blood flow was estimated from pulmonary O2 uptake and the leg arterial-venous O2 difference. Respiratory exchange ratio was higher in Con (0.94 +/- 0.01) compared with Int (0.91 +/- 0.01). Mean net leg FFA uptake was higher in Int (0.16 +/- 0.03 vs. 0.04 +/- 0.01 mmol/min), and net lactate efflux was reduced (Int, 1.55 +/- 0.36 vs. Con, 3.07 +/- 0.47 mmol/min). Leg net glucose uptake was unaffected by Int. Muscle glycogen degradation was 23% lower in Int [230 +/- 29 vs. 297 +/- 36 mmol glucosyl units/kg dry muscle (dm)]. Pyruvate dehydrogenase activity in the a form (PDHa) was lower during Int (1.61 +/- 0.17 vs. 2.22 +/- 0.24 mmol.min-1.kg wet muscle-1), and muscle citrate was higher (0.59 +/- 0.04 vs. 0.48 +/- 0.04 mmol/kg dm). Muscle lactate, phosphocreatine, ATP, acetyl-CoA, acetyl-carnitine, and P(i) were unaffected by Int. Calculated free AMP was significantly lower in Int compared with Con at 70 min of exercise (3.3 +/- 0.8 vs. 1.5 +/- 0.3 mumol/kg dm). The high FFA-induced reduction in glycogenolysis and carbohydrate oxidation at 65% VO2max appears to be due to regulation at several sites. The reduced flux through phosphorylase and phosphofructokinase during Int may have been due to reduced free AMP accumulation and increased cytoplasmic citrate. The mechanism for reduced PDH transformation to the a form is unknown but suggests reduced flux through PDH.

Effect of oral creatine supplementation on muscle [PCr] and short-term maximum power output.

Our purpose was to determine the effect of creatine supplementation on power output during a 30-s maximal cycling (Wingate) test. Nine males underwent 3 randomly ordered tests following ingestion of a creatine supplementation (CRE), placebo (PLA), and control (CON) CRE was ingested as creatine monohydrate (CrH2O) dissolved in a flavored drink (20g.d-1 for 3 d), while PLA consisted of the drink only. Tests were performed 14 d apart on a Monarch ergometer modified for immediate resistance loading. Needle biopsies were taken from the vastus lateralis at the end of each treatment period and before the exercise test. No difference was found between conditions for peak, mean 10-s, and mean 30-s power output, percent fatigue, or post-exercise blood lactate concentration. Similarly, no difference between conditions was observed for ATP, phosphocreatine (PCr), or total creatine (TCr); however, the TCr/ATP was higher in the CRE condition (P < 0.05) than in the CON and PLA conditions. Findings suggest that 3 d of oral Cr supplementation does not increase resting muscle PCr concentration and has no effect on performance during a single short-term maximal cycling task.

Human skeletal muscle malonyl-CoA at rest and during prolonged submaximal exercise.

Previous literature has indicated that contraction-induced decreases in malonyl-CoA are instrumental in the regulation of fatty acid oxidation during prolonged submaximal exercise. This study was designed to measure malonyl-CoA in human vastus lateralis muscle at rest and during submaximal exercise. Eight males and one female cycled for 70 min (10 min at 40% and 60 min at 65% maximal O2 uptake). Needle biopsies were obtained at rest and at 10 min, 20 min, and 70 min of exercise. Malonyl-CoA content in preexercise biopsy samples determined by high-performance liquid chromatography (HPLC) was 1.53 +/- 0.18 micromol/kg dry mass (dm). Malonyl-CoA content did not change significantly during exercise (1.39 +/- 0.21 at 10 min, 1.46 +/- 0.14 at 20 min, and 1.22 +/- 0.15 micromol/kg dm at 70 min). In contrast, malonyl-CoA content determined by HPLC in perfused rat red gastrocnemius muscle decreased significantly during 20 min of stimulation at 0.7 Hz [3.44 +/- 0.54 to 1.64 +/- 0.23 nmol/g dm, (n=9)]. We conclude that human skeletal muscle malonyl-CoA content 1) is less than reported in rat skeletal muscle at rest, 2) does not decrease with prolonged submaximal exercise, and 3) is not predictive of increased fatty acid oxidation during exercise.