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The Danish Fitness and Nutrition Council has examined the scientific literature to evaluate the performance and health-related aspects of consuming dietary supplements in the context of physical activity. Certain nutritional supplements such as creatine and caffeine have documented ergogenic effects in specific situations. However, for the moderately physically active adult and healthy individual, who already consumes an energy- and nutrient balanced diet, consuming any currently legal dietary supplement does not seem to confer additional benefits on performance or health. Udgivelsesdato: 2009-Aug-17

We studied the effect of local muscle adaptations on free fatty acid (FFA) metabolism during prolonged exercise in trained and untrained subjects. Six trained (T) and six untrained (UT) young human males exercised for 3 h at 60% of their individual maximal dynamic knee extension capacity. The contribution of blood and plasma metabolites as well as intramuscular substrates to oxidative metabolism in the thigh was calculated from arteriovenous differences and femoral-venous blood flow as well as from muscle biopsies in subjects that were continuously infused with [1-14C]palmitate. Arterial plasma FFA concentration increased over time in both T and UT. Fractional uptake of FFA across the thigh remained unchanged over time in T (15%) but decreased in UT (from 15 to 7%), especially during the last hour of exercise. Thus FFA uptake increased linearly over time in T (96 +/- 20 to 213 +/- 20 mumol.min-1.kg-1), whereas it leveled off after 2 h in UT (74 +/- 16 to 133 +/- 46) even though FFA delivery increased similarly in T and UT. Percentage oxidation was similar in T and UT; thus total FFA oxidation was higher in T. Glucose uptake increased in both groups over time and was significantly higher in UT during the last hour of exercise. In conclusion, during prolonged knee extension exercise, FFA uptake increases linearly with FFA delivery in the trained thigh, whereas in the untrained thigh uptake becomes saturated with time. This difference partly explains the increased lipid oxidation in T vs. UT and suggests, furthermore, that local muscle adaptations to training are important for the utilization of FFA during prolonged exercise.

1. The influence of training-induced adaptations in skeletal muscle tissue on the choice between carbohydrates (CHO) and lipids as well as the extra- vs. intracellular substrate utilization was investigated in seven healthy male subjects performing one-legged knee-extension exercise. In each subject one of the knee extensors was endurance trained for eight weeks, whereafter the trained (T) and non-trained (NT) thighs were investigated a week apart. 2. The activity of beta-hydroxy-acyl-coenzyme A dehydrogenase (HAD) and capillary density in the knee extensors were significantly larger in T than in NT. 3. During dynamic knee-extension exercise, performed at the same absolute intensity for 2 h, femoral venous blood flow was lower in T than in NT (P < 0.05), but oxygen uptake was similar. 4. Respiratory quotient (RQ) values over the exercising thigh, averaging 0.81 (T) vs. 0.91 (NT; P < 0.05) indicated that a shift towards a larger fat combustion occurred with endurance training. 5. Both free fatty acids (FFA) and serum triacylglycerol contributed to the utilization of fat in NT and T muscles with no significant contribution from muscle fibre triacylglycerol. 6. At high plasma FFA concentrations net uptake of FFA plateaued in NT but not in T muscles. 7. The findings suggest that FFA uptake in exercising muscle is a saturable process and that the transport capacity is enhanced by training. The lower CHO utilization in the T leg was mainly a function of the glycogenolysis of the muscle being reduced. Hormones such as insulin, noradrenaline and adrenaline are unlikely to play a role in this shift as differences in plasma levels during T and NT leg exercise were small and insignificant, implying that local structural and functional adaptations of the training muscle are crucial for the observed shifts in the metabolic response to exercise.

1. The effects of unaccustomed eccentric exercise on exercise metabolism during a subsequent bout of graded concentric exercise were investigated in seven healthy male subjects. Arterial and bilateral femoral venous catheters were inserted 2 days after eccentric exercise of one thigh (eccentric thigh) and blood samples were taken before and during graded two-legged concentric knee-extensor exercise. Muscle biopsies were obtained from the eccentric and control vastus lateralis before (rest) and after (post) the concentric exercise bout. 2. Maximal knee-extensor concentric exercise capacity was decreased by an average of 23 % (P < 0.05) in the eccentric compared with the control thigh. 3. The resting muscle glycogen content was lower in the eccentric thigh than in the control thigh (402 +/- 30 mmol (kg dry wt)-1 vs. 515 +/- 26 mmol (kg dry wt)-1, means +/- s.e.m., P < 0.05), and following the two-legged concentric exercise this difference substantially increased (190 +/- 46 mmol (kg dry wt)-1 vs. 379 +/- 58 mmol (kg dry wt)-1, P < 0.05) despite identical power and duration of exercise with the two thighs. 4. There was no measurable difference in glucose uptake between the eccentric and control thigh before or during the graded two-legged concentric exercise. Lactate release was higher from the eccentric thigh at rest and, just before termination of the exercise bout, release of lactate decreased from this thigh (suggesting decreased glycogenolysis), whereas no decrease was found from the contralateral control thigh. Lower glycerol release from the eccentric thigh during the first, lighter part of the exercise (P < 0.05) suggested impaired triacylglycerol breakdown. 5. At rest, sarcolemmal GLUT4 glucose transporter content and glucose transport were similar in the two thighs, and concentric exercise increased sarcolemmal GLUT4 content and glucose transport capacity similarly in the two thighs. 6. It is concluded that in muscle exposed to prior eccentric contractions, exercise at a given power output requires a higher relative workload than in undamaged muscle. This increases utilization of the decreased muscle glycogen stores, contributing to decreased endurance.

The effect of increasing plasma concentrations of free fatty acids on substrate utilization in muscle during exercise was investigated in 11 healthy young males. One hour of dynamic knee extension at 80% of knee-extensor maximal work capacity was performed first with one leg and then with the other leg during infusion of Intralipid and heparin. Substrate utilization was assessed from arterial and femoral venous blood sampling as well as from muscle biopsies. Intralipid infusion increased mean plasma free fatty acid concentrations from 0.54 +/- 0.08 to 1.12 +/- 0.09 (SE) mM. Thigh glucose uptake during rest, exercise, and recovery was decreased by 64, 33, and 42%, respectively, by Intralipid, whereas muscle glycogen breakdown and release of lactate, pyruvate, and citrate were unaffected. Concentrations of glucose, glucose 6-phosphate, and lactate in muscle before and at termination of exercise were unaffected by Intralipid. During exercise, net leg uptake of plasma free fatty acids was not measurably increased by Intralipid, whereas uptake of ketone bodies was. Local respiratory quotient across the leg was not changed by Intralipid (control 0.87 +/- 0.02, Intralipid 0.86 +/- 0.02). Arterial concentrations of insulin, norepinephrine, and epinephrine were similar in the two trials. It is concluded that at rest and during exercise at a moderate intensity (requiring approximately equal contributions from fat and carbohydrate metabolism), muscle carbohydrate metabolism is affected only with regard to uptake of glucose when plasma concentrations of lipid and lipid metabolites are increased. This effect may be by direct inhibition of glucose transport rather than by the classic glucose-fatty acid cycle.

SummaryExercise is essential in regulating energy metabolism and whole-body insulin sensitivity. To explore the exercise signaling network, we undertook a global analysis of protein phosphorylation in human skeletal muscle biopsies from untrained healthy males before and after a single high-intensity exercise bout, revealing 1,004 unique exercise-regulated phosphosites on 562 proteins. These included substrates of known exercise-regulated kinases (AMPK, PKA, CaMK, MAPK, mTOR), yet the majority of kinases and substrate phosphosites have not previously been implicated in exercise signaling. Given the importance of AMPK in exercise-regulated metabolism, we performed a targeted in vitro AMPK screen and employed machine learning to predict exercise-regulated AMPK substrates. We validated eight predicted AMPK substrates, including AKAP1, using targeted phosphoproteomics. Functional characterization revealed an undescribed role for AMPK-dependent phosphorylation of AKAP1 in mitochondrial respiration. These data expose the unexplored complexity of acute exercise signaling and provide insights into the role of AMPK in mitochondrial biochemistry.